@article{pham_linova_smith_brown_elhanafi_fan_lavoie_woodley_carbonell_2024, title={Novel multimodal cation-exchange membrane for the purification of a single-chain variable fragment from Pichia pastoris supernatant}, volume={1718}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2024.464682}, abstractNote={A novel salt-tolerant cation-exchange membrane, prepared with a multimodal ligand, 2-mercaptopyridine-3-carboxylic acid (MMC-MPCA), was examined for its purification properties in a bind-and-elute mode from the high conductivity supernatant of a Pichia pastoris fermentation producing and secreting a single-chain variable fragment (scFv). If successful, this approach would eliminate the need for a buffer exchange prior to product capture by ion-exchange. Two fed-batch fermentations of Pichia pastoris resulted in fermentation supernatants reaching an scFv titer of 395.0 mg/L and 555.7 mg/L, both with a purity of approximately 83%. The MMC-MPCA membrane performance was characterized in terms of pH, residence time (RT), scFv load, and scFv concentration to identify the resulting dynamic binding capacity (DBC), yield, and purity achieved under optimal conditions. The MMC-MPCA membrane exhibited the highest DBC of 39.06 mg/mL at pH 5.5, with a residence time of 1 minute, while reducing the pH below 5.0 resulted in a significant decrease of the DBC to around 2.5 mg/mL. With almost no diffusional limitations, reducing the RT from 2 to 0.2 min did not negatively impact the DBC of the MMC-MPCA membrane, resulting in a significant improvement in productivity of up to 180 mg/mL/min at 0.2 min RT. Membrane fouling was observed when reusing the membranes at 0.2 and 0.5 min RT, likely due to the enhanced adsorption of impurities on the membrane. Changing the amount of scFv loaded onto the membrane column did not show any changes in yield, instead a 10-20% loss of scFv was observed, which suggested that some of the produced scFv were fragmented or had aggregated. When performing the purification under the optimized conditions, the resulting purity of the product improved from 83% to approximately 92-95%.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Pham, Dan N. and Linova, Marina Y. and Smith, William K. and Brown, Hunter and Elhanafi, Driss and Fan, Jinxin and Lavoie, Joseph and Woodley, John M. and Carbonell, Ruben G.}, year={2024}, month={Mar} }
 @article{lavoie_fan_pourdeyhimi_boi_carbonell_2023, title={Advances in high-throughput, high-capacity nonwoven membranes for chromatography in downstream processing: A review}, volume={5}, ISSN={["1097-0290"]}, DOI={10.1002/bit.28457}, abstractNote={Abstract}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Lavoie, Joseph and Fan, Jinxin and Pourdeyhimi, Behnam and Boi, Cristiana and Carbonell, Ruben G.}, year={2023}, month={May} }
 @article{kilgore_chu_bhandari_fischler_carbonell_crapanzano_menegatti_2023, title={Development of peptide affinity ligands for the purification of polyclonal and monoclonal Fabs from recombinant fluids}, volume={1687}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2022.463701}, abstractNote={Engineered multi-specific monoclonal antibodies (msAbs) and antibody fragments offer valuable therapeutic options against metabolic disorders, aggressive cancers, and viral infections. The advancement in molecular design and recombinant expression of these next-generation drugs, however, is not equaled by the progress in downstream bioprocess technology. The purification of msAbs and fragments requires affinity adsorbents with orthogonal biorecognition of different portions of the antibody structure, namely its Fc (fragment crystallizable) and Fab (fragment antigen-binding) regions or the CH1-3 and CL chains. Current adsorbents rely on protein ligands that, while featuring high binding capacity and selectivity, need harsh elution conditions and suffer from high cost, limited biochemical stability, and potential release of immunogenic fragments. Responding to these challenges, we undertook the de novo discovery of peptide ligands that target different regions of human Fab and enable product release under mild conditions. The ligands were discovered by screening a focused library of 12-mer peptides against a feedstock comprising human Fab and Chinese hamster ovary host cell proteins (CHO HCPs). The identified ligands were evaluated via binding studies as well as molecular docking simulations, returning excellent values of binding capacity (Qmax ∼ 20 mg of Fab per mL of resin) and dissociation constant (KD = 2.16·10-6 M). Selected ligand FRWNFHRNTFFP and commercial Protein L ligands were further characterized by measuring the dynamic binding capacity (DBC10%) at different residence times (RT) and performing the purification of polyclonal and monoclonal Fabs from CHO-K1 cell culture fluids. The peptide ligand featured DBC10% ∼ 6-16 mg/mL (RT of 2 min) and afforded values of yield (93-96%) and purity (89-96%) comparable to those provided by Protein L resins.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Kilgore, Ryan and Chu, Wenning and Bhandari, Dipendra and Fischler, David and Carbonell, Ruben G. and Crapanzano, Michael and Menegatti, Stefano}, year={2023}, month={Jan} }
 @article{mukherjee_yow_sarakbi_menegatti_v. gurgel_carbonell_bobay_2023, title={Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase}, volume={102}, ISSN={["1476-928X"]}, DOI={10.1016/j.compbiolchem.2022.107797}, abstractNote={Butyrylcholinesterase (BChE) is recognized as a high value biotherapeutic in the treatment of Alzheimer's disease and drug addiction. This study presents the rational design and screening of an in-silico library of trimeric peptides against BChE and the experimental characterization of peptide ligands for purification. The selected peptides consistently afforded high BChE recovery (> 90 %) and purity, yielding up to a 1000-fold purification factor. This study revealed a marked anti-correlated conformational movement governed by the ionic strength and pH of the aqueous environment, which ultimately controls BChE binding and release during chromatographic purification; and highlighted the role of residues within and allosteric to the catalytic triad of BChE in determining biorecognition, thus providing useful guidance for ligand design and affinity maturation.}, journal={COMPUTATIONAL BIOLOGY AND CHEMISTRY}, author={Mukherjee, Rudra Palash and Yow, Geok-Yong and Sarakbi, Samuel and Menegatti, Stefano and V. Gurgel, Patrick and Carbonell, Ruben G. and Bobay, Benjamin G.}, year={2023}, month={Feb} }
 @article{fan_sripada_pham_linova_woodley_menegatti_boi_carbonell_2023, title={Purification of a monoclonal antibody using a novel high-capacity multimodal cation exchange nonwoven membrane}, volume={317}, ISSN={["1873-3794"]}, DOI={10.1016/j.seppur.2023.123920}, abstractNote={A high-capacity, multimodal cation exchange (MMC) chromatographic membrane was developed by conjugating a multimodal ligand – 2-mercaptopyridine-3-carboxylic acid (MPCA) – on a polybutylene terepthalate (PBT) nonwoven fabric. The membrane features an equilibrium binding capacity of ≈ 1000 mg of human polyclonal IgG (IgG) per g of membrane and dynamic binding capacities (DBC10%) ranging from 77.5 to 115.1 mg/mL (residence times of 1 and 5 min, respectively); these values are 2-to-3-fold higher than those of commercial MMC adsorbents. The effects of buffer composition, pH, conductivity on the binding behavior of the MMC-MPCA membrane were investigated in detail. As a moderate cation exchange binder, MPCA enables effective protein elution using buffers with mild pH (8.0–9.0) and conductivity (≈13 mS/cm), thus circumventing the harsh conditions often needed in multimodal chromatography. The MMC-MPCA membrane was evaluated for product capture in bind-and-elute mode on a Chinese hamster ovary (CHO) cell culture harvest containing therapeutic monoclonal antibodies, using commercial multimodal (Capto MMC and MX-Trp-650M) and affinity (AF-rProtein A HC-650F) resins as controls. The MMC-MPCA membrane outperformed the multimodal resins in terms of binding capacity as well as clearance of host cell proteins (HCPs) and aggregates. The membrane was then evaluated by polishing the mAb from a Protein A eluate in bind-and-elute mode. The MMC-MPCA membrane reduced the level of high molecular weight components from 11% to 4% and the HCP content from 1319.7 ppm to 48.7 ppm (LRV of 1.4). Most notably, proteomics analysis of the product demonstrated the clearance of a significant fraction of persistent, high-risk HCPs from the Protein A eluate.}, journal={SEPARATION AND PURIFICATION TECHNOLOGY}, author={Fan, Jinxin and Sripada, Sobhana A. and Pham, Dan N. and Linova, Marina Y. and Woodley, John M. and Menegatti, Stefano and Boi, Cristiana and Carbonell, Ruben G.}, year={2023}, month={Jul} }
 @article{boi_malavasi_carbonell_gilleskie_2022, title={A direct comparison between membrane adsorber and packed column chromatography performance (vol 1612, 460629, 2020)}, volume={1666}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2022.462852}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Boi, Cristiana and Malavasi, Andrea and Carbonell, Ruben G. and Gilleskie, Gary}, year={2022}, month={Mar} }
 @article{fan_barbieri_shastry_menegatti_boi_carbonell_2022, title={Purification of Adeno-Associated Virus (AAV) Serotype 2 from Spodoptera frugiperda (Sf9) Lysate by Chromatographic Nonwoven Membranes}, volume={12}, ISSN={["2077-0375"]}, DOI={10.3390/membranes12100944}, abstractNote={The success of adeno-associated virus (AAV)-based therapeutics in gene therapy poses the need for rapid and efficient processes that can support the growing clinical demand. Nonwoven membranes represent an ideal tool for the future of virus purification: owing to their small fiber diameters and high porosity, they can operate at high flowrates while allowing full access to target viral particles without diffusional limitations. This study describes the development of nonwoven ion-exchange membrane adsorbents for the purification of AAV2 from an Sf9 cell lysate. A strong anion-exchange (AEX) membrane was developed by UV grafting glycidyl methacrylate on a polybutylene terephthalate nonwoven followed by functionalization with triethylamine (TEA), resulting in a quaternary amine ligand (AEX-TEA membrane). When operated in bind-and-elute mode at a pH higher than the pI of the capsids, this membrane exhibited a high AAV2 binding capacity (9.6 × 1013 vp·mL−1) at the residence time of 1 min, and outperformed commercial cast membranes by isolating AAV2 from an Sf9 lysate with high productivity (2.4 × 1013 capsids·mL−1·min−1) and logarithmic reduction value of host cell proteins (HCP LRV ~ 1.8). An iminodiacetic acid cation-exchange nonwoven (CEX-IDA membrane) was also prepared and utilized at a pH lower than the pI of capsids to purify AAV2 in a bind-and-elute mode, affording high capsid recovery and impurity removal by eluting with a salt gradient. To further increase purity, the CEX-IDA and AEX-TEA membranes were utilized in series to purify the AAV2 from the Sf9 cell lysate. This membrane-based chromatography process also achieved excellent DNA clearance and a recovery of infectivity higher that that reported using ion-exchange resin chromatography.}, number={10}, journal={MEMBRANES}, author={Fan, Jinxin and Barbieri, Eduardo and Shastry, Shriarjun and Menegatti, Stefano and Boi, Cristiana and Carbonell, Ruben G.}, year={2022}, month={Oct} }
 @article{sripada_chu_williams_teten_mosley_carbonell_lenhoff_cramer_bill_yigzaw_et al._2022, title={Towards continuous mAb purification: Clearance of host cell proteins from CHO cell culture harvests via "flow-through affinity chromatography" using peptide-based adsorbents}, volume={119}, ISSN={["1097-0290"]}, url={https://doi.org/10.1002/bit.28096}, DOI={10.1002/bit.28096}, abstractNote={Abstract}, number={7}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, publisher={Wiley}, author={Sripada, Sobhana Alekhya and Chu, Wenning and Williams, Taufika Islam and Teten, Matthew A. and Mosley, Brian J. and Carbonell, Ruben G. and Lenhoff, Abraham M. and Cramer, Steven M. and Bill, Jerome and Yigzaw, Yinges and et al.}, year={2022}, month={Apr} }
 @article{lavoie_islam_blackburn_carbonell_menegatti_2021, title={Development of Peptide Ligands for Targeted Capture of Host Cell Proteins from Cell Culture Production Harvests}, volume={2261}, ISBN={["978-1-0716-1185-2"]}, ISSN={["1940-6029"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85099721618&partnerID=MN8TOARS}, DOI={10.1007/978-1-0716-1186-9_31}, abstractNote={Capture of host cell proteins (HCPs) from cell culture production harvests is critical to ensure the maximum levels specified by international regulatory bodies of product purity for therapeutic monoclonal antibodies (mAbs). Peptide ligands that selectively target the whole spectrum of the HCPs, while letting the mAb product flow through unbound, are an ideal complement to the affinity-based capture step via Protein A chromatography. In this work, we describe the development of HCP-binding peptide ligands, especially focusing on the steps of (1) peptide selection via library screening and (2) quantification of HCP removal via proteomics by mass spectrometry.}, journal={PROTEOMIC PROFILING, 2 EDITION}, author={Lavoie, R. Ashton and Islam, Taufika and Blackburn, Williams R. Kevin and Carbonell, Ruben G. and Menegatti, Stefano}, year={2021}, pages={489–506} }
 @article{fan_boi_lemma_lavoie_carbonell_2021, title={Iminodiacetic Acid (IDA) Cation-Exchange Nonwoven Membranes for Efficient Capture of Antibodies and Antibody Fragments}, volume={11}, ISSN={["2077-0375"]}, DOI={10.3390/membranes11070530}, abstractNote={There is strong need to reduce the manufacturing costs and increase the downstream purification efficiency of high-value therapeutic monoclonal antibodies (mAbs). This paper explores the performance of a weak cation-exchange membrane based on the coupling of IDA to poly(butylene terephthalate) (PBT) nonwoven fabrics. Uniform and conformal layers of poly(glycidyl methacrylate) (GMA) were first grafted to the surface of the nonwovens. Then IDA was coupled to the polyGMA layers under optimized conditions, resulting in membranes with very high permeability and binding capacity. This resulted in IgG dynamic binding capacities at very short residence times (0.1–2.0 min) that are much higher than those achieved by the best cation-exchange resins. Similar results were obtained in the purification of a single-chain (scFv) antibody fragment. As is customary with membrane systems, the dynamic binding capacities did not change significantly over a wide range of residence times. Finally, the excellent separation efficiency and potential reusability of the membrane were confirmed by five consecutive cycles of mAb capture from its cell culture harvest. The present work provides significant evidence that this weak cation-exchange nonwoven fabric platform might be a suitable alternative to packed resin chromatography for low-cost, higher productivity manufacturing of therapeutic mAbs and antibody fragments.}, number={7}, journal={MEMBRANES}, author={Fan, Jinxin and Boi, Cristiana and Lemma, Solomon Mengistu and Lavoie, Joseph and Carbonell, Ruben G.}, year={2021}, month={Jul} }
 @article{lemma_boi_carbonell_2021, title={Nonwoven Ion-Exchange Membranes with High Protein Binding Capacity for Bioseparations}, volume={11}, ISSN={["2077-0375"]}, DOI={10.3390/membranes11030181}, abstractNote={This study presents the preparation and characterization of UV-grafted polybutylene terepthalate (PBT) ion exchange nonwoven membranes for chromatographic purification of biomolecules. The PBT nonwoven was functionalized with sulfonate and secondary amine for cation and anion exchange (CEX and AEX), respectively. The anion exchange membrane showed an equilibrium static binding capacity of 1300 mg BSA/g of membrane, while the cationic membranes achieved a maximum equilibrium binding capacity of over 700 mg hIgG/g of membrane. The CEX and AEX membranes resulted in dynamic binding capacities under flow conditions, with a residence time of 0.1 min, of 200 mg hIgG/mL of membrane and 55 mg BSA/mL of membrane, respectively. The selectivity of the PBT-CEX membranes was demonstrated by purifying antibodies and antibody fragments (hIgG and scFv) from CHO cell culture supernatants in a bind-an-elute mode. The purity of the eluted samples exceeded 97%, with good log removal values (LRV) for both host cell proteins (HCPs) and DNA. The PBT-AEX nonwoven membranes exhibited a DNA LRV of 2.6 from hIgG solutions in a flow-through mode with little loss of product. These results indicate that these membranes have significant potential for use in downstream purification of biologics.}, number={3}, journal={MEMBRANES}, author={Lemma, Solomon Mengistu I and Boi, Cristiana and Carbonell, Ruben G.}, year={2021}, month={Mar} }
 @article{lavoie_chu_lavoie_hetzler_williams_carbonell_menegatti_2021, title={Removal of host cell proteins from cell culture fluids by weak partitioning chromatography using peptide-based adsorbents}, volume={257}, ISSN={["1873-3794"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85093930679&partnerID=MN8TOARS}, DOI={10.1016/j.seppur.2020.117890}, abstractNote={This work presents the removal of host cell proteins (HCPs) from a Chinese Hamster Ovary clarified cell culture fluid (CHO CCCF) containing a therapeutic monoclonal antibody (mAb) by weak partitioning chromatography (WPC). The chromatographic adsorbents were produced by functionalizing Toyopearl resin with HCP-binding tetrameric multipolar (4MP) or hexameric hydrophobic/cationic (6HP) peptides. The CCCF was loaded on columns packed with either 4MP-Toyopearl or 6HP-Toyopearl resin only, or a 4MP and 6HP resin mixture at different values of residence time (RT: 0.5, 1, 2, and 5 min). The temporal profiles of concentration of HCPs and mAb in the effluents confirmed the binding mechanism by WPC, where both HCPs and mAb are initially bound by the peptide ligands, but, as more CCCF is fed to the column, the incoming HCPs displace the bound mAbs. In particular, 4MP was shown to capture more selectively high molecular weight HCPs, while 6HP was more effective in binding low molecular weight HCPs. Under optimal loading conditions (~60–80 g of proteins per L of adsorbent; RT of 5 min), the 6HP+4MP-Toyopearl adsorbent provided mAb yield and purity of >80% and up to 90%, respectively. Conversely, the control resin Toyopearl SuperQ-650 M resulted in 70% yield and 75% purity under the same conditions. Proteomic analysis of the effluents demonstrated that 6HP+4MP-Toyopearl adsorbent removes HCPs known for their immunogenicity or IgG co-elution or degradation, demonstrating the potential of these peptide-based resins as HCP scrubbers in mAb purification processes.}, journal={SEPARATION AND PURIFICATION TECHNOLOGY}, author={Lavoie, R. Ashton and Chu, Wenning and Lavoie, Joseph H. and Hetzler, Zachary and Williams, Taufika Islam and Carbonell, Ruben and Menegatti, Stefano}, year={2021}, month={Feb} }
 @article{boi_malavasi_carbonell_gilleskie_2020, title={A direct comparison between membrane adsorber and packed column chromatography performance}, volume={1612}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2019.460629}, abstractNote={The purpose of this work was to compare side by side the performance of packed bed and membrane chromatography adsorption processes for protein purification. The comparison was performed using anion exchange media with the same ligand immobilized on the adsorbing surface, namely the strong Q quaternary ammonium group, R-CH2-N+-(CH3)3, and bovine serum albumin (BSA) as a model protein. In addition, the stationary phase volume was held constant for each geometry (3 mL) and runs were executed using the same mobile phase superficial velocity. As expected, the packed bed column showed higher equilibrium binding of BSA at 66.9 mg/mL versus 43.04 mg/mL for the membrane adsorber. Dynamic binding capacities were also higher in the packed bed; for example, at 97.5 cm/h, a capacity of 62.8 mg/mL was measured for the packed bed versus 20.7 mg/mL for the membrane adsorber. The higher equilibrium and dynamic capacities of the packed bed are likely due to the higher surface area per unit volume of the resin. However, the maximum productivity for the membrane adsorber was 111 mg/(mL h), a value that was 3.3 times higher than the one of the packed column. The bed utilization - defined as the ratio of the dynamic binding capacity at 10% breakthrough to the saturation binding capacity - was also higher for the packed column at long residence times and lower at short residence times confirming the better performance of membrane chromatography at high flow rates.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Boi, Cristiana and Malavasi, Andrea and Carbonell, Ruben G. and Gilleskie, Gary}, year={2020}, month={Feb} }
 @article{reese_xiao_shanahan_driessche_fourches_carbonell_hall_menegatti_2020, title={Novel peptide ligands for antibody purification provide superior clearance of host cell protein impurities}, volume={1625}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2020.461237}, abstractNote={The quest for ligands alternative to Protein A for the purification of monoclonal antibodies (mAbs) has been pursued for almost three decades. Yet, the IgG-binding peptides known to date still fall short of the host cell protein (HCP) logarithmic removal value (LRV) set by Protein A media (2.5-3.1). In this study, we present an integrated computational-experimental approach leading to the discovery of peptide ligands that provide HCP LRVs on par with Protein A. First, the screening of 60,000 peptide variants was performed using a high-throughput search algorithm to identify sequences that ensure IgG affinity binding. Select sequences WQRHGI, MWRGWQ, RHLGWF, and GWLHQR were then negatively screened in silico against a panel of model HCPs to ensure the selection of peptides with high binding selectivity. Candidate ligands WQRHGI and MWRGWQ were conjugated to chromatographic resins and characterized by isothermal binding and breakthrough assays to quantify static and dynamic binding capacity (Qmax and DBC10%), respectively. The resulting Qmax were 52.6 mg of IgG per mL of adsorbent for WQRHGI and 57.48 mg/mL for MWRGWQ, while the DBC10% (2 minutes residence time) were 30.1 mg/mL for WQRHGI and 36.4 mg/mL for MWRGWQ. Evaluation of the peptides by isothermal titration calorimetry (ITC) confirmed the binding energy predicted in silico, and an amino acid scanning study corroborated the affinity-like binding activity of the peptides. WQRHGI-WorkBeads resin was finally characterized by purification of a monoclonal antibody from a Chinese Hamster Ovary (CHO) cell culture harvest, affording a remarkable HCP LRV of 2.7, and consistent product yield and purity over 100 chromatographic cycles. These results demonstrate the potential of WQRHGI as an effective alternative to Protein A for antibody purification.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Reese, Hannah R. and Xiao, Xingqing and Shanahan, Calvin C. and Driessche, George A. and Fourches, Denis and Carbonell, Ruben G. and Hall, Carol K. and Menegatti, Stefano}, year={2020}, month={Aug} }
 @article{lavoie_fazio_williams_carbonell_menegatti_2020, title={Targeted capture of Chinese hamster ovary host cell proteins: Peptide ligand binding by proteomic analysis}, volume={117}, ISSN={["1097-0290"]}, url={http://europepmc.org/abstract/med/31654407}, DOI={10.1002/bit.27213}, abstractNote={Abstract}, number={2}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Lavoie, R. Ashton and Fazio, Alice and Williams, Taufika Islam and Carbonell, Ruben and Menegatti, Stefano}, year={2020}, month={Feb}, pages={438–452} }
 @article{lavoie_fazio_carbonell_menegatti_2019, title={Multiplexed Competitive Screening of One-Bead-One-Component Combinatorial Libraries Using a ClonePix 2 Colony Sorter}, volume={20}, ISSN={["1422-0067"]}, DOI={10.3390/ijms20205119}, abstractNote={Screening solid-phase combinatorial libraries of bioactive compounds against fluorescently labeled target biomolecules is an established technology in ligand and drug discovery. Rarely, however, do screening methods include comprehensive strategies—beyond mere library blocking and competitive screening—to ensure binding selectivity of selected leads. This work presents a method for multiplexed solid-phase peptide library screening using a ClonePix 2 Colony Picker that integrates (i) orthogonal fluorescent labeling for positive selection against a target protein and negative selection against competitor species with (ii) semi-quantitative tracking of target vs. competitor binding for every library bead. The ClonePix 2 technology enables global at-a-glance evaluation and customization of the parameters for bead selection to ensure high affinity and selectivity of the isolated leads. A case study is presented by screening a peptide library against green-labeled human immunoglobulin G (IgG) and red-labeled host cell proteins (HCPs) using ClonePix 2 to select HCP-binding ligands for flow-through chromatography applications. Using this approach, 79 peptide ligand candidates (6.6% of the total number of ligands screened) were identified as potential HCP-selective ligands, enabling a potential rate of >3,000 library beads screened per hour.}, number={20}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Lavoie, R. Ashton and Fazio, Alice and Carbonell, Ruben G. and Menegatti, Stefano}, year={2019}, month={Oct} }
 @article{islam_naik_hashimoto_menegatti_carbonell_2019, title={Optimization of Sequence, Display, and Mode of Operation of IgG-Binding Peptide Ligands to Develop Robust, High-Capacity Affinity Adsorbents That Afford High IgG Product Quality}, volume={20}, ISSN={["1422-0067"]}, DOI={10.3390/ijms20010161}, abstractNote={This work presents the use of peptide ligand HWRGWV and its cognate sequences to develop affinity adsorbents that compete with Protein A in terms of binding capacity and quality of the eluted product. First, the peptide ligand was conjugated to crosslinked agarose resins (WorkBeads) at different densities and using different spacer arms. The optimization of ligand density and display resulted in values of static and dynamic binding capacity of 85 mg/mL and 65 mg/mL, respectively. A selected peptide-WorkBeads adsorbent was utilized for purifying Mabs from Chinese Hamster Ovary (CHO) cell culture supernatants. The peptide-WorkBeads adsorbent was found able to withstand sanitization with strong alkaline solutions (0.5 M NaOH). The purity of the eluted product was consistently higher than 95%, with logarithmic removal value (LRV) of 1.5 for host cell proteins (HCPs) and 4.0 for DNA. HCP clearance was significantly improved by adding a post-load washing step with either 0.1 M Tris HCl pH 9 or 1 M NaCl. The cognate peptide of HWRGWV, constructed by replacing arginine (R) with citrulline, further increased the HCP LRV to 2.15. The peptide-based adsorbent also showed a remarkable performance in terms of removal of Mab aggregates; unlike Protein A, in fact, HWRGWV was found to bind only monomeric IgG. Collectively, these results demonstrate the potential of peptide-based adsorbents as alternative to Protein A for the purification of therapeutic antibodies.}, number={1}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Islam, Tuhidul and Naik, Amith D. and Hashimoto, Yasuhiro and Menegatti, Stefano and Carbonell, Ruben G.}, year={2019}, month={Jan} }
 @article{naika_islam_terasaka_ohara_hashimoto_menegatti_carbonell_2019, title={Silica resins and peptide ligands to develop disposable affinity adsorbents for antibody purification}, volume={145}, ISSN={["1873-295X"]}, DOI={10.1016/j.bej.2018.07.011}, abstractNote={A study is presented on the use of porous silica resins with tailored properties to develop affinity adsorbents for the purification of immunoglobulin G (IgG). Chromatorex® silica resins were utilized to study the dependence of IgG binding upon functional group density, pore size, and specific surface area. The IgG-binding peptide HWRGWV was chosen to demonstrate the potential of combining inexpensive substrates and ligands into efficient, yet disposable, adsorbents. The static binding capacity (SBC) of silica-peptide adsorbents depends significantly on surface area and pore size, yet minimally on ligand density. Chromatorex®-NH2 MB 800 HC (pore size 800 Å, surface area 31 m2/g) and MB 700 HC (700 Å, 44 m2/g) showed SBC of 55 and 75 mg IgG per mL resin, respectively. The dynamic binding capacity (DBC) reached values of up to 60 mg/mL at 5 min residence time, and was found to be almost independent of flow rate, thus offering a much higher productivity (capacity vs. residence time) than Sepharose resins. A selected adsorbent was utilized for purifying monoclonal antibodies from Chinese hamster ovary (CHO) cell culture supernatants, and polyclonal antibodies from llama and rabbit serum. Under optimized conditions, the silica-peptide adsorbent gave a Mab purity above 90%, 4 log removal of host cell DNA, 1.5 log removal of host cell proteins (HCPs) and Mab recovery of 89% and 92%. Similarly, llama and rabbit IgG were isolated at 80%–85% purity. These results demonstrate that porous silica, a non-traditional substrate for protein purification, shows great promise as potentially single-use affinity adsorbent for protein purification.}, journal={BIOCHEMICAL ENGINEERING JOURNAL}, author={Naika, Amith D. and Islam, Tuhidul and Terasaka, Takaaki and Ohara, Yuki and Hashimoto, Yasuhiro and Menegatti, Stefano and Carbonell, Ruben}, year={2019}, month={May}, pages={53–61} }
 @article{lavoie_fazio_blackburn_goshe_carbonell_menegatti_2019, title={Targeted Capture of Chinese Hamster Ovary Host Cell Proteins: Peptide Ligand Discovery}, volume={20}, ISSN={["1422-0067"]}, DOI={10.3390/ijms20071729}, abstractNote={The growing integration of quality-by-design (QbD) concepts in biomanufacturing calls for a detailed and quantitative knowledge of the profile of impurities and their impact on the product safety and efficacy. Particularly valuable is the determination of the residual level of host cell proteins (HCPs) secreted, together with the product of interest, by the recombinant cells utilized for production. Though often referred to as a single impurity, HCPs comprise a variety of species with diverse abundance, size, function, and composition. The clearance of these impurities is a complex issue due to their cell line to cell line, product-to-product, and batch-to-batch variations. Improvements in HCP monitoring through proteomic-based methods have led to identification of a subset of “problematic” HCPs that are particularly challenging to remove, both at the product capture and product polishing steps, and compromise product stability and safety even at trace concentrations. This paper describes the development of synthetic peptide ligands capable of capturing a broad spectrum of Chinese hamster ovary (CHO) HCPs with a combination of peptide species that allow for advanced mixed-mode binding. Solid phase peptide libraries were screened for identification and characterization of peptides that capture CHO HCPs while showing minimal binding of human IgG, utilized here as a model product. Tetrameric and hexameric ligands featuring either multipolar or hydrophobic/positive amino acid compositions were found to be the most effective. Tetrameric multipolar ligands exhibited the highest targeted binding ratio (ratio of HCP clearance over IgG loss), more than double that of commercial mixed-mode and anion exchange resins utilized by industry for IgG polishing. All peptide resins tested showed preferential binding to HCPs compared to IgG, indicating potential uses in flow-through mode or weak-partitioning-mode chromatography.}, number={7}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Lavoie, R. Ashton and Fazio, Alice and Blackburn, R. Kevin and Goshe, Michael B. and Carbonell, Ruben G. and Menegatti, Stefano}, year={2019}, month={Apr} }
 @article{islam_gurgel_rojas_carbonell_2019, title={Use of a Branched Linker for Enhanced Biosensing Properties in IgG Detection from Mixed Chinese Hamster Ovary Cell Cultures}, volume={30}, ISSN={["1043-1802"]}, DOI={10.1021/acs.bioconjchem.8b00918}, abstractNote={Tris(2-aminoethyl)-amine (TREN), a branched amine, was coupled to planar surfaces of alkanethiol self-assembled monolayers (SAMs) to increase the grafting density of IgG-binding peptide (HWRGWV or HWRGWVG) on gold surfaces. One of the three primary amine pendant groups of TREN anchors onto the SAM, while the other two are available for grafting with the C-termini of the peptide. The ellipsometric peptide density on the SAM-branched amine was 1.24 molecules nm-2. The surfaces carrying the peptides were investigated via surface plasmon resonance (SPR) to quantify the adsorption of IgG and showed maximum binding capacity, Qm of 4.45 mg m-2, and dissociation constant, Kd of 8.7 × 10-7 M. Real-time dynamic adsorption data was used to determine adsorption rate constants, ka values, and the values were dependent on IgG concentration. IgG binding from complex mixtures of Chinese hamster ovary supernatant (CHO) was investigated and regeneration studies were carried out. Compared to the unbranched amine-based surfaces, the branched amines increased the overall sensitivity and selectivity for IgG adsorption from complex mixtures. Regeneration of the branched amine-based surfaces was achieved with 0.1 M NaOH, with less than 10% decline in peptide activity after 12 cycles of regeneration-binding.}, number={3}, journal={BIOCONJUGATE CHEMISTRY}, author={Islam, Nafisa and Gurgel, Patrick V. and Rojas, Orlando J. and Carbonell, Ruben G.}, year={2019}, month={Mar}, pages={815–825} }
 @article{kish_roach_sachi_naik_menegatti_carbonell_2018, title={Purification of human erythropoietin by affinity chromatography using cyclic peptide ligands}, volume={1085}, ISSN={["1873-376X"]}, DOI={10.1016/j.jchromb.2018.03.039}, abstractNote={Prior work described the identification and characterization of erythropoietin-binding cyclic peptides SLFFLH, VVFFVH, FSLLHH and FSLLSH (all of the form cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], wherein X1-X6 is the listed sequences). In this work, the peptide ligands were synthesized on Toyopearl chromatographic resins and utilized for purifying recombinant human erythropoietin (rHuEPO) from complex sources. Elution buffer pH and composition were optimized to maximize the recovery of standard rHuEPO from the peptide resins. The peptide-based adsorbents were employed for separating rHuEPO from a mixture of albumin, myoglobin, and IgG to examine their selectivity. When using FSLLHH, the inclusion of low amounts of surfactants in the wash and elution buffers facilitated the recovery of rHuEPO with high yield and purity. Specifically, FSLLSH and VVFFVH afforded the most efficient separation of rHuEPO, with yield and purity of 85% and 95–97%, respectively. The affinity resins were also utilized to purify rHuEPO from spiked CHO cell culture fluid. In particular, FSLLSH provided the most successful separation from CHO, with yield and purity above 90%, and 1.0 log10 reduction of host cell proteins. The influence of conductivity and pH in the CHO-rHuEPO load was investigated. Finally, FSLLSH-based resins were used to purify rHuEPO spiked into a Pichia pastoris cell culture fluid, resulting in product yield and purity of 96% and 84%, respectively, and 1.3 log10 reduction of host DNA. These results compare well with values obtained using wheat germ agglutinin agarose and clearly indicate the potential of the cyclic peptide resins as a viable tool for rHuEPO purification.}, journal={JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES}, author={Kish, William S. and Roach, Matthew K. and Sachi, Hiroyuki and Naik, Amith D. and Menegatti, Stefano and Carbonell, Ruben G.}, year={2018}, month={May}, pages={1–12} }
 @article{kish_sachi_naik_roach_bobay_blackburn_menegatti_carbonell_2017, title={Design, selection, and development of cyclic peptide ligands for human erythropoietin}, volume={1500}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2017.04.019}, abstractNote={This work presents the selection and characterization of erythropoietin (EPO)-binding cyclic peptide ligands. The sequences were selected by screening a focused library of cyclic depsipeptides cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], whose structure and amino acid compositions were tailored to mimic the EPO receptor. The sequences identified through library screening were synthesized on chromatographic resin and characterized via binding-and-elution studies against EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity consistently showed stronger binding to EPO, with the exception of FSLLSH, which was noted for its lower hydrophobicity and high EPO binding. Mutagenesis studies performed on FSLLSH with natural and non-natural amino acid substitutions led to the identification of critical EPO-binding determinants, and the discovery of new peptide ligands. In particular, histidine-scanning mutagenesis performed on three lead sequences yielded the discovery of variants whose EPO-binding is more pH-sensitive, which facilitates EPO recovery. Selected ligands were studied to correlate the elution yield to the salinity of the binding buffer and the elution pH. Elution yields were consistently higher when EPO binding was performed at low ionic strength. The crystal structures of lead cyclic peptides were docked in silico against EPO to estimate the binding affinity in solution. Isotherm adsorption studies performed on FSLLSH indicated that the cyclic version of the ligand (KD = 0.46 μM) has a higher affinity for EPO than its corresponding linear variant (KD = 1.44 μM). Collectively, these studies set the stage for use of the cyclic peptide ligands as EPO purification and detection tools.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Kish, William S. and Sachi, Hiroyuki and Naik, Amith D. and Roach, Matthew K. and Bobay, Benjamin G. and Blackburn, Robert K. and Menegatti, Stefano and Carbonell, Ruben G.}, year={2017}, month={Jun}, pages={105–120} }
 @article{shen_rojas_genzer_gurgel_carbonell_2016, title={Affinity interactions of human immunoglobulin G with short peptides: role of ligand spacer on binding, kinetics, and mass transfer}, volume={408}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-015-9135-y}, abstractNote={The interaction affinity between human IgG and a short peptide ligand (hexameric HWRGWV) was investigated by following the shifts in frequency and energy dissipation in a quartz crystal microbalance (QCM). HWRGWV was immobilized by means of poly(ethylene glycol) tethered on QCM sensors coated with silicon oxide, which enhanced the accessibility of the peptide to hIgG and also passivated the surface. Ellipsometry and ToF-SIMS were employed for surface characterization. The peptide ligand density was optimized to 0.88 chains nm(-2), which enabled the interaction of each hIgG molecule with at least one ligand. The maximum binding capacity was found to be 4.6 mg m(-2), corresponding to a monolayer of hIgG, similar to the values for chromatographic resins. Dissociation constants were lower than those obtained from resins, possibly due to overestimation of bound mass by QCM. Equilibrium thermodynamic and kinetic parameters were determined, shedding light on interfacial effects important for detection and bioseparation. Graphical Abstract The interaction affinity between human IgG and a short peptide ligand was investigated by using quartz crystal microgravimetry, ellipsometry and ToF-SIMS. Equilibrium thermodynamic and kinetics parameters were determined, shedding light on interfacial effects important for detection and bioseparation.}, number={7}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Shen, Fei and Rojas, Orlando J. and Genzer, Jan and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2016}, month={Mar}, pages={1829–1841} }
 @article{menegatti_bobay_ward_islam_kish_naik_carbonell_2016, title={Design of protease-resistant peptide ligands for the purification of antibodies from human plasma}, volume={1445}, DOI={10.1016/j.chroma.2016.03.087}, abstractNote={A strategy is presented for developing variants of peptide ligands with enhanced biochemical stability for the purification of antibodies from animal sera. Antibody-binding sequences HWRGWV, HYFKFD, and HFRRHL, previously discovered by our group, were modified with non-natural amino acids to gain resistance to proteolysis, while maintaining target affinity and selectivity. As trypsin and α-chymotrypsin were chosen as models of natural proteolytic enzymes, the basic (arginine and lysine) and aromatic (tryptophan, phenylalanine, and tyrosine) amino acids were replaced with non-natural analogs. Using the docking software HADDOCK, a virtual library of peptide variants was designed and screened in-silico against the known HWRGWV binding site on the pFc fragment of IgG. A pool of selected sequences with the highest predicted free energy of binding was synthesized on chromatographic resin, and the resulting adsorbents were tested for IgG binding and resistance to proteases. The ligand variants exhibited binding capacities and specificities comparable to the original sequences, yet with much higher proteolytic resistances. The sequences HWMetCitGWMetV and HFMetCitCitHL was used for purifying polyclonal IgG from IgG-rich fractions of human plasma, with yields and purity above 90%. Notably, due to electrical neutrality, the variant showed higher selectivity than the original sequence. Binding isotherms were also constructed, which confirmed the docking predictions. This method represents a general strategy for enhancing the biochemical stability as well as the affinity and selectivity of natural or synthetic peptide ligands for bioseparations.}, journal={Journal of Chromatography A}, author={Menegatti, S. and Bobay, B. G. and Ward, K. L. and Islam, T. and Kish, W. S. and Naik, A. D. and Carbonell, R. G.}, year={2016}, month={May}, pages={93–104} }
 @article{heller_wimbish_gurgel_pourdeyhimi_carbonell_2016, title={Reducing diffusion limitations in Ion exchange grafted membranes using high surface area nonwovens}, volume={514}, ISSN={["1873-3123"]}, DOI={10.1016/j.memsci.2016.02.046}, abstractNote={Polybutylene terephthalate (PBT) nonwovens can be readily grafted with glycidyl methacrylate (GMA) via UV induced radical polymerization to create uniform and conformal polymer brush networks around each fiber that can be chemically modified to function as anion or cation exchangers. Protein binding capacities achieved by these grafted materials are many times larger than monolayer coverage around the fibers, but require very long residence times to reach equilibrium due to diffusional limitations within the grafted layers. The rates of adsorption of proteins by ion exchange were measured in an islands-in-the-sea (I/S) PBT nonwoven with average fiber diameter of approximately 1 µm and in a commercially available PBT nonwoven with average fiber diameter of approximately 3 µm. Both nonwovens were grafted successfully with poly(glycidyl methacrylate) (PGMA) and they showed almost identical ion exchange equilibrium protein binding capacities at similar weight % grafting. However, the grafted I/S nonwoven membrane exhibited a substantially higher amount of protein binding at short times and it was able to reach equilibrium in a fraction of the time required by the grafted commercial nonwoven with larger fiber diameters. The faster rate of protein adsorption observed with the I/S PBT nonwoven is the result of the thinner PGMA graft layer thicknesses around the fibers compared to those in the commercial PBT with the same weight % grafting. The data for the rate of adsorption of protein through the functionalized PGMA grafted layers was analyzed using a shrinking core model.}, journal={JOURNAL OF MEMBRANE SCIENCE}, author={Heller, Michael and Wimbish, Robert and Gurgel, Patrick V. and Pourdeyhimi, Behnam and Carbonell, Ruben G.}, year={2016}, month={Sep}, pages={53–64} }
 @article{liu_gurgel_carbonell_2015, title={Preparation and characterization of anion exchange adsorptive nonwoven membranes with high protein binding capacity}, volume={493}, ISSN={["1873-3123"]}, DOI={10.1016/j.memsci.2015.06.002}, abstractNote={An anion exchange poly(butylene therephthalate) (PBT) nonwoven membrane with high protein binding capacity was developed by covalent coupling of diethylamine (DEA) to photo-induced poly(glycidyl methacrylate) (polyGMA) brushes grafted to the PBT fibers. The grafted layers were characterized using FTIR and SEM. The rates of adsorption of bovine serum albumin (BSA) to membranes with different grafted layer thicknesses (different average DEA concentrations) were determined. The static BSA binding capacities were found to be 820, 400 and 183 mg BSA/g-membrane at average DEA concentrations of 0.84, 0.35 and 0.20 mmol DEA/g-membrane respectively. These high capacities are indicative of multilayer binding of protein within the grafted layers. The larger binding capacities required longer adsorption times to reach equilibrium, indicating a diffusional resistance to mass transfer within the grafted layers. The average diffusion coefficient was determined. A column packed with anion exchange nonwoven membranes was used to separate human immunoglobulin G (hIgG) from human serum albumin (HSA). The obtained purity and yield of hIgG flowing through the column were 93.4±2% and 94.5±1.5% respectively. The purity and yield of HSA bound and eluted from the membrane were 98±1% and 94±4% respectively. The nonwoven packed column exhibited a high flow permeability (1.1×10−8 cm2) due to high bed porosity (78%).}, journal={JOURNAL OF MEMBRANE SCIENCE}, author={Liu, Haiyan and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2015}, month={Nov}, pages={349–359} }
 @article{billakanti_fee_naik_carbonell_2014, title={Application of peptide chromatography for the isolation of antibodies from bovine skim milk, acid whey and colostrum}, volume={92}, ISSN={["1744-3571"]}, DOI={10.1016/j.fbp.2014.01.002}, abstractNote={Protein A mimetic peptide ligands have several benefits over conventional Protein A/G ligands, namely that they are small in size, have low production costs, are stable over a wide range of pH values and can withstand cleaning by harsh sanitization agents such as sodium hydroxide. In this paper, a hexamer peptide (HWRGWV) affinity matrix was used for the isolation of bovine immunoglobulins from various dairy streams (skim milk, acid whey and colostrum). Bound immunoglobulins were recovered in elution buffer (0.2 M sodium acetate buffer, pH 4.0) fractions with a purity of >85% in a single step. The peptide resin has achieved a maximum equilibrium adsorption capacity of 23 ± 0.58 mg mL−1 of resin for bovine IgG and had a dynamic binding capacity of 11.8 ± 0.03 mg mL−1 at residence time of 2 min. These results suggest that the hexamer peptide chromatography could potentially be used for the selective purification of bovine immunoglobulins from dairy streams. This method has promise as an alternative to conventional Protein A/G chromatography for direct capture of immunoglobulins from streams containing relatively high immunoglobulin concentrations such as colostrum, transgenic or hyper-immune milk.}, number={C2}, journal={FOOD AND BIOPRODUCTS PROCESSING}, author={Billakanti, Jagan M. and Fee, Conan J. and Naik, Amith D. and Carbonell, Ruben G.}, year={2014}, month={Apr}, pages={199–207} }
 @article{ruiz_gilleskie_brown_burnett_carbonell_2014, title={Comprehensive Hands-on Training for Influenza Vaccine Manufacturing: A WHO-BARDA-BTEC Partnership for Global Workforce Development}, volume={42}, ISSN={["1539-3429"]}, DOI={10.1002/bmb.20817}, abstractNote={Abstract}, number={5}, journal={BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION}, author={Ruiz, Jennifer and Gilleskie, Gary L. and Brown, Patty and Burnett, Bruce and Carbonell, Ruben G.}, year={2014}, pages={414–419} }
 @article{islam_shen_gurgel_rojas_carbonell_2014, title={Dynamic and equilibrium performance of sensors based on short peptide ligands for affinity adsorption of human IgG using surface plasmon resonance}, volume={58}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2014.02.069}, abstractNote={This paper characterizes the potential of novel hexameric peptide ligands for on-line IgG detection in bioprocesses. Surface Plasmon Resonance (SPR) was used to study the binding of human IgG to the hexameric peptide ligand HWRGWV, which was covalently grafted to alkanethiol self-assembled monolayers (SAM) on gold surfaces. Peptide coupling on SAMs was verified, followed by covalent grafting of peptides with a removable Fmoc or acetylated N-termini via their C-termini to produce active peptide SPR sensors that were tested for IgG binding. The dynamics and extent of peptide–IgG binding were compared with results from a conventional system using protein A attached on a gold surface via disulfide monolayers. IgG binding to protein A on disulfide monolayers yielded equilibrium dissociation constants of 1.4×10–7 M. The corresponding dissociation constant value for the acetylated version of the peptide (Ac-HWRGWV) supported on alkanethiol SAM was 5.8×10–7 M and that for HWRGWV on the alkanethiol SAM (after de-protection of Fmoc-HWRGWVA) was 1.2×10–6 M. Maximum IgG binding capacities, Qm of 6.7, 3.8, and 4.1 mg m−2 were determined for the protein A and the two forms of HWRGWV-based biosensors, respectively. Real-time data for the kinetics of adsorption were used to determine the apparent rate constants for adsorption and desorption. The results were analyzed to understand the mechanism of IgG binding to the protein and peptide ligands. It was found that the peptide–IgG binding was reaction controlled, however the protein A–IgG binding mechanism was partially mass transfer (diffusion) controlled. The adsorption rate constants, ka, for the protein A ligand increased with decreasing concentration of analyte and the peptide ligand ka values was constant at different IgG concentrations and flow rates.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Islam, Nafisa and Shen, Fei and Gurgel, Patrick V. and Rojas, Orlando J. and Carbonell, Ruben G.}, year={2014}, month={Aug}, pages={380–387} }
 @article{islam_gurgel_rojas_carbonell_2014, title={Effects of Composition of Oligo(ethylene glycol)-Based Mixed Monolayers on Peptide Grafting and Human Immunoglobulin Detection}, volume={118}, ISSN={["1932-7455"]}, DOI={10.1021/jp411469u}, abstractNote={Alkanethiols carrying ethylene glycol units (EGn, n = 3 or 6) with amine termini (EG3NH2 or EG6NH2) were coadsorbed with a “diluent”, hydroxyl-terminated alkanethiol (EG3OH), to form mixed self-assembled monolayers (SAMs). The mixed SAMs were characterized, and hexameric peptide ligand His-Trp-Arg-Gly-Trp-Val (HWRGWV), which shows affinity binding toward the Fc (constant fragment) of human immunoglobulin (IgG), was grafted onto different dilutions of EG6NH2–EG3OH mixed SAMs for preparation of IgG detection surfaces. The specificity toward IgG was optimal for peptides grafted on SAMs prepared from 10% EG6NH2 precursor solution, even though this surface did not have the highest number of peptides per unit area. Surface plasmon resonance (SPR) experiments showed that IgG bound to the peptides on the mixed SAM with a dissociation constant Kd of 9.33 × 10–7, maximum binding capacity Qm of 3.177 mg m–2, and adsorption rate constant ka of 1.99 m3 mol–1 s–1. IgG binding from complex mixtures of Chinese Hamster Ov...}, number={10}, journal={JOURNAL OF PHYSICAL CHEMISTRY C}, author={Islam, Nafisa and Gurgel, Patrick V. and Rojas, Orlando J. and Carbonell, Ruben G.}, year={2014}, month={Mar}, pages={5361–5373} }
 @article{susanti_han_kim_lee_carbonell_2013, title={A new strategy for ultralow biofouling membranes: Uniform and ultrathin hydrophilic coatings using liquid carbon dioxide}, volume={440}, ISSN={["1873-3123"]}, DOI={10.1016/j.memsci.2013.03.068}, abstractNote={Highly stable, uniform and ultrathin hydrophilic polymer coatings on the surface as well as in the pores of a PVDF microfiltration (MF) membrane are obtained by coating a hydrophilic monomer in liquid carbon dioxide (l-CO2) followed by subsequent crosslinking reaction. Polyethylene glycol diacrylate (PEGDA, Mn ~258 g/mol) is used as the l-CO2 soluble hydrophilic monomer source and azobisisobutyronitrile (AIBN) was used as a radical initiator. The extremely low surface tension and the low viscosity of l-CO2 result in ultrathin and uniform PEG coatings on the hydrophobic polyvinylidene fluoride (PVDF) microfiltration membrane. The chemical composition, morphology, and the depth profiles of the PEG-coated membranes are characterized in detail using X-ray photoelectron spectroscopy, scanning electron microscopy, electron probe microanalysis and energy dispersive X-ray microanalysis. Long-term permeation flux test using a bovine serum albumin solution shows that the 1.0 wt% PEGDA-coated membrane using l-CO2 exhibits 1.34 times larger BSA solution flux than that of the uncoated PVDF membrane, and 1.3 times larger flux than that of a commercial hydrophilic membrane. Fouling resistance estimation shows that the 1 wt% PEGDA-coated membrane exhibits ~30% lower internal fouling resistance than the pristine membrane, and ~24% lower internal fouling resistance than the commercial hydrophilic membrane.}, journal={JOURNAL OF MEMBRANE SCIENCE}, author={Susanti, Ratna F. and Han, Yang Soo and Kim, Jaehoon and Lee, Young Haeng and Carbonell, Ruben G.}, year={2013}, month={Aug}, pages={88–97} }
 @article{liu_gurgel_carbonell_2013, title={Affinity chromatographic purification of human immunoglobulin M from human B lymphocyte cell culture supernatant}, volume={70}, ISSN={["1873-295X"]}, DOI={10.1016/j.bej.2012.10.003}, abstractNote={Abstract Compared to immunoglobulin G purification with extensively studied affinity ligands such as protein A and protein G, little work has been done on affinity chromatographic purification of immunoglobulin M. Hexamer peptide ligand HWRGWV, previously shown to bind specifically to the Fc fragment of IgG, also demonstrated potential for IgM purification. This study presents further characterization and investigation of this ligand for its potential for purification of IgM. Different running conditions were employed in order to improve the recovery and purity of IgM. The final recovery and purity of the antibody is feedstock dependent, but can reach levels of both recovery and purity as high as 95%. The dependence of the recovery and purity on total loading amount and initial IgM concentration were investigated and discussed. Although relatively low dynamic binding capacities (DBC) in the range of 4.6–13.1 mg IgM/mL resin at linear flow rates from 173 to 35 cm/h were obtained for IgM compared to IgG because of the large molecular weight of IgM, the DBC value of HWRGWV for IgM is much greater than protein-based IgM affinity ligands found in the literature and is competitive with current commercially available affinity ligands, such as KAPTIVE-M, CaptureSelect IgM and Ultralink Immobilized Mannan Binding Protein.}, journal={BIOCHEMICAL ENGINEERING JOURNAL}, author={Liu, Zhuo and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2013}, month={Jan}, pages={63–70} }
 @article{liu_gurgel_carbonell_2013, title={Affinity chromatographic purification of human immunoglobulin a from chinese hamster ovary cell culture supernatant}, volume={29}, ISSN={["1520-6033"]}, DOI={10.1002/btpr.1652}, abstractNote={Abstract}, number={1}, journal={BIOTECHNOLOGY PROGRESS}, author={Liu, Zhuo and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2013}, pages={91–98} }
 @article{liu_zheng_gurgel_carbonell_2013, title={Affinity membrane development from PBT nonwoven by photo-induced graft polymerization, hydrophilization and ligand attachment}, volume={428}, ISSN={["0376-7388"]}, DOI={10.1016/j.memsci.2012.09.047}, abstractNote={Nonwoven fabrics are of great interest as potential materials for bioseparations due to their interconnected porous structure, relatively high surface area and low cost. In this paper we focus on the development of a potentially disposable affinity membrane for pathogen removal from biological systems such as human plasma. Poly glycidyl methacrylate (polyGMA) was grafted on the fiber surface of a polybutylene terephthalate (PBT) nonwoven using photo-induced graft polymerization. SEM and FTIR were used to characterize the pore structure and surface chemistry of the resulting material. To minimize nonspecific protein binding and hydrophilize the material, diethylene glycol (DEG) and diol groups were attached covalently to the grafted layer of polyGMA. The amount of nonspecific binding was quantified by the adsorption of bovine serum albumin (BSA) and an E. coli extract. The results showed that the grafted matrix containing DEG or diol groups bound significantly less total protein, compared with unmodified material. The DEG modified membrane was further developed by attachment of a specific proprietary ligand that binds to the prion protein, the agent responsible for transmissible spongiform encephalopathies. The affinity membrane showed good selectivity for the capture of prion protein from hamster brain homogenate.}, journal={JOURNAL OF MEMBRANE SCIENCE}, author={Liu, Haiyan and Zheng, Yong and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2013}, month={Feb}, pages={562–575} }
 @article{zhang_carbonell_rojas_2013, title={Bioactive Cellulose Nanofibrils for Specific Human IgG Binding}, volume={14}, ISSN={["1526-4602"]}, DOI={10.1021/bm4007979}, abstractNote={Bioactive films were produced by conjugation of a short peptide onto modified cellulose nanofibrils (CNF). Specifically, a hydrophilic copolymer, poly(2-aminoethyl methacrylate hydrochloride-co-2-hydroxyethylmethacrylate) (poly(AMA-co-HEMA)), was grafted via surface initiated polymerization from an initiator coupled to CNF. The poly(AMA-co-HEMA) was used as a spacer and support layer for immobilization of the peptide, acetylated-HWRGWVA, which has specific affinity with human immunoglobulin G (hIgG). Two methods for peptide grafting were compared: modification of CNF in aqueous suspension followed by assembly into a bioactive film and peptide grafting on a preformed CNF film. The CNF-based networks were examined on solid supports via atomic force microscopy (AFM) and extreme resolution imaging with ultralow electron landing energies (scanning low energy electron microscopy). The specific binding capability of hIgG and nonspecific protein resistance of the resultant peptide-modified CNF were evaluated by using quartz crystal microgravimetry (QCM). The effects of initiator concentration and thickness of poly(AMA-co-HEMA) layer on hIgG adsorption were investigated in the developed systems, which exhibited high signal-to-noise response.}, number={12}, journal={BIOMACROMOLECULES}, author={Zhang, Yanxia and Carbonell, Ruben G. and Rojas, Orlando J.}, year={2013}, month={Dec}, pages={4161–4168} }
 @article{kish_naik_menegatti_carbonell_2013, title={Peptide-based affinity adsorbents with high binding capacity for the purification of monoclonal antibodies}, volume={52}, DOI={10.1021/ie302345w}, abstractNote={High binding capacity and selectivity are key features for the successful application of affinity adsorbents for antibody purification. This study presents the development of affinity resins based on hexapeptide ligand HWRGWV for recovering monoclonal antibodies from cell culture fluids. Methods are presented for the immobilization of the peptide ligand and its variants on polymethacrylate and agarose based chromatographic supports using two main coupling strategies. The first one involves the formation of a peptide bond between the amino groups on the substrate and the peptide C-terminus activated with the uronium coupling agent HATU. The second approach involves resin activation with iodoacetic acid, followed by coupling of a cysteine-terminated variant of the ligand to form a thioether bond. The reaction conditions of peptide coupling were optimized to maximize the binding capacity of the resulting adsorbents. The peptide resins were characterized by measuring their static IgG binding capacities. The m...}, number={26}, journal={Industrial & Engineering Chemistry Research}, author={Kish, W. S. and Naik, A. D. and Menegatti, S. and Carbonell, R. G.}, year={2013}, pages={8800–8811} }
 @article{menegatti_ward_naik_kish_blackburn_carbonell_2013, title={Reversible cyclic peptide libraries for the discovery of affinity ligands}, volume={85}, DOI={10.1021/ac401954k}, abstractNote={A novel strategy is presented for the identification of cyclic peptide ligands from combinatorial libraries of reversible cyclic depsipeptides. A method for the solid-phase synthesis of individual cyclic depsipeptides and combinatorial libraries of these compounds is proposed, which employs lactic acid (Lact) and the dipeptide ester (Nα-Ac)-Ser(Ala)- as linkers for dilactonization. Upon alkaline treatment of the beads selected by screening a model library, the cyclic depsipeptides are linearized and released from the solid support to the liquid phase, to be sequenced via single-step tandem mass spectrometry (MS/MS). The protocol presented for library synthesis provides for wide structural diversity. Two model sequences, VVWVVK and AAWAAR, were chosen to present different structural examples for depsipeptide libraries and demonstrate the process of sequence determination by mass spectrometry. Further, a case study using the IgG binding cyclic depsipeptide cyclo[(Nα-Ac)-S(A)-RWHYFK-Lact-E] is presented to demonstrate the process of library screening and sequence determination on the selected beads. Finally, a method is shown for synthesis of the irreversible cyclic peptide corresponding to the proposed depsipeptide structure, to make the ligand stable to the aqueous acid and alkaline conditions encountered in affinity chromatographic applications. The cyclic peptide ligand was synthesized on a poly(methacrylate) resin and used for chromatographic binding of the target IgG.}, number={19}, journal={Analytical Chemistry}, author={Menegatti, S. and Ward, K. L. and Naik, A. D. and Kish, W. S. and Blackburn, R. K. and Carbonell, R. G.}, year={2013}, pages={9229–9237} }
 @article{zhang_islam_carbonell_rojas_2013, title={Specific Binding of Immunoglobulin G with Bioactive Short Peptides Supported on Antifouling Copolymer Layers for Detection in Quartz Crystal Microgravimetry and Surface Plasmon Resonance}, volume={85}, ISSN={["1520-6882"]}, DOI={10.1021/ac302874s}, abstractNote={A new peptide-based system supported on copolymer brushes grafted from gold sensors and with resistance to nonspecific adsorption is reported for selective binding of human immunoglobulin G (IgG). A random copolymer rich in primary amines, poly(2-aminoethyl methacrylate hydrochloride-co-2-hydroxyethyl methacrylate) (poly(AMA-co-HEMA)) was first grafted from initiator-coated gold substrates via activators regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP), followed by immobilization of acetylated-HWRGWVA peptide, which has specific binding affinity with IgG. The peptide ligands covalently linked to the soft copolymer layer were characterized by X-ray photoelectron spectroscopy (XPS), water contact angle, ellipsometry, and atomic force microscopy (AFM). The extent of binding, binding affinity, and selectivity for target IgG molecules as well as the capability to minimize nonspecific interactions with other proteins were examined by fluorescence imaging, surface plasmon resonance (SPR), and quartz crystal microgravimetry (QCM). The effect of copolymer molecular composition and analyte concentration was elucidated in order to design systems based on immobilized peptides for high signal-to-noise response and detection limits that meet the requirements for IgG biosensing in fluid matrixes.}, number={2}, journal={ANALYTICAL CHEMISTRY}, author={Zhang, Yanxia and Islam, Nafisa and Carbonell, Ruben G. and Rojas, Orlando J.}, year={2013}, month={Jan}, pages={1106–1113} }
 @article{zhang_islam_carbonell_rojas_2013, title={Specificity and Regenerability of Short Peptide Ligands Supported on Polymer Layers for Immunoglobulin G Binding and Detection}, volume={5}, ISSN={["1944-8244"]}, DOI={10.1021/am4021186}, abstractNote={We demonstrate the specificity, regenerability, and excellent storage stability of short peptide-based systems for detection of immunoglobulin G (IgG). The bioactive component consisted of acetylated-HWRGWVA (Ac-HWRGWVA), a peptide with high IgG binding affinity, which was immobilized onto copolymer matrixes of poly(2-aminoethyl methacrylate hydrochloride-co-2-hydroxyethyl methacrylate) (poly(AMA-co-HEMA)). Surface plasmon resonance (SPR) and quartz crystal microgravimetry (QCM) were utilized with other complementary techniques to systematically investigate interfacial activities, mainly IgG binding performance as a function of the graft density and degree of polymerization of the poly(AMA-co-HEMA) support layer. Results from sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorescence microscopy indicate that the bioactive system is highly specific to IgG and resistant to nonspecific interactions when tested in mixed protein solutions.}, number={16}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Zhang, Yanxia and Islam, Nafisa and Carbonell, Ruben G. and Rojas, Orlando J.}, year={2013}, month={Aug}, pages={8030–8037} }
 @article{menegatti_hussain_naik_carbonell_rao_2013, title={mRNA display selection and solid-phase synthesis of Fc-binding cyclic peptide affinity ligands}, volume={110}, DOI={10.1002/bit.24760}, abstractNote={Abstract}, number={3}, journal={Biotechnology and Bioengineering}, author={Menegatti, S. and Hussain, M. and Naik, A. D. and Carbonell, R. G. and Rao, B. M.}, year={2013}, pages={857–870} }
 @article{menegatti_naik_gurgel_carbonell_2012, title={Alkaline-stable peptide ligand affinity adsorbents for the purification of biomolecules}, volume={1245}, DOI={10.1016/j.chroma.2012.04.072}, abstractNote={A strategy of modification of resin surface chemistry is presented to produce hydrophilic peptide-based alkaline-stable affinity adsorbents for the purification of biopharmaceuticals from complex media. In this work, the peptide-based affinity adsorbent HWRGWV-Toyopearl resin for the purification of IgG is presented as an example. When prepared by direct peptide synthesis on the chromatographic matrix, the peptide-based resin showed lability under alkaline conditions. In fact, the regeneration with aqueous 0.1 M NaOH caused the leaching of 40% of the peptide ligand, resulting in a decrease of IgG yield from 85% to 23%. It was found that the ligand leaching was caused by the coupling of a significant amount of peptide by alkaline-labile ester bonds. A method was designed to prevent the formation of ester bonds and allow the synthesis of the ligand exclusively on alkaline-stable bonds. The method consists in activating the hydrophilic base resin, blocking the hydroxyl groups responsible for alkaline lability and performing the peptide synthesis exclusively via alkaline-stable amide bonds. Repeated cycles of IgG purification from a cell culture medium were performed, each followed by cleaning with aqueous NaOH (0.1 M, 0.5 M and 1 M). The IgG yield decreased from 91% to 85% after 200 purification cycles with 0.1 M NaOH. However, the IgG purity remained almost constant at around 95% based on SDS-PAGE analysis. The procedure presented is rapid, efficient and inexpensive and does not require any equipment other than the conventional instrumentation for peptide synthesis. The method also has a broad application since it is valid for any peptide ligand identified for the purification of a biopharmaceutical target.}, journal={Journal of Chromatography A}, author={Menegatti, S. and Naik, A. D. and Gurgel, P. V. and Carbonell, R. G.}, year={2012}, month={Jul}, pages={55–64} }
 @article{gera_hill_white_carbonell_rao_2012, title={Design of pH Sensitive Binding Proteins from the Hyperthermophilic Sso7d Scaffold}, volume={7}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0048928}, abstractNote={We have engineered pH sensitive binding proteins for the Fc portion of human immunoglobulin G (hIgG) (hFc) using two different strategies – histidine scanning and random mutagenesis. We obtained an hFc-binding protein, Sso7d-hFc, through mutagenesis of the Sso7d protein from the hyperthermophilic archaeon Sulfolobus solfataricus; Sso7d-hFc was isolated from a combinatorial library of Sso7d mutants using yeast surface display. Subsequently, we identified a pH sensitive mutant, Sso7d-his-hFc, through systematic evaluation of Sso7d-hFc mutants containing single histidine substitutions. In parallel, we also developed a yeast display screening strategy to isolate a different pH sensitive hFc binder, Sso7d-ev-hFc, from a library of mutants obtained by random mutagenesis of a pool of hFc binders. In contrast to Sso7d-hFc, both Sso7d-his-hFc and Sso7d-ev-hFc have a higher binding affinity for hFc at pH 7.4 than at pH 4.5. The Sso7d-mutant hFc binders can be recombinantly expressed at high yield in E. coli and are monomeric in solution. They bind an epitope in the CH3 domain of hFc that has high sequence homology in all four hIgG isotypes (hIgG1–4), and recognize hIgG1–4 as well as deglycosylated hIgG in western blotting assays. pH sensitive hFc binders are attractive candidates for use in chromatography, to achieve elution of IgG under milder pH conditions. However, the surface density of immobilized hFc binders, as well as the avidity effect arising from the multivalent interaction of dimeric hFc with the capture surface, influences the pH dependence of dissociation from the capture surface. Therefore, further studies are needed to evaluate if the Sso7d mutants identified in this study are indeed useful as affinity ligands in chromatography.}, number={11}, journal={PLOS ONE}, author={Gera, Nimish and Hill, Andrew B. and White, Dalon P. and Carbonell, Ruben G. and Rao, Balaji M.}, year={2012}, month={Nov} }
 @article{heldt_gurgel_jaykus_carbonell_2012, title={Porcine parvovirus removal using trimer and biased hexamer peptides}, volume={7}, ISSN={1860-6768}, url={http://dx.doi.org/10.1002/biot.201000397}, DOI={10.1002/biot.201000397}, abstractNote={Abstract}, number={4}, journal={Biotechnology Journal}, publisher={Wiley}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2012}, month={Apr}, pages={558–565} }
 @article{naik_menegatti_reese_gurgel_carbonell_2012, title={Process for purification of monoclonal antibody expressed in transgenic Lemna plant extract using dextran-coated charcoal and hexamer peptide affinity resin}, volume={1260}, DOI={10.1016/j.chroma.2012.08.043}, abstractNote={The production of therapeutic proteins using transgenic plants offers several advantages, including low production cost, absence of human pathogens, presence of glycosylation mechanisms, and the ability to fold complex therapeutic proteins into their proper conformation. However, impurities such as phenolic compounds and pigments encountered during purification are quite different from those faced during purification from mammalian cell culture supernatants. This paper deals with the development of a pretreatment and affinity separation process for the purification of a monoclonal antibody from transgenic Lemna plant extract. A pretreatment step is described using dextran-coated charcoal for the removal of pigments and phenolic compounds without reducing the antibody concentration. Then, the peptide affinity ligand HWRGWV coupled to a commercial polymethacrylate resin is used for the capture and purification of MAb from the pretreated plant extract. The final yield and purity of the MAb obtained were 90% and 96% respectively. The performance of the hexamer peptide resin after the pretreatment step was found to be similar to that obtained with a commercial Protein A resin.}, journal={Journal of Chromatography A}, author={Naik, A. D. and Menegatti, S. and Reese, H. R. and Gurgel, P. V. and Carbonell, R. G.}, year={2012}, pages={61–66} }
 @article{liu_gurgel_carbonell_2012, title={Purification of human immunoglobulins A, G and M from Cohn fraction II/III by small peptide affinity chromatography}, volume={1262}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2012.09.026}, abstractNote={This work describes attempts to purify human IgG, IgA and IgM from Cohn fraction II/III using HWRGWV affinity peptide resin. The effects of peptide density and different elution additives on recovery of the three antibodies were investigated. At low peptide density, salting-in salts such as magnesium chloride and calcium chloride facilitated antibody elution. Ethylene glycol, urea and arginine also facilitated elution because of their ability to decrease hydrophobic interactions, hydrogen bonding and electrostatic interactions. However, at high peptide density, no recovery improvements were observed because of increased non-specific hydrophobic interactions. The final elution conditions for each antibody were chosen based on the resulting yields and purities when a 10:2:1 mg/mL mixture of human IgG, IgA and IgM was used as starting material. Different pretreatment methods were employed in order to improve the purity of antibodies from Cohn fraction II/III. After pretreatment with caprylic acid precipitation or combination of caprylic acid and polyethylene glycol precipitation, purities over 95% and yields of about 60% were obtained for hIgG, which are comparable to current chromatographic purification methods involving two chromatography steps when hIgG is isolated from plasma fractions. A hIgA-enriched fraction with 42% hIgA and 56% hIgG, as well as a hIgM enriched fraction with 46% hIgM, 28% hIgA and 24% hIgG, were obtained as the by-products.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Liu, Zhuo and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2012}, month={Nov}, pages={169–179} }
 @article{menegatti_naik_gurgel_carbonell_2012, title={Purification of polyclonal antibodies from Cohn fraction II + III, skim milk, and whey by affinity chromatography using a hexamer peptide ligand}, volume={35}, ISSN={1615-9306}, url={http://dx.doi.org/10.1002/jssc.201200199}, DOI={10.1002/jssc.201200199}, abstractNote={HWRGWV, a peptide that binds specifically to the Fc fragment of human immunoglobulin G (IgG), was used for the purification of IgG from Cohn fraction II + III of human plasma and from bovine skim milk and whey. The concentration of sodium chloride and sodium caprylate in the binding buffer as well as the pH of the elution buffer were optimized to achieve high IgG yield and purity. Under optimized conditions, IgG was recovered from plasma fractions with yield and purity up to 84% and 95%, respectively. IgG was also purified from skim milk with 74% yield and 92% purity and from whey with 85% yield and 93% purity. Purification experiments were also performed with Protein A resin and the results were found to be similar to those obtained with the peptide adsorbent.}, number={22}, journal={Journal of Separation Science}, publisher={Wiley}, author={Menegatti, Stefano and Naik, Amith D. and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2012}, month={Jul}, pages={3139–3148} }
 @article{zheng_gurgel_carbonell_2011, title={Effects of UV Exposure and Initiator Concentration on the Spatial Variation of Poly(glycidyl methacrylate) Grafts on Nonwoven Fabrics}, volume={50}, ISSN={["0888-5885"]}, DOI={10.1021/ie1021333}, abstractNote={This paper describes the spatial uniformity of grafted layers of poly(glycydyl methacrylate) on the fibers of polypropylene nonwoven fabrics, and how they depend on the UV pretreatment step, the ad...}, number={10}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Zheng, Yong and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2011}, month={May}, pages={6115–6123} }
 @article{liu_gurgel_carbonell_2011, title={Effects of peptide density and elution pH on affinity chromatographic purification of human immunoglobulins A and M}, volume={1218}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2011.09.038}, abstractNote={A family of linear hexamer peptide ligands HWRGWV, HYFKFD and HFRRHL, initially identified for their affinity to the Fc portion of human immunoglobulin G (hIgG), also have potential for use in the purification of human immunoglobulins A (hIgA) and M (hIgM). HWRGWV demonstrated the strongest binding affinity to hIgM, followed by hIgA and hIgG respectively. The effects of N-terminal acetylation of the peptide, as well as elution buffer pH, on the chromatographic elution of human IgG, IgA and IgM from HWRGWV resins at various peptide densities (0.04–0.55 meq/g) were investigated. Over 80% recovery and 90% purity were achieved for human IgG and IgA isolation from complete minimum essential medium (cMEM) using HWRGWV resin at optimum peptide densities. For human IgM, 75.7% recovery and 86.0% purity were achieved by using HWRGWV at a low peptide density of 0.04 meq/g. Although HYFKFD and HFRRHL exhibited their ability for isolation of human IgG, IgA and IgM from cMEM as well, HWRGWV is the best option among them for large-scale purification of human IgG, IgA and IgM based on conditions tested.}, number={46}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Liu, Zhuo and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2011}, month={Nov}, pages={8344–8352} }
 @article{cain_roberts_kiserow_carbonell_2011, title={Modeling the thermodynamic and transport properties of decahydronaphthalene/propane mixtures: Phase equilibria, density, and viscosity}, volume={305}, ISSN={["0378-3812"]}, DOI={10.1016/j.fluid.2011.02.009}, abstractNote={Abstract The density and viscosity of propane mixed with 66/34 trans/cis -decahydronaphthalene were measured over a wide range of temperatures (323–423 K), pressures (2.5–208 bar), and compositions (0–65 mol% propane). For conditions giving two phases, the composition of the dense phase was measured in addition to the density and viscosity. The modified Sanchez-Lacombe Equation of State (MSLEOS) was used with a single linearly temperature-dependent pseudo-binary interaction parameter to correlate the phase compositions and densities. The compositions and densities of the mixtures were captured well with absolute average deviations between the model and the data of 5.3% and 2.3%, respectively. The mixture viscosities were computed from a free volume model (FVM) by using a single constant binary interaction parameter. Density predictions from the MSLEOS were used as input mixture density values required for the FVM. The FVM was found to correlate well with the mixture viscosity data with an absolute average deviation between the model and the data of 5.7%.}, number={1}, journal={FLUID PHASE EQUILIBRIA}, author={Cain, Nathaniel and Roberts, George and Kiserow, Douglas and Carbonell, Ruben}, year={2011}, month={Jun}, pages={25–33} }
 @article{naik_menegatti_gurgel_carbonell_2011, title={Performance of hexamer peptide ligands for affinity purification of immunoglobulin G from commercial cell culture media}, volume={1218}, DOI={10.1016/j.chroma.2010.11.071}, abstractNote={Previous work has reported on the identification and characterization of the hexapeptide ligands HWRGWV, HYFKFD, and HFRRHL for the affinity capture of IgG through specific binding to its Fc fragment. This paper addresses issues related to the successful application of these ligands, on a commercial methacrylate chromatographic resin, for the purification of IgG from mammalian cell culture fluids. The concentrations of sodium chloride and sodium caprylate in the binding buffer were optimized to maximize the purity and yield of IgG upon elution. Screening of several regeneration conditions found that either 2 M guanidine–HCl or a combination of 0.85% phosphoric acid followed by 2 M urea resulted in complete recovery of the IgG adsorption capacity and that the column could be reused over many cycles. The hexapeptide ligands were used for the purification of humanized and chimeric monoclonal antibodies from two commercial CHO cell culture fluids. The chimeric MAb of IgG1 subclass was purified using the HWRGWV resin whereas the humanized MAb of IgG4 subclass was purified using the HWRGWV, HYFKFD and HFRRHL resins. The purities and yields obtained for both the MAbs were found to be higher than 94% and 85% respectively. These results compare well with the yields and purities obtained using Protein G columns. The residual DNA and host cell protein reduction obtained by the HWRGWV resin was in the range of 4 log reduction value (LRV) and 2 LRV respectively, comparable to those reported for Protein A resins. The dynamic binding capacity of all three peptide resins for the humanized monoclonal antibody was in the range of 20 mg/mL.}, number={13}, journal={Journal of Chromatography A}, author={Naik, A. D. and Menegatti, S. and Gurgel, P. V. and Carbonell, R. G.}, year={2011}, month={Apr}, pages={1691–1700} }
 @article{cain_haywood_roberts_kiserow_carbonell_2011, title={Polystyrene/Decahydronaphthalene/Propane Phase Equilibria and Polymer Conformation Properties from Intrinsic Viscosities}, volume={49}, ISSN={["0887-6266"]}, DOI={10.1002/polb.22282}, abstractNote={Abstract}, number={15}, journal={JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS}, author={Cain, Nathaniel and Haywood, Alexander and Roberts, George and Kiserow, Douglas and Carbonell, Ruben}, year={2011}, month={Aug}, pages={1093–1100} }
 @article{herigstad_gurgel_carbonell_2011, title={Transport and Binding Characterization of a Novel Hybrid Particle Impregnated Membrane Material for Bioseparations}, volume={27}, ISSN={["1520-6033"]}, DOI={10.1002/btpr.502}, abstractNote={Abstract}, number={1}, journal={BIOTECHNOLOGY PROGRESS}, author={Herigstad, M. Omon and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2011}, pages={129–139} }
 @article{yang_gurgel_williams_bobay_cavanagh_muddiman_carbonell_2010, title={Binding site on human immunoglobulin G for the affinity ligand HWRGWV}, volume={23}, number={3}, journal={Journal of Molecular Recognition}, author={Yang, H. O. and Gurgel, P. V. and Williams, D. K. and Bobay, B. G. and Cavanagh, J. and Muddiman, D. C. and Carbonell, R. G.}, year={2010}, pages={271–282} }
 @article{kim_carbonell_2010, title={Deposition of palladium catalyzed copper films by the displacement of two immiscible supercritical phases and subsequent reaction}, volume={20}, ISSN={["0959-9428"]}, DOI={10.1039/b925959g}, abstractNote={Palladium (Pd) catalyzed copper (Cu) films were produced by forming films of Cu(II) compound (Cu(hfac)2·H2O) and Pd(II) compound (Pd(hfac)2) on silicon oxide (SiOx) and titanium nitride (TiN) substrates using a Displacement from two Immiscible Supercritical Phases (DISPs) technique followed by reduction of the organometallic compounds films in hydrogen at 200 °C. The morphology of Cu films was observed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In the absence of Pd(hfac)2, Cu particles in the range of 60–95 nm formed on SiOx or TiN during the 5 min reduction period. As the Pd(hfac)2 concentration increased to 5 mol% (relative to the amount of Cu(hfac)2·H2O), a morphology transition from particle formation to film formation was observed. When the Cu(hfac)2·H2O concentration varied from 0.1 wt% to 3 wt% at a fixed Pd(hfac)2 concentration of 5 mol%, highly uniform, dense and adherent films with 10–40 nm in thickness were produced. Root mean square (rms) roughness of these films, estimated by AFM images, is in the range of 1.7–5.8 nm. Chemical composition analysis of 5 mol% Pd catalyzed Cu film by X-ray photoelectron spectroscopy (XPS) revealed that approximately the ratio of Pd to Cu incorporated into the film was two times larger than the initial Pd(hfac)2 to Cu(hfac)2·H2O ratio.}, number={19}, journal={JOURNAL OF MATERIALS CHEMISTRY}, author={Kim, Jaehoon and Carbonell, Ruben G.}, year={2010}, pages={3973–3978} }
 @article{zheng_liu_gurgel_carbonell_2010, title={Polypropylene nonwoven fabrics with conformal grafting of poly(glycidyl methacrylate) for bioseparations}, volume={364}, ISSN={["0376-7388"]}, DOI={10.1016/j.memsci.2010.08.037}, abstractNote={Nonwovens fabrics are porous materials with great potential for use in the separation and purification of biotherapeutic proteins and other biomolecules after proper surface activation and modification. This work describes an activation process for polypropylene nonwoven membranes by conformal coating of poly(glycidyl methacrylate) (polyGMA) through a UV pretreatment–UV grafting process (UV–UV) in the presence of benzophenone as initiator. The grafting mechanism relies on the enhanced adsorption of benzophenone to the fiber surface after the UV pretreatment. It was found that this process results in highly conformal and uniform polyGMA grafts on the surface of the PP nonwoven fibers. After grafting, a hydrophilic spacer, diethylene glycol, an anion exchange ligand, diethyl amine, and a combination of diethylene glycol spacer-primary amine were attached to the PP nonwoven surface with the conformal polyGMA grafts. High equilibrium protein binding capacities for bovine serum albumin (BSA) under static and flow conditions were obtained (120 mg/g and 102 mg/g, respectively). A column packed with modified nonwovens exhibited higher permeability coefficient (1.08 × 10−7 cm2) than columns packed with chromatographic resins. The total porosity (to acetone) was found to be 0.80 and the interstitial porosity (to BSA) was 0.48, measured by pulse experiments using acetone and BSA respectively as tracers under nonbinding conditions.}, number={1-2}, journal={JOURNAL OF MEMBRANE SCIENCE}, author={Zheng, Yong and Liu, Haiyan and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2010}, month={Nov}, pages={362–371} }
 @article{kim_rolland_carbonell_desimone_2010, title={Ultrathin Cross-Linked Perfluoropolyether Film Coatings from Liquid CO2 and Subsequent UV Curing}, volume={22}, ISSN={["0897-4756"]}, DOI={10.1021/cm903598v}, abstractNote={Ultrathin fluorinated films with highly solvent-resistant and optically clear characteristics were produced using liquid carbon dioxide free-meniscus coating followed by UV curing. Unique film morphologies including mesh and droplets structures resulted due to autophobic dewetting behavior of hydrophilic terminated perfluoropolyether.}, number={8}, journal={CHEMISTRY OF MATERIALS}, author={Kim, Jaehoon and Rolland, Jason P. and Carbonell, Ruben G. and DeSimone, Joseph M.}, year={2010}, month={Apr}, pages={2411–2413} }
 @article{yang_gurgel_williams_bobay_cavanagh_muddiman_carbonell_2009, title={Binding site on human immunoglobulin G for the affinity ligand HWRGWV}, ISSN={0952-3499 1099-1352}, url={http://dx.doi.org/10.1002/jmr.967}, DOI={10.1002/jmr.967}, abstractNote={Abstract}, journal={Journal of Molecular Recognition}, publisher={Wiley}, author={Yang, Haiou and Gurgel, Patrick V. and Williams, D. Keith, Jr and Bobay, Benjamin G. and Cavanagh, John and Muddiman, David C. and Carbonell, Ruben G.}, year={2009}, pages={n/a-n/a} }
 @article{kim_taylor_deyoung_mcclain_desimone_carbonell_2009, title={Deposition of Copper Particles and Films by the Displacement of Two Immiscible Supercritical Phases and Subsequent Reaction}, volume={21}, ISSN={0897-4756 1520-5002}, url={http://dx.doi.org/10.1021/cm802659j}, DOI={10.1021/cm802659j}, abstractNote={Copper (Cu) particles and films were produced by forming Cu(II) compound (Cu(hfac)2·H2O) films on substrates using a displacement from two immiscible supercritical phases (DISP) technique followed ...}, number={5}, journal={Chemistry of Materials}, publisher={American Chemical Society (ACS)}, author={Kim, Jaehoon and Taylor, Douglas and DeYoung, James and McClain, James B. and DeSimone, Joseph M. and Carbonell, Ruben G.}, year={2009}, month={Mar}, pages={913–924} }
 @article{dong_carbonell_roberts_kiserow_2009, title={Determination of polystyrene-carbon dioxide-decahydronaphthalene solution properties by high pressure dynamic light scattering}, volume={50}, ISSN={["1873-2291"]}, DOI={10.1016/j.polymer.2009.09.069}, abstractNote={The diffusion coefficients of polystyrene (PS) in decahydronaphthalene (DHN) and in solutions of carbon dioxide (CO2) and DHN were measured for dilute PS solutions over a range of temperatures and CO2–DHN ratios using high pressure dynamic light scattering. Infinite dilution diffusion coefficients (D0) of PS and dynamic second virial coefficients (kD) were determined for essentially monodisperse 308 kDa PS. At a system pressure of 20.7 MPa, PS diffusion coefficients increased by a factor of 2.5, and the activation energy of diffusion decreased by approximately 16% when DHN was “expanded” with 44 mol% CO2. However, the hydrodynamic radius of PS at a given temperature was not particularly sensitive to the CO2 concentration. Solvent quality, as measured by kD, decreased at higher CO2 concentrations. The addition of CO2 to polymer solutions may offer a way to “tune” the properties of the solution to facilitate the heterogeneous catalytic hydrogenation of polymers.}, number={24}, journal={POLYMER}, author={Dong, Laura Beth and Carbonell, Ruben G. and Roberts, George W. and Kiserow, Douglas J.}, year={2009}, month={Nov}, pages={5728–5732} }
 @article{martín del valle eva m._galán miguel a._carbonell_2009, title={Drug Delivery Technologies: The Way Forward in the New Decade}, volume={48}, ISSN={0888-5885 1520-5045}, url={http://dx.doi.org/10.1021/ie800886m}, DOI={10.1021/ie800886m}, abstractNote={The design and development of drug delivery systems involves many different sciences that underpin the research. It is clear that significant advances will only be made through multidisciplinary teams that utilize the latest advances in the biological, chemical, physical, and engineering sciences. The underpinning sciences are also vital to the process of developing successful products. There are three key and interrelated areas of research. (i) Achieve a greater understanding of the biological fate and the targeting of drugs, particularly biopharmaceuticals, macromolecules and macromolecular delivery systems, at the molecular, membrane, and cellular level. (ii) Provide a greater understanding of the physicochemical properties of biopharmaceuticals, macromolecules, and macromolecular delivery systems and how these are modified within a biological environment affecting their activity. (iii) Promote the development of novel materials and delivery systems that will overcome these biological barriers. This ar...}, number={5}, journal={Industrial & Engineering Chemistry Research}, publisher={American Chemical Society (ACS)}, author={Martín del Valle Eva M. and Galán Miguel A. and Carbonell, Ruben G.}, year={2009}, month={Mar}, pages={2475–2486} }
 @article{heldt_gurgel_jaykus_carbonell_2009, title={Influence of Peptide Ligand Surface Density and Ethylene Oxide Spacer Arm on the Capture of Porcine Parvovirus}, volume={25}, ISSN={["1520-6033"]}, DOI={10.1002/btpr.236}, abstractNote={Abstract}, number={5}, journal={BIOTECHNOLOGY PROGRESS}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2009}, pages={1411–1418} }
 @article{zweber_wagner_deyoung_carbonell_2009, title={Mechanism of Extreme Ultraviolet Photoresist Development with a Supercritical CO2 Compatible Salt}, volume={25}, ISSN={["0743-7463"]}, DOI={10.1021/la8043158}, abstractNote={The mechanism of developing an extreme ultraviolet (EUV) commercial photoresist with supercritical carbon dioxide (scCO2) and a CO2 compatible salt (CCS) solution was studied. The cloud point of CCS in CO2 and the pressure at which the photoresist dissolves in CCS/scCO2 were determined for temperatures between 35 and 50 degrees C. For this temperature range, it was found that the CCS cloud point ranges between 11.2 and 16.1 MPa, while the photoresist dissolution point ranges from 15.5 to 21.3 MPa. The kinetics of the CCS/scCO2 development was modeled using a simplified rate equation, where the rate-limiting steps were photoresist dissolution and mass transfer. The effects of temperature, mass transfer, pressure, and CCS concentration on photoresist removal rate were further explored experimentally using a high-pressure quartz crystal microbalance (QCM). Increasing temperature (35-50 degrees C) at a constant fluid density of 0.896 g/mL was found to increase the removal rate following an Arrhenius behavior with a photoresist dissolution energy of activation, Ea, equal to 79.0 kJ/mol. The removal was zero order in CCS concentration, signifying photoresist phase transfer, photoresist mass transfer, or both were rate limiting. Mass transfer studies showed that circulation enhanced the photoresist removal rate, but that the mass transfer coefficient was independent of temperature from 35 degrees C to 50 degrees C. In pressure studies, increasing pressure (27.6-34.5 MPa) at a constant temperature of 40 degrees C increased the removal rate by enhancing the fluid density, but at 50 degrees C increasing pressure had little effect on the removal rate. When the total CCS concentration was in large global excess over the number of Bronsted acid groups in the polymer (2400:1 at 5 mM CCS concentration), the mass of photoresist removed varied linearly with time. At lower CCS concentrations but still in global excess of the number of Bronsted acid groups, the photoresist removal slowed (0.5 mm CCS, approximately 240:1) or was prevented (0.03 Mm CCS, approximately 15:1) due to partitioning of the CCS between the CO(2)-rich phase and the film. The CCS partitioning into the resist was found to decrease with increasing temperature, revealing an enthalpy-driven CCS absorption.}, number={11}, journal={LANGMUIR}, author={Zweber, Amy E. and Wagner, Mark and DeYoung, James and Carbonell, Ruben G.}, year={2009}, month={Jun}, pages={6176–6190} }
 @article{carla_hussain_grant_sarti_carbonell_doghieri_2009, title={Modeling Sorption Kinetics of Carbon Dioxide in Glassy Polymeric Films Using the Nonequilibrium Thermodynamics Approach}, volume={48}, ISSN={["0888-5885"]}, DOI={10.1021/ie800655w}, abstractNote={The nonequilibrium thermodynamics of glassy polymers (NET-GP) approach (Macromolecules 2005, 38, 10299.) has been applied to the development of a one-dimensional transport model aimed at describing the kinetics of sorption and dilation of polymeric films in supercritical carbon dioxide. The NET-GP model was combined with a simple rheological constitutive equation to build a sorption-diffusion-relaxation model able to describe mass uptake and swelling kinetics of polymeric films in contact with carbon dioxide over a wide range of pressures and temperatures. The model calculations are compared with data on mass sorption kinetics for CO2 in supported glassy poly(methyl methacrylate) (PMMA) films, measured in a high-pressure quartz crystal microbalance (QCM).}, number={8}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Carla, Vito and Hussain, Yazan and Grant, Christine and Sarti, Giulio C. and Carbonell, Ruben G. and Doghieri, Ferruccio}, year={2009}, month={Apr}, pages={3844–3854} }
 @article{yang_gurgel_carbonell_2009, title={Purification of human immunoglobulin G via Fc-specific small peptide ligand affinity chromatography}, volume={1216}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2008.12.004}, abstractNote={Chromatographic resins of a family of linear Fc-binding hexamer peptides (HWRGWV, HYFKFD, and HFRRHL) exhibited the ability to selectively adsorb and isolate human IgG (hIgG) from complete mammalian cell culture medium (cMEM). Among them, the HWRGWV resin with a peptide density of 0.08 mequiv./g of resin was able to purify hIgG from cMEM with both purity and yield as high as 95%, comparable to Protein A and A2P agarose gels. The influences of N-terminal acetylation of the HWRGWV resin, ligand density on the resin, initial hIgG concentration, and temperature on IgG isolation were also investigated. The results indicate that these small peptide ligands, especially HWRGWV, offer a potential alternative to the use of Protein A or Protein G for large scale affinity chromatography.}, number={6}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Yang, Haiou and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2009}, month={Feb}, pages={910–918} }
 @article{zweber_wagner_carbonell_2009, title={Sorption of CO2 and a CO2 Compatible Salt into an Extreme Ultraviolet Photoresist Film on a SiO2 Substrate}, volume={113}, ISSN={["1520-6106"]}, DOI={10.1021/jp900481j}, abstractNote={The development of standard extreme ultraviolet (EUV) lithography photoresists with a CO2 compatible salt (CCS) and supercritical carbon dioxide (scCO2) solution has several advantages over typical trimethylammonium hydroxide development, including reduced image collapse and line width roughness in the resulting microchip features. The mechanism and characteristics of the CCS/scCO2 development process are currently being examined. In this paper, the sorption behavior of CO2 and the CCS onto a bare SiO2 surface and into the photoresist was studied using a quartz crystal microbalance (QCM). From the adsorption studies of CO2 and CCS/CO2 onto a bare SiO2 surface, it was found that the CCS begins to adsorb at 8.0 MPa at a temperature of 35 degrees C and at 9.4 MPa at a temperature of 50 degrees C. The adsorption of the CCS was favored and driven by entropy changes. The absorption of CO2 into the glassy photoresist resin was also measured with QCM and found comparable to CO2 absorption in glassy polystyrene for 35 and 50 degrees C up to a pressure where the photoresist is believed to dewet from the substrate. The diffusion behavior during CO2 absorption was found to be comparable to that of small fluorescent molecule diffusion in a CO2 swollen polystyrene.}, number={29}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Zweber, Amy E. and Wagner, Mark and Carbonell, Ruben G.}, year={2009}, month={Jul}, pages={9687–9693} }
 @article{heldt_gurgel_jaykus_carbonell_2008, title={Identification of trimeric peptides that bind porcine parvovirus from mixtures containing human blood plasma}, volume={24}, ISSN={["1520-6033"]}, DOI={10.1021/bp070412c}, abstractNote={Abstract}, number={3}, journal={BIOTECHNOLOGY PROGRESS}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2008}, pages={554–560} }
 @misc{carbonell_shen_gurgel_wiltshire-lyerly_hammond_burton_2008, title={Prion protein binding materials and methods of use}, volume={7,393,658}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Shen, H. and Gurgel, P. V. and Wiltshire-Lyerly, V. and Hammond, D. J. and Burton, S. J.}, year={2008}, month={Jan} }
 @article{tombokan_aguda_danehower_kilpatrick_carbonell_2008, title={Three-component phase behavior of the sclareol-ethyl lactate-carbon dioxide system for GAS applications}, volume={45}, ISSN={["0896-8446"]}, DOI={10.1016/j.supflu.2007.12.007}, abstractNote={This paper focuses on the extraction of sclareol from the leaves of Salvia sclarea Lamiaceae, more commonly known as Clary sage. The process involves the extraction of sclareol using a CO2-soluble GRAS solvent such as ethyl lactate, followed by GAS anti-solvent precipitation from ethyl lactate solution with carbon dioxide. The three-component phase behavior of the sclareol–ethyl lactate–CO2 system at various pressures has been determined and indicates a slight cybotactic effect. The ability of thermodynamic models to predict the complex three-component phase behavior of this system is discussed, together with the implications of the thermodynamic behavior of the system on process design.}, number={2}, journal={JOURNAL OF SUPERCRITICAL FLUIDS}, author={Tombokan, Xenia C. and Aguda, Remil M. and Danehower, David A. and Kilpatrick, Peter K. and Carbonell, Ruben G.}, year={2008}, month={Jun}, pages={146–155} }
 @article{kim_carbonell_2007, title={Deposition of poly[2-(perfluorooctyl)ethyl acrylate] from liquid CO2 high-pressure free meniscus coating—Uniformity and morphology}, volume={42}, ISSN={0896-8446}, url={http://dx.doi.org/10.1016/j.supflu.2007.01.012}, DOI={10.1016/j.supflu.2007.01.012}, abstractNote={Abstract Ultrathin fluoropolymer films were prepared by depositing poly[2-(perfluorooctyl)ethyl acrylate] (PFOEA) on 12.5 cm diameter silicon wafer substrates using high-pressure free meniscus coating (hFMC) with liquid CO2 (l-CO2) as a coating solvent. Dry film thickness across the wafer substrate and the morphology of deposited films were characterized as a function of coating conditions—withdrawal velocities, solution concentrations and evaporation driving forces (ΔP). Thickness measurements by ellipsometry revealed that at zero or low evaporation driving forces (ΔP = 0–0.0138 MPa), highly uniform films with thicknesses in the range of 7–30 nm were deposited over the entire concentration range (1–7 wt.%). However, films deposited at high evaporation driving forces (ΔP = 0.0414–0.0552 MPa) or larger concentrations (5–7 wt.%) with a ΔP of 0.0276 MPa were thicker (35–70 nm) and less uniform. Optical microscopy and atomic force microscopy (AFM) were used to characterize film morphology including drying defects and film roughness. Films deposited at zero or low ΔP of 0.0138 MPa and low concentrations of 1–3 wt.% exhibited few drying defects and a low root mean square (RMS) roughness (∼2 nm). At higher evaporation driving forces and higher concentrations, ring-like drying defects were observed with diameters ranging 5–30 μm. The film thickness and morphology of PFOEA films deposited from l-CO2 hFMC were compared to those deposited from 1,1,2-trichlorotrifluoroethane (Freon113) by normal atmospheric dip coating. Films deposited from l-CO2 hFMC were much thinner and more uniform, and exhibit much fewer drying defects and lower RMS roughness.}, number={1}, journal={The Journal of Supercritical Fluids}, publisher={Elsevier BV}, author={Kim, Jaehoon and Carbonell, Ruben G.}, year={2007}, month={Aug}, pages={129–141} }
 @article{kim_mcclain_carbonell_2007, title={Deposition of poly[2-(perfluorooctyl)ethyl acrylate] on silicon wafers by the displacement of two immiscible supercritical phases (DISP)}, volume={43}, ISSN={["1872-8162"]}, DOI={10.1016/j.supflu.2007.05.003}, abstractNote={Abstract Deposition from two immiscible supercritical phases (DISP), in which a solution of supercritical carbon dioxide (scCO2) with a desired solute is displaced by supercritical helium (scHe), has been applied to deposit poly[2-(perfluorooctyl)ethyl acrylate] (PFOEA) on silicon wafer substrate coupons. The polymer was precipitated at the interfacial boundary between the supercritical He phase and the supercritical CO2/PFOEA solution phase and deposited on the substrates. Depending on the deposition conditions, two different deposition regimes – a particle formation regime and a film formation regime – were found. At low solution concentration or high displacement velocity, particles in the range of 1–3 μm in diameter formed while at high solution concentration or low displacement velocity, films in the range of 30–500 nm in thickness formed. The solute concentration, displacement velocity, and pressure all had a strong effect on the particle size and film thickness. Optical microscopy and atomic force microscopy (AFM) were used to characterize film morphology including drying defects and film roughness. Highly uniform films with no drying defects and low root-mean-square (RMS) roughness (∼2–3 nm) were obtained at high solution concentration. Films formed at low-to-moderate solution concentration displayed ring-like drying defects. The thickness and morphology of films deposited from DISP were compared with films prepared from high-pressure free meniscus coating (hFMC) with liquid CO2 (l-CO2) as a solvent and from normal dip coating with an organic solvent (1,1,2-trifluorotrichloroethane, Freon113). The film deposited from DISP was much thicker and more uniform than the film formed using Freon113.}, number={1}, journal={JOURNAL OF SUPERCRITICAL FLUIDS}, author={Kim, Jaehoon and McClain, James B. and Carbonell, Ruben G.}, year={2007}, month={Nov}, pages={139–149} }
 @article{rosa_santana_carbonell_2007, title={Determination of the liquid pool surfactant and protein concentration for semi-batch foam fractionation columns}, volume={24}, ISSN={["0104-6632"]}, DOI={10.1590/S0104-66322007000100001}, abstractNote={A model is derived for the change with time of the concentration of a surface-active component in the liquid pool of a semi-batch foam fractionation process. The transport of surface-active material to the gas-liquid interface was assumed to be limited by the mass transfer rates, and the concentration of the adsorbed material at the interface was assumed to be in equilibrium with the concentration of liquid adjacent to the bubble gas surface. This model was compared to experimental data obtained for semi-batch foam fractionation of aqueous solutions of bovine serum albumin and cetyltrimetylammonium bromide.}, number={1}, journal={BRAZILIAN JOURNAL OF CHEMICAL ENGINEERING}, author={Rosa, P. T. V. and Santana, C. C. and Carbonell, R. G.}, year={2007}, pages={1–14} }
 @article{marias_mancini_cansell_mercadier_2007, title={Hydrothermal oxidation treatment of solid particles between 250 and 350 degrees C: Modelling and experiments}, volume={41}, ISSN={["1872-8162"]}, DOI={10.1016/j.supflu.2007.01.002}, abstractNote={Abstract Hydrothermal oxidation is an efficient and clean way for the treatment of wastewater containing organic matter. The purpose of this work is to develop a mathematical model of a reactor for hydrothermal oxidation. This reactor is of the tank type and it is designed for the oxidation of solid particles of waste or biomass. According to some previous work, the experimental device developed by the Institut de Chimie et de la Matiere condensee de Bordeaux is known to behave as a battery of three completely stirred tank reactors (CSTR). To reach our goal, governing equations are written within each of the three CSTR. This set of equations is composed of the mass, species and energy balances for the fluid phase as well as equations allowing for the evaluation of the rate of shrinkage of a particle (shrinking core model) and a population balance. Thanks to this model, the particle size distribution (PSD) of the output of the reactor is computed as a function of the incoming one and of the operating parameters (temperature, residence time, pressure, …). The numerical predictions of the model are compared to experimental profiles obtained in the case of hydrothermal oxidation treatment of black carbon. These comparisons show very good agreement.}, number={3}, journal={JOURNAL OF SUPERCRITICAL FLUIDS}, author={Marias, F. and Mancini, F. and Cansell, F. and Mercadier, J.}, year={2007}, month={Jul}, pages={352–360} }
 @article{kim_efimenko_genzer_carbonell_2007, title={Surface properties of poly[2-(perfluorooctyl)ethyl acrylate] deposited from liquid CO2 high-pressure free meniscus coating}, volume={40}, ISSN={["1520-5835"]}, DOI={10.1021/ma0623791}, abstractNote={The surface characteristics of poly[2-(perfluorooctyl)ethyl acrylate] (PFOEA) films deposited using a high-pressure free meniscus coating (hFMC) process with liquid CO{sub 2} (l-CO{sub 2}) as the coating solvent on 12.5 cm diameter silicon wafer substrates were investigated using contact angle measurements, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and near-edge X-ray adsorption fine structure (NEXAFS) spectroscopy. The results were compared with surface property measurements of PFOEA films deposited from 1,1,2-trichlorotrifluoroethane (Freon 113) under normal dip coating conditions at atmospheric pressure. NEXAFS measurements showed that perfluoroalkyl groups in the films from l-CO{sub 2} and Freon 113 were well-organized and oriented normal to the substrate at the air/polymer interface. AFM images and XPS measurements revealed that a terrace-like structure of the PFOEA film from l-CO{sub 2} resulted in carbonyl group exposure at the air/polymer interface. This leads to smaller contact angles on the films cast from l-CO{sub 2} relative to the specimens deposited from Freon 113. Annealing the films deposited from the solvents resulted in droplet formation on the surface due to dewetting. The critical surface tension ({gamma}{sub c}) after annealing the film prepared from Freon 113 increased from 6.5 to 8.5 mJ/m{sup 2}, whereas {gamma}{sub c} of the film deposited frommore » l-CO{sub 2} decreased slightly from 9.7 to 8.9 mJ/m{sup 2}. We discuss how surface morphology changes before and after annealing play a role in the variation of {gamma}{sub c}.« less}, number={3}, journal={MACROMOLECULES}, author={Kim, Jaehoon and Efimenko, Kirill and Genzer, Jan and Carbonell, Ruben G.}, year={2007}, month={Feb}, pages={588–597} }
 @article{heldt_hernandez_mudiganti_gurgel_brown_carbonell_2006, title={A  colorimetric assay for viral agents that produce cytopathic effects}, volume={135}, DOI={10.1016/j.j.viromet.2006.01.022}, number={1}, journal={Journal of Virological Methods}, author={Heldt, C. L. and Hernandez, R. and Mudiganti, U. and Gurgel, P. V. and Brown, D. T. and Carbonell, R. G.}, year={2006}, pages={56–65} }
 @article{heldt_hernandez_mudiganti_gurgel_brown_carbonell_2006, title={A colorimetric assay for viral agents that produce cytopathic effects}, volume={135}, ISSN={0166-0934}, url={http://dx.doi.org/10.1016/j.jviromet.2006.01.022}, DOI={10.1016/j.jviromet.2006.01.022}, abstractNote={Many animal viruses produce cytopathic effects in their host cells during a productive infection. While some virus infections can be assayed by the production of plaques, many viruses, while producing cytotoxicity, do not easily form plaques, or do not form plaques at all. Additionally, viruses within families such as the parvoviruses may have different preferred forms of titration making comparative virology difficult even among related groups. Porcine parvovirus (PPV), canine parvovirus (CPV), and minute virus of mice (MVM) are usually titrated using different infectivity assays. A direct comparison of infectious virus titer between these parvoviruses was sought, and a tetrazolium salt assay, MTT has been applied to measure cytopathic effect produced by viral infection for different members of the parvovirus family. Infectious PPV measured using the MTT and the TCID50 assays exhibited excellent correlation and titers for CPV and MVM were consistently duplicated using the MTT assay. The MTT assay was also applied to an unrelated virus, Sindbis, which is routinely titrated by plaque assay. MTT titration of Sindbis virus mutants was found to be valuable for preliminary screening. This assay can be adapted, by correlation to an accepted titration method, to any viral system which produces measurable cytopathic effect.}, number={1}, journal={Journal of Virological Methods}, publisher={Elsevier BV}, author={Heldt, Caryn L. and Hernandez, Raquel and Mudiganti, Usharani and Gurgel, Patrick V. and Brown, Dennis T. and Carbonell, Ruben G.}, year={2006}, month={Jul}, pages={56–65} }
 @article{boggiano_vellenga_carbonell_ashby_desimone_2006, title={Alicyclic photoresists for CO2-based next-generation microlithography: A tribute to James E. McGrath}, volume={47}, ISSN={["1873-2291"]}, DOI={10.1016/j.polymer.2006.03.001}, abstractNote={Addition polymerization of norbornene-based monomers has been pursued toward the fabrication of photoresists for next-generation microlithography, using condensed carbon dioxide as the developing solvent. Addition polymers containing a norbornyl backbone, for dry plasma etch resistance and high thermal stability, were synthesized to include fluorinated moieties and chemical amplification switching groups. These materials have been characterized and their lithographic properties evaluated. Solubility differences between exposed and non-exposed resist have been observed in these novel systems, which should provide the necessary contrast for high-resolution imaging. Lithographic imaging produced dense lines as small as 3 μm.}, number={11}, journal={POLYMER}, author={Boggiano, Mary Kate and Vellenga, David and Carbonell, Ruben and Ashby, Valerie Sheares and DeSimone, Joseph M.}, year={2006}, month={May}, pages={4012–4017} }
 @article{kim_carbonell_2006, title={Deposition of small organic molecules by the displacement of two immiscible supercritical phases}, volume={22}, ISSN={["0743-7463"]}, DOI={10.1021/la052625m}, abstractNote={A new coating process is described (deposition from two immiscible supercritical phases, or DISP) in which a solution of supercritical carbon dioxide (scCO2) with a desired solute is displaced by supercritical helium (scHe). After depressurization, the solute is deposited on substrates initially submerged in the coating solvent. Micron-sized particles and thin films of sucrose octaacetate (SOA) were formed on silicon wafer substrate coupons from DISP at relatively low temperatures and pressures (< or = 6500 psi and < or = 60 degrees C). The particle size, film thickness, and morphology of SOA were characterized as a function of coating conditions-solution concentrations, withdrawal velocities, and pressures. Particles in the range of 1-14 microm in diameter were deposited at low solute concentrations (< or = 0.2 wt % at 4500 psi), whereas films in the range of 0.1-0.5 microm in thickness were deposited at higher solute concentrations (> or = 1.5 wt % at 4500 psi). Particle sizes decreased with increasing displacement velocity and increasing pressure. Estimates of characteristic times for diffusion and nucleation indicate that DISP is a diffusion-limited process. Optical microscopy and atomic force microscopy (AFM) were used to characterize film morphology, including defect formations and film roughness. Highly uniform films with low root-mean-square (RMS) roughness (approximately 10 angstroms) were obtained at a low displacement velocity of 0.0035 cm/s, while ring-like defect structures were observed in films deposited at a higher displacement velocity of 0.035 cm/s. The film thickness and morphology of the films deposited from DISP were compared with films from normal dip coating with typical organic solvents (acetone and toluene). Films deposited from scCO2 by DISP were much thicker, more uniform, and exhibited much fewer drying defects and lower RMS roughness compared with films from the organic solvents.}, number={5}, journal={LANGMUIR}, author={Kim, J and Carbonell, RG}, year={2006}, month={Feb}, pages={2117–2129} }
 @article{wang_carbonell_2006, title={Design of Adsorptive Columns for Specific Pathogen Removal: Application to Staphylococcal Enterotoxin B}, volume={22}, ISSN={8756-7938}, url={http://dx.doi.org/10.1021/bp060126l}, DOI={10.1021/bp060126l}, abstractNote={Abstract}, number={5}, journal={Biotechnology Progress}, publisher={Wiley}, author={Wang, Guangquan and Carbonell, Ruben G.}, year={2006}, pages={1358–1367} }
 @article{wang_carbonell_2006, title={Design of adsorptive columns for specific pathogen removal: Application to staphylococcal enterotoxin B}, volume={22}, DOI={10.1021/pb060126l}, number={5}, journal={Biotechnology Progress}, author={Wang, G. Q. and Carbonell, R. G.}, year={2006}, pages={1358–1367} }
 @article{gregori_gurgel_lathrop_edwardson_lambert_carbonell_burton_hammond_rohwer_2006, title={Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins}, volume={368}, ISSN={["0140-6736"]}, DOI={10.1016/S0140-6736(06)69897-8}, abstractNote={Background Transmissible spongiform encephalopathies (TSE) can be contracted through blood transfusion. Selective adsorption of the causative agent from donated blood might be one of the best ways of managing this risk. In our study, affinity resin L13, which reduces brain-derived infectivity spiked into human red blood cell concentrate by around 4 log10ID50, and its equivalent, L13A, produced on a manufacturing scale, were assessed for their ability to remove TSE infectivity endogenously present in blood. Methods 500 mL of scrapie-infected hamster whole blood was leucoreduced at full scale before passage through the affinity resins. Infectivity of whole blood, leucoreduced whole blood (challenge), and the recovered blood from each flow-through was measured by limiting dilution titration. Findings Leucoreduction removed 72% of input infectivity. 15 of 99 animals were infected by the challenge, whereas none of the 96 or 100 animals inoculated with the final flow-throughs from either resin developed the disease after 540 days. The limit of detection of the bioassay was 0·2 infectious doses per mL. The overall reduction of the challenge infectivity was more than 1·22 log10ID. The results showed removal of endogenous TSE infectivity from leucoreduced whole blood by affinity ligands. The same resins adsorb normal and abnormal prion protein from human infections with variant, sporadic, and familial Creutzfeldt-Jakob disease, in the presence of blood components. Interpretation TSE affinity ligands, when incorporated into appropriate devices, can be used to mitigate the risks from TSE-infected blood, blood products, and other materials exposed to TSE infectivity.}, number={9554}, journal={LANCET}, author={Gregori, Luisa and Gurgel, Patrick V. and Lathrop, Julia T. and Edwardson, Peter and Lambert, Brian C. and Carbonell, Ruben G. and Burton, Steven J. and Hammond, David J. and Rohwer, Robert G.}, year={2006}, month={Dec}, pages={2226–2230} }
 @article{gregori_lambert_gurgel_gheorghiu_edwardson_lathrop_macauley_carbonell_burton_hammond_et al._2006, title={Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands}, volume={46}, ISSN={["1537-2995"]}, DOI={10.1111/j.1537-2995.2006.00865.x}, abstractNote={BACKGROUND:  There is a demonstrated risk of infection by transmissible spongiform encephalopathies (TSEs) through transfusion from asymptomatic donors. Currently, blood‐borne TSE infectivity cannot be detected with a diagnostic test, nor is it likely to be amenable to inactivation; however, its depletion with specific adsorp‐tive ligand resins is possible.}, number={7}, journal={TRANSFUSION}, author={Gregori, Luisa and Lambert, Brian C. and Gurgel, Patrick V. and Gheorghiu, Liliana and Edwardson, Peter and Lathrop, Julia T. and MacAuley, Claudia and Carbonell, Ruben G. and Burton, Steven J. and Hammond, David and et al.}, year={2006}, month={Jul}, pages={1152–1161} }
 @article{visintin_eichenlaub_portnow_carbonell_beaudoin_schauer_desimone_2006, title={Studies on CO2-based slurries and fluorinated silica and alumina particles for chemical mechanical polishing of copper films}, volume={153}, ISSN={["1945-7111"]}, DOI={10.1149/1.2358085}, abstractNote={The microelectronics industry has an interest in implementing condensed-CO 2 -based processes in many segments of the integrated-circuit manufacturing process. Preliminary studies of the behavior of copper surfaces and functionalized nanoparticles were performed in an attempt to offer insight into potential chemical mechanical planarization (CMP) and post-CMP cleaning applications using condensed CO 2 . Micrometer- and nanometer-sized silica particle surfaces were covalently modified with C 8 F 17 CH 2 CH 2 Si(CH 3 ) 2 Cl to give C 8 F 17 -silica, and alumina particle surfaces were modified with C 8 F 17 CH 2 CH 2 Si(OEt) 3 and C 8 F 17 COOH to yield C 8 F 17 -alumina and C 8 F 17 COOH-alumina. Atomic force microscopy was used to examine adhesion between these functionalized microparticles and a copper substrate under a nitrogen atmosphere. The adhesion force significantly decreased for the functionalized particles compared to the unmodified particles. In separate studies, copper was exposed to peroxide/ P-diketone solvents containing functionalized nanoparticles to investigate the effect of the nanoparticles on the copper dissolution rate. It was found that copper removal was proportional to the surface oxide and hydroxyl group concentration.}, number={12}, journal={JOURNAL OF THE ELECTROCHEMICAL SOCIETY}, author={Visintin, Pamela M. and Eichenlaub, Sean K. and Portnow, Lauren E. and Carbonell, Ruben G. and Beaudoin, Stephen P. and Schauer, Cynthia K. and DeSimone, Joseph M.}, year={2006}, pages={G1064–G1071} }
 @article{kim_novick_desimone_carbonell_2006, title={Ultrathin film deposition by liquid CO2 free meniscus coating-uniformity and morphology}, volume={22}, ISSN={["0743-7463"]}, DOI={10.1021/la0521600}, abstractNote={Ultrathin organic films of sucrose octaacetate (SOA) were deposited on 12.5 cm diameter silicon wafer substrates using high-pressure free meniscus coating (hFMC) with liquid CO2 (l-CO2) as a coating solvent. The dry film thickness across the wafer and the morphology of deposited films were characterized as a function of coating conditions-withdrawal velocity, solution concentration, and evaporation driving force (deltaP). When no evaporation driving force was applied (deltaP = 0), highly uniform films were deposited with thickness in the range of 8-105 angstroms over the entire concentration range (3-11 wt%). Uniform films were also obtained at low concentrations (3-5 wt%) with a low evaporation driving force (deltaP = 0.0138 MPa). However, films deposited at medium to high concentrations (7-11 wt%) were thicker (110-570 angstroms) and less uniform, with larger nonuniformities at higher applied evaporation driving forces. Optical microscopy and atomic force microscopy (AFM) were used to characterize film morphology including drying defects and film roughness. Films deposited without evaporation had no apparent drying defects and very low root-mean-square (RMS) roughness (1.4-3.8 angstroms). Spinodal-like dewetting morphologies including holes with diameters in the range of 100-300 nm, and surface undulations were observed in films deposited at medium concentration (7 wt%) and low deltaP (0.0138-0.0276 MPa). At higher concentrations and higher evaporative driving forces, spinodal-like dewetting morphologies disappeared but concentric ring defect structures were observed with diameters in the range 20-125 microm. The film thickness and morphology of SOA films deposited from 1-CO2 hFMC were compared to those deposited from toluene and acetone under normal dip coating. Films deposited from l-CO2 hFMC were much thinner, more uniform, and exhibited much fewer drying defects and lower RMS roughness.}, number={2}, journal={LANGMUIR}, author={Kim, J and Novick, BJ and DeSimone, JM and Carbonell, RG}, year={2006}, month={Jan}, pages={642–657} }
 @article{wang_carbonell_2005, title={Characterization of a peptide affinity support that binds selectively to staphylococcal enterotoxin B}, volume={1078}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2005.05.010}, abstractNote={The influences of mass transfer and adsorption-desorption kinetics on the binding of staphylococcal enterotoxin B (SEB) to an affinity resin with the peptide ligand, Tyr-Tyr-Trp-Leu-His-His (YYWLHH) have been studied. The bed and particle porosities, the axial dispersion coefficient and the pore diffusivity were measured using pulse experiments under unretained conditions. Adsorption isotherms for SEB on YYWLHH resins with peptide densities in the range from 6 to 220 micromol/g were measured and fitted to a bi-Langmuir equation. At peptide densities below 9 micromol/g and above 50 micromol/g, dissociation constants were lower (2 x 10(-3) to 7 x 10(-3) mol/m3), and binding capacities were larger (43-47 mg SEB/g). In the range from 9 to 50 micromol/g dissociation constants were larger (13 x 10(-3) to 24 x 10(-3) mol/m3) and capacities were lower (33-37 mg SEB/g). These observations are consistent with a transition from single point attachment of the protein to the ligand at low peptide densities to multipoint attachment at high peptide densities. The general rate (GR) model of chromatography was used to fit experimental breakthrough curves under retained conditions to determine the intrinsic rate constants for adsorption, which varied from 0.13 to 0.50 m3 mol(-1) s(-1), and exhibited no clear trend with increasing peptide density. An analysis of the number of transfer units for the various mass transfer steps in the column indicated that film mass transfer, pore diffusion (POR) and the kinetics of adsorption can all play an important role in the overall rate of adsorption, with the intrinsic adsorption step apparently being the rate determining step at peptide densities below 50 micromol/g.}, number={1-2}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Wang, GQ and Carbonell, RG}, year={2005}, month={Jun}, pages={98–112} }
 @article{cotugno_di maio_mensitieri_iannace_roberts_carbonell_hopfenberg_2005, title={Characterization of microcellular biodegradable polymeric foams produced from supercritical carbon dioxide solutions}, volume={44}, ISSN={["0888-5885"]}, DOI={10.1021/ie049445c}, abstractNote={The formation of foams of biodegradable poly(e-caprolactone) (PCL) from CO2 solutions in molten PCL was investigated. This study included characterization of the CO2 diffusion and equilibrium solubility in molten PCL in contact with supercritical CO2 (scCO2). Experiments were performed at 70, 80, and 90 °C at CO2 pressures up to 25 MPa. The effective mutual diffusivity of CO2 in molten PCL was measured as a function of the CO2 pressure. The data revealed a dramatic increase in apparent effective diffusivity at elevated pressure, likely related to the formation of fluid bubbles, phase-separated from the previously homogeneous, molten PCL solution of CO2. Microcellular PCL foams were produced by starting from an equilibrium CO2−PCL solution at 70 °C over a wide range of initial pressures (from 6.9 to 32 MPa) by quenching down to foaming temperatures (from 24 to 30 °C) followed by rapid depressurization to atmospheric pressure. Foam structures were characterized by scanning electron microscopy, and cell size...}, number={6}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Cotugno, S and Di Maio, E and Mensitieri, G and Iannace, S and Roberts, GW and Carbonell, RG and Hopfenberg, HB}, year={2005}, month={Mar}, pages={1795–1803} }
 @article{visintin_carbonell_schauer_desimone_2005, title={Chemical functionalization of silica and alumina particles for dispersion in carbon dioxide}, volume={21}, ISSN={["0743-7463"]}, DOI={10.1021/la047823c}, abstractNote={The steric stabilization and flocculation of modified silica and alumina particle suspensions in condensed CO(2) were studied. Silica particles (average diameters of 7 and 12 nm) were functionalized using chlorosilanes of the form C(n)F(2n+1)CH(2)CH(2)Si(CH(3))(2)Cl (n = 8, 4, or 1) to give C(n)F(2n+1)-silica. Alumina particles (diameter of 8-14 nm) were grafted with C(8)F(17)CH(2)CH(2)Si(OEt)(3) and chemically modified with perfluorononanoic acid to yield C(8)F(17)-alumina and C(8)F(17)COOH-alumina, respectively. Elemental analysis and thermogravimetric analysis on the derivatized particles were carried out, and surface coverage was calculated. The stabilization of these modified particles in condensed CO(2) was quantified using turbidimetry. Particle stability was found to increase with increasing fluorinated tail length, temperature, and CO(2) density. Unmodified particles and those modified with only -CF(3) tails were unstable in condensed CO(2). Stabilization in supercritical CO(2) is continuous up to 24 h for the C(n)F(2n+1)-silica (n >/= 4) particles and 96 h for the C(8)F(17)-alumina particles. The C(8)F(17)COOH-alumina particles gave a significantly higher graft density than the C(8)F(17)-alumina particles but are not as stable in CO(2). The C(8)F(17)-alumina particles were stable at lower CO(2) densities than the modified silica particles. This stability difference may be attributed to the precursor organosilanes being monofunctional (modified silica) versus trifunctional (modified alumina), producing different structures on the surface.}, number={11}, journal={LANGMUIR}, author={Visintin, PM and Carbonell, RG and Schauer, CK and DeSimone, JM}, year={2005}, month={May}, pages={4816–4823} }
 @article{yang_gurgel_carbonell_2005, title={Hexamer peptide affinity resins that bind the Fc region of human immunoglobulin G}, volume={66}, ISSN={["1397-002X"]}, DOI={10.1111/j.1747-0285.2006.00342.x}, abstractNote={Abstract:  A family of linear hexapeptides composed of histidine on the N‐terminus followed by aromatic amino acid(s) and positively charged amino acid(s) has been identified through a three‐step screening of a synthetic solid phase library. These peptides were able to recognize human immunoglobulin G (HIgG) through its Fc region, and their selectivity to Fc is comparable to Protein A. This is the first known report of short peptides that are able to bind HIgG by recognizing its Fc portion. One of the ligands from the identified family, HWRGWV, was examined for its ability to isolate HIgG from complex mixtures. It was found that HWRGWV possessed the potential to purify HIgG from complete mammalian cell culture medium containing 10% fetal calf serum with purity comparable to commercially available resins, but using milder elution conditions. HWRGWV bound all HIgG subclasses and IgGs from bovine, mouse, goat, and rabbit. The broad affinity spectrum as well as its Fc recognition ability may be useful in capturing and detecting both polyclonal and monoclonal antibodies.}, journal={JOURNAL OF PEPTIDE RESEARCH}, author={Yang, H and Gurgel, PV and Carbonell, RG}, year={2005}, month={Dec}, pages={120–137} }
 @article{xu_carbonell_kiserow_roberts_2005, title={Hydrogenation of polystyrene in CO2-expanded solvents: Catalyst poisoning}, volume={44}, ISSN={["0888-5885"]}, DOI={10.1021/ie040243q}, abstractNote={Organic solvents expanded with supercritical carbon dioxide can be excellent media for hydrogenation reactions. However, catalyst poisoning by CO formed via the reverse water-gas-shift reaction occurs during many hydrogenations in the presence of CO2. In this research, the hydrogenation of polystyrene in CO2-expanded decahydronaphthalene was studied in a batch reactor using two hydrogenation catalysts, 5%Pd/BaSO4 and 65%Ni/Al2O3/SiO2. The 5%Pd/BaSO4 catalyst deactivated at 150 °C and CO2 pressures of 250−2250 psig (1.8−15.6 MPa). Approximately 50 ppm CO was present in the CO2-rich light phase after about 10 h at 150 °C, 750 psig H2 pressure, and 2250 psig CO2 pressure. A model that incorporates CO poisoning was developed to describe deactivation of the Pd/BaSO4 catalyst. The 65%Ni/Al2O3/SiO2 catalyst was more active for ring hydrogenation than 5%Pd/BaSO4, and very little CO was formed in the presence of CO2. The Ni catalyst deactivated in the presence of CO2 at 180 °C, possibly due to H2O formed in a meth...}, number={16}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Xu, DW and Carbonell, RG and Kiserow, DJ and Roberts, GW}, year={2005}, month={Aug}, pages={6164–6170} }
 @article{carla_wang_hussain_efimenko_genzer_grant_sarti_carbonell_doghieri_2005, title={Nonequilibrium model for sorption and swelling of bulk glassy polymer films with Supercritical carbon dioxide}, volume={38}, ISSN={["1520-5835"]}, DOI={10.1021/ma0506684}, abstractNote={A new procedure is introduced for the calculation of solubility isotherms of plasticizing agents in glassy polymer matrices with particular application to the case of absorption of supercritical gases in bulk glassy polymer films. The model presented is an extension of the nonequilibrium thermodynamics for glassy polymers (NET-GP) approach, modified to allow for the calculation of the effects of pressure, temperature, and gas concentration on the glass transition. Mass sorption and one- dimensional swelling behavior are analyzed for the carbon dioxide (CO2)-poly(methyl methacrylate) (PMMA) system at high pressure. A quantitative comparison is presented between the model performance and experimental data measured using quartz crystal microbalance (QCM) and high-pressure ellipsometry (HPE).}, number={24}, journal={MACROMOLECULES}, author={Carla, V and Wang, K and Hussain, Y and Efimenko, K and Genzer, J and Grant, C and Sarti, GC and Carbonell, RG and Doghieri, F}, year={2005}, month={Nov}, pages={10299–10313} }
 @article{xu_carbonell_roberts_kiserow_2005, title={Phase equilibrium for the hydrogenation of polystyrene in CO2–swollen solvents}, volume={34}, ISSN={0896-8446}, url={http://dx.doi.org/10.1016/j.supflu.2004.09.004}, DOI={10.1016/j.supflu.2004.09.004}, abstractNote={Polystyrene (PS) can be hydrogenated using a heterogeneous catalyst suspended in a solvent swollen by supercritical carbon dioxide (scCO2). Various phase equilibria are involved in this system. First, the application of scCO2 to a solution of PS can cause the polymer to precipitate. Therefore, the effect of CO2 pressure and temperature on the phase behavior of various solvents containing dissolved PS was investigated, leading to the selection of decahydronaphthalene (DHN) for in-depth study. It was found that the CO2 pressure required to precipitate PS from DHN increased with the temperature. The volume of solutions containing various concentrations of PS in DHN increased considerably as the CO2 pressure was increased. Volume expansions of 35–40% were obtained between 40 and 150 °C and between 3 and 9 wt.% PS. Moreover, calculations using the Peng–Robinson equation of state showed that the H2 concentration in the liquid phase was higher in CO2–swollen DHN than in the pure solvent, at a constant H2 partial pressure. The rate constant for PS hydrogenation was found to be higher in CO2–swollen DHN than in the pure solvent.}, number={1}, journal={The Journal of Supercritical Fluids}, publisher={Elsevier BV}, author={Xu, Dawei and Carbonell, Ruben G. and Roberts, George W. and Kiserow, Douglas J.}, year={2005}, month={May}, pages={1–9} }
 @article{wang_salm_gurgel_carbonell_2005, title={Small Peptide Ligands for Affinity Separations of Biological Molecules}, DOI={10.1002/0470025018.ch3}, abstractNote={This chapter contains sections titled: Downstream Processing in Biopharmaceutical Production Affinity Chromatography Advantages of Small Peptide Ligands Combinatorial Peptide Libraries Screening of One-Bead-One-Peptide Libraries Characterization of Peptide Ligands Future Challenges and Opportunities References}, journal={CHEMICAL ENGINEERING TRENDS AND DEVELOPMENTS}, author={Wang, Guangquan and Salm, Jeffrey R. and Gurgel, Patrick V. and Carbonell, Ruben G.}, year={2005}, pages={63–83} }
 @article{hoggan_wang_flowers_desimone_carbonell_2004, title={"dry" lithography using liquid and supercritical carbon dioxide based chemistries and processes}, volume={17}, ISSN={["1558-2345"]}, DOI={10.1109/tsm.2004.837002}, abstractNote={Novel carbon dioxide (CO/sub 2/) soluble photoresists were synthesized based on random copolymers of 1,1-dihydroperfluorooctylmethacrylate and 2-tetrahyrdopyranyl methacrylate. These resins, along with specially designed CO/sub 2/-soluble photoacid generators, were utilized to demonstrate the potential for a new "dry" lithographic process. Photoresist spin casting, development, and stripping were all carried out using only liquid and supercritical CO/sub 2/ as the processing medium. A novel high-pressure spin coating process was used to deposit the photoresist films. Parameters such as resist sensitivity, contrast, and resolution were investigated. Wafers were imaged using both 248and 193-nm radiation, demonstrating the potential of this new photoresist platform for use as a sustainable technology for the microelectronics industry.}, number={4}, journal={IEEE TRANSACTIONS ON SEMICONDUCTOR MANUFACTURING}, author={Hoggan, EN and Wang, K and Flowers, D and DeSimone, JM and Carbonell, RG}, year={2004}, month={Nov}, pages={510–516} }
 @article{wang_de_schoeniger_roe_carbonell_2004, title={A hexamer peptide ligand that binds selectively to staphylococcal enterotoxin B: isolation from a solid phase combinatorial library}, volume={64}, ISSN={["1397-002X"]}, DOI={10.1111/j.1399-3011.2004.00170.x}, abstractNote={By screening a solid-phase combinatorial peptide library, a short peptide ligand, YYWLHH, has been discovered that binds with high affinity and selectivity to staphylococcal enterotoxin B (SEB), but only weakly to other SEs that share sequence and structural homology with SEB. Using column affinity chromatography with an immobilized YYWLHH stationary phase, it was possible to separate SEB quantitatively from Staphylococcus aureus fermentation broth, a complex mixture of proteins, carbohydrates and other biomolecules. The immobilized peptide was also used to purify native SEB from a mixture containing denatured and hydrolyzed SEB, and showed little cross-reactivity with other SEs. To our knowledge this is the first report of a highly specific short peptide ligand for SEB. Such a ligand is a potential candidate to replace antibodies for detection, removal and purification strategies for SEB.}, number={2}, journal={JOURNAL OF PEPTIDE RESEARCH}, author={Wang, G and De, J and Schoeniger, JS and Roe, DC and Carbonell, RG}, year={2004}, month={Aug}, pages={51–64} }
 @misc{jones_zweber_deyoung_mcclain_carbonell_desimone_2004, title={Applications of "dry" processing in the microelectronics industry using carbon dioxide}, volume={29}, ISSN={["1547-6561"]}, DOI={10.1080/10408430490888968}, abstractNote={ABSTRACT Condensed carbon dioxide (CO2) has emerged as a leading enabler of advanced semiconductor manufacturing processes. By exploiting the physical properties of CO2, some of the current challenges encountered in microelectronics processing related to shrinking feature sizes and materials compatibility have been addressed. Furthermore, the potential for reduction of chemicals used in processing is realized. Applications of CO2 in microelectronics operations such as wafer cleaning, spin-coating, development, and stripping of photoresists, drying, low-k film preparation and repair, etching, and metal deposition are discussed.}, number={3-4}, journal={CRITICAL REVIEWS IN SOLID STATE AND MATERIALS SCIENCES}, author={Jones, CA and Zweber, A and DeYoung, JP and McClain, JB and Carbonell, R and DeSimone, JM}, year={2004}, pages={97–109} }
 @misc{desimone_carbonell_kendall_mcadams_2004, title={CO2-processes photoresists, polymers, and photoactive compounds for microlithography}, volume={6,764,809}, number={2004 July 20}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Carbonell, R. G. and Kendall, J. and McAdams, C. L.}, year={2004}, month={Jul} }
 @misc{desimone_birnbaum_carbonell_crette_mcclain_mccleskey_powell_romack_tumas_2004, title={Carbon dioxide-soluble polymers and swellable polymers for carbon dioxide applications}, volume={6,747,179}, number={2004 June 8}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Birnbaum, Eva and Carbonell, Ruben G. and Crette, Stephanie and McClain, James B. and McCleskey, T. Mark and Powell, Kimberly R. and Romack, Timothy J. and Tumas, William}, year={2004}, month={Jun} }
 @article{novick_desimone_carbonell_2004, title={Deposition of Thin Polymeric Films from Liquid Carbon Dioxide Using a High-Pressure Free-Meniscus Coating Process}, volume={43}, ISSN={0888-5885 1520-5045}, url={http://dx.doi.org/10.1021/ie030688z}, DOI={10.1021/ie030688z}, abstractNote={Free-meniscus coating processes can be used to deposit a wide variety of coatings. However, the physical properties of the coating solutions often lead to the deposition of nonuniform films. Recently, it has been recognized that compressed carbon dioxide can be used as an environmentally benign solvent for industrial processes. We investigate the use of liquid carbon dioxide as the solvent in free-meniscus coating processes because its physical properties are much different from standard coating solvents. The surface tension and viscosity of liquid carbon dioxide are an order of magnitude smaller than those of typical solvents. Additionally, the density of liquid carbon dioxide is strongly dependent on temperature and pressure. The Tallmadge four-force inertial theory is used to demonstrate that these unique physical properties will result in the formation of thinner films at the same withdrawal velocities as those used with conventional solvents. We then demonstrate experimentally that process variables ...}, number={2}, journal={Industrial & Engineering Chemistry Research}, publisher={American Chemical Society (ACS)}, author={Novick, Brian J. and DeSimone, Joseph M. and Carbonell, Ruben G.}, year={2004}, month={Jan}, pages={515–524} }
 @article{hoggan_flowers_wang_desimone_carbonell_2004, title={Spin coating of photoresists using liquid carbon dioxide}, volume={43}, ISSN={["0888-5885"]}, DOI={10.1021/ie0308543}, abstractNote={A novel high-pressure carbon dioxide (CO2) spin-coating apparatus was designed and constructed to produce high-quality thin films of CO2-soluble photoresists based on 1H,1H-perfluorooctyl methacrylate/tert-butyl methacrylate copolymers. Film thicknesses were correlated to various process variables including rotational speed, solution viscosity, and evaporative driving force. The effects of these operating conditions on the film thickness and uniformity were compared to those of a theoretical model adapted for spin coating in CO2. Excellent correlation was found between the theoretical predictions and observed film properties, with the final films being of sufficient quality for use in photolithography. The potential of this spin-coating process in CO2 for developing a novel “dry lithography” is discussed.}, number={9}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Hoggan, EN and Flowers, D and Wang, K and DeSimone, JM and Carbonell, RG}, year={2004}, month={Apr}, pages={2113–2122} }
 @article{zaki_carbonell_kilpatrick_2003, title={A novel process for demulsification of water-in-crude oil emulsions by dense carbon dioxide}, volume={42}, ISSN={["0888-5885"]}, DOI={10.1021/ie0303597}, abstractNote={CO2 was used to break several water-in-crude oil and water-in-model oil emulsions stabilized by asphaltenic films. The stability of asphaltenic films in model oils having varying H/C ratios (aromaticities) was also studied upon contact with liquid or supercritical CO2. The efficacy and kinetics of demulsification appeared to be enhanced with increased CO2 density and mole fraction. The proposed mechanism by which CO2 destabilizes water-in-crude oil emulsions involves asphaltene flocculation and precipitation. The emulsions break by flocculating the adsorbed asphaltenes, leading to film defects, film thinning, film rupture, and water coalescence. The various factors influencing asphaltene precipitation and emulsion destabilization were studied in model solvent systems containing asphaltenes and resins. Increasing CO2 pressure, residence time, temperature, and degree of mixing were found to increase the rate of asphaltene precipitation. Asphaltene precipitation by CO2 was found to increase in the presence o...}, number={25}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Zaki, NN and Carbonell, RG and Kilpatrick, PK}, year={2003}, month={Dec}, pages={6661–6672} }
 @misc{carbonell_desimone_novick_2003, title={Apparatus for meniscus coating with liquid carbon dioxide}, volume={6,517,633}, number={2003 Feb 11}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M. and Novick, B. J.}, year={2003}, month={Feb} }
 @article{xu_carbonell_kiserow_roberts_2003, title={Kinetic and transport processes in the heterogeneous catalytic hydrogenation of polystyrene}, volume={42}, ISSN={["0888-5885"]}, DOI={10.1021/ie0301841}, abstractNote={The heterogeneous catalytic hydrogenation of polystyrene (PS) dissolved in decahydronaphthalene was studied in a batch reactor using 5% Pd/BaSO4 as the catalyst. The effects of temperature and H2 partial pressure were investigated over the ranges from 90 to 180 °C and 1.72 to 6.89 MPa. The PS concentration ranged from 1 to 9 wt %. The rate of ring hydrogenation was approximately first-order with respect to PS, with an apparent activation energy of 59.6 kJ/mol. The hydrogenation rate depended on the agitation rate up to a threshold value, which increased with the concentration of PS in the solution. The possible influence of three mass-transfer steps (H2 transport from the gas into the polystyrene solution, PS transport to the surface of the catalyst particles, and PS diffusion in the pores of the catalyst) is analyzed. The last two steps do not appear to be kinetically important at the conditions of this study.}, number={15}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Xu, DW and Carbonell, RG and Kiserow, DJ and Roberts, GW}, year={2003}, month={Jul}, pages={3509–3515} }
 @article{shah_novick_hwang_lim_carbonell_johnston_korgel_2003, title={Kinetics of nonequilibrium nanocrystal monolayer formation: Deposition from liquid carbon dioxide}, volume={3}, ISSN={["1530-6984"]}, DOI={10.1021/nl034793+}, abstractNote={We observe the time-dependent structural reorganization of monolayers of gold nanocrystals deposited from liquid carbon dioxide. Compressed carbon dioxide does not exhibit dewetting instabilities, allowing deposition of spatially continuous monolayers at fast evaporation rates. Comparison of the translational and orientational correlation functions and a translational order parameter with a computer simulated equilibrium state indicates that the nanocrystal organization kinetics are slower than single particle diffusion limited assembly and are likely dominated by ensemble reorganization.}, number={12}, journal={NANO LETTERS}, author={Shah, PS and Novick, BJ and Hwang, HS and Lim, KT and Carbonell, RG and Johnston, KP and Korgel, BA}, year={2003}, month={Dec}, pages={1671–1675} }
 @misc{carbonell_desimone_novick_2003, title={Method for meniscuscoating a substrate with a polymeric precurso}, volume={6,652,920}, number={2003 Nov. 25}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M. and Novick, B. J.}, year={2003}, month={Nov} }
 @misc{zaki_kilpatrick_carbonell_2003, title={Methods of demulsifying emulsions using carbon dioxide}, volume={6,566,410}, number={2003 May 20}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Zaki, N. N. and Kilpatrick, P. K. and Carbonell, R. G.}, year={2003}, month={May} }
 @article{elbaccouch_bondar_carbonell_grant_2003, title={Phase equilibrium behavior of the binary systems CO2 plus nonadecane and CO2 plus soysolv and the ternary system CO2 plus soysolv plus quaternary ammonium chloride surfactant}, volume={48}, ISSN={["0021-9568"]}, DOI={10.1021/je020201d}, abstractNote={Liquid phase and molar volume data were measured for the binary system CO 2 + soysolv at (298.15, 313.15, 323.15, 333.15, and 343.15) K and the ternary system CO 2 + soysolv + quaternary ammonium chloride surfactant at (298.15, 313.15, and 333.15) K, where the composition of soysolv to the surfactant is 99:1 wt % and 80:20 wt % on a CO 2 -free basis. Data were collected stoichiometrically with a high-pressure Pyrex glass cell, where no sampling or chromatographic equipment is required. The accuracy of the experimental apparatus was tested with phase equilibrium measurements for the system CO 2 + nonadecane at 313.15 K. A pressure-decay technique was used to calculate the mass of CO 2 loaded into the equilibrium section of the apparatus, and its accuracy was verified with a blank nitrogen experiment. The generated data show that CO 2 modified soysolv is an effective transport medium for the quaternary ammonium chloride surfactant.}, number={6}, journal={JOURNAL OF CHEMICAL AND ENGINEERING DATA}, author={Elbaccouch, MM and Bondar, VI and Carbonell, RG and Grant, CS}, year={2003}, pages={1401–1406} }
 @article{kaufman_hentsch_baumbach_buettner_dadd_huang_hammond_carbonell_2002, title={Affinity purification of fibrinogen using a ligand from a peptide library}, volume={77}, ISSN={["0006-3592"]}, DOI={10.1002/bit.10120}, abstractNote={Abstract}, number={3}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Kaufman, DB and Hentsch, ME and Baumbach, GA and Buettner, JA and Dadd, CA and Huang, PY and Hammond, DJ and Carbonell, RG}, year={2002}, month={Feb}, pages={278–289} }
 @article{henon_carbonell_desimone_2002, title={Effect of polymer coatings from CO2 on water-vapor transport in porous media}, volume={48}, ISSN={["1547-5905"]}, DOI={10.1002/aic.690480504}, abstractNote={Abstract}, number={5}, journal={AICHE JOURNAL}, author={Henon, FE and Carbonell, RG and DeSimone, JM}, year={2002}, month={May}, pages={941–952} }
 @article{efimenko_novick_carbonell_desimone_genzer_2002, title={Formation of self-assembled monolayers of semifluorinated and hydrocarbon chlorosilane precursors on silica surfaces from liquid carbon dioxide}, volume={18}, ISSN={["0743-7463"]}, DOI={10.1021/la011813j}, abstractNote={We report on the formation and properties of self-assembled monolayers (SAMs) prepared by depositing semifluorinated and hydrocarbon trichlorosilane precursors, F(CF2)8(CH2)2SiCl3 (F8H2) and H(CH2)18SiCl3 (H18), respectively, from vapor, organic solvent, and liquid CO2 (l-CO2). Contact angle measurements of the SAM deposition kinetics reveal that regardless of the molecule type, the deposition rates from l-CO2 exceed those from vapor or organic solvents by several orders of magnitude. We derive two different transport models describing the formation of SAMs. We show that while the diffusion-limited model is not capable of describing the experimental data, the adsorption-limited model captures the major features of the adsorption kinetics quite well. We apply the results of the adsorption-limited model to conclude that the observed behavior is a consequence of (i) a relatively high bulk concentration (l-CO2 vs vapor) and (ii) higher solution diffusivity (l-CO2 vs organic solvent) of the silanes in l-CO2. N...}, number={16}, journal={LANGMUIR}, author={Efimenko, K and Novick, B and Carbonell, RG and DeSimone, JM and Genzer, J}, year={2002}, month={Aug}, pages={6170–6179} }
 @article{lakota_levec_carbonell_2002, title={Hydrodynamics of trickling flow in packed beds: Relative permeability concept}, volume={48}, ISSN={["1547-5905"]}, DOI={10.1002/aic.690480408}, abstractNote={Abstract}, number={4}, journal={AICHE JOURNAL}, author={Lakota, A and Levec, J and Carbonell, RG}, year={2002}, month={Apr}, pages={731–738} }
 @misc{carbonell_desimone_2002, title={Spin cleaning methods}, volume={6,500,273}, number={2002 Feb 06}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M.}, year={2002}, month={Feb} }
 @misc{desimone_carbonell_2001, title={Apparatus for liquid carbon dioxide systems}, volume={6,383,289}, number={2002 May 7}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Carbonell, R. G.}, year={2001}, month={Feb} }
 @misc{desimone_carbonell_crette_kendall_2001, title={Enzyme catalysis in carbon dioxide fluids}, volume={6,211,422}, number={2001 April 3}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Carbonell, R. G. and Crette, S. A. and Kendall, J. L.}, year={2001}, month={Apr} }
 @article{chernyak_henon_harris_gould_franklin_edwards_desimone_carbonell_2001, title={Formation of perfluoropolyether coatings by the rapid expansion of supercritical solutions (RESS) process. Part 1: Experimental results}, volume={40}, ISSN={["0888-5885"]}, DOI={10.1021/ie010267m}, abstractNote={The rapid expansion of supercritical solutions (RESS) process is a promising environmentally benign technology for fine droplet or particle formation. The absence of organic solvents and narrow size distribution of RESS precipitates make this process attractive for polymer coating applications. In our work, this technique has been used to produce droplets of perfluoropolyethers from CO2 solutions without the aid of cosolvents for the coating of porous materials applied in monumental and civil infrastructures. The present work is aimed at gaining an understanding of the relationship between droplet and spray characteristics and RESS process conditions. As such, a combined experimental/computational approach is applied to a representative binary system consisting of a low-molecular-weight perfluoropolyether diamide (PFD) dissolved in supercritical CO2. Part 1 of this work presents phase equilibria measurements and polymer droplet size characterizations under different operating conditions. The effects of te...}, number={26}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Chernyak, Y and Henon, F and Harris, RB and Gould, RD and Franklin, RK and Edwards, JR and DeSimone, JM and Carbonell, RG}, year={2001}, month={Dec}, pages={6118–6126} }
 @article{franklin_edwards_chernyak_gould_henon_carbonell_2001, title={Formation of perfluoropolyether coatings by the rapid expansion of supercritical solutions (RESS) process. Part 2: Numerical modeling}, volume={40}, ISSN={["0888-5885"]}, DOI={10.1021/ie010268e}, abstractNote={The rapid expansion of supercritical solutions (RESS) process is a promising method for the production of ultrafine powders and aerosols of narrow size distribution for coatings and other applications. In this article, part 2 of a two-part study, the nucleation and subsequent growth of 2500 Mw perfluoropolyether diamide (PFD) from supercritical carbon dioxide (CO2) by expansion through a small-diameter nozzle is modeled in a three-stage, multidimensional fashion. The stages include a hydrodynamic solution, solvent−solute phase equilibria analyses, and an aerosol transport model. The hydrodynamics model successfully captures the vapor−liquid transition that occurs as carbon dioxide is expanded to ambient conditions. Cloud-point pressures and equilibrium compositions of the separated solvent−solute system are determined and are used in a multidimensional aerosol transport model. This model incorporates various mechanisms influencing droplet growth. Parametric studies are conducted to investigate the influen...}, number={26}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Franklin, RK and Edwards, JR and Chernyak, Y and Gould, RD and Henon, F and Carbonell, RG}, year={2001}, month={Dec}, pages={6127–6139} }
 @article{gurgel_carbonell_swaisgood_2001, title={Identification of peptide ligands generated by combinatorial chemistry that bind alpha-lactalbumin}, volume={36}, ISSN={["0149-6395"]}, DOI={10.1081/SS-100106100}, abstractNote={α-Lactalbumin is a whey protein with high digestibility and low potential for causing allergic problems in infants, making it a strong candidate for use in infant formulas. The development of an efficient and scalable process for isolation of α-lactalbumin is necessary to allow its use on a large scale. Affinity chromatography using short peptides as ligands is a promising technique because it allows the recovery of specific proteins without the use of harsh chemicals or problems due to ligand release. In the present paper we describe the identification of the hexapeptide WHWRKR, obtained from a combinatorial library, that shows affinity for α-lactalbumin.}, number={11}, journal={SEPARATION SCIENCE AND TECHNOLOGY}, author={Gurgel, PV and Carbonell, RG and Swaisgood, HE}, year={2001}, pages={2411–2431} }
 @misc{desimone_carbonell_2001, title={Methods of spin cleaning substrates using carbon dioxide liquid}, volume={6,240,936}, number={2001 June 5}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Carbonell, R. G.}, year={2001}, month={Jun} }
 @article{martinache_royer_siripurapu_henon_genzer_khan_carbonell_2001, title={Processing of polyamide 11 with supercritical carbon dioxide}, volume={40}, ISSN={["0888-5885"]}, DOI={10.1021/ie010410b}, abstractNote={The supercritical carbon dioxide induced swelling and plasticization of polyamide 11 were investigated. The swelling kinetics exhibit an initial region of large swelling, in which the diffusion of CO2 into the polymer follows Fickian behavior, and a subsequent region of small volume increase that asymptotically approaches an equilibrium swelling value. The diffusion coefficient of CO2 in polyamide 11 was calculated from the initial slope of the swelling kinetics data. CO2, injected up to 3 wt % using an extrusion rheometer, is shown to be an effective plasticizer for polyamide 11, lowering the viscosity of the polymer melt by as much as 50%. The use of CO2 as a blowing agent was also investigated, and we report preliminary foaming attempts using a batch process. We obtained homogeneously distributed foams, featuring well-defined closed cells with an average diameter of 30 μm that had an unfoamed skin layer.}, number={23}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Martinache, JD and Royer, JR and Siripurapu, S and Henon, FE and Genzer, J and Khan, SA and Carbonell, RG}, year={2001}, month={Nov}, pages={5570–5577} }
 @article{gurgel_carbonell_swaisgood_2001, title={Studies of the binding of alpha-lactalbumin to immobilized peptide ligands}, volume={49}, ISSN={["1520-5118"]}, DOI={10.1021/jf010462b}, abstractNote={The present work investigates the mechanism of binding of α-lactalbumin to the peptide ligand WHWRKR and its variants HWRKR and acetylated WHWRKR immobilized on a polymethacrylate chromatographic resin. The presence of two temperature-dependent binding mechanisms and one temperature-independent mechanism was demonstrated. Injections of different forms of α-lactalbumin (apo-α-lactalbumin, D87A mutant α-lactalbumin) displayed similar behaviors when compared to native α-lactalbumin, while lysozyme showed little or no binding to the WHWRKR and AcWHWRKR resins. An alternative process for isolation of α-lactalbumin from WPI was shown, using consecutive injections of WPI with limited elution. Keywords: α-Lactalbumin; peptide ligands; bioselective adsorption; binding mechanism}, number={12}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Gurgel, PV and Carbonell, RG and Swaisgood, HE}, year={2001}, month={Dec}, pages={5765–5770} }
 @article{kaufman_hayes_buettner_hammond_carbonell_2000, title={Chromatographic resolution of tryptophan enantiomers with L-Leu-L-Leu-L-Leu peptide - Effects of mobile phase composition and chromatographic support}, volume={874}, ISSN={["0021-9673"]}, DOI={10.1016/S0021-9673(99)01299-6}, abstractNote={Tryptophan enantiomers have been separated by zwitterion pair chromatography using L-leucine-L-leucine-L-leucine peptide as the zwitterion pairing agent. The peptide ligand is adsorbed onto an octadecylsilane support with excess ligand present in bulk solution. This article examines the roles of the hydrophobic matrix and the mobile phase components on tryptophan enantiomer binding and resolution. Capacity factors and enantioselectivites are given for both hydrophobic and hydrophilic matrices using mobile phases containing Leu-Leu-Leu peptide and/or salt. A decrease in selectivity upon the addition of mobile phase salt suggests that quadrupolar ion-pairing contributes to chiral recognition. Results indicate that binding is significantly reduced and separation is not achieved when Leu-Leu-Leu is coupled onto cross-linked or polymerized hydrophilic resins as well as onto macroporous polystyrene resin. However, resin-immobilized Leu-Leu-Asp-Leu-Leu-Leu, Leu-Leu-Glu-Leu-Leu-Leu, and Leu-Leu-Leu-Glu-Leu-Leu peptides, with ion-pairing sites designed to mimic the Leu-Leu-Leu-saturated C18 support, also do not resolve tryptophan enantiomers. This suggests the Leu-Leu-Leu structure is critical for enantiomer resolution. Because D- and L-tryptophan are separated in the absence of bulk Leu-Leu-Leu, chiral discrimination is believed to occur at the surface of the octadecylsilane support.}, number={1}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Kaufman, DB and Hayes, T and Buettner, J and Hammond, DJ and Carbonell, RG}, year={2000}, month={Mar}, pages={21–26} }
 @article{bastek_land_baumbach_hammond_carbonell_2000, title={Discovery of alpha-1-proteinase inhibitor binding peptides from the screening of a solid phase combinatorial peptide library}, volume={35}, ISSN={["0149-6395"]}, DOI={10.1081/SS-100102488}, abstractNote={Alpha-1-proteinase inhibitor (A1PI, also known as alpha-1-antitrypsin), a blood plasma protein, was radiolabeled and screened against a portion of a hexameric, solid-phase combinatorial peptide library. The screening of 2% of a library containing 34 million peptides yielded 19 sequences. All 19 sequences bound A1PI when immobilized to a chromatographic support, but with varying avidities. Several of these sequences proved capable of purifyingA1PI from aqueous mixtures with human serum albumin and from Effluent II+III, a process intermediate in the Cohn plasma fractionation process. A single chromatography step was shown to provide high yields with significant purification and no measurable loss in activity.}, number={11}, journal={SEPARATION SCIENCE AND TECHNOLOGY}, author={Bastek, PD and Land, JM and Baumbach, GA and Hammond, DH and Carbonell, RG}, year={2000}, pages={1681–1706} }
 @article{gurgel_carbonell_swaisgood_2000, title={Fractionation of whey proteins with a hexapeptide ligand affinity resin}, volume={9}, ISSN={["0923-179X"]}, DOI={10.1023/A:1011191818927}, abstractNote={The isolation of individual proteins from whey would allow production of more consistent and reliable products by the food industry and possibly would also increase their use in the pharmaceutical industry. Alpha-lactalbumin is the second most prevalent protein in bovine milk whey and has many uses including serving as an excellent protein source in infant formulas, power drinks and other beverages that require soluble, nutritional protein. In this study, we describe two methods for production of alpha-lactalbumin from whey protein isolate using bioselective adsorption. The use of a peptide ligand (WHWRKR) attached to a resin allowed production of an alpha-lactalbumin-rich fraction with a purity of 90.6% and a recovery of 47.9%, while also producing other fractions of commercial interest. The combined use of an amino resin followed by the WHWRKR resin produce a highly purified alpha-lactalbumin (100%) with a yield of 35.2%.}, number={6}, journal={BIOSEPARATION}, author={Gurgel, PV and Carbonell, RG and Swaisgood, HE}, year={2000}, pages={385–392} }
 @article{roberts_carbonell_saez_2000, title={Gas-lift reactors for rapid reactions with appreciable gas consumption}, volume={23}, DOI={10.1002/(sici)1521-4125(200001)23:1<80::aid-ceat80>3.0.co;2-m}, abstractNote={Gas-lift reactors offer important advantages for a number of gas/liquid and gas/liquid/solid reactions. However, the design and operation of these reactors can be complex when there is a substantial change in the molar gas flow rate along the length of the reactor, e.g., when a gaseous reactant is converted into a liquid product. In this situation, there is a strong coupling between reactor hydrodynamics and reaction kinetics, which arises from the fact that the rate of liquid circulation through the reactor and the longitudinal profile of gas holdup in the riser are mutually dependent. Several one-dimensional models have been developed to describe kinetic/hydrodynamic coupling in gas-lift reactors. These models offer useful insights into the parameters that affect reactor performance. The models can also be used to explore different approaches to scale-up.}, number={1}, journal={Chemical Engineering & Technology}, author={Roberts, G. W. and Carbonell, R. G. and Saez, A. E.}, year={2000}, pages={80–87} }
 @misc{carbonel_desimone_henon_2000, title={Method and compositions for protecting civil infrastructure}, volume={6,127,000}, number={2000 Oct. 3}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonel, R. G. and DeSimone, J. M. and Henon, F. E.}, year={2000}, month={Oct} }
 @misc{carbonell_desimone_novick_2000, title={Method for meniscus coating with liquid carbon}, volume={6,497,921}, number={2002 Dec. 24}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M. and Novick, B. J.}, year={2000}, month={Jun} }
 @misc{carbonell_desimone_novick_2000, title={Method for meniscus coating with liquid carbon dioxide}, volume={6,083,565}, number={2000 July 4}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M. and Novick, B. J.}, year={2000}, month={Jul} }
 @article{carbonell_2000, title={Multiphase flow models in packed beds}, volume={55}, ISSN={["1953-8189"]}, DOI={10.2516/ogst:2000030}, abstractNote={This paper presents a review of theories for gas and liquid flows in packed beds as applied to chemical reactor design. Significant progress has been made in understanding multiphase flow phenomena in packed beds and the ability to make quantitative predictions of flow behavior. Successful theories use spatially averaged continuity and momentum equations for the gas and liquid phases, coupled with constitutive equations for drag forces between the fluid phases and the particles and for capillary pressure effects in the column. The result is a self-consistent set of equations that are able to model experimental data for liquid holdup and pressure drop under steady-state conditions. These theories have also been used to generate information on the stability of these steady-state flows. Remarkable agreement has been found between the theoretical predictions of the transitions from the low-interaction to the high-interaction regimes and experimental observations. In addition, the same set of equations has been successful in modeling both cocurrent and countercurrent flows of gas and liquid phases in packed beds. This is a robust approach based on fundamental principles of fluid mechanics that can be applied to other reactor configurations. A similar formulation has also led to improvements in understanding of gas lift reactor hydrodynamics, and some of these results will be presented for comparison. A summary of challenges that exist in extending these hydrodynamic models to include the effects of heat transfer, mass transfer and reaction rates will also be presented.}, number={4}, journal={OIL & GAS SCIENCE AND TECHNOLOGY-REVUE D IFP ENERGIES NOUVELLES}, author={Carbonell, RG}, year={2000}, pages={417–425} }
 @article{chen_carbonell_serad_2000, title={Recovery of proteins and other biological compounds from food processing wastewaters using fibrous materials and polyelectrolytes}, volume={34}, ISSN={["0043-1354"]}, DOI={10.1016/S0043-1354(99)00152-9}, abstractNote={A combined system of cellulose-based fibrous materials and polyelectrolytes has been studied for the recovery of proteins and other biological compounds from wastewaters from a typical food processing plant. Carboxymethyl cellulose (CMC) interacts with biomolecules by electrostatic and polymer bridging, while cellulose triacetate fibrets (CTF) facilitate floc growth by adsorption and bridging of primary particles and by entrapment of small aggregates within their highly fibrillated microstructure. Final slurries have good filtration properties, resulting in a dry and easy to handle filter cake, which could be recovered as animal feed. The final filtrate has high water clarity and low protein concentration. This recovery system exhibits high reductions in total suspended solids (TSS), total Kjeldahl nitrogen (TKN), ammonia, oils and greases, biochemical oxygen demand (BOD) and total fecal coliforms. The final levels of TSS, oils and greases and ammonia are below regulatory limits. Reduction of BOD reached 90%, although final concentrations are slightly higher than the regulatory levels.}, number={2}, journal={WATER RESEARCH}, author={Chen, LA and Carbonell, RG and Serad, GA}, year={2000}, month={Feb}, pages={510–518} }
 @article{kabin_withers_grant_carbonell_saez_2000, title={Removal of solid organic films from rotating disks using emulsion cleaners}, volume={228}, ISSN={["0021-9797"]}, DOI={10.1006/jcis.2000.6832}, abstractNote={Measurements have been made of the rate of removal of a solid organic film (phenanthrene) from the surface of a rotating disk using emulsions containing water, the nonionic surfactant Tween 20, and d-limonene as the organic phase. The results show that phenanthrene removal initially occurs by the uptake of phenanthrene into the emulsion drops as small aggregates. Simultaneously, the organic phase penetrates into the phenanthrene film, diminishing the adhesive force between the film and the substrate. After sufficient time, the phenanthrene film detaches from the rotating disk surface as a solid. This detachment mechanism accounts for the vast majority of the phenanthrene removal ( approximately 90%). Initial solubilization rates were analyzed using two solubilization models. Both models assume that phenanthrene removal occurs via a mass transfer limited removal of phenanthrene-laden emulsion drops from the phenanthrene film surface into the bulk solution. One model treats the emulsion as homogeneous while the other accounts for the finite size of the emulsion droplets. The latter model was also used to relate the flux of organic phase impacting the phenanthrene film to the detachment times. Copyright 2000 Academic Press.}, number={2}, journal={JOURNAL OF COLLOID AND INTERFACE SCIENCE}, author={Kabin, JA and Withers, ST and Grant, CS and Carbonell, RG and Saez, AE}, year={2000}, month={Aug}, pages={344–358} }
 @article{huang_carbonell_1999, title={Affinity chromatographic screening of soluble combinatorial peptide libraries}, volume={63}, ISSN={["0006-3592"]}, DOI={10.1002/(SICI)1097-0290(19990620)63:6<633::AID-BIT1>3.0.CO;2-C}, abstractNote={Affinity chromatography using immobilized S-protein was used for the screening of affinity peptide ligands from two soluble peptide libraries. Peptide library I consisted of octamers with glycine (G) at both termini of each peptide, i.e. GXXXXXXG. The six center positions were constructed using random sequences of six L-amino acids (Y, N, F, E, V, and L). Peptide library II also consisted of octamers but with glycine and valine (V) at both termini of each peptide (GVZZZZVG). The four variable center positions of peptide library II were random sequences of 18 L-amino acids. Peptides that were retained specifically on the immobilized S-protein column were eluted by 2% acetic acid. The peptides in the acid eluate were further separated using reversed-phase HPLC. Each separated peptide fraction was collected and the peptide sequences deconvoluted by mass spectrometry (MS/MS). The screenings of peptide libraries I and II resulted in 12 and 7 affinity peptides, respectively. Eight out of the twelve peptides from peptide library I contained the clear consensus sequence NFEV. Peptide library II resulted in affinity peptides with the sequences GVNFEVVG, GVNFTVVG and GVFFEL(I)VG. The advantages and limitations of affinity chromatography in peptide library screening are discussed.}, number={6}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Huang, PY and Carbonell, RG}, year={1999}, month={Jun}, pages={633–641} }
 @article{marquez_saez_carbonell_roberts_1999, title={Coupling of hydrodynamics and chemical reaction in gas-lift reactors}, volume={45}, DOI={10.1002/aic.690450220}, abstractNote={Abstract}, number={2}, journal={AIChE Journal}, author={Marquez, H. A. and Saez, A. E. and Carbonell, R. G. and Roberts, G. W.}, year={1999}, pages={410–423} }
 @article{marquez_amend_carbonell_saez_roberts_1999, title={Hydrodynamics of gas-lift reactors with a fast, liquid-phase reaction}, volume={54}, ISSN={["0009-2509"]}, DOI={10.1016/S0009-2509(98)00351-0}, abstractNote={The reactive absorption of CO2 into concentrated KOH solutions was studied in an external-loop, gas-lift reactor. Three different inlet gas compositions were used: air, 50–50 vol% air–CO2, and pure CO2. The downcomer liquid velocity and the axial profile of the cross-sectionally averaged gas holdup in the riser were measured. The reaction is so fast that the CO2 is consumed appreciably along the riser, and this causes a significant reduction in the liquid circulation relative to a system with no reaction. A one-dimensional, pseudo-steady-state model has been developed to describe the interactions of hydrodynamics, mass transfer, and chemical reaction for the bubbly flow regime in the riser. The model considers mass transfer from the gas to the liquid phase and its enhancement due to the chemical reaction, and is based on the spatially averaged equations of continuity, momentum, and macroscopic mechanical energy. The rate of liquid circulation, and the axial variation of gas holdup, gas composition, pressure, and gas and liquid velocity, are predicted. The gas/liquid mass transfer coefficient and the bubble radius at the sparger, neither of which was known a priori, were used to minimize the error of the data with respect to the model.}, number={13-14}, journal={CHEMICAL ENGINEERING SCIENCE}, author={Marquez, MA and Amend, RJ and Carbonell, RG and Saez, AE and Roberts, GW}, year={1999}, month={Jul}, pages={2263–2271} }
 @article{lucena_carbonell_santana_1999, title={Peptide affinity chromatography process for adsorption of fibrinogen}, volume={101}, ISSN={["0032-5910"]}, DOI={10.1016/S0032-5910(98)00169-7}, abstractNote={Fibrinogen is a 340 kDa protein molecule also known as Factor I. Its synthesis occurs in the liver of animals. In human beings around 2.6 g/l fibrinogen is found in the circulatory plasma playing a very important role in the blood coagulation. Due to the biological functions and characteristics of fibrinogen, the development of new techniques for separating and purifying fibrinogen from human plasma is a current challenge. Affinity chromatography based on peptide libraries has become known as a powerful technique for dealing with protein molecules. The lack of many important parameters involved in such systems has limited the scale up. In this paper a way to obtain parameters such as the adsorption rate constants, by fitting the breakthrough curves, is presented. Dynamic experiments were carried out on HPLC (High Performance Liquid Chromatography) columns packed with resins, where the peptide FLLVPL was immobilized. This modified resin was also used for equilibrium experiments. This set of experiments allowed us to determine the maximum binding capacity, the dissociation constant and the lumped and intrinsic forward rate constants for resins with two different peptide densities (41.3 and 67.7 μmol of peptide/g resin). The mathematical model describing the breakthrough curve uses the Langmuir type isotherm, and the axial dispersion was ignored.}, number={2}, journal={POWDER TECHNOLOGY}, author={Lucena, SL and Carbonell, RG and Santana, CC}, year={1999}, month={Feb}, pages={173–177} }
 @article{moraes_santana_carbonell_1999, title={Preparation and characterization of liposomal systems entrapping the boronated compound o-carboranylpropylamine}, volume={16}, DOI={10.1080/026520499288834}, abstractNote={Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when the stable isotope, Boron-10, is irradiated with low-energy thermal neutrons to yield ionizing Helium and Lithium ions that are highly damaging and usually lethal to cells. The successful treatment of cancer by BNCT requires the selective concentration of Boron-10 within malignant tumours. Liposomes have been used as therapeutic compound delivery vehicles for in vivo application, including several anticancer agents. The ability of the boron-containing compound, o-carboranylpropylamine chloride, to accumulate within unilamellar liposomes in response to a transmembrane pH gradient is evaluated. Characterization of the systems obtained is performed for conventional and polyethylene glycol (PEG)-modified (stealth) liposomes, in terms of lipid and CPA contents, vesicle size and stability in detergent solutions. Results demonstrate that CPA loading and vesicle stability can be controlled by the experimental procedure. The loading of CPA into liposomes with average diameters of 100 nm is estimated at 13000 molecules per vesicle for the most stable systems. CPA toxicity to normal human peripheral blood lymphocytes and to adherent glioblastoma multiforme SK-MG-1 cells in vitro is observed to decrease as a result of the entrapment of CPA in liposomes.}, number={5}, journal={Journal of Microencapsulation}, author={Moraes, A. M. and Santana, M. H. A. and Carbonell, R. G.}, year={1999}, pages={647–664} }
 @article{chen_carbonell_serad_1999, title={Recovery of proteins and other biological compounds using fibrous materials: I. Adsorption by salt addition}, volume={74}, DOI={10.1002/(sici)1097-4660(199908)74:8<733::aid-jctb111>3.0.co;2-4}, abstractNote={An adsorption and filtration process for the recovery of proteins and other biological compounds from aqueous streams has been developed, using cellulose-based fibrous materials. Of the many cellulose derivatives studied, cellulose acetate fibrets (CAF) and cellulose triacetate fibrets (CTF) have been shown to be the most effective. In the presence of salts, they lead to protein adsorption by hydrophobic interactions. Model proteins, such as bovine serum albumin (BSA), have been recovered by incubating these solutions with CTF in the presence of ammonium sulfate, followed by filtration through a 20 µm pore size filter. The amount of salt necessary varies with the protein type, but decreases with increasing temperature and protein concentration. High protein recovery has been obtained from an actual wastewater system at low salt dosages. 
 
 
 
© 1999 Society of Chemical Industry}, number={8}, journal={Journal of Chemical Technology and Biotechnology}, author={Chen, L. A. and Carbonell, R. G. and Serad, G. A.}, year={1999}, pages={733–739} }
 @article{chen_carbonell_serad_1999, title={Recovery of proteins and other biological compounds using fibrous materials: II. Flocculation by polyelectrolyte addition}, volume={74}, ISSN={["1097-4660"]}, DOI={10.1002/(SICI)1097-4660(199908)74:8<740::AID-JCTB112>3.0.CO;2-1}, abstractNote={Polyelectrolytes have been used in wastewater treatment processes to destabilize colloidal suspensions of proteins, cells and other biological compounds, resulting in flocculation. When a solution containing a single model protein, bovine serum albumin (BSA), is treated with a polyelectrolyte, carboxymethyl cellulose (CMC), large and strong flocs are formed, which are easily retained by a 20 µm pore size filter. However, when a mixture of proteins, cells, and fats from an actual wastewater sample is treated in the same manner, smaller and weaker flocs are observed. An adsorption and filtration process for the recovery of valuable biological compounds using cellulose-based fibrous materials has been developed. When used simultaneously with CMC, cellulose acetate and triacetate fibrets (CAF and CTF) resulted in high recovery of biomolecules from solution at very low dosages of both polyelectrolyte and fibrets. CMC interacts with biomolecules by electrostatic interactions and polymer bridging, while CTF/CAF facilitate floc growth by adsorption and bridging of primary particles and by entrapment of small aggregates within their highly fibrillated microstructure. 
 
 
 
© 1999 Society of Chemical Industry}, number={8}, journal={JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY}, author={Chen, LA and Carbonell, RG and Serad, GA}, year={1999}, month={Aug}, pages={740–750} }
 @article{kabin_saez_grant_carbonell_1999, title={Removal rates of major and trace components of an organic film using aqueous nonionic surfactant solutions}, volume={38}, ISSN={["0888-5885"]}, DOI={10.1021/ie980587e}, abstractNote={This work examines the cleaning of organic films composed of a primary component (abietic acid) mixed with trace amounts of a second contaminant (benzoic acid). Films were removed from a rotating disk in the presence of aqueous solutions of two poly(ethylene glycol) alkyl ether surfactants: C 12 E 5 and C 16 E 8 . With C 12 E 5 the abietic acid was removed from the disk in three successive cleaning stages - solubilization, shear removal, and rollup - whereas the benzoic acid was almost completely removed during the initial solubilization stage. Also, with C 12 E 5 the results show that the micellar solubilization rate of the trace contaminant is directly proportional to its concentration in the film. The ratio of the molar removal rates of benzoic acid to abietic acid with C 12 E 5 is an order of magnitude greater than the ratio of the mole fractions of the two components in the contaminant film. Solutions of C 16 E 8 removed the abietic acid by only the solubilization and rollup stages. The ratio of the molar removal rates of benzoic acid to abietic acid with C 16 E 8 was equal to the ratio of the mole fractions of the two components in the contaminant film. A mathematical model is proposed to quantify the simultaneous removal of benzoic acid and abietic acid during the micellar solubilization stage. The model takes into account the mass-transfer rate between the film and the bulk solution, as well as the micellization rates at the film/surfactant solution interface. The model adequately represents the experimental data.}, number={3}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Kabin, JA and Saez, AE and Grant, CS and Carbonell, RG}, year={1999}, month={Mar}, pages={683–691} }
 @misc{desimone_carbonell_1999, title={Spin coating method and apparatus for liquid carbon dioxide systems}, volume={6,001,418}, number={1999 Dec.14}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={DeSimone, J. M. and Carbonell, R. G.}, year={1999}, month={Dec} }
 @article{henon_camaiti_burke_carbonell_desimone_piacenti_1999, title={Supercritical CO2 as a solvent for polymeric stone protective materials}, volume={15}, ISSN={["1872-8162"]}, DOI={10.1016/S0896-8446(99)00005-4}, abstractNote={The utilization of CO2 as a potential solvent for fluoropolymers used for the protection of civil infrastructures (buildings, bridges, monuments, etc.) is of major environmental as well as economic importance. The cloud points of six perfluoropolyethers at different weight concentrations in CO2 have been measured over a wide range of pressures. The results show that these fluorinated polymers are readily soluble in pure CO2 (no cosolvent or surfactant needed) at temperatures close to 30°C and pressures below 210 bars. The solubilities of the different polymeric products are strongly depend on the polymer hydrogen content and molecular weight.}, number={2}, journal={JOURNAL OF SUPERCRITICAL FLUIDS}, author={Henon, FE and Camaiti, M and Burke, ALC and Carbonell, RG and DeSimone, JM and Piacenti, F}, year={1999}, month={Jun}, pages={173–179} }
 @article{saez_marquez_roberts_carbonell_1998, title={Hydrodynamic model for gas-lift reactors}, volume={44}, ISSN={["0001-1541"]}, DOI={10.1002/aic.690440619}, abstractNote={Abstract}, number={6}, journal={AICHE JOURNAL}, author={Saez, AE and Marquez, MA and Roberts, GW and Carbonell, RG}, year={1998}, month={Jun}, pages={1413–1423} }
 @article{kabin_tolstedt_saez_grant_carbonell_1998, title={Removal of organic films from rotating disks using aqueous solutions of nonionic surfactants: Effect of surfactant molecular structure}, volume={206}, DOI={10.1006/jcis.1998.5689}, abstractNote={In prior work, we examined the removal of abietic acid films from rotating fiberglass laminate disks by aqueous solutions of a nonionic surfactant. A three-stage cleaning mechanism was found, consisting successively of solubilization, shear-driven cleaning, and roll-up. We extend this work by exploring the influence of the surfactant molecular structure on the kinetics of the cleaning process. Five different poly(ethylene glycol) alkyl ether surfactants (CxEy) were used. Both the alkyl (x) and ethoxy (y) chain lengths were varied. Not all of the surfactants exhibited a three-stage cleaning mechanism. It was found that for surfactants with relatively high solubilization rates, the shear-driven cleaning stage did not occur. The selection of the most efficient surfactant depends on whether the surfactant concentration is below or above its critical micelle concentration (CMC). At submicellar concentrations, faster cleaning is obtained by surfactants that can induce shear-driven removal. At concentrations above the CMC, it is found that surfactant efficiency for a fixed alkyl or ethoxy chain length increases as the surfactant becomes more hydrophilic. This is attributed in part to the lower viscosity that the film achieves with the more hydrophilic surfactants due to their partitioning into the film, as well as their ability to carry water into the film. Copyright 1998 Academic Press.}, number={1}, journal={Journal of Colloid and Interface Science}, author={Kabin, J. A. and Tolstedt, S. L. and Saez, A. E. and Grant, Christine and Carbonell, R. G.}, year={1998}, pages={102–111} }
 @article{mondorf_kaufman_carbonell_1998, title={Screening of combinatorial peptide libraries: Identification of ligands for affinity purification of proteins using a radiological approach}, volume={52}, DOI={10.1111/j.1399-3011.1998.tb01257.x}, abstractNote={Abstract:}, number={6}, journal={Journal of Peptide Research}, author={Mondorf, K. and Kaufman, D. B. and Carbonell, R. G.}, year={1998}, pages={526–536} }
 @misc{carbonell_chen_serad_1997, title={Methods of treating wastewater}, volume={5,695,647}, number={1997 Dec. 9}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Chen, Li Ang and Serad, G. A.}, year={1997}, month={Dec} }
 @article{kilpatrick_lisi_carbonell_1997, title={Selective precipitation of antibody with ligand-modified phospholipids: Effect of lipid chain length}, volume={13}, ISSN={["1520-6033"]}, DOI={10.1021/bp9700521}, abstractNote={Abstract}, number={4}, journal={BIOTECHNOLOGY PROGRESS}, author={Kilpatrick, PK and Lisi, JF and Carbonell, RG}, year={1997}, pages={446–452} }
 @article{beaudoin_carbonell_grant_1996, title={Dynamic and equilibrium phase behavior in the C(12)E(5) abietic acid H2O system}, volume={182}, ISSN={["0021-9797"]}, DOI={10.1006/jcis.1996.0489}, abstractNote={Abstract Previous research has investigated the removal of representative flux residues (abietic acid (AA) in isopropyl alcohol (IPA)) from printed wiring assemblies using aqueous solutions of a nonionic surfactant (pentaethylene glycol mono-n-dodecyl ether (C12E5)). To optimize cleaning with this surfactant, greater understanding of the equilibrium and dynamic phase behavior in the AA-C12E5-H2O system is required. In this research, partial ternary phase diagrams were developed at 60 and 45°C (above the binary cloud point). Increasing the AA content of the system caused isotropic surfactant (L2) and lamellar liquid crystalline (La) phases to form at lower temperatures than in the binary C12E5–H2O system. As the temperature increased, the solubility of AA in the L2 phase increased considerably, while the AA content of the La phase was not affected as strongly. The dynamic phase behavior resulting from contact of micellar C12E5solutions with AA or AA/IPA particles at 24°C (below the binary cloud point) and 45°C was also observed. When AA or AA/IPA particles were contacted with 4.1 × 10−3MC12E5solutions, the surfactant and water penetrated into the particles to create isotropic liquid aggregates. When particles were contacted with more concentrated micellar C12E5solutions (0.25M), a new concentrated surfactant phase surrounded the particles and solubilized the AA.}, number={2}, journal={JOURNAL OF COLLOID AND INTERFACE SCIENCE}, author={Beaudoin, SP and Carbonell, RG and Grant, CS}, year={1996}, month={Sep}, pages={465–472} }
 @article{kabin_saez_grant_carbonell_1996, title={Removal of organic films from rotating disks using aqueous solutions of nonionic surfactants: Film morphology and cleaning mechanisms}, volume={35}, ISSN={["0888-5885"]}, DOI={10.1021/ie960195c}, abstractNote={In this work, we consider the cleaning of an organic liquid film, consisting initially of a concentrated solution of abietic acid in isopropyl alcohol, from the surface of a rotating disk by using aqueous solutions of a nonionic surfactant, pentaethylene glycol mono-n-dodecyl ether. The results show that the removal process takes place in three consecutive stages. The first stage is controlled by the solubilization of the abietic acid by surfactant penetration and subsequent mass transfer from the interface to the bulk of the aqueous solution. During the first stage, the film absorbs water from the aqueous solution and breaks up into drops that leave portions of the surface exposed. The absorption of surfactant and water reduces the organic-phase viscosity, until the drops start to move on the disk surface under the action of shear forces. These drops aggregate into spiral-shaped continuous rivulets through which the organic phase flows until it comes off the disk edge. Such behavior occurs during the sec...}, number={12}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={Kabin, JA and Saez, AE and Grant, CS and Carbonell, RG}, year={1996}, month={Dec}, pages={4494–4506} }
 @article{beaudoin_grant_carbonell_1995, title={REMOVAL OF ORGANIC FILMS FROM SOLID-SURFACES USING AQUEOUS-SOLUTIONS OF NONIONIC SURFACTANTS .1. EXPERIMENTS}, volume={34}, ISSN={["0888-5885"]}, DOI={10.1021/ie00037a017}, abstractNote={An important step in the production of printed wiring assemblies (PWAs) is the postsolder removal of flux residues from the surface. Traditionally, this has been accomplished using CFC-113-based solutions, but the Montreal Protocol and the Clean Air Acts have forced the development of alternative cleaners. This is a study of the mechanisms by which aqueous solutions of a nonionic surfactant (pentaethylene glycol mono-n-dodecyl either (C{sub 12}E{sub 5})) remove films of flux residues (abietic acid in isopropyl alcohol) from PWA surfaces. Cleaning rates were studied in a rotating disk apparatus to control hydrodynamic conditions. The cleaning process followed a three-step mechanism. In the first stage, surfactant liquefies the organic by partitioning into the film. In the second and third stages, shear stresses at the PWA surface remove aggregates of the surfactant-laden liquefied AA from the bulk AA film and the PWA substrate, respectively.}, number={10}, journal={INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH}, author={BEAUDOIN, SP and GRANT, CS and CARBONELL, RG}, year={1995}, month={Oct}, pages={3307–3317} }
 @article{beaudoin_grant_carbonell_1995, title={Removal of organic films from solid surfaces using aqueous solutions of nonionic surfactants. 2. Theory}, volume={34}, DOI={10.1021/ie00037a018}, abstractNote={The removal of organic films of solder flux components (abietic acid in isopropyl alcohol) from disks of epoxy-glass laminate by aqueous solutions of nonionic surfactant (C{sub 12}-E{sub 5}) proceeds through three stages. The controlling mechanisms in each stage were deduced from experimental observations. In this paper, theoretical models are developed to analyze the cleaning rates in the three different stages. The duration of the first stage is calculated assuming that convective and diffusive transport of surfactant monomer into the organic film controls the stage. The second stage is analyzed considering that shear forces remove aggregates from a continuous film of liquefied residue, while the third stage cleaning rate model is based on the shear-induced removal of isolated aggregates adsorbed directly to the solid substrate. Parameters in the models are evaluated using experimental cleaning rate data.}, number={10}, journal={Industrial & Engineering Chemistry Research}, author={Beaudoin, S. P. and Grant, Christine and Carbonell, R. G.}, year={1995}, pages={3318–3325} }
 @misc{bastek_lang_baumbach_carbonell, title={Alpha-1 proteinase inhibitor binding peptides}, volume={5,985,836}, number={1999 Nov. 16}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Bastek, P. D. and Lang, J. M. and Baumbach, G. A. and Carbonell, R. G.} }
 @misc{carbonell_kilpatrick_torres_guzman, title={Chromatography apparatus}, volume={5,045,190}, number={1991 Sep. 3}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Kilpatrick, P. K. and Torres, J. L. and Guzman, R.} }
 @misc{carbonell_desimone_henon, title={Compositions for protecting civil infrastructure}, volume={6,736,996}, number={2004 May 18}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and DeSimone, J. M. and Henon, F. E.} }
 @misc{valle_galan_carbonell, title={Drug delivery technologies: The way forward in the new decade}, volume={48}, number={5}, journal={Industrial & Engineering Chemistry Research}, author={Valle, E. M. M. and Galan, M. A. and Carbonell, R. G.}, pages={2475–2486} }
 @misc{roberts_xu_kiserow_carbonell, title={Hydrogenation of polymers in the presence of supercritical carbon dioxide}, volume={7,408,009}, number={2007 Apr. 11}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Roberts, G. W. and Xu, D. and Kiserow, D. J. and Carbonell, R. G.} }
 @misc{carbonell_kilpatrick_jones_singh, title={Immunodiagnostic assay using liposomes carrying labels thereof on outer liposome surface}, volume={5,494,803}, number={1996 Feb. 27}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Kilpatrick, P. K. and Jones, M. A. and Singh, A. K.} }
 @misc{carbonell_kilpatrick_saki, title={Methods and compositions for removing residues and substances from substrates using environmentally friendly solvents}, volume={7,465,395}, number={2008 Dec. 16}, author={Carbonell, R. G. and Kilpatrick, P. and Saki, N.} }
 @misc{zaki_kilpatrick_carbonell, title={Methods of deresinating crude oils using carbon dioxide}, volume={7,622,035}, number={1999 Nov. 24}, author={Zaki, N. N. and Kilpatrick, P. K. and Carbonell, R. G.} }
 @misc{mondorf_carbonell_buettner, title={Peptide ligands for affinity purification of fibrinogen}, volume={5,783,663}, number={1998 Jul. 21}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Mondorf, K. and Carbonell, R. C. and Buettner, J. A.} }
 @article{xu_carbonell_roberts_kiserow, title={Phase equilibrium for the hydrogenation of polystyrene in CO2-swollen solvents}, volume={34}, number={1}, journal={Journal of Supercritical Fluids}, author={Xu, D. W. and Carbonell, R. G. and Roberts, G. W. and Kiserow, D. J.}, pages={09-} }
 @misc{carbonell_guzman_kilpatrick, title={Precipitation of multivalent antiligands with affinity surfactants}, volume={5,167,925}, number={1992 Dec. 1}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Guzman, R. and Kilpatrick, P. K} }
 @misc{carbonell_guzman_kilpatrick, title={Precipitation of multivalent antiligands with affinity surfactants}, volume={5,112,770}, number={1992 May 12}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Guzman, R. and Kilpatrick, P. K} }
 @article{brennecke_johnston_carbonell, title={Preface: Seventh International Symposium on Supercritical Fluids (ISSF2005)}, volume={45}, number={10}, journal={Industrial & Engineering Chemistry Research}, author={Brennecke, J. F. and Johnston, K. P. and Carbonell, R. G.}, pages={3327} }
 @misc{hammond_carbonell_shen_gurgel_wiltshire-lyerly_burton, title={Prion protein binding materials and methods of use}, volume={7,510,848}, number={2009 Mar. 31}, author={Hammond, D. J. and Carbonell, R. G. and Shen, H. and Gurgel, P. V. and Wiltshire-Lyerly, V. and Burton, S. J.} }
 @misc{kilpatrick_carbonell_powers, title={Purification by affinity binding to liposomes}, volume={4,913,902}, number={1990 Apr. 3}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Kilpatrick, P. K. and Carbonell, R. G. and Powers, J. D.} }
 @misc{carbonell_yang_gurgel, title={Purification of immunoglobulins using affinity chromatography and peptide ligands}, volume={7,408,030}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Carbonell, R. G. and Yang, H. and Gurgel, P. V.} }
 @misc{chen_buettner_carbonell, title={Recombinant factor VIII binding peptides}, volume={6,191,256}, number={2001 Feb. 20}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Chen, C. L. and Buettner, J. A. and Carbonell, R. G.} }