@article{overchuk_rickard_tulino_tan_ligler_huang_rizvi_2024, title={Overcoming the effects of fluid shear stress in ovarian cancer cell lines: Doxorubicin alone or photodynamic priming to target platinum resistance}, volume={6}, ISSN={["1751-1097"]}, url={https://doi.org/10.1111/php.13967}, DOI={10.1111/php.13967}, abstractNote={Abstract Resistance to platinum‐based chemotherapies remains a significant challenge in advanced‐stage high‐grade serous ovarian carcinoma, and patients with malignant ascites face the poorest outcomes. It is, therefore, important to understand the effects of ascites, including the associated fluid shear stress (FSS), on phenotypic changes and therapy response, specifically FSS‐induced chemotherapy resistance and the underlying mechanisms in ovarian cancer. This study investigated the effects of FSS on response to cisplatin, a platinum‐based chemotherapy, and doxorubicin, an anthracycline, both of which are commonly used to manage advanced‐stage ovarian cancer. Consistent with prior research, OVCAR‐3 and Caov‐3 cells cultivated under FSS demonstrated significant resistance to cisplatin. Examination of the role of mitochondria revealed an increase in mitochondrial DNA copy number and intracellular ATP content in cultures grown under FSS, suggesting that changes in mitochondria number and metabolic activity may contribute to platinum resistance. Interestingly, no resistance to doxorubicin was observed under FSS, the first such observation of a lack of resistance under these conditions. Finally, this study demonstrated the potential of photodynamic priming using benzoporphyrin derivative, a clinically approved photosensitizer that localizes in part to mitochondria and endoplasmic reticula, to enhance the efficacy of cisplatin, but not doxorubicin, thereby overcoming FSS‐induced platinum resistance.}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Overchuk, Marta and Rickard, Brittany P. and Tulino, Justin and Tan, Xianming and Ligler, Frances S. and Huang, Huang-Chiao and Rizvi, Imran}, year={2024}, month={Jun} }
 @article{moatti_connard_de britto_dunn_rastogi_rai_schnabel_ligler_hutson_fitzpatrick_et al._2024, title={Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs}, volume={15}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2024.1348172}, abstractNote={Introduction: One major obstacle in validating drugs for the treatment or prevention of hearing loss is the limited data available on the distribution and concentration of drugs in the human inner ear. Although small animal models offer some insights into inner ear pharmacokinetics, their smaller organ size and different barrier (round window membrane) permeabilities compared to humans can complicate study interpretation. Therefore, developing a reliable large animal model for inner ear drug delivery is crucial. The inner and middle ear anatomy of domestic pigs closely resembles that of humans, making them promising candidates for studying inner ear pharmacokinetics. However, unlike humans, the anatomical orientation and tortuosity of the porcine external ear canal frustrates local drug delivery to the inner ear.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Moatti, Adele and Connard, Shannon and De Britto, Novietta and Dunn, William A. and Rastogi, Srishti and Rai, Mani and Schnabel, Lauren V. and Ligler, Frances S. and Hutson, Kendall A. and Fitzpatrick, Douglas C. and et al.}, year={2024}, month={Jan} }
 @article{moatti_silkstone_martin_abbey_hutson_fitzpatrick_zdanski_cheng_ligler_greenbaum_2023, title={Assessment of drug permeability through an ex vivo porcine round window membrane model}, volume={26}, ISSN={["2589-0042"]}, DOI={10.1016/j.isci.2023.106789}, abstractNote={Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy may cause damage to the inner ear. An alternative approach is to administer drugs into the middle ear using an intratympanic injection, with the drugs primarily passing through the RWM to the inner ear. However, the RWM is a barrier, only permeable to a small number of molecules. To study and enhance the RWM permeability, we developed an ex vivo porcine RWM model, similar in structure and thickness to the human RWM. The model is viable for days, and drug passage can be measured at multiple time points. This model provides a straightforward approach to developing effective and non-invasive delivery methods to the inner ear.}, number={6}, journal={ISCIENCE}, author={Moatti, Adele and Silkstone, Dylan and Martin, Taylor and Abbey, Keith and Hutson, Kendall A. and Fitzpatrick, Douglas C. and Zdanski, Carlton J. and Cheng, Alan G. and Ligler, Frances S. and Greenbaum, Alon}, year={2023}, month={Jun} }
 @article{overchuk_ruhi_rickard_ligler_rizvi_2023, title={Development of a light emitting device for the treatment of peritoneal car- cinomatosis of ovarian origin by intracavitary photodynamic therapy}, volume={41}, ISSN={["1873-1597"]}, DOI={10.1016/j.pdpdt.2023.103406}, abstractNote={Peritoneal carcinomatosis of ovarian origin (PCO) is an evolution of ovarian cancer, which is the fourth leading cause of death by cancer in women in France. PCO is defined by dissemination of cancerous cells from ovarian cancer to the peritoneal cavity. Photodynamic therapy (PDT) has been proposed in complement to the standard of care, consisting of surgery and chemotherapy. However, litterature has highlighted the lack of selectivity of available photosensitizers (PS) leading to inconclusive results [1, 2]. In this context, PRODYNOV project, initiated by our research team INSERM U1189 ONCOTHAI, has enabled the development of a patented PS. The high selectivity of this PS makes possible to carry out relevant PDT for PCO provided that an adequate illumination device would exist. In this study, we developed and assessed such a device. First, a test bench aiming to evaluate quantity and homogeneity of the delivered illumination has been developed. It is composed of a fantom of peritoneal cavity in which seven optical probes connected to a power-meter were placed in strategic zones characterised by high recurrence risk. Then, three illumination devices were implemented and assessed. The first one consisted of six fixed light emitting fabrics (LEF), the second one was a moving luminous wand, and the last one, a hybrid one, combined a fixed luminous wand and six fixed LEF. Light doses received by the probes have been calculated by integrating measured powers over illumination time. Each of the seven optical probes received a mean light dose of 0.68 mJ with the first illumination device (minimum: 18.37 10−3 mJ, maximum: 2.66 mJ), 0.11 mJ with the second one (minimum: 5.25 10−3 mJ, maximum: 0.35 mJ) and 0.65 mJ with the third one (minimum: 48.19 10−3 mJ, maximum: 1.27 mJ). With a variation coefficient of 77.1% (versus 93.1% for the first device and 119.5% for the second one), the hybrid device enabled to homogeneously illuminate the largest part of the cavity. For these reasons, the hybrid method has been selected as illumination process for PDT of PCO. Illumination solutions for PDT of PCO have been proposed and tested. One of these solutions has been approved. The light dose necessary for an effective treatment remains to be determined and first feasability tests will be led on mini-pig by the end of the year.}, journal={PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY}, author={Overchuk, Marta and Ruhi, Mustafa Kemal and Rickard, Brittany and Ligler, Frances and Rizvi, Imran}, year={2023}, month={Mar} }
 @article{rickard_overchuk_tulino_tan_ligler_bae-jump_fenton_rizvi_2023, title={Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines}, volume={22}, ISSN={["1476-069X"]}, url={https://europepmc.org/articles/PMC10720226}, DOI={10.1186/s12940-023-01034-2}, abstractNote={Abstract}, number={1}, journal={ENVIRONMENTAL HEALTH}, author={Rickard, Brittany P. and Overchuk, Marta and Tulino, Justin and Tan, Xianming and Ligler, Frances S. and Bae-Jump, Victoria L. and Fenton, Suzanne E. and Rizvi, Imran}, year={2023}, month={Dec} }
 @article{wang_sadeghi_velayati_paul_hetzler_danilov_ligler_wei_2023, title={Low-rate smartphone videoscopy for microsecond luminescence lifetime imaging with machine learning}, volume={2}, ISSN={["2752-6542"]}, url={https://doi.org/10.1093/pnasnexus/pgad313}, DOI={10.1093/pnasnexus/pgad313}, abstractNote={Abstract}, number={10}, journal={PNAS NEXUS}, author={Wang, Yan and Sadeghi, Sina and Velayati, Alireza and Paul, Rajesh and Hetzler, Zach and Danilov, Evgeny and Ligler, Frances S. and Wei, Qingshan}, editor={Reis, RuiEditor}, year={2023}, month={Sep} }
 @article{overchuk_ruhi_rickard_ligler_rizvi_2023, title={Targeted PDT Combinations to Overcome Fluid Shear Stress-induced Plat- inum Resistance in Ovarian Cancer}, volume={41}, ISSN={["1873-1597"]}, DOI={10.1016/j.pdpdt.2023.103405}, abstractNote={Ovarian cancer is the deadliest gynecologic malignancy — in 2020 alone, ovarian cancer claimed lives of 13,940 patients in the United States and 29,000 in Europe [1]. Such high ovarian cancer mortality can be explained by the fact that most patients are diagnosed with advanced-stage disease and 70% of them develop resistance to platinum-based therapies within the first 5 years [1]. One of the potential contributing factors to treatment failure in ovarian cancer is malignant ascites, or excessive fluid buildup in the peritoneal cavity. Ascites creates a unique molecular and biophysical environment, providing cancer cells with a nutrient- and growth factor-rich media and exposing them to abnormal physical stress. Our research group has been studying the effects of fluid shear stress (FSS) on ovarian cancer cell phenotypes and treatment responsiveness [2]. It was found that FSS confers resistance to carboplatin, activates the epidermal growth factor receptor (EGFR) as well as the downstream signaling cascades, and promotes epithelial-mesenchymal transition. These findings revealed the need for strategies that would remain effective under flow conditions and aid the effectiveness of standard of care treatments. Photodynamic therapy (PDT), which utilizes photosensitizers and light to generate cytotoxic reactive molecular species, provides a mechanistically distinct way of targeting chemoresistant cell populations. It was demonstrated that low-dose PDT with EGFR-targeted benzoporphyrin derivative photoimmunoconjugates remains effective in a 3D perfusion model for ovarian cancer, under conditions that induce resistance to carboplatin and EGFR overexpression and activation [2]. Encouraged by these findings, we continue exploring benzoporphyrin derivative-enabled PDT as a stand-alone therapy or in combination with cisplatin under static and flow conditions. Overall, we believe that photodynamic therapy has a potential to become an indispensable tool in late-stage ovarian cancer treatment, effectively destroying and/or sensitizing chemoresistant cell populations, decreasing the required chemotherapy dose and expanding the therapeutic window.}, journal={PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY}, author={Overchuk, Marta and Ruhi, Mustafa Kemal and Rickard, Brittany and Ligler, Frances and Rizvi, Imran}, year={2023}, month={Mar} }
 @article{moatti_cai_li_popowski_cheng_ligler_greenbaum_2023, title={Tissue clearing and three-dimensional imaging of the whole cochlea and vestibular system from multiple large-animal models}, volume={4}, ISSN={["2666-1667"]}, DOI={10.1016/j.xpro.2023.102220}, abstractNote={The inner ear of humans and large animals is embedded in a thick and dense bone that makes dissection challenging. Here, we present a protocol that enables three-dimensional (3D) characterization of intact inner ears from large-animal models. We describe steps for decalcifying bone, using solvents to remove color and lipids, and imaging tissues in 3D using confocal and light sheet microscopy. We then detail a pipeline to count hair cells in antibody-stained and 3D imaged cochleae using open-source software. For complete details on the use and execution of this protocol, please refer to (Moatti et al., 2022).1.}, number={2}, journal={STAR PROTOCOLS}, author={Moatti, Adele and Cai, Yuheng and Li, Chen and Popowski, Kristen D. and Cheng, Ke and Ligler, Frances S. and Greenbaum, Alon}, year={2023}, month={Jun} }
 @article{agarwalla_ogunnaike_ahn_froehlich_jansson_ligler_dotti_brudno_2022, title={Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells}, volume={3}, ISSN={["1546-1696"]}, DOI={10.1038/s41587-022-01245-x}, abstractNote={Despite their clinical success, chimeric antigen receptor (CAR)-T cell therapies for B cell malignancies are limited by lengthy, costly and labor-intensive ex vivo manufacturing procedures that might lead to cell products with heterogeneous composition. Here we describe an implantable Multifunctional Alginate Scaffold for T Cell Engineering and Release (MASTER) that streamlines in vivo CAR-T cell manufacturing and reduces processing time to a single day. When seeded with human peripheral blood mononuclear cells and CD19-encoding retroviral particles, MASTER provides the appropriate interface for viral vector-mediated gene transfer and, after subcutaneous implantation, mediates the release of functional CAR-T cells in mice. We further demonstrate that in vivo-generated CAR-T cells enter the bloodstream and control distal tumor growth in a mouse xenograft model of lymphoma, showing greater persistence than conventional CAR-T cells. MASTER promises to transform CAR-T cell therapy by fast-tracking manufacture and potentially reducing the complexity and resources needed for provision of this type of therapy.}, journal={NATURE BIOTECHNOLOGY}, author={Agarwalla, Pritha and Ogunnaike, Edikan A. and Ahn, Sarah and Froehlich, Kristen A. and Jansson, Anton and Ligler, Frances S. and Dotti, Gianpietro and Brudno, Yevgeny}, year={2022}, month={Mar} }
 @article{hetzler_wang_krafft_jamalzadegan_overton_kudenov_ligler_wei_2022, title={Flexible sensor patch for continuous carbon dioxide monitoring}, volume={10}, ISSN={["2296-2646"]}, DOI={10.3389/fchem.2022.983523}, abstractNote={Monitoring and measurement of carbon dioxide (CO2) is critical for many fields. The gold standard CO2 sensor, the Severinghaus electrode, has remained unchanged for decades. In recent years, many other CO2 sensor formats, such as detection based upon pH-sensitive dyes, have been demonstrated, opening the door for relatively simple optical detection schemes. However, a majority of these optochemical sensors require complex sensor preparation steps and are difficult to control and repeatably execute. Here, we report a facile CO2 sensor generation method that suffers from none of the typical fabrication issues. The method described here utilizes polydimethylsiloxane (PDMS) as the flexible sensor matrix and 1-hydroxypyrene-3,6,8-trisulfonate (HPTS), a pH-sensitive dye, as the sensing material. HPTS, a base (NaOH), and glycerol are loaded as dense droplets into a thin PDMS layer which is subsequently cured around the droplet. The fabrication process does not require prior knowledge in chemistry or device fabrication and can be completed as quickly as PDMS cures (∼2 h). We demonstrate the application of this thin-patch sensor for in-line CO2 quantification in cell culture media. To this end, we optimized the sensing composition and quantified CO2 in the range of 0–20 kPa. A standard curve was generated with high fidelity (R2 = 0.998) along with an analytical resolution of 0.5 kPa (3.7 mm Hg). Additionally, the sensor is fully autoclavable for applications requiring sterility and has a long working lifetime. This flexible, simple-to-manufacture sensor has a myriad of potential applications and represents a new, straightforward means for optical carbon dioxide measurement.}, journal={FRONTIERS IN CHEMISTRY}, author={Hetzler, Zach and Wang, Yan and Krafft, Danny and Jamalzadegan, Sina and Overton, Laurie and Kudenov, Michael W. and Ligler, Frances S. and Wei, Qingshan}, year={2022}, month={Sep} }
 @article{lee_huang_aw_rathod_cho_ligler_polacheck_2022, title={Multilayer microfluidic platform for the study of luminal, transmural, and interstitial flow}, volume={14}, ISSN={["1758-5090"]}, DOI={10.1088/1758-5090/ac48e5}, abstractNote={Abstract}, number={2}, journal={BIOFABRICATION}, author={Lee, Gi-hun and Huang, Stephanie A. and Aw, Wen Y. and Rathod, Mitesh L. and Cho, Crescentia and Ligler, Frances S. and Polacheck, William J.}, year={2022}, month={Apr} }
 @article{moatti_li_sivadanam_cai_ranta_piedrahita_cheng_ligler_greenbaum_2022, title={Ontogeny of cellular organization and LGR5 expression in porcine cochlea revealed using tissue clearing and 3D imaging}, volume={25}, ISSN={["2589-0042"]}, DOI={10.1016/j.isci.2022.104695}, abstractNote={Over 11% of the world's population experience hearing loss. Although there are promising studies to restore hearing in rodent models, the size, ontogeny, genetics, and frequency range of hearing of most rodents' cochlea do not match that of humans. The porcine cochlea can bridge this gap as it shares many anatomical, physiological, and genetic similarities with its human counterpart. Here, we provide a detailed methodology to process and image the porcine cochlea in 3D using tissue clearing and light-sheet microscopy. The resulting 3D images can be employed to compare cochleae across different ages and conditions, investigate the ontogeny of cochlear cytoarchitecture, and produce quantitative expression maps of LGR5, a marker of cochlear progenitors in mice. These data reveal that hair cell organization, inner ear morphology, cellular cartography in the organ of Corti, and spatiotemporal expression of LGR5 are dynamic over developmental stages in a pattern not previously documented.}, number={8}, journal={ISCIENCE}, author={Moatti, Adele and Li, Chen and Sivadanam, Sasank and Cai, Yuheng and Ranta, James and Piedrahita, Jorge A. and Cheng, Alan G. and Ligler, Frances S. and Greenbaum, Alon}, year={2022}, month={Aug} }
 @article{carter_popowski_cheng_greenbaum_ligler_moatti_2021, title={Enhancement of Bone Regeneration Through the Converse Piezoelectric Effect, A Novel Approach for Applying Mechanical Stimulation}, volume={9}, ISSN={["2576-3113"]}, url={https://doi.org/10.1089/bioe.2021.0019}, DOI={10.1089/bioe.2021.0019}, abstractNote={Serious bone injuries have devastating effects on the lives of patients including limiting working ability and high cost. Orthopedic implants can aid in healing injuries to an extent that exceeds the natural regenerative capabilities of bone to repair fractures or large bone defects. Autografts and allografts are the standard implants used, but disadvantages such as donor site complications, a limited quantity of transplantable bone, and high costs have led to an increased demand for synthetic bone graft substitutes. However, replicating the complex physiological properties of biological bone, much less recapitulating its complex tissue functions, is challenging. Extensive efforts to design biocompatible implants that mimic the natural healing processes in bone have led to the investigation of piezoelectric smart materials because the bone has natural piezoelectric properties. Piezoelectric materials facilitate bone regeneration either by accumulating electric charge in response to mechanical stress, which mimics bioelectric signals through the direct piezoelectric effect or by providing mechanical stimulation in response to electrical stimulation through the converse piezoelectric effect. Although both effects are beneficial, the converse piezoelectric effect can address bone atrophy from stress shielding and immobility by improving the mechanical response of a healing defect. Mechanical stimulation has a positive impact on bone regeneration by activating cellular pathways that increase bone formation and decrease bone resorption. This review will highlight the potential of the converse piezoelectric effect to enhance bone regeneration by discussing the activation of beneficial cellular pathways, the properties of piezoelectric biomaterials, and the potential for the more effective administration of the converse piezoelectric effect using wireless control.}, journal={BIOELECTRICITY}, publisher={Mary Ann Liebert Inc}, author={Carter, Amber and Popowski, Kristen and Cheng, Ke and Greenbaum, Alon and Ligler, Frances S. and Moatti, Adele}, year={2021}, month={Sep} }
 @article{ogunnaike_valdivia_yazdimamaghani_leon_nandi_hudson_du_khagi_gu_savoldo_et al._2021, title={Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma}, volume={7}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.abg5841}, abstractNote={In situ fibrin gel promotes the survival and the biodistribution of CAR-T cells, eliminating residual GBM cells after surgery.}, number={41}, journal={SCIENCE ADVANCES}, author={Ogunnaike, Edikan A. and Valdivia, Alain and Yazdimamaghani, Mostafa and Leon, Ernesto and Nandi, Seema and Hudson, Hannah and Du, Hongwei and Khagi, Simon and Gu, Zhen and Savoldo, Barbara and et al.}, year={2021}, month={Oct} }
 @article{martins_wilkins_ligler_daniele_freytes_2021, title={Microphysiological System for High-Throughput Computer Vision Measurement of Microtissue Contraction}, volume={6}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.0c02172}, abstractNote={The ability to measure microtissue contraction in vitro can provide important information when modeling cardiac, cardiovascular, respiratory, digestive, dermal, and skeletal tissues. However, measuring tissue contraction in vitro often requires the use of high number of cells per tissue construct along with time-consuming microscopy and image analysis. Here, we present an inexpensive, versatile, high-throughput platform to measure microtissue contraction in a 96-well plate configuration using one-step batch imaging. More specifically, optical fiber microprobes are embedded in microtissues, and contraction is measured as a function of the deflection of optical signals emitted from the end of the fibers. Signals can be measured from all the filled wells on the plate simultaneously using a digital camera. An algorithm uses pixel-based image analysis and computer vision techniques for the accurate multiwell quantification of positional changes in the optical microprobes caused by the contraction of the microtissues. Microtissue constructs containing 20,000-100,000 human ventricular cardiac fibroblasts (NHCF-V) in 6 mg/mL collagen type I showed contractile displacements ranging from 20-200 μm. This highly sensitive and versatile platform can be used for the high-throughput screening of microtissues in disease modeling, drug screening for therapeutics, physiology research, and safety pharmacology.}, number={3}, journal={ACS SENSORS}, author={Martins, Ana Maria Gracioso and Wilkins, Michael D. and Ligler, Frances S. and Daniele, Michael A. and Freytes, Donald O.}, year={2021}, month={Mar}, pages={985–994} }
 @misc{giri_pandey_shrestha_pokharel_ligler_neupane_2021, title={Review of analytical performance of COVID-19 detection methods}, volume={413}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-020-02889-x}, abstractNote={Abstract}, number={1}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Giri, Basant and Pandey, Shishir and Shrestha, Retina and Pokharel, Krisha and Ligler, Frances S. and Neupane, Bhanu B.}, year={2021}, month={Jan}, pages={35–48} }
 @article{roosa_muhamed_young_nellenbach_daniele_ligler_brown_2021, title={Synthesis of sonicated fibrin nanoparticles that modulate fibrin clot polymerization and enhance angiogenic responses}, volume={204}, ISSN={0927-7765}, url={http://dx.doi.org/10.1016/j.colsurfb.2021.111805}, DOI={10.1016/j.colsurfb.2021.111805}, abstractNote={Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin sealants, do not provide an optimal environment for native cell proliferation and subsequent tissue regeneration. Therefore, new treatments outside the confines of these conventional fibrin bulk gel therapies are required. We have previously developed flowable, low-density fibrin nanoparticles that, when coupled to keratinocyte growth factor, promote cell migration and epithelial wound closure in vivo. Here, we report a new high throughput method for generating the fibrin nanoparticles using probe sonication, which is less time intensive than the previously reported microfluidic method, and investigate the ability of the sonicated fibrin nanoparticles (SFBN) to promote clot formation and cell migration in vitro. The SFBNs can form a fibrin gel when combined with fibrinogen in the absence of exogenous thrombin, and the polymerization rate and fiber density in these fibrin clots is tunable based on SFBN concentration. Furthermore, fibrin gels made with SFBNs support cell migration in an in vitro angiogenic sprouting assay, which is relevant for wound healing. In this report, we show that SFBNs may be a promising wound healing therapy that can be easily produced and delivered in a flowable formulation.}, journal={Colloids and Surfaces B: Biointerfaces}, publisher={Elsevier BV}, author={Roosa, Colleen A. and Muhamed, Ismaeel and Young, Ashlyn T. and Nellenbach, Kimberly and Daniele, Michael A. and Ligler, Frances S. and Brown, Ashley C.}, year={2021}, month={Aug}, pages={111805} }
 @article{su_huang_mathews_scharf_hu_li_frame_cores_dinh_daniele_et al._2020, title={Cardiac Stromal Cell Patch Integrated with Engineered Microvessels Improves Recovery from Myocardial Infarction in Rats and Pigs}, volume={6}, ISSN={["2373-9878"]}, DOI={10.1021/acsbiomaterials.0c00942}, abstractNote={The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiosphere-derived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV-CSC patch). We showed that BMV-CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV-CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV-CSC patch as compared to those that received control treatments. These findings establish the BMV-CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.}, number={11}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Su, Teng and Huang, Ke and Mathews, Kyle G. and Scharf, Valery F. and Hu, Shiqi and Li, Zhenhua and Frame, Brianna N. and Cores, Jhon and Dinh, Phuong-Uyen and Daniele, Michael A. and et al.}, year={2020}, month={Nov}, pages={6309–6320} }
 @article{shirwaiker_fisher_anderson_schuchard_warren_maze_grondin_ligler_pourdeyhimi_2020, title={High-Throughput Manufacture of 3D Fiber Scaffolds for Regenerative Medicine}, volume={26}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2020.0098}, abstractNote={Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency, or architectural control in three dimensions. As such, a gap exists in efficiently producing clinically relevant, anatomically sized scaffolds comprising fibers in the 1–100 μm range that are highly organized. This study introduces a new high-throughput, additive fibrous scaffold fabrication process, designated in this study as 3D melt blowing (3DMB). The 3DMB system described in this study is modified from larger nonwovens manufacturing machinery to accommodate the lower volume, high-cost polymers used for tissue engineering and implantable biomedical devices and has a fiber collection component that uses adaptable robotics to create scaffolds with predetermined geometries. The fundamental process principles, system design, and key parameters are described, and two examples of the capabilities to create scaffolds for biomedical engineering applications are demonstrated. Impact statement Three-dimensional melt blowing (3DMB) is a new, high-throughput, additive manufacturing process to produce scaffolds composed of highly organized fibers in the anatomically relevant 1–100 μm range. Unlike conventional melt-blowing systems, the 3DMB process is configured for efficient use with the relatively expensive polymers necessary for biomedical applications, decreasing the required amounts of material for processing while achieving high throughputs compared with 3D printing or electrospinning. The 3DMB is demonstrated to make scaffolds composed of multiple fiber materials and organized into complex shapes, including those typical of human body parts.}, number={7}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Shirwaiker, Rohan A. and Fisher, Matthew B. and Anderson, Bruce and Schuchard, Karl G. and Warren, Paul B. and Maze, Benoit and Grondin, Pierre and Ligler, Frances S. and Pourdeyhimi, Behnam}, year={2020}, month={Jul}, pages={364–374} }
 @article{griffith_huang_cho_khare_rich_lee_ligler_diekman_polacheck_2020, title={Microfluidics for the study of mechanotransduction}, volume={53}, ISSN={["1361-6463"]}, DOI={10.1088/1361-6463/ab78d4}, abstractNote={Mechanical forces regulate a diverse set of biological processes at cellular, tissue, and organismal length scales. Investigating the cellular and molecular mechanisms that underlie the conversion of mechanical forces to biological responses is challenged by limitations of traditional animal models and in vitro cell culture, including poor control over applied force and highly artificial cell culture environments. Recent advances in fabrication methods and material processing have enabled the development of microfluidic platforms that provide precise control over the mechanical microenvironment of cultured cells. These devices and systems have proven to be powerful for uncovering and defining mechanisms of mechanotransduction. In this review, we first give an overview of the main mechanotransduction pathways that function at sites of cell adhesion, many of which have been investigated with microfluidics. We then discuss how distinct microfluidic fabrication methods can be harnessed to gain biological insight, with description of both monolithic and replica molding approaches. Finally, we present examples of how microfluidics can be used to apply both solid forces (substrate mechanics, strain, and compression) and fluid forces (luminal, interstitial) to cells. Throughout the review, we emphasize the advantages and disadvantages of different fabrication methods and applications of force in order to provide perspective to investigators looking to apply forces to cells in their own research.}, number={22}, journal={JOURNAL OF PHYSICS D-APPLIED PHYSICS}, author={Griffith, Christian M. and Huang, Stephanie A. and Cho, Crescentia and Khare, Tanmay M. and Rich, Matthew and Lee, Gi-hun and Ligler, Frances S. and Diekman, Brian O. and Polacheck, William J.}, year={2020}, month={May} }
 @article{agarwalla_ogunnaike_ahn_ligler_dotti_brudno_2020, title={Scaffold-Mediated Static Transduction of T Cells for CAR-T Cell Therapy}, volume={9}, ISSN={["2192-2659"]}, url={https://doi.org/10.1002/adhm.202000275}, DOI={10.1002/adhm.202000275}, abstractNote={Abstract}, number={14}, journal={ADVANCED HEALTHCARE MATERIALS}, publisher={Wiley}, author={Agarwalla, Pritha and Ogunnaike, Edikan A. and Ahn, Sarah and Ligler, Frances S. and Dotti, Gianpietro and Brudno, Yevgeny}, year={2020}, month={Jul} }
 @article{moatti_cai_li_sattler_edwards_piedrahita_ligler_greenbaum_2020, title={Three-dimensional imaging of intact porcine cochlea using tissue clearing and custom-built light-sheet microscopy}, volume={11}, ISSN={["2156-7085"]}, url={http://dx.doi.org/10.1364/boe.402991}, DOI={10.1364/BOE.402991}, abstractNote={Hearing loss is a prevalent disorder that affects people of all ages. On top of the existing hearing aids and cochlear implants, there is a growing effort to regenerate functional tissues and restore hearing. However, studying and evaluating these regenerative medicine approaches in a big animal model (e.g. pigs) whose anatomy, physiology, and organ size are similar to a human is challenging. In big animal models, the cochlea is bulky, intricate, and veiled in a dense and craggy otic capsule. These facts complicate 3D microscopic analysis that is vital in the cochlea, where structure-function relation is time and again manifested. To allow 3D imaging of an intact cochlea of newborn and juvenile pigs with a volume up to ∼ 250 mm3, we adapted the BoneClear tissue clearing technique, which renders the bone transparent. The transparent cochleae were then imaged with cellular resolution and in a timely fashion, which prevented bubble formation and tissue degradation, using an adaptive custom-built light-sheet fluorescence microscope. The adaptive light-sheet microscope compensated for deflections of the illumination beam by changing the angles of the beam and translating the detection objective while acquiring images. Using this combination of techniques, macroscopic and microscopic properties of the cochlea were extracted, including the density of hair cells, frequency maps, and lower frequency limits. Consequently, the proposed platform could support the growing effort to regenerate cochlear tissues and assist with basic research to advance cures for hearing impairments.}, number={11}, journal={BIOMEDICAL OPTICS EXPRESS}, publisher={The Optical Society}, author={Moatti, Adele and Cai, Yuheng and Li, Chen and Sattler, Tyler and Edwards, Laura and Piedrahita, Jorge and Ligler, Frances S. and Greenbaum, Alon}, year={2020}, month={Nov}, pages={6181–6196} }
 @article{su_huang_ma_liang_dinh_chen_shen_allen_qiao_li_et al._2019, title={Biomimetics: Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury (Adv. Funct. Mater. 4/2019)}, volume={29}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/ADFM.201970019}, DOI={10.1002/ADFM.201970019}, abstractNote={In article number 1803567, Ke Cheng and co-workers introduce platelet-inspired nanocells that target the heart after injury and that incorporates both a prostaglandin E2-modified platelet membrane and cardiac stromal cell-secreted factors. This approach represents a promising therapeutic delivery platform for treating myocardial ischemia/reperfusion injury.}, number={4}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Su, Teng and Huang, Ke and Ma, Hong and Liang, Hongxia and Dinh, Phuong-Uyen and Chen, Justin and Shen, Deliang and Allen, Tyler A. and Qiao, Li and Li, Zhenhua and et al.}, year={2019}, month={Jan}, pages={1970019} }
 @article{rich_mohd_ligler_walker_2019, title={Characterization of glass frit capillary pumps for microfluidic devices}, volume={23}, ISSN={["1613-4990"]}, DOI={10.1007/s10404-019-2238-6}, number={5}, journal={MICROFLUIDICS AND NANOFLUIDICS}, author={Rich, Matthew and Mohd, Omar and Ligler, Frances S. and Walker, Glenn M.}, year={2019}, month={May} }
 @article{muhamed_sproul_ligler_brown_2019, title={Fibrin Nanoparticles Coupled with Keratinocyte Growth Factor Enhance the Dermal Wound-Healing Rate}, volume={11}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/acsami.8b21056}, DOI={10.1021/acsami.8b21056}, abstractNote={Expediting the wound-healing process is critical for patients chronically ill from nonhealing wounds and diseases such as hemophilia or diabetes or who have suffered trauma including easily infected open wounds. FDA-approved external tissue sealants include the topical application of fibrin gels, which can be 500 times denser than natural fibrin clots. With lower clot porosity and higher polymerization rates than physiologically formed fibrin clots, the commercial gels quickly stop blood loss but impede the later clot degradation kinetics and thus retard tissue-healing rates. The fibrin nanoparticles (FBNs) described here are constructed from physiologically relevant fibrin concentrations that support new tissue and dermal wound scaffold formation when coupled with growth factors. The FBNs, synthesized in a microfluidic droplet generator, support cell adhesion and traction generation, and when coupled to keratinocyte growth factor (KGF), support cell migration and in vivo wound healing. The FBN-KGF particles enhance cell migration in vitro greater than FBN alone or free KGF and also improve healing outcomes in a murine full thickness injury model compared to saline, bulk fibrin sealant, free KGF, or bulk fibrin mixed with KGF treatments. Furthermore, FBN can be potentially administered with other tissue-healing factors and inflammatory mediators to improve wound-healing outcomes.}, number={4}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Muhamed, Ismaeel and Sproul, Erin P. and Ligler, Frances S. and Brown, Ashley C.}, year={2019}, month={Jan}, pages={3771–3780} }
 @article{ligler_gooding_2019, title={Lighting Up Biosensors: Now and the Decade To Come}, volume={91}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.9b00793}, abstractNote={Optical biosensors are defined as portable optical devices that use biorecognition molecules to interrogate a sample for the presence of a target. The capabilities of optical biosensors have expanded rapidly with advances in miniature optical components and molecular engineering. Biosensors to meet the needs in health and environmental monitoring and food safety have become commercially available, with many more in the pipeline. We review the innovative approaches to overcoming existing hurdles to practical biosensor designs and explore potential areas for future breakthroughs in optical biosensor technology.}, number={14}, journal={ANALYTICAL CHEMISTRY}, author={Ligler, Frances S. and Gooding, J. Justin}, year={2019}, month={Jul}, pages={8732–8738} }
 @article{sotoudegan_mohd_ligler_walker_2019, title={Paper-based passive pumps to generate controllable whole blood flow through microfluidic devices}, volume={19}, ISSN={["1473-0189"]}, DOI={10.1039/c9lc00822e}, abstractNote={Grooved paper pumps provide controllable flow of complex biofluids within microfluidic devices.}, number={22}, journal={LAB ON A CHIP}, author={Sotoudegan, Mohamad S. and Mohd, Omar and Ligler, Frances S. and Walker, Glenn M.}, year={2019}, month={Nov}, pages={3787–3795} }
 @article{chen_hu_dukhovlinova_chen_ahn_wang_ogunnaike_ligler_dotti_gu_2019, title={Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells}, volume={31}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201900192}, abstractNote={Abstract}, number={23}, journal={ADVANCED MATERIALS}, author={Chen, Qian and Hu, Quanyin and Dukhovlinova, Elena and Chen, Guojun and Ahn, Sarah and Wang, Chao and Ogunnaike, Edikan A. and Ligler, Frances S. and Dotti, Gianpietro and Gu, Zhen}, year={2019}, month={Jun} }
 @article{su_huang_ma_liang_dinh_chen_shen_allen_qiao_li_et al._2019, title={Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury}, volume={29}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.201803567}, abstractNote={Abstract}, number={4}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Su, Teng and Huang, Ke and Ma, Hong and Liang, Hongxia and Dinh, Phuong-Uyen and Chen, Justin and Shen, Deliang and Allen, Tyler A. and Qiao, Li and Li, Zhenhua and et al.}, year={2019}, month={Jan} }
 @article{su_huang_daniele_hensley_young_tang_allen_vandergriff_erb_ligler_et al._2018, title={Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction}, volume={10}, ISSN={["1944-8252"]}, DOI={10.1021/acsami.8b13571}, abstractNote={Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyogenesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.}, number={39}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Su, Teng and Huang, Ke and Daniele, Michael A. and Hensley, Michael Taylor and Young, Ashlyn T. and Tang, Junnan and Allen, Tyler A. and Vandergriff, Adam C. and Erb, Patrick D. and Ligler, Frances S. and et al.}, year={2018}, month={Oct}, pages={33088–33096} }
 @article{ligler_macuare_2018, title={THE NAI FELLOW PROFILE: AN INTERVIEW WITH DR. FRANCES LIGLER}, volume={19}, ISSN={["1949-825X"]}, DOI={10.21300/19.3.2018.645}, abstractNote={1Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh and Chapel Hill, NC, USA 2National Academy of Inventors, Tampa, FL, USA Technology and Innovation, Vol. 19, pp. 645-651, 2018 Printed in the USA. All rights reserved. Copyright © 2018 National Academy of Inventors. ISSN 1949-8241 • E-ISSN 1949-825X http://dx.doi.org/10.21300/19.3.2018.645 www.technologyandinnovation.org}, number={3}, journal={TECHNOLOGY AND INNOVATION}, author={Ligler, Frances S. and Macuare, Kimberly A.}, year={2018}, pages={645–651} }
 @article{yu_qian_zhang_cui_zhu_shen_ligler_buse_gu_2017, title={Hypoxia and H2O2 Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b03848}, abstractNote={A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.}, number={2}, journal={NANO LETTERS}, author={Yu, Jicheng and Qian, Chenggen and Zhang, Yuqi and Cui, Zheng and Zhu, Yong and Shen, Qundong and Ligler, Frances S. and Buse, John B. and Gu, Zhen}, year={2017}, month={Feb}, pages={733–739} }
 @article{wang_zhang_archibong_ligler_gu_2017, title={Leveraging H2O2 Levels for Biomedical Applications}, volume={1}, ISSN={2366-7478}, url={http://dx.doi.org/10.1002/ADBI.201700084}, DOI={10.1002/ADBI.201700084}, abstractNote={Hydrogen peroxide (H2O2)‐responsive materials have been employed as drug delivery or diagnostic systems to treat or detect diseases with abnormal oxidative stress. A number of H2O2‐responsive systems have been developed, and they have achieved great progress in controlled drug delivery for disease treatment. However, pathological sites with elevated H2O2 level, such as cancer and inflammation, have their own characteristics; therefore the material structures and the subsequent formulations should be reasonably designed to acquire maximized therapeutic effects. In this progress report, we overview the development of H2O2‐responsive functional groups for constructing H2O2‐responsive formulations, as well as the guidance for designing suitable formulations to treat each specific pathological condition. The challenges and perspectives in this field are also discussed.}, number={9}, journal={Advanced Biosystems}, publisher={Wiley}, author={Wang, Jinqiang and Zhang, Yuqi and Archibong, Edikan and Ligler, Frances S. and Gu, Zhen}, year={2017}, month={Sep}, pages={1700084} }
 @article{divito_daniele_roberts_ligler_adams_2017, title={Microfabricated blood vessels undergo neoangiogenesis}, volume={138}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2017.05.012}, abstractNote={The greatest ambition and promise of tissue engineering is to manufacture human organs. Before "made-to-measure" tissues can become a reality [1], [2], [3], however, three-dimensional tissues must be reconstructed and characterized. The current inability to manufacture operational vasculature has limited the growth of engineered tissues. Here, free-standing, small diameter blood vessels with organized cell layers that recapitulate normal biological functionality are fabricated using microfluidic technology. Over time in culture, the endothelial cells form a monolayer on the luminal wall and remodel the scaffold with human extracellular matrix proteins. After integration into three-dimensional gels containing fibroblasts, the microvessels sprout and generate extended hollow branches that anastomose with neighboring capillaries to form a network. Both the microfabricated vessels and the extended sprouts support perfusion of fluids and particles. The ability to create cellularized microvessels that can be designed with a diameter of choice, produced by the meter, and undergo angiogenesis and anastomoses will be an extremely valuable tool for vascularization of engineered tissues. To summarize, ultraviolet (UV) photo-crosslinkable poly(ethylene glycol) and gelatin methacrylate polymers used in combination with sheath-flow microfluidics allow for the fabrication of small diameter blood vessels which undergo neoangiogenesis as well as other developmental processes associated with normal human blood vessel maturation. Once mature, these vessels can be embedded; perfused; cryogenically stored and respond to stimuli such as chemokines and shear stresses to mimic native human blood vessels. The applications range from tissue-on-chip systems for drug screening, characterization of normal and pathologic processes, and creation and characterization of engineered tissues for organ repair.}, journal={BIOMATERIALS}, author={DiVito, Kyle A. and Daniele, Michael A. and Roberts, Steven A. and Ligler, Frances S. and Adams, Andre A.}, year={2017}, month={Sep}, pages={142–152} }
 @article{cummins_chinthapatla_lenin_ligler_walker_2017, title={Modular pumps as programmable hydraulic batteries for microfluidic devices}, volume={5}, ISSN={["2345-7740"]}, DOI={10.1142/s2339547817200011}, abstractNote={ Simple fluid pumps have been developed to improve microfluidic device portability, but they cannot be easily programmed, produce repeatable pumping performance, or generate complex flow profiles — key requirements for increasing the functionality of portable microdevices. We present a detachable, paper-based, “hydraulic battery” that can be connected to the outlet of a microfluidic channel to pump fluid at varying flow rates over time, including step changes, ramping flows, and oscillating flows. }, number={1}, journal={TECHNOLOGY}, author={Cummins, Brian M. and Chinthapatla, Rukesh and Lenin, Balaji and Ligler, Frances S. and Walker, Glenn M.}, year={2017}, month={Mar}, pages={21–30} }
 @article{chen_wang_sun_archibong_kahkoska_zhang_lu_ligler_buse_gu_2017, title={Synthetic beta cells for fusion-mediated dynamic insulin secretion}, volume={14}, ISSN={1552-4450 1552-4469}, url={http://dx.doi.org/10.1038/NCHEMBIO.2511}, DOI={10.1038/NCHEMBIO.2511}, abstractNote={Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AβCs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AβCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin 'exocytosis'.}, number={1}, journal={Nature Chemical Biology}, publisher={Springer Science and Business Media LLC}, author={Chen, Zhaowei and Wang, Jinqiang and Sun, Wujin and Archibong, Edikan and Kahkoska, Anna R and Zhang, Xudong and Lu, Yue and Ligler, Frances S and Buse, John B and Gu, Zhen}, year={2017}, month={Oct}, pages={86–93} }
 @article{cummins_chinthapatla_ligler_walker_2017, title={Time-Dependent Model for Fluid Flow in Porous Materials with Multiple Pore Sizes}, volume={89}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ACS.ANALCHEM.6B04717}, DOI={10.1021/ACS.ANALCHEM.6B04717}, abstractNote={An understanding of fluid transport through porous materials is critical for the development of lateral flow assays and analytical devices based on paper microfluidics. Models of fluid transport within porous materials often assume a single capillary pressure and permeability value for the material, implying that the material comprises a single pore size and that the porous material is fully saturated behind the visible wetted front. As a result, current models can lead to inaccuracies when modeling transport over long distances and/or times. A new transport model is presented that incorporates a range of pore sizes to more accurately predict the capillary transport of fluid in porous materials. The model effectively predicts the time-dependent saturation of rectangular strips of Whatman filter no. 1 paper using the manufacturer's data, published pore-size distribution measurements, and the fluid's properties.}, number={8}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Cummins, Brian M. and Chinthapatla, Rukesh and Ligler, Frances S. and Walker, Glenn M.}, year={2017}, month={Mar}, pages={4377–4381} }
 @article{divito_daniele_roberts_ligler_adams_2017, title={“Data characterizing microfabricated human blood vessels created via hydrodynamic focusing”}, volume={14}, ISSN={2352-3409}, url={http://dx.doi.org/10.1016/J.DIB.2017.07.011}, DOI={10.1016/J.DIB.2017.07.011}, abstractNote={This data article provides further detailed information related to our research article titled "Microfabricated Blood Vessels Undergo Neovascularization" (DiVito et al., 2017) [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF). Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into 'bullseye-like" cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016) [2], [3], [4], [5], [6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.}, journal={Data in Brief}, publisher={Elsevier BV}, author={DiVito, Kyle A. and Daniele, Michael A. and Roberts, Steven A. and Ligler, Frances S. and Adams, André A.}, year={2017}, month={Oct}, pages={156–162} }
 @article{taitt_anderson_ligler_2016, title={Evanescent wave fluorescence biosensors: Advances of the last decade}, volume={76}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/J.BIOS.2015.07.040}, DOI={10.1016/J.BIOS.2015.07.040}, abstractNote={Biosensor development has been a highly dynamic field of research and has progressed rapidly over the past two decades. The advances have accompanied the breakthroughs in molecular biology, nanomaterial sciences, and most importantly computers and electronics. The subfield of evanescent wave fluorescence biosensors has also matured dramatically during this time. Fundamentally, this review builds on our earlier 2005 review. While a brief mention of seminal early work will be included, this current review will focus on new technological developments as well as technology commercialized in just the last decade. Evanescent wave biosensors have found a wide array applications ranging from clinical diagnostics to biodefense to food testing; advances in those applications and more are described herein.}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Taitt, Chris Rowe and Anderson, George P. and Ligler, Frances S.}, year={2016}, month={Feb}, pages={103–112} }
 @article{steward_cole_ligler_loboa_2016, title={Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells}, volume={22}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2015.0533}, abstractNote={Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine.}, number={15-16}, journal={TISSUE ENGINEERING PART A}, author={Steward, Andrew J. and Cole, Jacqueline H. and Ligler, Frances S. and Loboa, Elizabeth G.}, year={2016}, month={Aug}, pages={997–1005} }
 @article{roberts_divito_ligler_adams_daniele_2016, title={Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures}, volume={10}, ISSN={1932-1058}, url={http://dx.doi.org/10.1063/1.4963145}, DOI={10.1063/1.4963145}, abstractNote={Integrating a perfusable microvasculature system in vitro is a substantial challenge for “on-chip” tissue models. We have developed an inclusive on-chip platform that is capable of maintaining laminar flow through porous biosynthetic microvessels. The biomimetic microfluidic device is able to deliver and generate a steady perfusion of media containing small-molecule nutrients, drugs, and gases in three-dimensional cell cultures, while replicating flow-induced mechanical stimuli. Here, we characterize the diffusion of small molecules from the perfusate, across the microvessel wall, and into the matrix of a 3D cell culture.}, number={5}, journal={Biomicrofluidics}, publisher={AIP Publishing}, author={Roberts, Steven A. and DiVito, Kyle A. and Ligler, Frances S. and Adams, André A. and Daniele, Michael A.}, year={2016}, month={Sep}, pages={054109} }
 @article{neupane_chen_wei_fang_ligler_wang_2016, title={Nanosecond Time-Resolution Study of Gold Nanorod Rotation at the Liquid-Solid Interface}, volume={17}, ISSN={["1439-7641"]}, DOI={10.1002/cphc.201600174}, abstractNote={Abstract}, number={14}, journal={CHEMPHYSCHEM}, author={Neupane, Bhanu and Chen, Fang and Wei, Yanli and Fang, Ning and Ligler, Frances S. and Wang, Gufeng}, year={2016}, month={Jul}, pages={2218–2224} }
 @article{cummins_ligler_walker_2016, title={Point-of-care diagnostics for niche applications}, volume={34}, ISSN={0734-9750}, url={http://dx.doi.org/10.1016/J.BIOTECHADV.2016.01.005}, DOI={10.1016/J.BIOTECHADV.2016.01.005}, abstractNote={Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted.}, number={3}, journal={Biotechnology Advances}, publisher={Elsevier BV}, author={Cummins, Brian M. and Ligler, Frances S. and Walker, Glenn M.}, year={2016}, month={May}, pages={161–176} }
 @article{giri_pandey_neupane_ligler_2016, title={Signal amplification strategies for microfluidic immunoassays}, volume={79}, ISSN={0165-9936}, url={http://dx.doi.org/10.1016/J.TRAC.2015.10.021}, DOI={10.1016/J.TRAC.2015.10.021}, abstractNote={Immunoassays have become much more sophisticated since the enzyme linked immunoassays became widely used. Microfluidics in particular, coupled with advanced optical and electrochemical readout systems have reduced the limits of detection, decreased assay time, and simplified automation. Yet the sensitivity of the microfluidic immunoassays is still limited by the ability of the detector to discriminate between signal and background. Three main approaches to produce higher signal/background are reviewed and critiqued: target preconcentration, reaction confinement in a small detection volume and signal amplification strategies. Combinations of these strategies can be used to increase sensitivity and may provide clinical diagnostics for biomarkers present in very low concentrations.}, journal={TrAC Trends in Analytical Chemistry}, publisher={Elsevier BV}, author={Giri, Basant and Pandey, Binod and Neupane, Bhanu and Ligler, Frances S.}, year={2016}, month={May}, pages={326–334} }
 @article{daniele_boyd_mott_ligler_2015, title={3D hydrodynamic focusing microfluidics for emerging sensing technologies}, volume={67}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/J.BIOS.2014.07.002}, DOI={10.1016/j.bios.2014.07.002}, abstractNote={While the physics behind laminar flows has been studied for 200 years, understanding of how to use parallel flows to augment the capabilities of microfluidic systems has been a subject of study primarily over the last decade. The use of one flow to focus another within a microfluidic channel has graduated from a two-dimensional to a three-dimensional process and the design principles are only now becoming established. This review explores the underlying principles for hydrodynamic focusing in three dimensions (3D) using miscible fluids and the application of these principles for creation of biosensors, separation of cells and particles for sample manipulation, and fabrication of materials that could be used for biosensors. Where sufficient information is available, the practicality of devices implementing fluid flows directed in 3D is evaluated and the advantages and limitations of 3D hydrodynamic focusing for the particular application are highlighted.}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Daniele, Michael A. and Boyd, Darryl A. and Mott, David R. and Ligler, Frances S.}, year={2015}, month={May}, pages={25–34} }
 @article{pacardo_neupane_rikard_lu_mo_mishra_tracy_wang_ligler_gu_2015, title={A dual wavelength-activatable gold nanorod complex for synergistic cancer treatment}, volume={7}, ISSN={["2040-3372"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000357805700034&KeyUID=WOS:000357805700034}, DOI={10.1039/c5nr01568e}, abstractNote={A multifunctional gold nanorod complex was formulated for synergistic anticancer treatment upon ultraviolet (UV) and infrared (IR) light dual irradiations.}, number={28}, journal={NANOSCALE}, author={Pacardo, Dennis B. and Neupane, Bhanu and Rikard, S. Michaela and Lu, Yue and Mo, Ran and Mishra, Sumeet R. and Tracy, Joseph B. and Wang, Gufeng and Ligler, Frances S. and Gu, Zhen}, year={2015}, pages={12096–12103} }
 @article{pacardo_neupane_wang_gu_walker_ligler_2015, title={A temperature microsensor for measuring laser-induced heating in gold nanorods}, volume={407}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-014-8222-9}, abstractNote={Measuring temperature is an extensively explored field of analysis, but measuring a temperature change in a nanoparticle is a new challenge. Here, a microsensor is configured to measure temperature changes in gold nanorods in solution upon laser irradiation. The device consists of a silicon wafer coated with silicon nitride in which a microfabricated resistance temperature detector was embedded and attached to a digital multimeter. A polydimethylsiloxane mold served as a microcontainer for the sample attached on top of the silicon membrane. This enables laser irradiation of the gold nanorods and subsequent measurement of temperature changes. The results showed a temperature increase of 8 to 10 °C and good correlation with theoretical calculations and bulk sample direct temperature measurements. These results demonstrate the suitability of this simple temperature microsensor for determining laser-induced heating profiles of metallic nanomaterials; such measurements will be essential for optimizing therapeutic and catalytic applications.}, number={3}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Pacardo, Dennis B. and Neupane, Bhanu and Wang, Gufeng and Gu, Zhen and Walker, Glenn M. and Ligler, Frances S.}, year={2015}, month={Jan}, pages={719–725} }
 @article{neupane_jin_mellor_loboa_ligler_wang_2015, title={Continuous-wave stimulated emission depletion microscope for imaging actin cytoskeleton in fixed and live cells}, volume={15}, number={9}, journal={Sensors (Basel, Switzerland)}, author={Neupane, B. and Jin, T. and Mellor, L. F. and Loboa, E. G. and Ligler, F. S. and Wang, G. F.}, year={2015}, pages={24178–24190} }
 @article{daniele_boyd_adams_ligler_2015, title={Microfluidic strategies for design and assembly of microfibers and nanofibers with tissue engineering and regenerative medicine applications}, volume={4}, number={1}, journal={Advanced Healthcare Materials}, author={Daniele, M. A. and Boyd, D. A. and Adams, A. A. and Ligler, F. S.}, year={2015} }
 @article{daniele_boyd_adams_ligler_2015, title={Microfluidics: Microfluidic Strategies for Design and Assembly of Microfibers and Nanofibers with Tissue Engineering and Regenerative Medicine Applications (Adv. Healthcare Mater. 1/2015)}, volume={4}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201570002}, DOI={10.1002/ADHM.201570002}, abstractNote={Recent applications in tissue engineering and regenerative medicine have highlighted the utility of microfluidic fiber fabrication. On page 11 M. A. Daniele and team show how this process uses microflow shaping to generate a core-sheath profile, which can be subsequently solidified into microfibers of various shapes and chemistries, providing the capability to incorporate and organize both fragile biomolecules and cell-cultures within individual fibers and bioactive textiles.}, number={1}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Daniele, Michael A. and Boyd, Darryl A. and Adams, André A. and Ligler, Frances S.}, year={2015}, month={Jan}, pages={2–2} }
 @article{yu_zhang_ye_disanto_sun_ranson_ligler_buse_gu_2015, title={Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery}, volume={112}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1505405112}, abstractNote={Significance}, number={27}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Yu, Jicheng and Zhang, Yuqi and Ye, Yanqi and DiSanto, Rocco and Sun, Wujin and Ranson, Davis and Ligler, Frances S. and Buse, John B. and Gu, Zhen}, year={2015}, month={Jul}, pages={8260–8265} }
 @misc{pacardo_ligler_gu_2015, title={Programmable nanomedicine: synergistic and sequential drug delivery systems}, volume={7}, ISSN={["2040-3372"]}, DOI={10.1039/c4nr07677j}, abstractNote={Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.}, number={8}, journal={NANOSCALE}, author={Pacardo, Dennis B. and Ligler, Frances S. and Gu, Zhen}, year={2015}, pages={3381–3391} }
 @article{sweedler_armstrong_baba_desmet_dovichi_ewing_fenselau_kennedy_larive_ligler_et al._2015, title={The Scope of Analytical Chemistry}, volume={87}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ACS.ANALCHEM.5B02231}, DOI={10.1021/ACS.ANALCHEM.5B02231}, abstractNote={T field of analytical chemistry is wide-ranging, and accordingly, as its flagship journal, Analytical Chemistry publishes articles encompassing a broad spectrum of scientific and engineering disciplines related to measurement science. Each month, we receive multiple inquiries about whether or not a specific article fits the scope of our journal. Historically speaking, in 1949, Walter Murphy (Editor from 1943−1956) defined our scope as the publication of “Fundamental studies on the properties of matter which can be adapted to measuring qualitatively and quantitatively chemical compounds and elements.” Not surprisingly, the focus of our field has greatly expanded over the past 65 years and so we no longer limit articles to those involving qualitative and quantitative measurements. Perhaps the most concise definition of today’s journal scope was advanced in Royce Murray’s 2007 editorial: Analytical Chemistry publishes “... f undamental and practical applications of how to measure important chemical things, which include concentrations, rate constants, lifetimes, and whatever−as long as what is measured is a chemically important parameter.” If you are interested in a more detailed description, we provide you the following from our author guidelines: “Analytical Chemistry is devoted to the dissemination of original knowledge in all branches of analytical chemistry. Fundamental articles may address the general principles of chemical measurement science and need not directly address existing or potential analytical methodology. Articles may be entirely theoretical with regard to analysis, or they may report experimental results. They may contribute to any phase of analytical operations, including sampling, chemical reactions, separations, instrumentation, measurements, and data processing. Papers dealing with known analytical methods should of fer a signif icant, original application of the method, a noteworthy improvement, or results on an important analyte.” Keep in mind that these “rules” balance details with brevity, as too long a set of guidelines hinders their use. Thus, we acknowledge that there remains room for interpretation, not only by the author, who may suggest a new topic of interest, but also the handling editor, who makes the definitive decision about an article’s suitability for the journal. So, what are some key factors to consider when deciding to submit your article to Analytical Chemistry? The fit is obvious when a major focus of your manuscript is to advance measurement science, and it directly deals with the process of making or improving an analytical measurement. Another way of determining if your article fits the journal’s scope is to see if we have published similar articles in the recent past, with the caveat that topics that were once novel and publishable can become routine and thus no longer fit our scope. The most challenging questions we receive about suitability for the journal involve “applications” articles. We welcome manuscripts on difficult applications, so difficult that nothing comparable has yet been published, even though attempts have been made. We also encourage applications that evaluate unique or rare samples such as moon rocks, meteorite samples, novel deep-sea samples, artwork, and rare biological samples, as well as applications in which the measurement data is part of an important larger narrative, and the analytical data provides a noteworthy addition to the story. The problem to be solved should be important, or the proposed technique must greatly improve the measurement conditions, perhaps by major decreases in analysis times or costs, or by large improvements in the measurement figures of merit. Let’s consider another scenario. When the major goal of an article is to advance another field of science, which is acceptable, but the analytical methods used are not novel or significantly improved over existing ones, the manuscript may not fit our journal. What else may factor into a decision that an article is not appropriate for Analytical Chemistry? Some typical examples are reports of minor modifications to well-established methods, or standard applications of existing analytical approaches. Together we hope that this editorial has provided you with some insight on what we look for when evaluating manuscript submissions. Finally, we leave you with the following, overarching message: we look forward to receiving articles describing advances in all fields of measurement science, using a broad range of measurement techniques. Surprise us with something new! The Editors of Analytical Chemistry Jonathan V. Sweedler Daniel W. Armstrong Yoshinobu Baba Gert Desmet Norman Dovichi Andrew Ewing Catherine C. Fenselau Robert T. Kennedy Cynthia K. Larive Frances S. Ligler Richard L. McCreery Reinhard Niessner Jeanne E. Pemberton Weihong Tan David R. Walt John R. Yates, III Renato Zenobi Xinrong Zhang}, number={13}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Sweedler, Jonathan V. and Armstrong, Daniel W. and Baba, Yoshinobu and Desmet, Gert and Dovichi, Norman and Ewing, Andrew and Fenselau, Catherine C. and Kennedy, Robert T. and Larive, Cynthia K. and Ligler, Frances S. and et al.}, year={2015}, month={Jun}, pages={6425–6425} }
 @article{lu_hu_lin_pacardo_wang_sun_ligler_dickey_gu_2015, title={Transformable liquid-metal nanomedicine}, volume={6}, ISSN={["2041-1723"]}, DOI={10.1038/ncomms10066}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, publisher={Springer Nature}, author={Lu, Yue and Hu, Quanyin and Lin, Yiliang and Pacardo, Dennis B. and Wang, Chao and Sun, Wujin and Ligler, Frances S. and Dickey, Michael D. and Gu, Zhen}, year={2015}, month={Dec} }
 @article{boyd_naciri_fontana_pacardo_shields_verbarg_spillmann_ligler_2014, title={Facile Fabrication of Color Tunable Film and Fiber Nanocomposites via Thiol Click Chemistry}, volume={47}, ISSN={["1520-5835"]}, DOI={10.1021/ma401636e}, abstractNote={A simple method for the fabrication of nanocomposite materials using thiol click chemistry is reported. The thiol click nanocomposite materials produced each displayed distinctive colors which were found to be dependent on both the ligand used to functionalize the nanoparticles and the concentration of nanoparticles in the materials. Functionalized metallic nanospheres were combined with thiol click solutions forming viscous prepolymer solutions which were then polymerized upon UV light exposure. Films were fabricated in a custom-built film mold, and microfibers were fabricated using hydrodynamic focusing in a microfluidic channel. For this study, three unique thiolated ligands—including a newly synthesized ligand—were used to functionalize the nanospheres, thus assisting in the facile incorporation and stability of the nanospheres within the polymers. In comparison to a previously reported method in which thiol–ene nanocomposite films were fabricated, the method reported herein reduces the fabrication ti...}, number={2}, journal={MACROMOLECULES}, author={Boyd, Darryl A. and Naciri, Jawad and Fontana, Jake and Pacardo, Dennis B. and Shields, Adam R. and Verbarg, Jasenka and Spillmann, Christopher M. and Ligler, Frances S.}, year={2014}, month={Jan}, pages={695–704} }
 @article{daniele_adams_naciri_north_ligler_2014, title={Interpenetrating networks based on gelatin methacrylamide and PEG formed using concurrent thiol click chemistries for hydrogel tissue engineering scaffolds}, volume={35}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/J.BIOMATERIALS.2013.11.009}, DOI={10.1016/J.BIOMATERIALS.2013.11.009}, abstractNote={The integration of biological extracellular matrix (ECM) components and synthetic materials is a promising pathway to fabricate the next generation of hydrogel-based tissue scaffolds that more accurately emulate the microscale heterogeneity of natural ECM. We report the development of a bio/synthetic interpenetrating network (BioSINx), containing gelatin methacrylamide (GelMA) polymerized within a poly(ethylene glycol) (PEG) framework to form a mechanically robust network capable of supporting both internal cell encapsulation and surface cell adherence. The covalently crosslinked PEG network was formed by thiol-yne coupling, while the bioactive GelMA was integrated using a concurrent thiol-ene coupling reaction. The physical properties (i.e. swelling, modulus) of BioSINx were compared to both PEG networks with physically-incorporated gelatin (BioSINP) and homogenous hydrogels. BioSINx displayed superior physical properties and significantly lower gelatin dissolution. These benefits led to enhanced cytocompatibility for both cell adhesion and encapsulation; furthermore, the increased physical strength provided for the generation of a micro-engineered tissue scaffold. Endothelial cells showed extensive cytoplasmic spreading and the formation of cellular adhesion sites when cultured onto BioSINx; moreover, both encapsulated and adherent cells showed sustained viability and proliferation.}, number={6}, journal={Biomaterials}, publisher={Elsevier BV}, author={Daniele, Michael A. and Adams, André A. and Naciri, Jawad and North, Stella H. and Ligler, Frances S.}, year={2014}, month={Feb}, pages={1845–1856} }
 @article{boyd_adams_daniele_ligler_2014, title={Microfluidic Fabrication of Polymeric and Biohybrid Fibers with Predesigned Size and Shape}, ISSN={["1940-087X"]}, DOI={10.3791/50958}, abstractNote={A “sheath” fluid passing through a microfluidic channel at low Reynolds number can be directed around another “core” stream and used to dictate the shape as well as the diameter of a core stream. Grooves in the top and bottom of a microfluidic channel were designed to direct the sheath fluid and shape the core fluid. By matching the viscosity and hydrophilicity of the sheath and core fluids, the interfacial effects are minimized and complex fluid shapes can be formed. Controlling the relative flow rates of the sheath and core fluids determines the cross-sectional area of the core fluid. Fibers have been produced with sizes ranging from 300 nm to ~1 mm, and fiber cross-sections can be round, flat, square, or complex as in the case with double anchor fibers. Polymerization of the core fluid downstream from the shaping region solidifies the fibers. Photoinitiated click chemistries are well suited for rapid polymerization of the core fluid by irradiation with ultraviolet light. Fibers with a wide variety of shapes have been produced from a list of polymers including liquid crystals, poly(methylmethacrylate), thiol-ene and thiol-yne resins, polyethylene glycol, and hydrogel derivatives. Minimal shear during the shaping process and mild polymerization conditions also makes the fabrication process well suited for encapsulation of cells and other biological components.}, number={83}, journal={JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, author={Boyd, Darryl A. and Adams, Andre A. and Daniele, Michael A. and Ligler, Frances S.}, year={2014}, month={Jan} }
 @article{daniele_boyd_adams_ligler_2014, title={Microfluidic Strategies for Design and Assembly of Microfibers and Nanofibers with Tissue Engineering and Regenerative Medicine Applications}, volume={4}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201400144}, DOI={10.1002/ADHM.201400144}, abstractNote={Fiber‐based materials provide critical capabilities for biomedical applications. Microfluidic fiber fabrication has recently emerged as a very promising route to the synthesis of polymeric fibers at the micro and nanoscale, providing fine control over fiber shape, size, chemical anisotropy, and biological activity. This Progress Report summarizes advanced microfluidic methods for the fabrication of both microscale and nanoscale fibers and illustrates how different methods are enabling new biomedical applications. Microfluidic fabrication methods and resultant materials are explained from the perspective of their microfluidic device principles, including co‐flow, cross‐flow, and flow‐shaping designs. It is then detailed how the microchannel design and flow parameters influence the variety of synthesis chemistries that can be utilized. Finally, the integration of biomaterials and microfluidic strategies is discussed to manufacture unique fiber‐based systems, including cell scaffolds, cell encapsulation, and woven tissue matrices.}, number={1}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Daniele, Michael A. and Boyd, Darryl A. and Adams, André A. and Ligler, Frances S.}, year={2014}, month={May}, pages={11–28} }
 @article{daniele_radom_ligler_adams_2014, title={Microfluidic fabrication of multiaxial microvessels via hydrodynamic shaping}, volume={4}, ISSN={2046-2069}, url={http://dx.doi.org/10.1039/C4RA03667K}, DOI={10.1039/c4ra03667k}, abstractNote={Fabrication of small, hydrogel microvessels (radii <250 um) through hydrodynamic shaping and photoinitiated polymerization is demonstrated. Photopolymerized hydrogel microvessels were produced and examined. The process is modular and amenable to generating an array of microvessel sizes and shapes.}, number={45}, journal={RSC Adv.}, publisher={Royal Society of Chemistry (RSC)}, author={Daniele, Michael A. and Radom, Kathryn and Ligler, Frances S. and Adams, André A.}, year={2014}, pages={23440–23446} }
 @misc{neupane_ligler_wang_2014, title={Review of recent developments in stimulated emission depletion microscopy: Applications on cell imaging}, volume={19}, number={8}, journal={Journal of Biomedical Optics}, author={Neupane, B. and Ligler, F. S. and Wang, G. F.}, year={2014} }
 @article{lu_mo_tai_sun_pacardo_qian_shen_ligler_gu_2014, title={Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc07004f}, abstractNote={Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.}, number={95}, journal={CHEMICAL COMMUNICATIONS}, author={Lu, Yue and Mo, Ran and Tai, Wanyi and Sun, Wujin and Pacardo, Dennis B. and Qian, Chenggen and Shen, Qundong and Ligler, Frances S. and Gu, Zhen}, year={2014}, pages={15105–15108} }
 @article{boyd_bezares_pacardo_ukaegbu_hosten_ligler_2014, title={Small-Molecule Detection in Thiol-Yne Nanocomposites via Surface-Enhanced Raman Spectroscopy}, volume={86}, ISSN={["1520-6882"]}, DOI={10.1021/ac503607b}, abstractNote={Surface-enhanced Raman spectroscopy (SERS) is generally performed on planar surfaces, which can be difficult to prepare and may limit the interaction of the sensing surface with targets in large volume samples. We propose that nanocomposite materials can be configured that both include SERS probes and provide a high surface area-to-volume format, i.e., fibers. Thiol-yne nanocomposite films and fibers were fabricated using exposure to long-wave ultraviolet light after the inclusion of gold nanoparticles (AuNPs) functionalized with thiophenol. A SERS response was observed that was proportional to the aggregation of the AuNPs within the polymers and the amount of thiophenol present. Overall, this proof-of-concept fabrication of SERS active polymers indicated that thiol-yne nanocomposites may be useful as durable film or fiber SERS probes. Properties of the nanocomposites were evaluated using various techniques including UV-vis spectroscopy, μ-Raman spectroscopy, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, and transmission electron microscopy.}, number={24}, journal={ANALYTICAL CHEMISTRY}, author={Boyd, Darryl A. and Bezares, Francisco J. and Pacardo, Dennis B. and Ukaegbu, Maraizu and Hosten, Charles and Ligler, Frances S.}, year={2014}, month={Dec}, pages={12315–12320} }
 @article{golden_verbarg_howell_shriver-lake_ligler_2013, title={Automated processing integrated with a microflow cytometer for pathogen detection in clinical matrices}, volume={40}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2012.08.015}, DOI={10.1016/j.bios.2012.08.015}, abstractNote={A spinning magnetic trap (MagTrap) for automated sample processing was integrated with a microflow cytometer capable of simultaneously detecting multiple targets to provide an automated sample-to-answer diagnosis in 40 min. After target capture on fluorescently coded magnetic microspheres, the magnetic trap automatically concentrated the fluorescently coded microspheres, separated the captured target from the sample matrix, and exposed the bound target sequentially to biotinylated tracer molecules and streptavidin-labeled phycoerythrin. The concentrated microspheres were then hydrodynamically focused in a microflow cytometer capable of 4-color analysis (two wavelengths for microsphere identification, one for light scatter to discriminate single microspheres and one for phycoerythrin bound to the target). A three-fold decrease in sample preparation time and an improved detection limit, independent of target preconcentration, was demonstrated for detection of Escherichia coli 0157:H7 using the MagTrap as compared to manual processing. Simultaneous analysis of positive and negative controls, along with the assay reagents specific for the target, was used to obtain dose-response curves, demonstrating the potential for quantification of pathogen load in buffer and serum.}, number={1}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Golden, J.P. and Verbarg, J. and Howell, P.B., Jr. and Shriver-Lake, L.C. and Ligler, F.S.}, year={2013}, month={Feb}, pages={10–16} }
 @article{verbarg_plath_shriver-lake_howell_erickson_golden_ligler_2013, title={Catch and Release: Integrated System for Multiplexed Detection of Bacteria}, volume={85}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/AC303801V}, DOI={10.1021/AC303801V}, abstractNote={An integrated system with automated immunomagnetic separation and processing of fluidic samples was demonstrated for multiplexed optical detection of bacterial targets. Mixtures of target-specific magnetic bead sets were processed in the NRL MagTrap with the aid of rotating magnet arrays that entrapped and moved the beads within the channel during reagent processing. Processing was performed in buffer and human serum matrixes with 10-fold dilutions in the range of 10(2)-10(6) cells/mL of target bacteria. Reversal of magnets' rotation post-processing released the beads back into the flow and moved them into the microflow cytometer for optical interrogation. Identification of the beads and the detection of PE fluorescence were performed simultaneously for multiplexed detection. Multiplexing was performed with specifically targeted bead sets to detect E. coli 0157.H7, Salmonella Common Structural Antigen, Listeria sp., and Shigella sp., dose-response curves were obtained, and limits of detection were calculated for each target in the buffer and clinical matrix. Additional tests demonstrated the potential for using the MagTrap to concentrate target from larger volumes of sample prior to the addition of assay reagents.}, number={10}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Verbarg, Jasenka and Plath, William D. and Shriver-Lake, Lisa C. and Howell, Peter B., Jr. and Erickson, Jeffrey S. and Golden, Joel P. and Ligler, Frances S.}, year={2013}, month={Apr}, pages={4944–4950} }
 @article{mcewen_ligler_swager_2013, title={Chemical and biological detection}, volume={42}, ISSN={["1460-4744"]}, DOI={10.1039/c3cs90078a}, abstractNote={A graphical abstract is available for this content}, number={22}, journal={CHEMICAL SOCIETY REVIEWS}, author={McEwen, Charles N. and Ligler, Frances S. and Swager, Timothy M.}, year={2013}, pages={8581–8583} }
 @article{boyd_shields_howell_ligler_2013, title={Design and fabrication of uniquely shaped thiol–ene microfibers using a two-stage hydrodynamic focusing design}, volume={13}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/C3LC50413A}, DOI={10.1039/C3LC50413A}, abstractNote={Microfluidic systems have advantages that are just starting to be realized for materials fabrication. In addition to the more common use for fabrication of particles, hydrodynamic focusing has been used to fabricate continuous polymer fibers. We have previously described such a microfluidics system which has the ability to generate fibers with controlled cross-sectional shapes locked in place by in situ photopolymerization. The previous fiber fabrication studies produced relatively simple round or ribbon shapes, demonstrated the use of a variety of polymers, and described the interaction between sheath-core flow-rate ratios used to control the fiber diameter and the impact on possible shapes. These papers documented the fact that no matter what the intended shape, higher flow-rate ratios produced rounder fibers, even in the absence of interfacial tension between the core and sheath fluids. This work describes how to fabricate the next generation of fibers predesigned to have a much more complex geometry, as exemplified by the "double anchor" shape. Critical to production of the pre-specified fibers with complex features was independent control over both the shape and the size of the fabricated microfibers using a two-stage hydrodynamic focusing system. Design and optimization of the channels was performed using finite element simulations and confocal imaging to characterize each of the two stages theoretically and experimentally. The resulting device design was then used to generate thiol-ene fibers with a unique double anchor shape. Finally, proof-of-principle functional experiments demonstrated the ability of the fibers to transport fluids and to interlock laterally.}, number={15}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Boyd, Darryl A. and Shields, Adam R. and Howell, Peter B. and Ligler, Frances S.}, year={2013}, pages={3105} }
 @article{daniele_north_naciri_howell_foulger_ligler_adams_2013, title={Microfabrication: Rapid and Continuous Hydrodynamically Controlled Fabrication of Biohybrid Microfibers (Adv. Funct. Mater. 6/2013)}, volume={23}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/ADFM.201370031}, DOI={10.1002/ADFM.201370031}, abstractNote={Hydrodynamic shaping is used as a versatile method for the in situ encapsulation of bacteria in microfibers. On page 698 André A. Adams and co-workers report the production of biohybrid microfibers by hydrodynamic shaping of a cell-containing pre-gel and inert sheath fluid, subsequently polymerized via photoinitiation.}, number={6}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Daniele, Michael A. and North, Stella H. and Naciri, Jawad and Howell, Peter B. and Foulger, Stephen H. and Ligler, Frances S. and Adams, André A.}, year={2013}, month={Feb}, pages={697–697} }
 @article{ligler_white_2013, title={Nanomaterials in Analytical Chemistry}, volume={85}, ISSN={["1520-6882"]}, DOI={10.1021/ac403331m}, abstractNote={ADVERTISEMENT RETURN TO ISSUEEditorialNEXTNanomaterials in Analytical ChemistryFrances S. Ligler† and Henry S. White‡View Author Information† Biomedical Engineering Department, North Carolina State University and University of North Carolina at Chapel Hill‡ Department of Chemistry, The University of UtahCite this: Anal. Chem. 2013, 85, 23, 11161–11162Publication Date (Web):December 3, 2013Publication History Published online3 December 2013Published inissue 3 December 2013https://pubs.acs.org/doi/10.1021/ac403331mhttps://doi.org/10.1021/ac403331meditorialACS PublicationsCopyright © 2013 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views6080Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (121 KB) Get e-AlertscloseSUBJECTS:Genetics,Metal nanoparticles,Nanomaterials,Nanoparticles,Plasmonic nanoparticles Get e-Alerts}, number={23}, journal={ANALYTICAL CHEMISTRY}, author={Ligler, Frances S. and White, Henry S.}, year={2013}, month={Dec}, pages={11161–11162} }
 @article{shriver-lake_golden_bracaglia_ligler_2013, title={Simultaneous assay for ten bacteria and toxins in spiked clinical samples using a microflow cytometer}, volume={405}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-013-6980-4}, DOI={10.1007/S00216-013-6980-4}, abstractNote={Bacterial infection and intoxication can present with common symptoms. The ability to identify a bacteria or toxin rapidly in clinical samples is critical for administering the appropriate treatment. The microflow cytometer has previously demonstrated the ability to test for six bacteria and toxins simultaneously in buffer. In this study, the number of bacteria and toxins analyzed was increased to ten, positive and negative controls were incorporated in all assays, and most importantly, multiplexed immunoassays were demonstrated in clinical matrices. The multiplexed assays using the microflow cytometer demonstrated detection limits similar to or better than other reported antibody-based methods for pathogen detection (ELISA, lateral flow, array biosensors). In most cases, detection from complex clinical matrices (serum and nasal wash) achieved limits of detection equivalent to those for spiked buffer samples. Clinical samples spiked with bacteria and/or toxins were also analyzed successfully in blind trials.}, number={16}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Shriver-Lake, Lisa C. and Golden, Joel and Bracaglia, Laura and Ligler, Frances S.}, year={2013}, month={May}, pages={5611–5614} }
 @article{boyd_shields_naciri_ligler_2012, title={Hydrodynamic Shaping, Polymerization, and Subsequent Modification of Thiol Click Fibers}, volume={5}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/am3022834}, DOI={10.1021/am3022834}, abstractNote={Hydrodynamic focusing in microfluidic channels is used to produce highly uniform, shaped polymer fibers at room temperature and under "green" conditions. Core streams of thiol-ene and thiol-yne prepolymer solutions were guided using a phase-matched sheath stream through microfluidic channels with grooved walls to determine shape. Size was dictated by the ratio of the flow rates of the core and sheath streams. Thiol click reactions were initiated using UV illumination to lock in predesigned cross-sectional shapes and sizes. This approach proved to be much more flexible than electrospinning in that highly uniform fibers can be produced from prepolymer solutions with varying compositions and viscosities with made-to-order sizes and shapes. Furthermore, a very simple manipulation of the composition provided reactive groups on the fiber surface for attachment of active ligands and biological components. A proof-of-principle experiment demonstrated that biotin attached to thiol groups on the fiber surface could specifically bind a fluorescent protein.}, number={1}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Boyd, Darryl A. and Shields, Adam R. and Naciri, Jawad and Ligler, Frances S.}, year={2012}, month={Dec}, pages={114–119} }
 @article{justin_denisin_nasir_shriver-lake_golden_ligler_2012, title={Hydrodynamic focusing for impedance-based detection of specifically bound microparticles and cells: Implications of fluid dynamics on tunable sensitivity}, volume={166-167}, ISSN={0925-4005}, url={http://dx.doi.org/10.1016/j.snb.2012.02.077}, DOI={10.1016/j.snb.2012.02.077}, abstractNote={A 4-electrode impedance-based microfluidic sensor was designed to achieve tunable sensitivity, while simultaneously decreasing the channel clogging and nonspecific binding that often adversely impact device function. Hydrodynamic focusing – a characteristic of laminar flow at low Reynold's number – provides highly controllable sensitivity in impedance-based microfluidic biosensors, by creating a "virtual" microchannel with soft walls and adjustable dimensions. Enhanced sensitivity, limited nonspecific binding, and a reduction in microchannel clogging have been achieved using hydrodynamic focusing within a 250 μm deep by 1 mm wide microchannel. The microfluidic sensor was able to detect microparticles as small as 5 μm in diameter specifically bound between co-planar platinum micro-electrodes. However, detection of submicron particles and E. coli cells in similar fashion proved to be challenging. A theoretical analysis of forces exerted by the fluids within the microchannel allowed specification of flow rates amenable to decreased nonspecific binding of interfering cells or microparticles, while ensuring minimal disruption to specifically bound targets. Simulations revealed that complex flow behavior of the hydrodynamically focused streams around specifically bound micron-sized particles reduces sensitivity. An improved understanding is thus presented of the parameters that impact the sensitivity of impedance-based biosensors implementing hydrodynamic focusing and specific target binding.}, journal={Sensors and Actuators B: Chemical}, publisher={Elsevier BV}, author={Justin, Gusphyl A. and Denisin, Aleksandra K. and Nasir, Mansoor and Shriver-Lake, Lisa C. and Golden, Joel P. and Ligler, Frances S.}, year={2012}, month={May}, pages={386–393} }
 @article{shields_spillmann_naciri_howell_thangawng_ligler_2012, title={Hydrodynamically directed multiscale assembly of shaped polymer fibers}, volume={8}, ISSN={1744-683X 1744-6848}, url={http://dx.doi.org/10.1039/c2sm07429j}, DOI={10.1039/c2sm07429j}, abstractNote={A long-sought goal of material science is the development of fabrication processes by which synthetic materials can be made to mimic the multiscale organization many natural materials utilize to achieve unique functional and material properties. Here we demonstrate how the microfluidic fabrication of polymer fibers can take advantage of hydrodynamic forces to simultaneously direct assembly at the molecular and micron scales. The microfluidic device generates long fibers by initiating polymerization of a continuously flowing fluid via UV irradiation within the microfluidic channel. Prior to polymerization, hydrodynamic shear forces direct molecular scale assembly and a combination of hydrodynamic focusing and advection driven by grooves in the channel walls manipulate the cross-sectional shape of the pre-polymer stream. Polymerization subsequently locks in both molecular scale alignment and micron-scale fiber shape. This simple method for generating structures with multiscale organization could be useful for fabricating materials with multifunctionality or enhanced mechanical properties.}, number={24}, journal={Soft Matter}, publisher={Royal Society of Chemistry (RSC)}, author={Shields, Adam R. and Spillmann, Christopher M. and Naciri, Jawad and Howell, Peter B. and Thangawng, Abel L. and Ligler, Frances S.}, year={2012}, pages={6656} }
 @article{daniele_north_naciri_howell_foulger_ligler_adams_2012, title={Rapid and Continuous Hydrodynamically Controlled Fabrication of Biohybrid Microfibers}, volume={23}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/adfm.201202258}, DOI={10.1002/adfm.201202258}, abstractNote={Abstract}, number={6}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Daniele, Michael A. and North, Stella H. and Naciri, Jawad and Howell, Peter B. and Foulger, Stephen H. and Ligler, Frances S. and Adams, André A.}, year={2012}, month={Sep}, pages={698–704} }
 @article{verbarg_kamgar-parsi_shields_howell_ligler_2012, title={Spinning magnetic trap for automated microfluidic assay systems}, volume={12}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/c2lc21189k}, DOI={10.1039/c2lc21189k}, abstractNote={While sophisticated analyses have been performed using lab-on-chip devices, in most cases the sample preparation is still performed off chip. The global need for easy-to-use, disposable testing devices necessitates that sample processing is automated and that transport complexity between the processing and analytical components is minimal. We describe a complete sample manipulation unit for performing automated target capture, efficient mixing with reagents, and controlled target release in a microfluidic channel, using an array of spinning magnets. The "MagTrap" device consists of 6 pairs of magnets in a rotating wheel, situated immediately beneath the microchannel. Rotation of the wheel in the direction opposite to the continuous flow entraps and concentrates the bead-target complexes and separates them from the original sample matrix. As the wheel rotates and the active pair of magnets moves away from the microchannel, the beads are released and briefly flow downstream before being trapped and pulled upstream by the next pair of magnets. This dynamic and continuous movement of the beads ensures that the full surface area of each bead is exposed to reagents and prevents aggregation. The release of the target-bead complexes for further analysis is facilitated by reversing the rotational direction of the wheel to sweep the beads downstream. Sample processing with the MagTrap was demonstrated for the detection of E. coli in a range of concentrations (1 × 10(3), 1 × 10(4) and 1 × 10(6) cells ml(-1)). Results show that sample processing with the MagTrap outperformed the standard manual protocols, improving the detection capability while simultaneously reducing the processing time.}, number={10}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Verbarg, Jasenka and Kamgar-Parsi, Kian and Shields, Adam R. and Howell, Peter B. and Ligler, Frances S.}, year={2012}, pages={1793} }
 @article{justin_nasir_ligler_2011, title={Erratum to: Hydrodynamic and electrical considerations in the design of a four-electrode impedance-based microfluidic device}, volume={400}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-011-5011-6}, DOI={10.1007/S00216-011-5011-6}, number={9}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Justin, Gusphyl and Nasir, Mansoor and Ligler, Frances S.}, year={2011}, month={May}, pages={3177–3177} }
 @article{justin_nasir_ligler_2011, title={Hydrodynamic and electrical considerations in the design of a four-electrode impedance-based microfluidic device}, volume={400}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-011-4872-Z}, DOI={10.1007/S00216-011-4872-Z}, abstractNote={A four-electrode impedance-based microfluidic device has been designed with tunable sensitivity for future applications to the detection of pathogens and functionalized microparticles specifically bound to molecular recognition molecules on the surface of a microfluidic channel. In order to achieve tunable sensitivity, hydrodynamic focusing was employed to confine the electric current by simultaneous introduction of two fluids (high- and low-conductivity solutions) into a microchannel at variable flow-rate ratios. By increasing the volumetric flow rate of the low-conductivity solution (sheath fluid) relative to the high-conductivity solution (sample fluid), increased focusing of the high-conductivity solution over four coplanar electrodes was achieved, thereby confining the current during impedance interrogation. The hydrodynamic and electrical properties of the device were analyzed for optimization and to resolve issues that would impact sensitivity and reproducibility in subsequent biosensor applications. These include variability in the relative flow rates of the sheath and sample fluids, changes in microchannel dimensions, and ionic concentration of the sample fluid. A comparative analysis of impedance measurements using four-electrode versus two-electrode configurations for impedance measurements also highlighted the advantages of using four electrodes for portable sensor applications.}, number={5}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Justin, Gusphyl and Nasir, Mansoor and Ligler, Frances S.}, year={2011}, month={Mar}, pages={1347–1358} }
 @article{golden_justin_nasir_ligler_2011, title={Hydrodynamic focusing—a versatile tool}, volume={402}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-011-5415-3}, DOI={10.1007/S00216-011-5415-3}, abstractNote={The control of hydrodynamic focusing in a microchannel has inspired new approaches for microfluidic mixing, separations, sensors, cell analysis, and microfabrication. Achieving a flat interface between the focusing and focused fluids is dependent on Reynolds number and device geometry, and many hydrodynamic focusing systems can benefit from this understanding. For applications where a specific cross-sectional shape is desired for the focused flow, advection generated by grooved structures in the channel walls can be used to define the shape of the focused flow. Relative flow rates of the focused flow and focusing streams can be manipulated to control the cross-sectional area of the focused flows. This paper discusses the principles for defining the shape of the interface between the focused and focusing fluids and provides examples from our lab that use hydrodynamic focusing for impedance-based sensors, flow cytometry, and microfabrication to illustrate the breadth of opportunities for introducing new capabilities into microfluidic systems. We evaluate each example for the advantages and limitations integral to utilization of hydrodynamic focusing for that particular application.}, number={1}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Golden, Joel P. and Justin, Gusphyl A. and Nasir, Mansoor and Ligler, Frances S.}, year={2011}, month={Sep}, pages={325–335} }
 @article{erickson_hashemi_sullivan_weidemann_ligler_2011, title={In SituPhytoplankton Analysis: There’s Plenty of Room at the Bottom}, volume={84}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac201623k}, DOI={10.1021/ac201623k}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTIn Situ Phytoplankton Analysis: There’s Plenty of Room at the BottomJeffrey S. Erickson†, Nastaran Hashemi†, James M. Sullivan‡, Alan D. Weidemann§, and Frances S. Ligler*†View Author Information† Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Code 6900, Washington, D.C. 20375-5438, United States ‡ WET Laboratories, Inc., Department of Research, 70 Dean Knauss Drive, Narragansett, Rhode Island 02882, United States § Hydro-Optics, Sensors, and Systems Section, Naval Research Laboratory, Code 7333, Stennis Space Center, Mississippi 39529-5004, United States *E-mail: [email protected]Cite this: Anal. Chem. 2012, 84, 2, 839–850Publication Date (Web):July 14, 2011Publication History Received24 June 2011Published online26 September 2011Published inissue 17 January 2012https://doi.org/10.1021/ac201623kCopyright © 2011 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2061Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (6 MB) Get e-AlertsSUBJECTS:Dyes and pigments,Fluorescence,Light,Mathematical methods,Microscopy Get e-Alerts}, number={2}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Erickson, Jeffrey S. and Hashemi, Nastaran and Sullivan, James M. and Weidemann, Alan D. and Ligler, Frances S.}, year={2011}, month={Sep}, pages={839–850} }
 @article{hashemi_erickson_golden_jackson_ligler_2011, title={Microflow Cytometer for optical analysis of phytoplankton}, volume={26}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2011.03.042}, DOI={10.1016/j.bios.2011.03.042}, abstractNote={Analysis of the intrinsic fluorescence profiles of individual marine algae can be used in general classification of organisms based on cell size and fluorescence properties. We describe the design and fabrication of a Microflow Cytometer on a chip for characterization of phytoplankton. The Microflow Cytometer measured distinct side scatter and fluorescence properties of Synechococcus sp., Nitzschia d., and Thalassiosira p.; measurements were confirmed using the benchtop Accuri C6 flow cytometer. The Microflow Cytometer proved sensitive enough to detect and characterize picoplankton with diameter approximately 1 μm and larger phytoplankton of up to 80 μm in length. The wide range in size discrimination coupled with detection of intrinsic fluorescent pigments suggests that this Microflow Cytometer will be able to distinguish different populations of phytoplankton on unmanned underwater vehicles.}, number={11}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Hashemi, Nastaran and Erickson, Jeffrey S. and Golden, Joel P. and Jackson, Kirsten M. and Ligler, Frances S.}, year={2011}, month={Jul}, pages={4263–4269} }
 @article{smith_sapsford_tan_ligler_2011, title={Optimization of antibody-conjugated magnetic nanoparticles for target preconcentration and immunoassays}, volume={410}, ISSN={0003-2697}, url={http://dx.doi.org/10.1016/j.ab.2010.11.005}, DOI={10.1016/j.ab.2010.11.005}, abstractNote={Biosensors based on antibody recognition have a wide range of monitoring applications that apply to clinical, environmental, homeland security, and food problems. In an effort to improve the limit of detection of the Naval Research Laboratory (NRL) Array Biosensor, magnetic nanoparticles (MNPs) were designed and tested using a fluorescence-based array biosensor. The MNPs were coated with the fluorescently labeled protein, AlexaFluor647-chicken IgG (Alexa647-chick IgG). Antibody-labeled MNPs (Alexa647-chick-MNPs) were used to preconcentrate the target via magnetic separation and as the tracer to demonstrate binding to slides modified with anti-chicken IgG as a capture agent. A full optimization study of the antibody-modified MNPs and their use in the biosensor was performed. This investigation looked at the Alexa647-chick-MNP composition, MNP surface modifications, target preconcentration conditions, and the effect that magnetic extraction has on the Alexa647-chick-MNP binding with the array surface. The results demonstrate the impact of magnetic extraction using the MNPs labeled with fluorescent proteins both for target preconcentration and for subsequent integration into immunoassays performed under flow conditions for enhanced signal generation.}, number={1}, journal={Analytical Biochemistry}, publisher={Elsevier BV}, author={Smith, Joshua E. and Sapsford, Kim E. and Tan, Weihong and Ligler, Frances S.}, year={2011}, month={Mar}, pages={124–132} }
 @article{hashemi_erickson_golden_ligler_2011, title={Optofluidic characterization of marine algae using a microflow cytometer}, volume={5}, ISSN={1932-1058}, url={http://dx.doi.org/10.1063/1.3608136}, DOI={10.1063/1.3608136}, abstractNote={The effects of global warming, pollution in river effluents, and changing ocean currents can be studied by characterizing variations in phytoplankton populations. We demonstrate the design and fabrication of a Microflow Cytometer for characterization of phytoplankton. Guided by chevron-shaped grooves on the top and bottom of a microfluidic channel, two symmetric sheath streams wrap around a central sample stream and hydrodynamically focus it in the center of the channel. The lasers are carefully chosen to provide excitation light close to the maximum absorbance wavelengths for the intrinsic fluorophores chlorophyll and phycoerythrin, and the excitation light is coupled to the flow cytometer through the use of an optical fiber. Fluorescence and light scatter are collected using two multimode optical fibers placed at 90-degree angles with respect to the excitation fiber. Light emerging from these collection fibers is directed through optical bandpass filters into photomultiplier tubes. The cytometer measured the optical and side scatter properties of Karenia b., Synechococcus sp., Pseudo-Nitzchia, and Alexandrium. The effect of the sheath-to-sample flow-rate ratio on the light scatter and fluorescence of these marine microorganisms was investigated. Reducing the sample flow rate from 200 μL/min to 10 μL/min produced a more tightly focused sample stream and less heterogeneous signals.}, number={3}, journal={Biomicrofluidics}, publisher={AIP Publishing}, author={Hashemi, Nastaran and Erickson, Jeffrey S. and Golden, Joel P. and Ligler, Frances S.}, year={2011}, month={Sep}, pages={032009} }
 @article{nasir_mott_kennedy_golden_ligler_2011, title={Parameters affecting the shape of a hydrodynamically focused stream}, volume={11}, ISSN={1613-4982 1613-4990}, url={http://dx.doi.org/10.1007/S10404-011-0778-5}, DOI={10.1007/S10404-011-0778-5}, number={2}, journal={Microfluidics and Nanofluidics}, publisher={Springer Science and Business Media LLC}, author={Nasir, Mansoor and Mott, David R. and Kennedy, Matthew J. and Golden, Joel P. and Ligler, Frances S.}, year={2011}, month={Feb}, pages={119–128} }
 @article{thangawng_howell, jr_spillmann_naciri_ligler_2011, title={UV polymerization of hydrodynamically shaped fibers}, volume={11}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/c0lc00392a}, DOI={10.1039/c0lc00392a}, abstractNote={Most natural and man-made fibers have circular cross-sections; thus the properties of materials composed of non-circular fibers are largely unexplored. We demonstrate the technology for fabricating fibers with predetermined cross-sectional shape. Passive hydrodynamic focusing and UV polymerization of a shaped acrylate stream produced metre-long fibers for structural and mechanical characterization.}, number={6}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Thangawng, Abel L. and Howell, Jr, Peter B. and Spillmann, Christopher M. and Naciri, Jawad and Ligler, Frances S.}, year={2011}, pages={1157} }
 @article{thangawng_kim_golden_anderson_robertson_low_ligler_2010, title={A hard microflow cytometer using groove-generated sheath flow for multiplexed bead and cell assays}, volume={398}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-010-4019-7}, DOI={10.1007/S00216-010-4019-7}, abstractNote={With a view toward developing a rugged microflow cytometer, a sheath flow system was micromachined in hard plastic (polymethylmethacrylate) for analysis of particles and cells using optical detection. Six optical fibers were incorporated into the interrogation region of the chip, in which hydrodynamic focusing narrowed the core stream to ~35 μm × 40 μm. The use of a relatively large channel at the inlet as well as in the interrogation region (375 μm × 125 μm) successfully minimized the risk of clogging. The device could withstand pressures greater than 100 psi without leaking. Assays using both coded microparticles and cells were demonstrated using the microflow cytometer. Multiplexed immunoassays detected nine different bacteria and toxins using a single mixture of coded microspheres. A549 cancer cells processed with locked nucleic acid probes were evaluated using fluorescence in situ hybridization.}, number={5}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Thangawng, Abel L. and Kim, Jason S. and Golden, Joel P. and Anderson, George P. and Robertson, Kelly L. and Low, Vyechi and Ligler, Frances S.}, year={2010}, month={Jul}, pages={1871–1881} }
 @article{hashemi_howell, jr._erickson_golden_ligler_2010, title={Dynamic reversibility of hydrodynamic focusing for recycling sheath fluid}, volume={10}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/c004696e}, DOI={10.1039/c004696e}, abstractNote={The phenomenon of "unmixing" has been demonstrated in microfluidic mixers, but here we manipulate laminar flow streams back to their original positions in order to extend the operational utility of an analytical device where no mixing is desired. Using grooves in the channel wall, we passively focus a sample stream with two sheath streams to center it in a microchannel for optical analysis. Even though the sample stream is completely surrounded by sheath fluid, reversing the orientation of the grooves in the channel walls returns the sample stream to its original position with respect to the sheath streams. We demonstrate the separation of the sample stream from the contiguous sheath streams and the recycling of the sheath fluid using the reversibility of laminar flow. Polystyrene microspheres and fluorescent dye were used to quantify the performance of the unsheathing process. We found that the maximum numbers of microspheres and all of the fluorescent dye were recaptured at sheath recycling levels <92%. The use of this sheathing technique has previously been demonstrated in a sensitive microflow cytometer; the unsheathing capability now provides the opportunity to recover particles from the sensor with minimal dilution or to recycle the sheath fluid for long-term unattended operation.}, number={15}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Hashemi, Nastaran and Howell, Jr., Peter B. and Erickson, Jeffrey S. and Golden, Joel P. and Ligler, Frances S.}, year={2010}, pages={1952} }
 @article{nasir_price_shriver-lake_ligler_2010, title={Effect of diffusion on impedance measurements in a hydrodynamic flow focusing sensor}, volume={10}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/c005257d}, DOI={10.1039/c005257d}, abstractNote={This paper investigated the effects of diffusion between non-conductive sheath and conductive sample fluids in an impedance-based biosensor. Impedance measurements were made with 2- and 4-electrode configurations. The 4-electrode design offers the advantage of impedance measurements at low frequencies (<1 kHz) without the deleterious effects of double layer impedance which are present in the 2-electrode design. Hydrodynamic flow focusing was achieved with a modified T-junction design with a smaller cross-section for the sample channel than for the focusing channel, which resulted in 2D focusing of the sample stream with just one sheath stream. By choosing a non-conductive sheath fluid and a conductive sample fluid, the electric field was confined to the focused stream. In order to utilize this system for biosensing applications, we characterized it for electrical and flow parameters. In particular, we investigated the effects of varying flow velocities and flow-rate ratios on the focused stream. Increasing flow-rate ratios reduced the cross-sectional area of the focused streams as was verified by finite element modeling and confocal microscopy. Antibody mediated binding of Escherichia coli to the electrode surface caused an increase in solution resistance at low frequencies. The results also showed that the diffusion mass transport at the interface of the two streams limited the benefits of increased flow focusing. Increasing flow velocities could be used to offset the diffusion effect. To optimize detection sensitivity, flow parameters and mass transport must be considered in conjunction, with the goal of reducing diffusion of conducting species out of the focused stream while simultaneously minimizing its cross-sectional area.}, number={20}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Nasir, Mansoor and Price, Dorielle T. and Shriver-Lake, Lisa C. and Ligler, Frances}, year={2010}, pages={2787} }
 @article{nasir_ateya_burk_golden_ligler_2010, title={Hydrodynamic focusing of conducting fluids for conductivity-based biosensors}, volume={25}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2009.10.033}, DOI={10.1016/j.bios.2009.10.033}, abstractNote={Hydrodynamic focusing of a conducting fluid by a non-conducting fluid to form a constricted current path between two sensing electrodes is implemented in order to enhance the sensitivity of a 4-electrode conductance-based biosensor. The sensor has a simple two-inlet T-junction design and performs four-point conductivity measurements to detect particles immobilized between the sensing electrode pair. Computational simulations conducted in conjunction with experimental flow studies using confocal microscopy show that a flat profile for the focused layer is dependent on the Reynolds number for the chosen flow parameters. The results also indicate that a flat focused layer is desirable for both increased sensitivity as well as surface-binding efficiency. Proof of concept for conductance measurements in a hydrodynamically focused conducting fluid was demonstrated with entrapped magnetic beads.}, number={6}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Nasir, Mansoor and Ateya, Daniel A. and Burk, Diana and Golden, Joel P. and Ligler, Frances S.}, year={2010}, month={Feb}, pages={1363–1369} }
 @article{lin_johnson_rubin_malanoski_ligler_2010, title={Iron chelation by cranberry juice and its impact on Escherichia coli growth}, volume={37}, ISSN={0951-6433}, url={http://dx.doi.org/10.1002/biof.110}, DOI={10.1002/biof.110}, abstractNote={Abstract}, number={2}, journal={BioFactors}, publisher={Wiley}, author={Lin, Baochuan and Johnson, Brandy J. and Rubin, Robert A. and Malanoski, Anthony P. and Ligler, Frances S.}, year={2010}, month={Aug}, pages={121–130} }
 @article{kim_taitt_ligler_anderson_2010, title={Multiplexed magnetic microsphere immunoassays for detection of pathogens in foods}, volume={4}, ISSN={1932-7587 1932-9954}, url={http://dx.doi.org/10.1007/S11694-010-9097-X}, DOI={10.1007/S11694-010-9097-X}, abstractNote={Foodstuffs have traditionally been challenging matrices for conducting immunoassays. Proteins, carbohydrates, and other macromolecules present in food matrices may interfere with both immunoassays and PCR-based tests, and removal of particulate matter may also prove challenging prior to analyses. This has been found true when testing for bacterial contamination of foods using the standard polystyrene microspheres utilized with Luminex flow cytometers. Luminex MagPlex microspheres are encoded with the same dyes as standard xMAP microspheres, but have superparamagnetic properties to aid in preparation of samples in complex matrices. In this work, we present results demonstrating use of MagPlex for sample preparation and identification of bacteria and a toxin spiked into a variety of food samples. Fluorescence-coded MagPlex microsphere sets coated with antibodies for Salmonella, Campylobacter, Escherichia coli, Listeria, and staphylococcal enterotoxin B (SEB) were used to capture these bacteria and toxin from spiked foodstuffs and then evaluated by the Luminex system in a multiplex format; spiked foods included apple juice, green pepper, tomato, ground beef, alfalfa sprouts, milk, lettuce, spinach, and chicken washes. Although MagPlex microspheres facilitated recovery of the microspheres and targets from the complex matrices, assay sensitivity was sometimes inhibited by up to one to three orders of magnitude; for example the detection limits E. coli spiked into apple juice or milk increased 100-fold, from 1000 to 100,000 cfu/mL. Thus, while the magnetic and fluorescent properties of the Luminex MagPlex microspheres allow for rapid, multiplexed testing for bacterial contamination in typically problematic food matrices, our data demonstrate that achieving desired limits of detection is still a challenge.}, number={2}, journal={Sensing and Instrumentation for Food Quality and Safety}, publisher={Springer Science and Business Media LLC}, author={Kim, Jason S. and Taitt, Chris R. and Ligler, Frances S. and Anderson, George P.}, year={2010}, month={May}, pages={73–81} }
 @article{kim_ligler_2010, title={Utilization of microparticles in next-generation assays for microflow cytometers}, volume={398}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-010-3848-8}, DOI={10.1007/S00216-010-3848-8}, abstractNote={Micron-sized particles have primarily been used in microfabricated flow cytometers for calibration purposes and proof-of-concept experiments. With increasing frequency, microparticles are serving as a platform for assays measured in these small analytical devices. Light scattering has been used to measure the agglomeration of antibody-coated particles in the presence of an antigen. Impedance detection is another technology being integrated into microflow cytometers for microparticle-based assays. Fluorescence is the most popular detection method in flow cytometry, enabling highly sensitive multiplexed assays. Finally, magnetic particles have also been used to measure antigen levels using a magnetophoretic micro-device. We review the progress of microparticle-based assays in microflow cytometry in terms of the advantages and limitations of each approach.}, number={6}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Kim, Jason S. and Ligler, Frances S.}, year={2010}, month={Jun}, pages={2373–2382} }
 @article{thangawng_howell jr_richards_erickson_ligler_2009, title={A simple sheath-flow microfluidic device for micro/nanomanufacturing: fabrication of hydrodynamically shaped polymer fibers}, volume={9}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b910581f}, DOI={10.1039/b910581f}, abstractNote={A simple sheath flow microfluidic device is used to fabricate polymer micro/nanofibers that have precisely controlled shapes and sizes. Poly(methylmethacrylate) (PMMA) was used as the model polymer for these experiments. The sheath-flow device uses straight diagonal and chevron-shaped grooves integrated in the top and bottom walls of the flow channel to move sheath fluid completely around the polymer stream. Portions of the sheath stream are deflected in such a way as to define the cross-sectional shape of the polymer core. The flow-rate ratio between the sheath and core solution determines the fiber diameter. Round PMMA fibers with a diameter as small as 300 nm and flattened fibers with a submicron thickness are demonstrated.}, number={21}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Thangawng, Abel L. and Howell Jr, Peter B. and Richards, Jeffrey J. and Erickson, Jeffrey S. and Ligler, Frances S.}, year={2009}, pages={3126} }
 @misc{ligler_2009, title={Common and uncommon sense for sensingIntegrated Analytical Systems, R. Poryrailo (Ed.), Springer (2009)}, volume={25}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2009.07.035}, DOI={10.1016/j.bios.2009.07.035}, number={2}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Ligler, Frances S.}, year={2009}, month={Oct}, pages={537} }
 @article{golden_kim_erickson_hilliard_howell_anderson_nasir_ligler_2009, title={Multi-wavelength microflow cytometer using groove-generated sheath flow}, volume={9}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b822442k}, DOI={10.1039/b822442k}, abstractNote={A microflow cytometer was developed that ensheathed the sample (core) fluid on all sides and interrogated each particle in the sample stream at four different wavelengths. Sheathing was achieved by first sandwiching the core fluid with the sheath fluid laterally via fluid focusing. Chevron-shaped groove features fabricated in the top and bottom of the channel directed sheath fluid from the sides to the top and bottom of the channel, completely surrounding the sample stream. Optical fibers inserted into guide channels provided excitation light from diode lasers at 532 and 635 nm and collected the emission wavelengths. Two emission collection fibers were connected to PMTs through a multimode fiber splitter and optical filters for detection at 635 nm (scatter), 665 nm and 700 nm (microsphere identification) and 565 nm (phycoerythrin tracer). The cytometer was capable of discriminating microspheres with different amounts of the fluorophores used for coding and detecting the presence of a phycoerythrin antibody complex on the surface of the microspheres. Assays for Escherichia coli were compared with a commercial Luminex flow cytometer.}, number={13}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Golden, Joel P. and Kim, Jason S. and Erickson, Jeffrey S. and Hilliard, Lisa R. and Howell, Peter B. and Anderson, George P. and Nasir, Mansoor and Ligler, Frances S.}, year={2009}, pages={1942} }
 @article{kim_anderson_erickson_golden_nasir_ligler_2009, title={Multiplexed Detection of Bacteria and Toxins Using a Microflow Cytometer}, volume={81}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac9005827}, DOI={10.1021/ac9005827}, abstractNote={A microfabricated flow cytometer was used to demonstrate multiplexed detection of bacteria and toxins using fluorescent coded microspheres. Antibody-coated microspheres bound biothreat targets in a sandwich immunoassay format. The microfluidic cytometer focused the microspheres in three dimensions within the laser interrogation region using passive groove structures to surround the sample stream with sheath fluid. Optical analysis at four different wavelengths identified the coded microspheres and quantified target bound by the presence of phycoerythrin tracer. The multiplexed assays in the microflow cytometer had performance approaching that of a commercial benchtop flow cytometer. The respective limits of detection for bacteria (Escherichia coli, Listeria, and Salmonella) were found to be 10(3), 10(5), and 10(4) cfu/mL for the microflow cytometer and 10(3), 10(6), and 10(5) cfu/mL for the commercial system. Limits of detection for the toxins (cholera toxin, staphylococcal enterotoxin B, and ricin) were 1.6, 0.064, and 1.6 ng/mL for the microflow cytometer and 1.6, 0.064, and 8.0 ng/mL for the commercial system.}, number={13}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Kim, Jason S. and Anderson, George P. and Erickson, Jeffrey S. and Golden, Joel P. and Nasir, Mansoor and Ligler, Frances S.}, year={2009}, month={Jul}, pages={5426–5432} }
 @article{wojciechowski_shriver-lake_yamaguchi_füreder erwin_pieler_schamesberger_winder_prall hans jürgen_sonnleitner_ligler_2009, title={Organic Photodiodes for Biosensor Miniaturization}, volume={81}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac8027323}, DOI={10.1021/ac8027323}, abstractNote={Biosensors have successfully demonstrated the capability to detect multiple pathogens simultaneously at very low levels. Miniaturization of biosensors is essential for use in the field or at the point of care. While microfluidic systems reduce the footprint for biochemical processing devices and electronic components are continually becoming smaller, optical components suitable for integration--such as LEDs and CMOS chips--are generally still too expensive for disposable components. This paper describes the integration of polymer diodes onto a biosensor chip to create a disposable device that includes both the detector and the sensing surface coated with immobilized capture antibody. We performed a chemiluminescence immunoassay on the OPD substrate and measured the results using a hand-held reader attached to a laptop computer. The miniaturized biosensor with the disposable slide including the organic photodiode detected Staphylococcal enterotoxin B at concentrations as low as 0.5 ng/mL.}, number={9}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Wojciechowski, Jason R. and Shriver-Lake, Lisa C. and Yamaguchi, Mariko Y. and Füreder Erwin and Pieler, Roland and Schamesberger, Martin and Winder, Christoph and Prall Hans Jürgen and Sonnleitner, Max and Ligler, Frances S.}, year={2009}, month={May}, pages={3455–3461} }
 @article{ligler_2009, title={Perspective on Optical Biosensors and Integrated Sensor Systems}, volume={81}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac8016289}, DOI={10.1021/ac8016289}, abstractNote={Optical biosensors have begun to move from the laboratory to the point of use. This trend will be accelerated by new concepts for molecular recognition, integration of microfluidics and optics, simplified fabrication technologies, improved approaches to biosensor system integration, and dramatically increased awareness of the applicability of sensor technology to improve public health and environmental monitoring. Examples of innovations are identified that will lead to smaller, faster, cheaper optical biosensor systems with capacity to provide effective and actionable information.}, number={2}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Ligler, Frances S.}, year={2009}, month={Jan}, pages={519–526} }
 @article{hu_erickson_taitt_lin_ligler_blaney_malanoski_ligler_2008, title={A Parametric Study of Sample Lysis and DNA Purification Techniques for Use in Automated Devices}, volume={41}, ISSN={0003-2719 1532-236X}, url={http://dx.doi.org/10.1080/00032710802162186}, DOI={10.1080/00032710802162186}, abstractNote={Abstract We present a parametric study on the efficiency of several automatable procedures for the extraction and purification of DNA from a variety of pathogens. Based on the results of this work, an optimized protocol has been developed for use with both spiked buffers and nasal wash. All steps of this protocol are suitable for incorporation into a field-portable, automated sample preparation device. From introduction of the sample to elution of DNA, the entire process was completed in less than 60 min, and the time could be reduced further by automation. The recovered DNA is of sufficient quality for real-time or multiplex PCR amplification. The protocol was demonstrated on nasal wash samples spiked with E. coli containing the J7R and crmB genes. Subsequent testing on resequencing microarrays correctly identified the samples as Variola major virus.}, number={10}, journal={Analytical Letters}, publisher={Informa UK Limited}, author={Hu, J. E. and Erickson, J. S. and Taitt, C. R. and Lin, B. and Ligler, A. G. and Blaney, K. M. and Malanoski, A. P. and Ligler, F. S.}, year={2008}, month={Jul}, pages={1701–1719} }
 @article{howell_mott_ligler_golden_kaplan_oran_2008, title={A combinatorial approach to microfluidic mixing}, volume={18}, ISSN={0960-1317 1361-6439}, url={http://dx.doi.org/10.1088/0960-1317/18/11/115019}, DOI={10.1088/0960-1317/18/11/115019}, abstractNote={A new computational approach to the modeling and design of efficient microfluidic mixers is demonstrated. The mixers created provide far more rapid mixing than previous designs. A set of mixer components is created and mapped using a traditional Navier–Stokes fluid solver. The maps are used to quickly model the effect each component has on the lateral distribution of species in the channel. For a mixer of a given length, all the possible combinations of components can be evaluated, and the best mixer for a given metric can be found. Although the mixers presented in this study are short (length-to-width ratios below 8), they show degrees of mixing comparable to much longer mixers found in the literature.}, number={11}, journal={Journal of Micromechanics and Microengineering}, publisher={IOP Publishing}, author={Howell, Peter B, Jr and Mott, David R and Ligler, Frances S and Golden, Joel P and Kaplan, Carolyn R and Oran, Elaine S}, year={2008}, month={Oct}, pages={115019} }
 @article{erickson_ligler_2008, title={Home diagnostics to music}, volume={456}, ISSN={0028-0836 1476-4687}, url={http://dx.doi.org/10.1038/456178a}, DOI={10.1038/456178a}, number={7219}, journal={Nature}, publisher={Springer Science and Business Media LLC}, author={Erickson, Jeffrey S. and Ligler, Frances S.}, year={2008}, month={Nov}, pages={178–179} }
 @article{johnson_delehanty_lin_ligler_2008, title={Immobilized Proanthocyanidins for the Capture of Bacterial Lipopolysaccharides}, volume={80}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac7024128}, DOI={10.1021/ac7024128}, abstractNote={Proanthocyanidins (PACs) are an abundant class of compounds found in a variety of plant materials. Here we demonstrate the application of these materials as capture molecules for the removal of bacterial lipopolysaccharide (LPS) from solution. PACs from whole cranberries, grape juice, black tea, and cranberry juice were purified and immobilized onto thiol-activated Sepharose beads. This material was used in pull-down type assays for the capture of LPS. The binding of LPS by PACs has been shown to compete with that of polymyxin B which is known to bind the lipid A component of LPS. Assays conducted in the presence of lipid A verified that at least some component of the LPS binding activity of the PACs is via the lipid A moiety. Molar comparison of polymyxin B to proanthocyanidins indicated that the Sepharose immobilized PACs have a binding affinity for LPS similar to that of polymyxin B.}, number={6}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Johnson, Brandy J. and Delehanty, James B. and Lin, Baochuan and Ligler, Frances S.}, year={2008}, month={Mar}, pages={2113–2117} }
 @article{johnson_lin_dinderman_rubin_malanoski_ligler_2008, title={Impact of cranberry on Escherichia coli cellular surface characteristics}, volume={377}, ISSN={0006-291X}, url={http://dx.doi.org/10.1016/j.bbrc.2008.10.098}, DOI={10.1016/j.bbrc.2008.10.098}, abstractNote={The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.}, number={3}, journal={Biochemical and Biophysical Research Communications}, publisher={Elsevier BV}, author={Johnson, Brandy J. and Lin, Baochuan and Dinderman, Michael A. and Rubin, Robert A. and Malanoski, Anthony P. and Ligler, Frances S.}, year={2008}, month={Dec}, pages={992–994} }
 @article{ateya_erickson_howell_hilliard_golden_ligler_2008, title={The good, the bad, and the tiny: a review of microflow cytometry}, volume={391}, ISSN={1618-2642 1618-2650}, url={http://dx.doi.org/10.1007/S00216-007-1827-5}, DOI={10.1007/S00216-007-1827-5}, abstractNote={Recent developments in microflow cytometry have concentrated on advancing technology in four main areas: (1) focusing the particles to be analyzed in the microfluidic channel, (2) miniaturization of the fluid-handling components, (3) miniaturization of the optics, and (4) integration and applications development. Strategies for focusing particles in a narrow path as they pass through the detection region include the use of focusing fluids, nozzles, and dielectrophoresis. Strategies for optics range from the use of microscope objectives to polymer waveguides or optical fibers embedded on-chip. While most investigators use off-chip fluidic control, there are a few examples of integrated valves and pumps. To date, demonstrations of applications are primarily used to establish that the microflow systems provide data of the same quality as laboratory systems, but new capabilities—such as automated sample staining—are beginning to emerge. Each of these four areas is discussed in detail in terms of the progress of development, the continuing limitations, and potential future directions for microflow cytometers.}, number={5}, journal={Analytical and Bioanalytical Chemistry}, publisher={Springer Science and Business Media LLC}, author={Ateya, Daniel A. and Erickson, Jeffrey S. and Howell, Peter B., Jr and Hilliard, Lisa R. and Golden, Joel P. and Ligler, Frances S.}, year={2008}, month={Jan}, pages={1485–1498} }
 @article{howell jr_golden_hilliard_erickson_mott_ligler_2008, title={Two simple and rugged designs for creating microfluidic sheath flow}, volume={8}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b719381e}, DOI={10.1039/b719381e}, abstractNote={A simple design capable of 2-dimensional hydrodynamic focusing is proposed and successfully demonstrated. In the past, most microfluidic sheath flow systems have often only confined the sample solution on the sides, leaving the top and bottom of the sample stream in contact with the floor and ceiling of the channel. While relatively simple to build, these designs increase the risk of adsorption of sample components to the top and bottom of the channel. A few designs have been successful in completely sheathing the sample stream, but these typically require multiple sheath inputs and several alignment steps. In the designs presented here, full sheathing is accomplished using as few as one sheath input, which eliminates the need to carefully balance the flow of two or more sheath inlets. The design is easily manufactured using current microfabrication techniques. Furthermore, the sample and sheath fluid can be subsequently separated for recapture of the sample fluid or re-use of the sheath fluid. Designs were demonstrated in poly(dimethylsiloxane) (PDMS) using soft lithography and poly(methyl methacrylate) (PMMA) using micromilling and laser ablation.}, number={7}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Howell Jr, Peter B. and Golden, Joel P. and Hilliard, Lisa R. and Erickson, Jeffrey S. and Mott, David R. and Ligler, Frances S.}, year={2008}, pages={1097} }
 @article{kulagina_shaffer_ligler_taitt_2007, title={Antimicrobial peptides as new recognition molecules for screening challenging species}, volume={121}, ISSN={0925-4005}, url={http://dx.doi.org/10.1016/j.snb.2006.09.044}, DOI={10.1016/j.snb.2006.09.044}, abstractNote={The goal of this study was to evaluate binding of four targets of biodefense interest to immobilized antimicrobial peptides (AMPs) in biosensor assays. Polymyxins B and E, melittin, cecropins A, B, and P, parasin, bactenecin and magainin-1, as well as control antibodies, were used as capture molecules for detection of Cy3-labeled Venezuelan equine encephalitis virus (VEE), vaccinia virus, Coxiella burnetti and Brucella melitensis. Although VEE, vaccinia virus and C. burnetti did not show any binding activity to their corresponding capture antibodies, B. melitensis bound to immobilized anti-Brucella monoclonal antibodies. The majority of the immobilized AMPs included in this study bound labeled VEE, vaccinia virus and C. burnetti in a concentration-dependent manner, and B. melitensis bound to polymyxin B, polymyxin E, and bactenecin. No binding was observed on immobilized magainin-1. In contrast to all bacterial targets tested to date, VEE and vaccinia virus demonstrated similar patterns of binding to all peptides. While the direct assay is generally replaced by a sandwich assay for analysis of real-world samples, direct binding experiments are commonly used to characterize specificity and sensitivity of binding molecules. In this case, they clearly demonstrate the capability of AMPs as recognition molecules for four biothreat agents.}, number={1}, journal={Sensors and Actuators B: Chemical}, publisher={Elsevier BV}, author={Kulagina, N and Shaffer, K and Ligler, F and Taitt, C}, year={2007}, month={Jan}, pages={150–157} }
 @article{erickson_hu_anderson_salls_gray_golden_lin_ligler_2007, title={Automated module for hybridization and staining of commercially produced nucleic acid microarrays}, volume={3}, ISSN={1613-4982 1613-4990}, url={http://dx.doi.org/10.1007/S10404-007-0155-6}, DOI={10.1007/S10404-007-0155-6}, number={5}, journal={Microfluidics and Nanofluidics}, publisher={Springer Science and Business Media LLC}, author={Erickson, J. S. and Hu, J. E. and Anderson, G. P. and Salls, A. C. and Gray, S. A. and Golden, J. P. and Lin, B. and Ligler, F. S.}, year={2007}, month={Feb}, pages={623–628} }
 @article{delehanty_johnson_hickey_pons_ligler_2007, title={Binding and Neutralization of Lipopolysaccharides by Plant Proanthocyanidins}, volume={70}, ISSN={0163-3864 1520-6025}, url={http://dx.doi.org/10.1021/np0703601}, DOI={10.1021/np0703601}, abstractNote={Proanthocyanidins (PACs), polyphenolic metabolites that are widely distributed in higher plants, have been associated with potential positive health benefits including antibacterial, chemotherapeutic, and antiatherosclerotic activities. In this paper, we analyze the binding of PACs from cranberries, tea, and grapes to lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria and the cause of several human illnesses. We demonstrate that in the case of cranberries, the most potent LPS-binding activity is contained within a PAC fraction composed of polymers with an average degree of polymerization of 21. The PAC fraction modestly inhibits the binding of LPS to the surface of HEK 293 cells expressing the full complement of LPS receptors (TLR4/MD2 and CD14), while it significantly abrogates the endocytosis of LPS. This PAC fraction also inhibits LPS-induced nuclear factor-kappaB activation in a manner that is not readily overcome by excess LPS. Such an effect is mediated through the inhibition of LPS interaction with TLR4/MD2 and the partial abrogation of LPS interaction with CD14. Importantly, PAC concentrations that mediate effective LPS neutralization elicit minimal in vitro cytotoxicity. Our results identify PACs as a new class of LPS-binding compound and suggest that they have potential utility in applications that necessitate either the purification and removal of LPS or the in vivo neutralization of LPS.}, number={11}, journal={Journal of Natural Products}, publisher={American Chemical Society (ACS)}, author={Delehanty, James B. and Johnson, Brandy J. and Hickey, Thomas E. and Pons, Thomas and Ligler, Frances S.}, year={2007}, month={Nov}, pages={1718–1724} }
 @article{shriver‐lake_erickson_sapsford_ngundi_shaffer_kulagina_hu_gray_golden_ligler_et al._2007, title={Blind Laboratory Trials for Multiple Pathogens in Spiked Food Matrices}, volume={40}, ISSN={0003-2719 1532-236X}, url={http://dx.doi.org/10.1080/00032710701672798}, DOI={10.1080/00032710701672798}, abstractNote={Abstract Previously developed assays for Salmonella typhimurium and staphylococcal enterotoxin B (SEB) were combined into a single multiplexed test and integrated into a fully automated prototype of the NRL Array Biosensor. Tests were performed on 216 blind samples of water, apple juice, and milk spiked with SEB (1–10,000 pg/ml) and S. typhimurium (5×103−5×107 colony‐forming units/ml). SEB and S. typhimurium were routinely detected in both water and apple juice at 100 pg/ml and 5×105 colony‐forming units/ml respectively. Inclusion of milk as a sample matrix decreased the sensitivity of the assays by an order of magnitude.}, number={17}, journal={Analytical Letters}, publisher={Informa UK Limited}, author={Shriver‐Lake, Lisa C. and Erickson, Jeffrey S. and Sapsford, Kim E. and Ngundi, Miriam M. and Shaffer, Kara M. and Kulagina, Nadezhda V. and Hu, Jenny E. and Gray, Samuel A., III and Golden, Joel P. and Ligler, Frances S. and et al.}, year={2007}, month={Dec}, pages={3219–3231} }
 @article{johnson-white_lin_ligler_2007, title={Combination of Immunosensor Detection with Viability Testing and Confirmation Using the Polymerase Chain Reaction and Culture}, volume={79}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac061229l}, DOI={10.1021/ac061229l}, abstractNote={Rapid and accurate differential determination of viable versus nonviable microbes is critical for formulation of an appropriate response after pathogen detection. Sensors for rapid bacterial identification can be used for applications ranging from environmental monitoring and homeland defense to food process monitoring, but few provide viability information. This study combines the rapid screening capability of the array biosensor using an immunoassay format with methods for determination of viability. Additionally, cells captured by the immobilized antibodies can be cultured following fluorescence imaging to further confirm viability and for cell population expansion for further characterization, e.g., strain identification or antibiotic susceptibility testing. Finally, we demonstrate analysis of captured bacteria using the polymerase chain reaction (PCR). PCR results for waveguide-captured cells were 3 orders of magnitude more sensitive than the fluorescence immunoassay and can also provide additional genetic information on the captured microbes. These approaches can be used to rapidly detect and distinguish viable versus nonviable and pathogenic versus nonpathogenic captured organisms, provide culture materials for further analysis on a shorter time scale, and assess the efficacy of decontamination or sterilization procedures.}, number={1}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Johnson-White, Brandy and Lin, Baochuan and Ligler, Frances S.}, year={2007}, month={Jan}, pages={140–146} }
 @article{lassman_rahbar_medintz_ligler_2007, title={Incorporation of18Oxygen into Peptide Mixtures and Analysis with Multi‐Dimensional Chromatography and Mass‐Spectroscopy}, volume={40}, ISSN={0003-2719 1532-236X}, url={http://dx.doi.org/10.1080/00032710701384659}, DOI={10.1080/00032710701384659}, abstractNote={Abstract Enzymatic labeling with 18oxygen has the potential to become a widely applied method of isotope labeling for differential protein expression analysis by mass spectrometry because it is not amino acid specific and the reagents are cost‐effective and readily available. In this work, we investigate experimental parameters that affect efficient 18O incorporation with a model bovine serum albumin protein system and then use optimized chemistries for labeling the c‐terminus of peptides in a yeast proteome. Additionally, the role of sample handling, including the use of liquid chromatography was examined. An analytical methodology was developed which demonstrates the application of multi‐dimensional chromatography in conjunction with enzymatic labeling.}, number={10}, journal={Analytical Letters}, publisher={Informa UK Limited}, author={Lassman, Michael E. and Rahbar, Amir and Medintz, Igor L. and Ligler, Frances S.}, year={2007}, month={Aug}, pages={1864–1878} }
 @article{o’shaughnessy_hu_kulp_daly_ligler_2007, title={Laser ablation of micropores for formation of artificial planar lipid bilayers}, volume={9}, ISSN={1387-2176 1572-8781}, url={http://dx.doi.org/10.1007/S10544-007-9099-6}, DOI={10.1007/S10544-007-9099-6}, abstractNote={Artificial lipid bilayers are a powerful tool for studying synthetic or reconstituted ion channels. Key to forming these lipid bilayers is having a small aperture in a septum separating two solution chambers. Traditional methods of aperture generation involve manually punching the aperture into the septum. While these techniques work, they are difficult to implement reliably and do not produce consistently sized apertures. Presented here is a method of using a UV excimer laser with a nanosecond scale pulse width to laser ablate apertures from 4 to 105 microm in 20 microm thick polycarbonate films for use in artificial lipid bilayer experiments. The data demonstrate that the apertures produced by laser ablation are highly reproducible and can support both the formation of stable, long-lasting lipid bilayers as well as the recording of ion channels incorporated into the bilayers.}, number={6}, journal={Biomedical Microdevices}, publisher={Springer Science and Business Media LLC}, author={O’Shaughnessy, Thomas J. and Hu, Jenny E. and Kulp, John L., III and Daly, Susan M. and Ligler, Frances S.}, year={2007}, month={Jun}, pages={863–868} }
 @article{golden_floyd-smith_mott_ligler_2007, title={Target delivery in a microfluidic immunosensor}, volume={22}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2006.12.017}, DOI={10.1016/j.bios.2006.12.017}, abstractNote={A study is presented that examines the effect of microfluidic mixing elements on direct and sandwich assays performed in microchannels. Patterned grooves were embossed in the top of microchannels made in PDMS using soft lithography. The grooves redirected the fluid flowing in the channel, enhancing delivery of the target from the bulk fluid to the surface and preventing the formation of a depletion layer at the surface. Comparing assays in grooved and plain channels demonstrated that the mixers improved assay results by 26–46%. A computational flow analysis showed that the grooves caused virtual particles in the bulk flow to come close to the surface (∼11 μm) which is consistent with the signal increase seen experimentally. Direct assays for several concentrations of CY5-labeled biotin were performed in the microchannels. The mixers also improved signal intensity in sandwich assays for botulinum toxin which required mixing of the reagents as well as the direction of the target to the surface.}, number={11}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Golden, Joel P. and Floyd-Smith, Tamara M. and Mott, David R. and Ligler, Frances S.}, year={2007}, month={May}, pages={2763–2767} }
 @article{sanchez-carbayo_shriver-lake_cordon-cardo_ligler_2006, title={982: A Multianalyte Biosensor for Bladder Cancer Diagnostics}, volume={175}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/S0022-5347(18)33207-5}, DOI={10.1016/S0022-5347(18)33207-5}, abstractNote={You have accessJournal of UrologyPodium, Monday, May 22, 2006, 3:30 - 5:30 pm1 Apr 2006982: A Multianalyte Biosensor for Bladder Cancer Diagnostics Marta Sanchez-Carbayo, Lisa C. Shriver-Lake, Carlos Cordon-Cardo, and Frances S. Ligler Marta Sanchez-CarbayoMarta Sanchez-Carbayo More articles by this author , Lisa C. Shriver-LakeLisa C. Shriver-Lake More articles by this author , Carlos Cordon-CardoCarlos Cordon-Cardo More articles by this author , and Frances S. LiglerFrances S. Ligler More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33207-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "982: A Multianalyte Biosensor for Bladder Cancer Diagnostics." The Journal of Urology, 175(4S), pp. 316–317 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 316-317 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Marta Sanchez-Carbayo More articles by this author Lisa C. Shriver-Lake More articles by this author Carlos Cordon-Cardo More articles by this author Frances S. Ligler More articles by this author Expand All Advertisement PDF DownloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Sanchez-Carbayo, Marta and Shriver-Lake, Lisa C. and Cordon-Cardo, Carlos and Ligler, Frances S.}, year={2006}, month={Apr}, pages={316–317} }
 @article{sapsford_soto_blum_chatterji_lin_johnson_ligler_ratna_2006, title={A cowpea mosaic virus nanoscaffold for multiplexed antibody conjugation: Application as an immunoassay tracer}, volume={21}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2005.09.003}, DOI={10.1016/j.bios.2005.09.003}, abstractNote={Cowpea mosaic virus (CPMV), an icosahedral 30 nm virus, offers a uniquely programmable biological nanoscaffold. This study reports initial optimization of the simultaneous modification of two CPMV mutants with AlexaFluor® 647 fluorescent dyes and either IgG proteins or antibodies at specific sites on the virus scaffold. The capacity of CPMV as a simultaneous carrier for different types of molecules was demonstrated, specifically, when applied as a tracer in direct and sandwich immunoassays. The ability to label the virus capsid with antibody and up to 60 fluorescent dyes resulted in an improved limit of detection in SEB sandwich immunoassays, when used as a tracer, relative to a mole equivalent of dye-labeled antibody.}, number={8}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Sapsford, Kim E. and Soto, Carissa M. and Blum, Amy Szuchmacher and Chatterji, Anju and Lin, Tianwei and Johnson, John E. and Ligler, Frances S. and Ratna, Banahalli R.}, year={2006}, month={Feb}, pages={1668–1673} }
 @article{kulagina_shaffer_anderson_ligler_taitt_2006, title={Antimicrobial peptide-based array for Escherichia coli and Salmonella screening}, volume={575}, ISSN={0003-2670}, url={http://dx.doi.org/10.1016/j.aca.2006.05.082}, DOI={10.1016/j.aca.2006.05.082}, abstractNote={Numerous bacteria, plants, and higher organisms produce antimicrobial peptides (AMPs) as part of their innate immune system, providing a chemical defense mechanism against microbial invasion. Many AMPs exert their antimicrobial activity by binding to components of the microbe's surface and disrupting the membrane. The goal of this study was to incorporate AMPs into screening assays for detection of pathogenic species. Surface-immobilized AMPs such as polymyxins B and E could be used to detect Salmonella typhimurium and Escherichia coli O157:H7 in two assay formats: direct and sandwich. Both types of assay confirmed that the peptides were immobilized in active form and could bind cells in a concentration-dependent manner. Cell binding to the AMPs was peptide-density dependent. This method for monitoring pathogen binding was extended to include other cationic AMPs such as cecropin A, magainin I and parasin. Detection limits (LODs) for E. coli O157:H7 and S. typhimurium obtained with AMPs during sandwich assays were in the ranges of 5 × 104 to 5 × 105 and 1 × 105 to 5 × 106 cells mL−1, respectively. The different AMPs showed significantly different affinities for the two bacterial species; the potential for classification of pathogens based on different binding patterns to AMPs is discussed.}, number={1}, journal={Analytica Chimica Acta}, publisher={Elsevier BV}, author={Kulagina, Nadezhda V. and Shaffer, Kara M. and Anderson, George P. and Ligler, Frances S. and Taitt, Chris R.}, year={2006}, month={Aug}, pages={9–15} }
 @article{ngundi_qadri_wallace_moore_lassman_shriver-lake_ligler_taitt_2006, title={Detection of Deoxynivalenol in Foods and Indoor Air Using an Array Biosensor}, volume={40}, ISSN={0013-936X 1520-5851}, url={http://dx.doi.org/10.1021/es052396q}, DOI={10.1021/es052396q}, abstractNote={Deoxynivalenol (DON), a mycotoxin produced by several Fusaruim species, is a worldwide contaminant of foods and feeds. Because of the potential dangers due to accidental or intentional contamination of foods with DON, there is a need to develop a rapid and highly sensitive method for easy identification and quantification of DON. In this study, we have developed and utilized a competitive immunoassay technique to detect DON in various food matrixes and indoor air samples using an array biosensor. A DON-biotin conjugate, immobilized on a NeutrAvidin-coated optical waveguide, competed with the DON in the sample for binding to fluorescently labeled DON monoclonal antibodies. To demonstrate a simple procedure amenable for on-site use, DON-spiked cornmeal, cornflakes, wheat, barley, and oats were extracted with methanol-water (3:1) and assayed without cleanup or preconcentration. The limits of detection ranged from 0.2 ng/mL in buffer to 50 ng/g in oats. The detection limit of DON spiked into an aqueous effluent from an air sampler was 4 ng/mL.}, number={7}, journal={Environmental Science & Technology}, publisher={American Chemical Society (ACS)}, author={Ngundi, Miriam M. and Qadri, Syed A. and Wallace, Elizabeth V. and Moore, Martin H. and Lassman, Michael E. and Shriver-Lake, Lisa C. and Ligler, Frances S. and Taitt, Chris R.}, year={2006}, month={Apr}, pages={2352–2356} }
 @article{ngundi_taitt_mcmurry_kahne_ligler_2006, title={Detection of bacterial toxins with monosaccharide arrays}, volume={21}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2005.05.001}, DOI={10.1016/j.bios.2005.05.001}, abstractNote={A large number of bacterial toxins, viruses and bacteria target carbohydrate derivatives on the cell surface to attach and gain entry into the cell. We report here the use of a monosaccharide-based array to detect protein toxins. The array-based technique provides the capability to perform simultaneous multianalyte analyses. Arrays of N-acetyl galactosamine (GalNAc) and N-acetylneuraminic acid (Neu5Ac) derivatives were immobilized on the surface of a planar waveguide and were used as receptors for protein toxins. These arrays were probed with fluorescently labeled bacterial cells and protein toxins. While Salmonella typhimurium, Listeria monocytogenes, Escherichia coli and staphylococcal enterotoxin B (SEB) did not bind to either of the monosaccharides, both cholera toxin and tetanus toxin bound to GalNAc and Neu5Ac. The results show that the binding of the toxins to the carbohydrates is density dependent and semi-selective. Both toxins were detectable at 100 ng/ml.}, number={7}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Ngundi, Miriam M. and Taitt, Chris R. and McMurry, Scott A. and Kahne, Daniel and Ligler, Frances S.}, year={2006}, month={Jan}, pages={1195–1201} }
 @article{ligler_erickson_2006, title={Diagnosis on disc}, volume={440}, ISSN={0028-0836 1476-4687}, url={http://dx.doi.org/10.1038/440159a}, DOI={10.1038/440159a}, abstractNote={Highly complex immunoassays that identify and quantify many different antigens simultaneously need high-resolution imaging capability. A simple, low-cost technique could be music to our ears.}, number={7081}, journal={Nature}, publisher={Springer Science and Business Media LLC}, author={Ligler, Frances S. and Erickson, Jeffrey S.}, year={2006}, month={Mar}, pages={159–160} }
 @article{moreno-bondi_taitt_shriver-lake_ligler_2006, title={Multiplexed measurement of serum antibodies using an array biosensor}, volume={21}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2005.12.018}, DOI={10.1016/j.bios.2005.12.018}, abstractNote={The array biosensor provides the capability for simultaneously measuring titers of antibody against multiple antigens. Human antibodies against four different targets, tetanus toxin, diphtheria toxin, staphylococcal enterotoxin B (SEB) and hepatitis B, were measured simultaneously in sera from eight different donors in a single assay and titers were determined. The assays could measure amounts of bound antibody as low as approximately 100 fg. Each individual serum exhibited a different pattern of reactivity against the four target antigens. Applications of this biosensor capability include monitoring for exposure to pathogens and for efficacy of vaccination.}, number={10}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Moreno-Bondi, Maria C. and Taitt, Chris Rowe and Shriver-Lake, Lisa C. and Ligler, Frances S.}, year={2006}, month={Apr}, pages={1880–1886} }
 @article{soper_brown_ellington_frazier_garcia-manero_gau_gutman_hayes_korte_landers_et al._2006, title={Point-of-care biosensor systems for cancer diagnostics/prognostics}, volume={21}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2006.01.006}, DOI={10.1016/j.bios.2006.01.006}, abstractNote={With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments—DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.}, number={10}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Soper, Steven A. and Brown, Kathlynn and Ellington, Andrew and Frazier, Bruno and Garcia-Manero, Guillermo and Gau, Vincent and Gutman, Steven I. and Hayes, Daniel F. and Korte, Brenda and Landers, James L. and et al.}, year={2006}, month={Apr}, pages={1932–1942} }
 @article{johnson-white_buquo_zeinali_ligler_2006, title={Prevention of Nonspecific Bacterial Cell Adhesion in Immunoassays by Use of Cranberry Juice}, volume={78}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac051700v}, DOI={10.1021/ac051700v}, abstractNote={The ability of Vaccinum macrocarpon, the North American cranberry, to prevent bacterial adhesion has been used to advantage in the prevention of urinary tract infections and has recently been described for the prevention of adhesion of bacteria responsible for oral infections and stomach ulcers. This report documents the ability of cranberry juice to reduce nonspecific adhesion of bacteria to the borosilicate glass microscope slides used in an immunoarray biosensor format. Nonspecific binding of analytes in the array sensor leads to high background signals that cause increased detection limits and false positives. Reduction in background-to-signal ratios can be seen as the juice concentration is increased from 0 to 50% of the sample. This impact cannot be duplicated with grape, orange, apple, or white cranberry juice. Sugar content and pH have been eliminated as the agents in the juice responsible for the anti-adhesive activity.}, number={3}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Johnson-White, Brandy and Buquo, Lauren and Zeinali, Mazyar and Ligler, Frances S.}, year={2006}, month={Feb}, pages={853–857} }
 @article{sapsford_ngundi_moore_lassman_shriver-lake_taitt_ligler_2006, title={Rapid detection of foodborne contaminants using an Array Biosensor}, volume={113}, ISSN={0925-4005}, url={http://dx.doi.org/10.1016/j.snb.2005.07.008}, DOI={10.1016/j.snb.2005.07.008}, abstractNote={Foodborne contaminants come in a variety of sizes ranging from simple chemical compounds to entire bacterial cells. Due to public health concerns, there is a current need in the food industry for a sensitive, specific and rapid method to monitor for the presence of these toxic species, either as a result of natural or deliberate contamination. The Array Biosensor developed at the NRL encompasses these qualities, including the ability to measure multiple analytes simultaneously on a single substrate. In this study, we demonstrate the Array Biosensor's ability to measure both large pathogens, such as the bacteria Campylobacter jejuni (C. jejuni), and small toxins, including the mycotoxins ochratoxin A, fumonisin B, aflatoxin B1 and deoxynivalenol. Sandwich immunoassays were used to measure C. jejuni in buffer and a number of food matrices, while competitive immunoassays, taking only 15 min, were developed for the simultaneous detection of multiple mycotoxins. The combination of sandwich and competitive immunoassay formats on a single substrate was demonstrated, allowing the simultaneous detection of both large (C. jejuni) and small (aflatoxin B1) food contaminants.}, number={2}, journal={Sensors and Actuators B: Chemical}, publisher={Elsevier BV}, author={Sapsford, Kim E. and Ngundi, Miriam M. and Moore, Martin H. and Lassman, Michael E. and Shriver-Lake, Lisa C. and Taitt, Chris R. and Ligler, Frances S.}, year={2006}, month={Feb}, pages={599–607} }
 @article{ngundi_taitt_ligler_2006, title={Simultaneous determination of kinetic parameters for the binding of cholera toxin to immobilized sialic acid and monoclonal antibody using an array biosensor}, volume={22}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2005.12.007}, DOI={10.1016/j.bios.2005.12.007}, abstractNote={Interactions between protein toxins and carbohydrate receptors are often semi-selective processes and the kinetic parameters that define the binding of a receptor to different toxins may vary with each interaction. In this study, we have determined the affinity constants for binding of cholera toxin (CT) to immobilized sialic acid and to anti-CT antibody (as a simultaneous reference) by measuring real-time binding processes using an array biosensor. N-Acetylneuraminic acid (Neu5Ac), a member of the sialic acid family, was covalently immobilized onto maleimide-activated planar waveguides via a thiol-terminated linker attached to the anomeric carbon of the sugar. Control antibodies were immobilized using two different approaches: covalent attachment onto maleimide-activated slides via the thiol on cysteine residues and non-covalent attachment using a biotin-NeutrAvidin linkage. Cy5-labeled CT was flowed over the immobilized receptors and the fluorescent intensity of the bound CT-receptor complex was recorded as a function of time. The association constants for CT binding to covalently attached Neu5Ac, to covalently attached anti-CT monoclonal antibody, and to antibody tethered by biotin-NeutrAvidin interactions were determined to be 1.3 x 10(8), 2.1 x 10(8) and 5.7 x 10(8)M(-1), respectively.}, number={1}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Ngundi, Miriam M. and Taitt, Chris R. and Ligler, Frances S.}, year={2006}, month={Jul}, pages={124–130} }
 @article{kayagil_richardson_archer_ligler_erickson_2006, title={The beadwhacker for maintaining even dispersion of micron-sized beads}, volume={18}, ISSN={0957-0233 1361-6501}, url={http://dx.doi.org/10.1088/0957-0233/18/1/N01}, DOI={10.1088/0957-0233/18/1/N01}, abstractNote={This design note describes an automatic device for maintaining an even dispersion of solid phase extraction beads in small volume tubes. The 'beadwhacker' is especially designed for use in laboratories developing interfacial chemistries or immunomagnetic separations. The advantages of the beadwhacker include automatic operation, multiple sample capability and reproducible operation for extended periods of time. Furthermore, the device is completely portable and can be placed into a controlled environment, making it useful not only for the testing of final products but also for the synthesis and chemical modification of the beads themselves. The beadwhacker is low cost and constructed from commercially available parts. Preliminary mixing data are presented. Finally, suggestions are given for additional parts that may be necessary if the beadwhacker is to be incorporated as a module in a larger automated system.}, number={1}, journal={Measurement Science and Technology}, publisher={IOP Publishing}, author={Kayagil, T A and Richardson, J A and Archer, M J and Ligler, F S and Erickson, J S}, year={2006}, month={Nov}, pages={N1–N4} }
 @article{mott_howell, jr._golden_kaplan_ligler_oran_2006, title={Toolbox for the design of optimized microfluidic components}, volume={6}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b516459a}, DOI={10.1039/b516459a}, abstractNote={A computational "toolbox" for the a priori design of optimized microfluidic components is presented. These components consist of a microchannel under low-Reynolds number, pressure-driven flow, with an arrangement of grooves cut into the top and bottom to generate a tailored cross-channel flow. An advection map for each feature (i.e., groove of a particular shape and orientation) predicts the lateral transport of fluid within the channel due to that feature. We show that applying these maps in sequence generates an excellent representation of the outflow distribution for complex designs that combine these basic features. The effect of the complex three-dimensional flow field can therefore be predicted without solving the governing flow equations through the composite geometry, and the resulting distribution of fluids in the channel is used to evaluate how well a component performs a specified task. The generation and use of advection maps is described, and the toolbox is applied to determine optimal combinations of features for specified mixer sizes and mixing metrics.}, number={4}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Mott, David R. and Howell, Jr., Peter B. and Golden, Joel P. and Kaplan, Carolyn R. and Ligler, Frances S. and Oran, Elaine S.}, year={2006}, pages={540} }
 @article{howell, jr._mott_fertig_kaplan_golden_oran_ligler_2005, title={A microfluidic mixer with grooves placed on the top and bottom of the channel}, volume={5}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b418243j}, DOI={10.1039/b418243j}, abstractNote={A new microfluidic mixer is presented consisting of a rectangular channel with grooves placed in the top and bottom. This not only increases the driving force behind the lateral flow, but allows for the formation of advection patterns that cannot be created with structures on the bottom alone. Chevrons, pointing in opposite directions on the top and bottom, are used to create a pair of vortices positioned side by side. Stripes running the width of the channel generate a pair of vertically stacked vortices. Computational fluid dynamics (CFD) simulations are used to model the behavior of the systems and provide velocity maps at cross-sections within the mixer. Experiments demonstrate the mixing that results when two segregated species enter the mixer side-by-side and pass through two cycles of the mixer (i.e., two alternating sets of four stripes and four chevrons).}, number={5}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Howell, Jr., Peter B. and Mott, David R. and Fertig, Stephanie and Kaplan, Carolyn R. and Golden, Joel P. and Oran, Elaine S. and Ligler, Frances S.}, year={2005}, pages={524} }
 @article{golden_taitt_shriverlake_shubin_ligler_2005, title={A portable automated multianalyte biosensor}, volume={65}, ISSN={0039-9140}, url={http://dx.doi.org/10.1016/j.talanta.2004.03.072}, DOI={10.1016/j.talanta.2004.03.072}, abstractNote={The array biosensor employs an array of capture molecules on a planar optical waveguide to interrogate multiple samples simultaneously for multiple targets. In assay development and demonstration studies published previously, we have quantified this biosensor's capability for rapid identification of a wide variety of targets in complex sample media. This paper describes the miniaturization and automation of the array biosensor for portability and on-site use. The fluidics have been redesigned and constructed with reliability and commercial production of disposable components in mind. To demonstrate the automated operation, simultaneous assays were automatically conducted on samples containing both ovalbumin and staphylococcal enterotoxin B. Results demonstrate the capability of the biosensor for detection and quantification.}, number={5}, journal={Talanta}, publisher={Elsevier BV}, author={Golden, J and Taitt, C and Shriverlake, L and Shubin, Y and Ligler, F}, year={2005}, month={Mar}, pages={1078–1085} }
 @article{golden_shriver-lake_sapsford_ligler_2005, title={A “do-it-yourself” array biosensor}, volume={37}, ISSN={1046-2023}, url={http://dx.doi.org/10.1016/j.ymeth.2005.05.010}, DOI={10.1016/j.ymeth.2005.05.010}, abstractNote={We have developed an array biosensor for the simultaneous detection of multiple targets in multiple samples within 15–30 min. The biosensor is based on a planar waveguide, a modified microscope slide, with a pattern of small (mm2) sensing regions. The waveguide is illuminated by launching the emission of a 635 nm diode laser into the proximal end of the slide via a line generator. The evanescent field excites fluorophores bound in the sensing region and the emitted fluorescence is measured using a Peltier-cooled CCD camera. Assays can be performed on the waveguide in multichannel flow chambers and then interrogated using the detection system described here. This biosensor can detect many different targets, including proteins, toxins, cells, virus, and explosives with detection limits rivaling those of the ELISA detection system.}, number={1}, journal={Methods}, publisher={Elsevier BV}, author={Golden, Joel and Shriver-Lake, Lisa and Sapsford, Kim and Ligler, Frances}, year={2005}, month={Sep}, pages={65–72} }
 @article{kulagina_lassman_ligler_taitt_2005, title={Antimicrobial Peptides for Detection of Bacteria in Biosensor Assays}, volume={77}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac050639r}, DOI={10.1021/ac050639r}, abstractNote={Bacteria, plants, and higher and lower animals have evolved an innate immune system as a first line of defense against microbial invasion. Some of these organisms produce antimicrobial peptides (AMPs) as a part of this chemical immune system. AMPs exert their antimicrobial activity by binding to components of the microbe's surface and disrupting the membrane. The overall goal of this study was to apply the AMP magainin I as a recognition element for Escherichia coli O157:H7 and Salmonella typhimurium detection on an array-based biosensor. We immobilized magainin I on silanized glass slides using biotin-avidin chemistry, as well as through direct covalent attachment. Cy5-labeled, heat-killed cells were used to demonstrate that the immobilized magainin I can bind Salmonella with detection limits similar to analogous antibody-based assays. Detection limits for E. coli were higher than in analogous antibody-based assays, but it is expected that other AMPs may possess higher affinities for this target. The results showed that both specific and nonspecific binding strongly depend on the method used for peptide immobilization. Direct attachment of magainin to the substrate surface not only decreased nonspecific cell binding but also resulted in improved detection limits for both Salmonella and E. coli.}, number={19}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Kulagina, Nadezhda V. and Lassman, Michael E. and Ligler, Frances S. and Taitt, Chris Rowe}, year={2005}, month={Oct}, pages={6504–6508} }
 @article{ngundi_shriver-lake_moore_lassman_ligler_taitt_2005, title={Array Biosensor for Detection of Ochratoxin A in Cereals and Beverages}, volume={77}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac048957y}, DOI={10.1021/ac048957y}, abstractNote={Contamination of food by mycotoxins occurs in minute quantities, and therefore, there is a need for a highly sensitive and selective device that can detect and quantify these organic toxins. We report the development of a rapid and highly sensitive array biosensor for the detection and quantitation of ochratoxin A (OTA). The array biosensor utilizes a competitive immunoassay format. Immobilized OTA derivatives compete with toxin in solution for binding to fluorescent anti-OTA antibody spiked into the sample. This competition is quantified by measuring the formation of the fluorescent immunocomplex on the waveguide surface. The fluorescent signal is inversely proportional to the concentration of OTA in the sample. Analyses for OTA in buffer and a variety of food and beverage samples were performed. Samples were extracted with methanol, without any sample cleanup or preconcentration step prior to analysis. The limit of detection for OTA in several cereals ranged from 3.8 to 100 ng/g, while in coffee and wine, detection limits were 7 and 38 ng/g, respectively.}, number={1}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Ngundi, Miriam M. and Shriver-Lake, Lisa C. and Moore, Martin H. and Lassman, Michael E. and Ligler, Frances S. and Taitt, Chris R.}, year={2005}, month={Jan}, pages={148–154} }
 @article{floyd-smith_golden_howell_ligler_2005, title={Characterization of passive microfluidic mixers fabricated using soft lithography}, volume={2}, ISSN={1613-4982 1613-4990}, url={http://dx.doi.org/10.1007/S10404-005-0060-9}, DOI={10.1007/S10404-005-0060-9}, number={2}, journal={Microfluidics and Nanofluidics}, publisher={Springer Science and Business Media LLC}, author={Floyd-Smith, T.M. and Golden, J.P. and Howell, P.B. and Ligler, F.S.}, year={2005}, month={Dec}, pages={180–183} }
 @article{taitt_anderson_ligler_2005, title={Evanescent wave fluorescence biosensors}, volume={20}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2004.10.026}, DOI={10.1016/j.bios.2004.10.026}, abstractNote={Since discovery and first use in the mid-1970s, evanescent wave fluorescence biosensors have developed into a diverse range of instruments, each designed to meet a particular detection need. In this review, we provide a brief synopsis of what evanescent wave fluorescence biosensors are, how they work, and how they are used. In addition, we have summarized the important patents that have impacted the evolution from laboratory curiosities to fully automated commercial products. Finally, we address the critical issues that evanescent wave fluorescence biosensors will face in the coming years.}, number={12}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Taitt, Chris Rowe and Anderson, George P. and Ligler, Frances S.}, year={2005}, month={Jun}, pages={2470–2487} }
 @article{taitt_golden_shubin_shriver-lake_sapsford_rasooly_ligler_2004, title={A Portable Array Biosensor for Detecting Multiple Analytes in Complex Samples}, volume={47}, ISSN={0095-3628 1432-184X}, url={http://dx.doi.org/10.1007/S00248-003-1011-1}, DOI={10.1007/S00248-003-1011-1}, abstractNote={The Multi-Analyte Array Biosensor (MAAB) has been developed at the Naval Research Laboratory (NRL) with the goal of simultaneously detecting and identifying multiple target agents in complex samples with minimal user manipulation. This paper will focus on recent improvements in the biochemical and engineering aspects of this instrument. These improvements have enabled the expansion of the repertoire of analytes detected to include Salmonella typhimurium and Listeria monocytogenes, and also expanded the different sample matrices tested. Furthermore, all components of the biochemical assays could be prepared well in advance of sample testing, resulting in a "plug-and-play" methodology. Simultaneous detection of three toxins (ricin, staphylococcal enterotoxin B, and cholera toxin) was demonstrated using a novel fluidics cube module that limits the number of manipulations to only the initial sample loading. This work demonstrates the utility of the MAAB for rapid analysis of complex samples with multianalyte capability, with a minimum of operator manipulations required for either sample preparation or final analysis.}, number={2}, journal={Microbial Ecology}, publisher={Springer Science and Business Media LLC}, author={Taitt, C.R. and Golden, J. P. and Shubin, Y. S. and Shriver-Lake, L. C. and Sapsford, K. E. and Rasooly, A. and Ligler, F. S.}, year={2004}, month={Feb}, pages={175–185} }
 @article{howell, jr_mott_golden_ligler_2004, title={Design and evaluation of a Dean vortex-based micromixer}, volume={4}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b407170k}, DOI={10.1039/b407170k}, abstractNote={A mixer, based on the Dean vortex, is fabricated and tested in an on-chip format. When fluid is directed around a curve under pressure driven flow, the high velocity streams in the center of the channel experience a greater centripetal force and so are deflected outward. This creates a pair of counter-rotating vortices moving fluid toward the inner wall at the top and bottom of the channel and toward the outer wall in the center. For the geometries studied, the vortices were first seen at Reynolds numbers between 1 and 10 and became stronger as the flow velocity is increased. Vortex formation was monitored in channels with depth/width ratios of 0.5, 1.0, and 2.0. The lowest aspect ratio strongly suppressed vortex formation. Increasing the aspect ratio above 1 appeared to provide improved mixing. This design has the advantages of easy fabrication and low surface area.}, number={6}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Howell, Jr, Peter B. and Mott, David R. and Golden, Joel P. and Ligler, Frances S.}, year={2004}, pages={663} }
 @article{sapsford_rasooly_taitt_ligler_2004, title={Detection ofCampylobacterandShigellaSpecies in Food Samples Using an Array Biosensor}, volume={76}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac035122z}, DOI={10.1021/ac035122z}, abstractNote={Campylobacter and Shigella bacteria are common causes of food- and water-borne illness worldwide. There is a current need in food, medical, environmental, and military markets for a rapid and user-friendly method of detecting such pathogens. The array biosensor developed at the NRL encompasses these qualities. In this study, 25-min, sandwich immunoassays were developed for the detection of Campylobacter and Shigella species in both buffer and a variety of food and beverage samples. The limit of detection for Shigella dysenteriae in buffer and chicken carcass wash was 4.9 x 10(4) cfu mL(-)(1), whereas Campylobacter jejuni could be measured at concentrations as low as 9.7 x 10(2) cfu mL(-)(1). The limits of detection and dynamic range were found to vary depending on the sample matrix, but could be improved by running the sample over the waveguide surface for longer periods of time. Samples were run with no preconcentration or enrichment steps and little-to-no sample pretreatment prior to analysis.}, number={2}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Sapsford, Kim E. and Rasooly, Avraham and Taitt, Chris R. and Ligler, Frances S.}, year={2004}, month={Jan}, pages={433–440} }
 @article{sapsford_shubin_delehanty_golden_taitt_shriver-lake_ligler_2004, title={Fluorescence-based array biosensors for detection of biohazards}, volume={96}, ISSN={1364-5072 1365-2672}, url={http://dx.doi.org/10.1046/j.1365-2672.2003.02115.x}, DOI={10.1046/j.1365-2672.2003.02115.x}, abstractNote={Total internal reflection fluorescence (TIRF) is a process whereby fluorophores that are either attached to or are in close proximity with the surface of a waveguide are selectively excited via an evanescent wave. Planar waveguides provide the possibility of immobilizing multiple capture biomolecules onto a single surface and therefore, offer the exciting prospect of multi-analyte detection. The production of arrays and the results of various groups which use TIRF to interrogate such surfaces is reviewed, along with a look at how far the field has advanced toward the production of an automated, portable, multi-analyte array biosensor for real-time biohazard detection. In particular, a miniaturized, fully automated, stand-alone array biosensor developed at the Naval Research Laboratory is reported that monitors interactions between binding partners either as the final image or in real-time. A variety of analytes including toxins, bacteria and viruses have been detected both in buffer and complex matrices, such as blood and soil suspensions, with comparable detection limits. A number of developments have led to a TIRF array biosensor weighing only 5.5 kg which is automated for environmental, clinical and food monitoring or for detection of bioterrorist agents.}, number={1}, journal={Journal of Applied Microbiology}, publisher={Wiley}, author={Sapsford, K.E. and Shubin, Y.S. and Delehanty, J.B. and Golden, J.P. and Taitt, C.R. and Shriver-Lake, L.C. and Ligler, F.S.}, year={2004}, month={Jan}, pages={47–58} }
 @article{sapsford_ligler_2004, title={Real-time analysis of protein adsorption to a variety of thin films}, volume={19}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2003.10.002}, DOI={10.1016/j.bios.2003.10.002}, abstractNote={The ability of a fluorescence-based array biosensor to screen surfaces for the adsorption of biomolecules in real-time is demonstrated. Glass microscope slides were coated with silanes, including 3-mercaptopropyl-triethoxysilane, 3-glycidyloxypropyltrimethoxysilane, 3-aminopropyltrimethoxy-silane, octadecyl-trichlorosilane, and 2-methoxy((polyethylenoxy)propyl)tri-methoxysilane, or with polymer thin films, including polystyrene, polyimide, sol–gel, poly(dimethylsiloxane), and agarose. The adsorption of Cy5-labeled proteins, bovine serum albumin, fibrinogen, and lysozyme onto these surfaces was measured using total internal reflection spectroscopy over a period of 50 min. The majority of the modified surfaces, apart from notable exceptions including the thiol silane and PDMS, behaved as expected upon protein adsorption, and the observations could be related to the properties of both the individual surfaces and proteins. This study highlights the complex nature of the mechanisms involved when a protein interacts at a solid–liquid interface. However, it also demonstrates a comparatively generic method with which to screen surfaces for their protein resistant properties and to measure surface interactions in real time. Furthermore, since the array biosensor can perform multiple measurements simultaneously, the interactions of a variety of proteins with a single surface can be monitored.}, number={9}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Sapsford, Kim E and Ligler, Frances S}, year={2004}, month={Apr}, pages={1045–1055} }