@article{queener_ahmmed_victorio_twiddy_dehn_brewer_lobaton_bozkurt_pozdin_daniele_2023, place={Vienna, Austria}, title={Conformal Micropatterned Organic-Metal Electrodes for Physiological Recording}, ISSN={["1930-0395"]}, url={http://dx.doi.org/10.1109/sensors56945.2023.10324963}, DOI={10.1109/SENSORS56945.2023.10324963}, abstractNote={Conformal electrodes provide a soft and conforming interface with the skin for reduced impedance, comfortable skin contact, and improved signal quality compared to commercial electrodes. In this paper, we present conformal micropatterned organic-metal (CMOM) electrodes and our investigation on the effect of perforation micropatterning and PEDOT:PSS coating. CMOM electrodes were characterized then evaluated in vivo against commercial-off-the-shelf electrodes. PEDOT:PSS was found to reduce the overall impedance in each electrode variant, resulting in a >97% decrease in impedance at low frequencies. The change in impedance at high frequencies was not significant for the control or $30\ \mu \mathrm{m}$ vias electrodes, but the impedance was significantly greater following EPD for $60\ \mu \mathrm{m}$ vias electrodes.}, journal={2023 IEEE SENSORS}, author={Queener, Kirstie M. and Ahmmed, Parvez and Victorio, Mauro and Twiddy, Jack and Dehn, Ashley and Brewer, Alec and Lobaton, Edgar and Bozkurt, Alper and Pozdin, Vladimir and Daniele, Michael}, year={2023} } @article{rivera_bilton_burclaff_czerwinski_liu_trueblood_hinesley_breau_deal_joshi_et al._2023, title={Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity}, volume={16}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2023.07.012}, abstractNote={Hypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs).hISCs were exposed to <1.0% oxygen in the MPS for 6, 24, 48, and 72 hours. Viability, hypoxia-inducible factor 1a (HIF1a) response, transcriptomics, cell cycle dynamics, and response to cytokines were evaluated in hISCs under hypoxia. HIF stabilizers and inhibitors were screened to evaluate HIF-dependent responses.The MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs maintain viability until 72 hours and exhibit peak HIF1a at 24 hours. hISC activity was reduced at 24 hours but recovered at 48 hours. Hypoxia induced increases in the proportion of hISCs in G1 and expression changes in 16 IL receptors. Prolyl hydroxylase inhibition failed to reproduce hypoxia-dependent IL-receptor expression patterns. hISC activity increased when treated IL1β, IL2, IL4, IL6, IL10, IL13, and IL25 and rescued hISC activity caused by 24 hours of hypoxia.Hypoxia pushes hISCs into a dormant but reversible proliferative state and primes hISCs to respond to a subset of ILs that preserves hISC activity. These findings have important implications for understanding intestinal epithelial regeneration mechanisms caused by inflammatory hypoxia.}, number={5}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Rivera, Kristina R. and Bilton, R. Jarrett and Burclaff, Joseph and Czerwinski, Michael J. and Liu, Jintong and Trueblood, Jessica M. and Hinesley, Caroline M. and Breau, Keith A. and Deal, Halston E. and Joshi, Shlok and et al.}, year={2023}, pages={823–846} } @article{prodromou_moore_chu_deal_san miguel_brown_daniele_pozdin_menegatti_2023, title={Molecular Engineering of Cyclic Azobenzene-Peptide Hybrid Ligands for the Purification of Human Blood Factor VIII via Photo-Affinity Chromatography}, volume={1}, ISSN={["1616-3028"]}, url={http://dx.doi.org/10.1002/adfm.202213881}, DOI={10.1002/adfm.202213881}, abstractNote={The use of benign stimuli to control the binding and release of labile biologics for their isolation from complex feedstocks is a key goal of modern biopharmaceutical technology. This study introduces cyclic azobenzene‐peptide (CAP) ligands for the rapid and discrete photo‐responsive capture and release of blood coagulation factor VIII (FVIII). A predictive method—based on amino acid sequence and molecular architecture of CAPs—is developed to correlate the conformation of cis/trans‐CAP photo‐isomers to FVIII binding and release. Combined in silico ‐ in vitro analysis of FVIII:peptide interactions guide the design of a rational approach to optimize isomerization kinetics and biorecognition of CAPs. A photoaffinity adsorbent, prepared by conjugating selected CAP G‐cycloAZOB[Lys‐YYKHLYN‐Lys]‐G on translucent chromatographic beads, features high binding capacity (>6 mg of FVIII per mL of resin) and rapid photo‐isomerization kinetics (τ < 30 s) when exposed to 420–450 nm light at the intensity of 0.1 W cm−2. The adsorbent purifies FVIII from a recombinant harvest using a single mobile phase, affording high product yield (>90%), purity (>95%), and blood clotting activity. The CAPs introduced in this report demonstrate a novel route integrating gentle operational conditions in a rapid and efficient bioprocess for the purification of life‐saving biotherapeutics.}, journal={ADVANCED FUNCTIONAL MATERIALS}, publisher={Wiley}, author={Prodromou, Raphael and Moore, Brandyn David and Chu, Wenning and Deal, Halston and San Miguel, Adriana and Brown, Ashley Carson and Daniele, Michael Angelo-Anthony and Pozdin, Vladimir Aleksandrovich and Menegatti, Stefano}, year={2023}, month={Jan} } @article{pozdin_dieffenderfer_2022, title={Towards Wearable Health Monitoring DevicesY}, volume={12}, ISSN={["2079-6374"]}, DOI={10.3390/bios12050322}, abstractNote={Humans have searched far beyond our planet to understand the fundamental principles and mechanisms of life [...].}, number={5}, journal={BIOSENSORS-BASEL}, author={Pozdin, Vladimir A. and Dieffenderfer, James}, year={2022}, month={May} } @article{prodromou_day_saberi-bosari_schneible_mabe_san miguel_daniele_pozdin_menegatti_2021, title={Engineering Next Generation Cyclized Peptide Ligands for Light-Controlled Capture and Release of Therapeutic Proteins}, volume={31}, ISSN={["1616-3028"]}, url={http://dx.doi.org/10.1002/adfm.202101410}, DOI={10.1002/adfm.202101410}, abstractNote={Photo‐affinity adsorbents (i.e., translucent matrices functionalized with ligands featuring light‐controlled biorecognition) represent a futuristic technology for purifying labile biologics. In this study, a framework for prototyping photo‐affinity adsorbents comprising azobenzene‐cyclized peptides (ACPs) conjugated to translucent porous beads (ChemMatrix) is presented. This approach combines computational and experimental tools for designing ACPs and investigating their light‐controlled isomerization kinetics and protein biorecognition. First, a modular design for tailoring ACP's conformation, facilitating sequencing, and streamlining the in silico modeling of cis/trans isomers and their differential protein binding is introduced. Then, a spectroscopic system for measuring the photo‐isomerization kinetics of ACPs on ChemMatrix beads is reported; using this device, it is demonstrated that the isomerization at different light intensities is correlated to the cyclization geometry, specifically the energy difference of trans versus cis isomers as calculated in silico. Also, a microfluidic device for sorting ACP‐ChemMatrix beads to select and validate photo‐affinity ligands using Vascular Cell Adhesion Molecule 1 (VCAM‐1) as target protein and cycloAZOB[GVHAKQHRN‐K*]‐G‐ChemMatrix as model photo‐affinity adsorbent is presented. The proposed ACPs exhibit rapid and defined light‐controlled isomerization and biorecognition. Controlling the adsorption and release of VCAM‐1 using light demonstrates the potential of photo‐affinity adsorbents for targets whose biochemical liability poses challenges to its purification.}, number={27}, journal={ADVANCED FUNCTIONAL MATERIALS}, publisher={Wiley}, author={Prodromou, Raphael and Day, Kevin N. and Saberi-Bosari, Sahand and Schneible, John D. and Mabe, Matthew D. and San Miguel, Adriana and Daniele, Michael A. and Pozdin, Vladimir and Menegatti, Stefano}, year={2021}, month={Jul} } @article{pozdin_erb_downey_rivera_daniele_2021, title={Monitoring of random microvessel network formation by in-line sensing of flow rates: A numerical and in vitro investigation}, volume={331}, ISSN={["1873-3069"]}, DOI={10.1016/j.sna.2021.112970}, abstractNote={The directed or de novo formation of microvasculature in engineered tissue constructs is essential for accurately replicating physiological function. A limiting factor of a system relying on spontaneous microvessel formation is the inability to precisely quantify the development of the microvascular network and control fluid moving through formed vessels. Herein, we report a strategy to monitor the dynamic formation of microscale fluid networks, which can be translated to the monitoring of microvasculature development in engineered tissue constructs. The non-invasive, non-destructive monitoring and characterization of the fluid network is achieved via in-line sensing of fluid flow rate and correlating this measurement to the hydrodynamic resistance of the fluid network to model the progression of microvessel formation and connectivity. Computational fluid dynamics, equivalent circuit, and experimental models were compared, which simulated multi-generational branching or splitting microvessel networks. The networks simulated vessels with varying cross-sectional area, up to 16 branching vessels, and microvessel network volume ranging from ˜20−30 mm3. In all models, the increasing degree of network complexity and volume corresponded to a decrease in jumper flow-rate measured; however, vessel cross-section also impacted the measured jumper flow rate, i.e. at low vessel height (<200 μm) response was dominated by increased network volume and at higher vessel height (>200 μm) the response was dominated by resistance of narrow channels. An approximately 2% error was exhibited between the models, which was attributed to variation in the geometry of the fabricated models and illustrates the potential to precisely and non-destructively monitor microvessel network development and volumetric changes.}, journal={SENSORS AND ACTUATORS A-PHYSICAL}, author={Pozdin, Vladimir A. and Erb, Patrick D. and Downey, McKenna and Rivera, Kristina R. and Daniele, Michael}, year={2021}, month={Nov} } @article{yuen_pozdin_young_turner_giles_naciri_trammell_charles_stenger_daniele_2020, title={Perylene-diimide-based n-type semiconductors with enhanced air and temperature stable photoconductor and transistor properties}, volume={174}, ISSN={["1873-3743"]}, DOI={10.1016/j.dyepig.2019.108014}, abstractNote={We report the synthesis and characterization of highly air and temperature stable, solution-processed, n-type organic semiconductors: a perylene-diimide monomer and a perylene-diimide-based pendant polymer. When integrated into a transistor structure, both materials possess pure n-type transport with mobility as high as 10−5 cm2 V−1 s−1 for the polymer. The organic semiconductors exhibit good photoconductor properties, with photocurrent to dark current ratios of up to 103 for the monomer, despite its lower FET mobility. The differences in transistor and photoconductor properties suggest different applications for each material. Both materials can be processed in air, and their transport properties have good air stability, improving with annealing even up to 200 °C in air. It is notable that such air-stable photoconductivity and transport properties have rarely been reported for n-type organic semiconductors before, as most n-type organic semiconductors are not stable in air. Hence, these materials may have potential in a wide range of applications.}, journal={DYES AND PIGMENTS}, author={Yuen, Jonathan D. and Pozdin, Vladimir A. and Young, Ashlyn T. and Turner, Brendan L. and Giles, Ian D. and Naciri, Jawad and Trammell, Scott A. and Charles, Paul T. and Stenger, David A. and Daniele, Michael A.}, year={2020}, month={Mar} } @article{day_schneible_young_pozdin_driessche_gaffney_prodromou_freytes_fourches_daniele_et al._2020, title={Photoinduced reconfiguration to control the protein-binding affinity of azobenzene-cyclized peptides}, volume={8}, ISSN={["2050-7518"]}, DOI={10.1039/d0tb01189d}, abstractNote={The impact of next-generation biorecognition elements (ligands) will be determined by the ability to remotely control their binding activity for a target biomolecule in complex environments. Compared to conventional mechanisms for regulating binding affinity (pH, ionic strength, or chaotropic agents), light provides higher accuracy and rapidity, and is particularly suited for labile targets. In this study, we demonstrate a general method to develop azobenzene-cyclized peptide ligands with light-controlled affinity for target proteins. Light triggers a cis/trans isomerization of the azobenzene, which results in a major structural rearrangement of the cyclic peptide from a non-binding to a binding configuration. Critical to this goal are the ability to achieve efficient photo-isomerization under low light dosage and the temporal stability of both cis and trans isomers. We demonstrated our method by designing photo-switchable peptides targeting vascular cell adhesion marker 1 (VCAM1), a cell marker implicated in stem cell function. Starting from a known VCAM1-binding linear peptide, an ensemble of azobenzene-cyclized variants with selective light-controlled binding were identified by combining in silico design with experimental characterization via spectroscopy and surface plasmon resonance. Variant cycloAZOB[G-VHAKQHRN-K] featured rapid, light-controlled binding of VCAM1 (KD,trans/KD,cis ∼ 130). Biotin-cycloAZOB[G-VHAKQHRN-K] was utilized to label brain microvascular endothelial cells (BMECs), showing co-localization with anti-VCAM1 antibodies in cis configuration and negligible binding in trans configuration.}, number={33}, journal={JOURNAL OF MATERIALS CHEMISTRY B}, author={Day, Kevin and Schneible, John D. and Young, Ashlyn T. and Pozdin, Vladimir A. and Driessche, George and Gaffney, Lewis A. and Prodromou, Raphael and Freytes, Donald O. and Fourches, Denis and Daniele, Michael and et al.}, year={2020}, month={Sep}, pages={7413–7427} } @article{yokus_songkakul_pozdin_bozkurt_daniele_2020, title={Wearable multiplexed biosensor system toward continuous monitoring of metabolites}, volume={153}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2020.112038}, abstractNote={Comprehensive metabolic panels are the most reliable and common methods for monitoring general physiology in clinical healthcare. Translation of this clinical practice to personal health and wellness tracking requires reliable, non-invasive, miniaturized, ambulatory, and inexpensive systems for continuous measurement of biochemical analytes. We report the design and characterization of a wearable system with a flexible sensor array for non-invasive and continuous monitoring of human biochemistry. The system includes signal conditioning, processing, and transmission parts for continuous measurement of glucose, lactate, pH, and temperature. The system can operate three discrete electrochemical cells. The system draws 15 mA under continuous operation when powered by a 3.7 V 150 mAh battery. The analog front-end of the electrochemical cells has four potentiostats and three multiplexers for multiplexed and parallel readout from twelve working electrodes. Utilization of redundant working electrodes improves the measurement accuracy of sensors by averaging chronoamperometric responses across the array. The operation of the system is demonstrated in vitro by simultaneous measurement of glucose and lactate, pH, and skin temperature. In benchtop measurements, the sensors are shown to have sensitivities of 26.31 μA mM-1·cm-2 for glucose, 1.49 μA mM-1·cm-2 for lactate, 54 mV·pH-1 for pH, and 0.002 °C-1 for temperature. With the custom wearable system, these values were 0.84 ± 0.03 mV μM-1·cm-2 or glucose, 31.87 ± 9.03 mV mM-1·cm-2 for lactate, 57.18 ± 1.43 mV·pH-1 for pH, and 63.4 μV·°C-1 for temperature. This miniaturized wearable system enables future evaluation of temporal changes of the sweat biomarkers.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Yokus, Murat A. and Songkakul, Tanner and Pozdin, Vladimir A. and Bozkurt, Alper and Daniele, Michael A.}, year={2020}, month={Apr} } @article{rivera_pozdin_young_erb_wisniewski_magness_daniele_2019, title={Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems}, volume={123}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2018.07.035}, abstractNote={Physiological processes, such as respiration, circulation, digestion, and many pathologies alter oxygen concentration in the blood and tissue. When designing culture systems to recapitulate the in vivo oxygen environment, it is important to integrate systems for monitoring and controlling oxygen concentration. Herein, we report the design and engineering of a system to remotely monitor and control oxygen concentration inside a device for 3D cell culture. We integrate a photonic oxygen biosensor into the 3D tissue scaffold and regulate oxygen concentration via the control of purging gas flow. The integrated phosphorescence-based oxygen biosensor employs the quenching of palladium-benzoporphyrin by molecular oxygen to transduce the local oxygen concentration in the 3D tissue scaffold. The system is validated by testing the effects of normoxic and hypoxic culture conditions on healthy and tumorigenic breast epithelial cells, MCF-10A cells and BT474 cells, respectively. Under hypoxic conditions, both cell types exhibited upregulation of downstream target genes for the hypoxia marker gene, hypoxia-inducible factor 1α (HIF1A). Lastly, by monitoring the real-time fluctuation of oxygen concentration, we illustrated the formation of hypoxic culture conditions due to limited diffusion of oxygen through 3D tissue scaffolds.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Rivera, Kristina R. and Pozdin, Vladimir A. and Young, Ashlyn T. and Erb, Patrick D. and Wisniewski, Natalie A. and Magness, Scott T. and Daniele, Michael}, year={2019}, month={Jan}, pages={131–140} } @misc{rivera_yokus_erb_pozdin_daniele_2019, title={Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations}, volume={144}, ISSN={["1364-5528"]}, DOI={10.1039/c8an02201a}, abstractNote={Quantifying and regulating oxygen in a microphysiological models can be achievedviaan array of technologies, and is an essential component of recapitulating tissue-specific microenvironments.}, number={10}, journal={ANALYST}, author={Rivera, Kristina R. and Yokus, Murat A. and Erb, Patrick D. and Pozdin, Vladimir A. and Daniele, Michael}, year={2019}, month={May}, pages={3190–3215} }