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VIIBRE

Home > VIIBRE - Systems Biology, Biological Physics and Biomedical Engineering Research

VIIBRE - Systems Biology, Biological Physics and Biomedical Engineering Research

Since its founding in 2001 by John Wikswo, the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) has established a broad program to develop and utilize a variety of BioMicroElectroMechanical Systems (BioMEMS) devices and advanced instrumentation to address pressing questions in integrative and systems biology and biomedical engineering. 1 The focus has been on devising novel micro- and nanosystems and techniques that enable measurements on biological systems that have previously been either impossible or difficult to do with high throughput. The work frequently targets the dynamics of biophysical and physiological processes. The first major VIIBRE effort in this area has been led by the Cliffel group to design, optimize, and apply advanced multianalyte electrochemical sensors in MicroPhysiometers to determine the effects of chemical and biological toxins on metabolic dynamics. 2-15 Their work now includes electrochemical detection of insulin, 16 single-cell scanning electrochemical microscopy (SECM), 17 and applications of metallic nanoparticles. 18-20 VIIBRE’s measurements of metabolic dynamics have been extended to nanoliter and picoliter volumes by the Baudenbacher group with custom NanoPhysiometers with microfabricated electrochemical sensors 11,21-27 to study cardiac excitation-contraction coupling in single cardiomyocytes, 28-30 PicoCalorimeters 31-33 that are now being applied to the study of cellular metabolism and biochemical reactions, and pulse-delivery microfluidics for cellular signaling. 34 The Wikswo, Seale, and McCawley groups have developed novel sample-handling procedures and microfluidic pumps and valves, 35-39 a dynamic amino-acid flux analyzer, 40 and devices for long-term culture of small populations of cells in NanoBioreactors 41-44 and for the growth of cultured cardiomyocytes during electrical stimulation. 45 A major effort is under way, as a collaboration between the Wikswo, McLean, and Cliffel groups at Vanderbilt, the Lipson group at Cornell, and the Vallabhajosyula group at CFD Research Corporation, to apply symbolic regression, 46 machine learning, 47,48 electrochemical 11 and optical sensing, and nanoelectrospray and MALDI and UPLC ion mobility-mass spectrometry 49-78 to infer the equations underlying metabolic and signaling dynamics, 79-83 ultimately to control biological systems. 83-85 The Li and Webb groups are advancing the study of neural co-cultures. 86 The Rosenthal, Cliffel, Wikswo, and McLean groups apply nanocrystals to biology. 87-90 This work lays the foundation for a new organ-on-chip initiative funded by DARPA, DTRA, NIH, and Vanderbilt, 91 and will build upon the Perkin-Elmer Opera QEHS automated confocal microscope 92 and three Waters Synapt G2 ion mobility mass spectrometers.

Several different classes of microfluidic and other devices are being developed by VIIBRE faculty, staff, and students for the study of chemotaxis and haptotaxis in cultured cells, 93-104 cellular forces, 105-109 predator-prey dynamics in bacteria-protozoal communities maintained in microfabricated environments, 36,110,111 metabolic oscillations in pancreatic islets, 112-115 protein binding and configuration control in support of fundamental studies of haptotaxis, 116 angiogenesis, 117 and the dynamics of inter- and intracellular signaling during the immune response in non-adherent immune cells and immune cell pairs restrained in arrays of microfabricated traps. 118 Electrical stimulation has been used to control cell fate, 45 and VIIBRE’s microfluidic devices are being applied in the tracking of differentiation of stem cells 119 and apoptosis of cancer cells. 120 A variety of broadly applicable microfluidic and optical techniques support these efforts, 35,37-39,121-127 and have led to a number of patents. 128-136 Image processing provides new tools for studying cell motility and mechanical activity, 137,138 and mathematical modeling inspires new research directions. 139 VIIBRE supported tissue engineering in the Shastri group. 140-149

Shane Hutson is using advanced optics and microfluidics to study Drosophila and C. elegans morphogenesis and wound healing 150-157 (supported by an NSF career award) and laser tissue ablation. 158-163 The Baudenbacher group has developed ultrahigh resolution scanning superconducting quantum interference device (SQUID) microscopes 164,165 for studies of algal 166 and mammalian electrophysiology, 167 cell sorting, and geomagnetism.168-170 Kirill Bolotin and his group are pioneering new graphene-based sensors. 171 All of these studies contribute to a larger effort to develop devices and models that will enable the “instrumentation and control” of single cells and small populations of cells, and to thereby eventually probe the complexities of systems biology. 172,173

At the larger scale of the isolated mouse and rabbit heart, a collaboration between the Baudenbacher, Sidorov, and Wikswo groups and Dr. Richard Gray of the Food and Drug Administration is utilizing advanced electrical, magnetic, 165,167,174 and optical 175,176 measurements, stimulators 177-180 and image processing 181,182 to explore cardiac electrophysiology and metabolism, and their connection to heart disease. 183-191 SQUID imaging has been extended to include magnetic measurements of gastrointestinal electrical activity. 192,193 VIIBRE supported faculty recruitments that strengthened functional magnetic resonance imaging at Vanderbilt. 194

The Systems Biology and Bioengineering Undergraduate Research Experience (SyBBURE), funded by Vanderbilt alumnus Gideon Searle, actively involves students in VIIBRE research. Directed by Kevin Seale, the year-round, multiyear SyBBURE Searle Undergraduate Research Program trains thirty undergraduates from across the entire university in microfabrication, cell biology, and microscopy and has them work with graduate students, postdocs, faculty, and staff as the students develop their own, independent research projects. 195

VIIBRE research, which spans molecules, cells, tissues, and organisms, has been funded in part by the NIH, DOD, Whitaker Foundation, NSF, Human Frontier Science Program, and industry. These and new efforts that have not yet led to publications or external funding are the result of active, multidisciplinary projects already established between VIIBRE and collaborating faculty, and will provide key components of the technical foundation for many projects at the intersection of medicine, biology, engineering, and the physical sciences.

 

VIIBRE PUBLICATIONS 2001-2013  

  1. He,B et al. Grand Challenges in Inaterfacing Engineering With Life Sciences and Medicine, IEEE Transactions on Biomedical Engineering, In press, doi:  10.1109/TBME.2013.2244886, 2013
  2. Eklund,S and Cliffel,DE. Synthesis and Catalytic Properties of Soluble Platinum Nanoparticles Protected by a Thiol Monolayer, Langmuir, 20, 6012-6018, 2004
  3. Eklund,SE et al. A Microphysiometer for Simultaneous Measurement of Changes in Extracellular Glucose, Lactate, Oxygen, and Acidification Rate, Anal. Chem., 76, 519-527, 2004
  4. Eklund,SE et al. Multianalyte Microphysiometry As a Tool in Metabolomics and Systems Biology, J. Electroanal. Chem., 587, 333-339, 2006
  5. Eklund,SE et al. Modification of the Cytosensor TM Microphysiometer to Simultaneously Measure Extracellular Acidification and Oxygen Consumption Rates, Anal. Chim. Acta, 496, 93-101, 2003
  6. Eklund,SE et al. Real-Time Cell Dynamics With a Multianalyte Physiometer. In: NanoBiotechnology Protocols.  Methods in Molecular Biology, Methods in Molecular Biology, Rosenthal,S and Wright,D, eds. Humana Press, Totawa, NJ, 209-223, 2005
  7. Eklund,SE et al. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer, Sensors, 9, 2117-2133, 2009
  8. Wikswo,JP, Baudenbacher,FJ, McGuinness,O, Device and Methods for Monitoring the Status of at Least One Cell, US Pat.No. 7,435,578 B2, Oct. 14, 2008
  9. Velkovsky,M et al. Modeling the Measurements of Cellular Fluxes in Microbioreactor Devices Using Thin Enzyme Electrodes, Journal of Mathematical Chemistry, 49, 251-275, 2011
  10. Snider,RM et al. The Effects of Cholera Toxin on Cellular Energy Metabolism, Toxins, 2, 632-648, 2010
  11. Lima,E et al. Multichamber Multipotentiostat System for Cellular Microphysiometry, Rev. Sci. Instrum., In preparation, 2011
  12. Hiatt,LA et al. A Printed Superoxide Dismutase Coated Electrode for the Study of Macrophage Oxidative Burst, Biosens. Bioelectron., 33, 128-133, 2012
  13. Harry,RS et al. Metabolic Impact of 4-Hydroxynonenal on Macrophage-Like RAW 264.7 Function and Activation, Chem. Res. Toxicol., 25, 1643-1651, 2012
  14. Kimmel,DW et al. Electrochemical Sensors and Biosensors, Anal. Chem., 84, 685-707, 2012
  15. McKenzie,JR et al. Metabolic Multianalyte Microphysiometry Reveals Extracellular Acidosis Is an Essential Mediator of Neuronal Preconditioning, ACS Chem. Neurosci., 3, 510-518, 2012
  16. Snider,RM et al. A Multiwalled Carbon Nanotube/Dihydropyran Composite Film Electrode for Insulin Detection in a Microphysiometer Chamber, Anal. Chim. Acta, 609, 44-52, 2008
  17. Ciobanu,M et al. Glucose and Lactate Biosensors for Scanning Electrochemical Microscopy Imaging of Single Live Cells, Anal. Chem., 80, 2717-2727, 2008
  18. Harkness,KM et al. Nanoscale Phase Segregation of Mixed Thiolates on Gold Nanoparticles, Angew. Chem. -Int. Ed., 50, 10554-10559, 2011
  19. Harkness,KM et al. Ag-44(SR)304-: A Silver-Thiolate Superatom Complex, Nanoscale, 4, 4269-4274, 2012
  20. Harkness,KM et al. Biomimetic Monolayer-Protected Gold Nanoparticles for Immunorecognition, Nanoscale, 4, 3843-3851, 2012
  21. Werdich,A et al. A Microfluidic Device to Confine a Single Cardiac Myocyte in a Sub-Nanoliter Volume on Planar Microelectrodes for Extracellular Potential Recordings, Lab Chip, 4, 357-362, 2004
  22. Ges,IA et al. Thin-Film IrOx PH Microelectrode for Microfluidic-Based Microsystems, Biosens. Bioelectron., 21, 248-256, 2005
  23. Ges,IA et al. Differential PH Measurements of Metabolic Cellular Activity in Nl Culture Volumes Using Microfabricated Iridium Oxide Electrodes, Biosens. Bioelectron., 22, 1303-1310, 2007
  24. Ges,IA, Dzhura,IA, Baudenbacher,FJ. On-Chip Acidification Rate Measurements From Single Cardiac Cells Confined in Sub-Nanoliter Volumes, Biomed. Microdevices, 10, 347-354, 2008
  25. Ges,IA and Baudenbacher,F. Enzyme Electrodes to Monitor Glucose Consumption of Single Cardiac Myocytes in Sub-Nanoliter Volumes, Biosens. Bioelectron., 25, 1019-1024, 2010
  26. Ges,IA and Baudenbacher,F. Microfluidic Device to Confine Single Cardiac Myocytes in Sub-Nanoliter Volumes for Extracellular PH Measurements, J. Exp. Nanosci., 3, 63-75, 2008
  27. Ges,IA and Baudenbacher,F. Enzyme-Coated Microelectrodes to Monitor Lactate Production in a Nanoliter Microfluidic Cell Culture Device, Biosens. Bioelectron., 26, 828-833, 2010
  28. Werdich,AA et al. Differential Effects of Phospholamban and Ca2+/Calmodulin-Dependent Kinase II on [Ca2+]i Transients in Cardiac Myocytes at Physiological Stimulation Frequencies, Am. J. Physiol. Heart, 294, 2352-2362, 2008
  29. Werdich,AA et al. Polymorphic Ventricular Tachycardia and Abnormal Calcium Handling in Very-Long-Chain Acyl-CoA Dehydrogenase Null Mice, Am. J. Physiol. Heart, 292, H2202-H2211, 2007
  30. Baudenbacher,F et al. Myofilament Ca2+ Sensitization Causes Susceptibility to Cardiac Arrhythmia in Mice, J. Clin. Invest., 118, 3893-3903, 2008
  31. Chancellor,EB et al. Heat Conduction Calorimeter for Massively Parallel High Throughput Measurements With Picoliter Sample Volumes, Appl. Phys. Lett., 85, 2408-2410, 2004
  32. Xu,J et al. A Microfabricated Nanocalorimeter:  Design, Characterization, and Chemical Calibration, Anal. Chem., 80, 2728-2733, 2008
  33. Lubbers,B and Baudenbacher,F. Isothermal Titration Calorimetry in Nanoliter Droplets With Subsecond Time Constants, Anal. Chem., 80, 7955-7961, 2011
  34. Botzolakis,EJ et al. Achieving Synaptically Relevant Pulses of Neurotransmitter Using PDMS Microfluidics, J. Neurosci. Methods, 177, 294-302, 2009
  35. Markov,DA et al. Tape Underlayment Rotary-Node (TURN) Valves for Simple on-Chip Microfluidic Flow Control, Biomed. Microdevices, 12, 135-144, 2010
  36. Markov,DA et al. Window on a Microworld: Simple Microfluidic Systems for Studying Microbial Transport in Porous Media, JoVE, 39, 2010
  37. Markov,DA et al. A Method for Periodic Sterile Sample Collection During Continuous Cell Culture in Microfluidic Devices, Chips and Tips Online, RSC Publishing, 2010
  38. Darby,S et al. A Metering Rotary Nanopump for Microfluidic Systems, Lab Chip, 10, 3218-3226, 2010
  39. Seale,KT et al. Macro to Nano:  A Simple Method for Transporting Cultured Cells From Milliliter Scale to Nanoliter Scale, Exp. Biol. Med., 235, 777-783, 2010
  40. Greene,J, Henderson,JW, Jr., Wikswo,JP. Rapid and Precise Determination of Cellular Amino Acid Flux Rates Using HPLC With Automated Derivatization With Absorbance Detection. Application Note, 5990-3283EN, Agilent Technologies , 2009
  41. Prokop,A et al. NanoLiterBioReactor:  Monitoring of Long-Term Mammalian Cell Physiology at Nanofabricated Scale. In: Biological and Bioinspired Materials and Devices, Aizenberg,J et al., eds. MRS, W9.5/O5.5, 2004
  42. Prokop,A et al. NanoLiterBioReactor:  Long-Term Mammalian Cell Culture at Nanofabricated Scale, Biomed. Microdevices, 6, 325-339, 2004
  43. Wikswo,JP, Baudenbacher,FJ, Prokop,A et al., Capillary Perfused Bioreactors With Multiple Chambers, US Pat.No. 7,534,601 B2, May 19, 2009
  44. Markov,DA et al. Thick-Tissue Bioreactor As a Platform for Long-Term Organotypic Culture and Drug Delivery, Lab Chip, 12, 4560-4568, 2012
  45. Yang,Z et al. Rapid Stimulation Causes Electrical Remodeling in Cultured Atrial Myocytes, J. Mol. Cell. Cardiol., 38, 299-308, 2005
  46. Schmidt,M and Lipson,H. Age-Fitness Pareto Optimization. In: Genetic programming theory and practice VIII, Genetic and evolutionary computation, Riolo,R et al., eds. Springer, New York, 129-146, 2011
  47. Ly,DL and Lipson,H. Learning Symbolic Representations of Hybrid Dynamical Systems, J. Mach. Learn. Res., 13, 3585-3618, 2012
  48. Chattopadhyay,I and Lipson,H. Abductive Learning of Quantized Stochastic Processes With Probabilistic Finite Automata, Phil. Trans. R. Soc. A, 371, 20110543, 2013
  49. Fenn,LS and Mclean,JA. Simultaneous Glycoproteomics on the Basis of Structure Using Ion Mobility-Mass Spectrometry, Mol. Biosyst., I5, 1298-1302, 2009
  50. Enders,JR and Mclean,JA. Chiral and Structural Analysis of Biomolecules Using Mass Spectrometry and Ion Mobility-Mass Spectrometry, Chirality, 21, E253-E264, 2009
  51. Fenn,LS et al. Characterizing Ion Mobility-Mass Spectrometry Conformation Space for the Analysis of Complex Biological Samples, Anal. Bioanal. Chem., 394, 235-244, 2009
  52. Mclean,JA. The Mass-Mobility Correlation Redux:  the Conformational Landscape of Anhydrous Biomolecules, J. Am. Soc. Mass. Spect., 20, 1775-1781, 2009
  53. Harkness,KM, Cliffel,DE, McLean,JA. Characterization of Thiolate-Protected Gold Nanoparticles by Mass Spectrometry, The Analyst, 135, 868-874, 2010
  54. Kliman,M et al. Structural Mass Spectrometry Analysis of Lipid Changes in a Drosophila Epilepsy Model Brain, Mol. Biosyst., 6, 958-966, 2010
  55. Ridenour,WB et al. Structural Characterization of Phospholipids and Peptides Directly From Tissue Sections by MALDI Traveling-Wave Ion Mobility-Mass Spectrometry, Anal. Chem., 82, 1881-1889, 2010
  56. Gant-Branum,RL et al. Identification of Phosphorylation Sites Within the Signaling Adaptor APPL1 by Mass Spectrometry, J. Proteome. Res., 9, 1541-1548, 2010
  57. Sundarapandian,S, May,JC, McLean,JA. Dual Source Ion Mobility-Mass Spectrometer for Direct Comparison of Electrospray Ionization and MALDI Collision Cross Section Measurements, Anal. Chem., 82, 3247-3254, 2010
  58. McLean,JR et al. Factors That Influence Helical Preferences for Singly Charged Gas-Phase Peptide Ions: The Effects of Multiple Potential Charge-Carrying Sites, J. Phys. Chem. B, 114, 809-816, 2010
  59. Kerr,TJ, Gant-Branum,RL, McLean,JA. Multiplexed Analysis of Peptide Functionality Using Lanthanide-Based Structural Shift Reagents, Int. J. Mass Spectrom., 307, 28-32, 2011
  60. Kliman,M, May,JC, McLean,JA. Lipid Analysis and Lipidomics by Structurally Selective Ion Mobility-Mass Spectrometry, Biochimica Et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1811, 935-945, 2011
  61. Enders,JR et al. Advanced Structural Mass Spectrometry for Systems Biology:  Pulling the Needles From Haystacks, Spectroscopy Supp. Curr. Trends Mass Spectrometry, July, 18-23, 2011
  62. McLean,JA, Schultz,JA, Woods,AS. Ion Mobility-Mass Spectrometry for Biological and Structural Mass Spectrometry. In: Electrospray and MALDI mass spectrometry: fundamentals, instrumentation, practicalities, and biological applications, Cole,RB, ed. Wiley, Hoboken, N.J., 411-439, 2010
  63. May,JC and McLean,JA. The Conformational Landscape of Biomolecules in Ion Mobility-Mass Spectrometry. In: Ion Mobility Spectrometry-mass Spectrometry: Theory and applications, Wilkins,CL and Trimpin,S, eds. CRC Press, Boca Raton, FL, 327-343, 2010
  64. Enders,JR et al. Peptide and Protein Analysis Using Ion Mobility-Mass Spectrometry. In: Peptide and Protein Mass Spectrometry in Drug Discovery, Gross,ML et al., eds. J. Wiley & Sons, 139-174, 2011
  65. Fenn,LS and McLean,JA. Structural Separations by Ion Mobility-MS for Glycomics and Glycoproteomics. In: Mass spectrometry of glycoproteins: methods and protocols, Methods in molecular biology, Kohler,J and Patrie,SM, eds. Humana Press, New York, 171-193, 2013
  66. Matusch,A et al. Combined Elemental and Biomolecular Mass Spectrometry Imaging (MSI)  for Probing the Inventory of Tissue at the Micrometer Scale, Anal. Chem., 84, 3170-3178, 2012
  67. Goodwin,CR et al. Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products, J. Nat. Prod., 75, 48-53, 2012
  68. May,JC, Goodwin,CR, McLean,JA. Gas-Phase Ion Mobility-Mass Spectrometry(IM-MS)and Tandem IM-MS/MS Strategies for Metabolism Studies and Metabolomics. In: Encyclopedia of drug metabolism and interactions, Lyubimov,AV, ed. Wiley, Hoboken, N.J., 1-29, 2012
  69. Enders,JR et al. A Dual-Column Solid Phase Extraction Strategy for Online Collection and Preparation of Continuously Flowing Effluent Streams for Mass Spectrometry, Anal. Chem., 84, 8467-8474, 2012
  70. Mclean,JA, Ridenour,WB, Caprioli,RM. Profiling and Imaging of Tissues by Imaging Ion Mobility-Mass Spectrometry, J. Mass Spectrom., 42, 1099-1105, 2007
  71. Fenn,LS and Mclean,JA. Biomolecular Structural Separations by Ion Mobility-Mass Spectrometry, Anal. Bioanal. Chem., 391, 905-909, 2008
  72. Gies,AP et al. Characterization of Branching in Aramid Polymers Studied by MALDI-Ion Mobility/Mass Spectrometry, Macromolecules, 41, 8299-8301, 2008
  73. Fenn,LS and Mclean,JA. Enhanced Carbohydrate Structural Selectivity in Ion Mobility-Mass Spectrometry Analyses by Boronic Acid Derivatization, Chem. Commun., Issue 43, 5505-5507, 2008
  74. Phelan,VV et al. Adenylation Enzyme Characterization Using G-18O4-ATP Pyrophosphate Exchange, Chemistry & Biology, 16, 473-478, 2009
  75. Gant-Branum,RL, Kerr,TJ, Mclean,JA. Labeling Strategies in Mass Spectrometry-Based Protein Quantitation, Analyst, 134, 1525-1530, 2009
  76. Hines,KM, Enders,JR, McLean,JA. Multidimensional Separations by Ion Mobility-Mass Spectrometry. In: Encyclopedia of Analytical Chemistry (on-line), Myers,RA and Muddiman,D, eds. John Wiley & Sons, Ltd, doi: 10.1002/9780470027318.a9313, 2012
  77. Forsythe,JG et al. Semitransparent Nanostructured Films for Imaging Mass Spectrometry and Optical Microscopy, Analytical Chemistry, 84, 10665-10670, 2012
  78. Derewacz,DK et al. Antimicrobial Drug Resistance Affects Broad Changes in Metabolomic Phenotype in Addition to Secondary Metabolism, Proceedings of the National Academy of Sciences, 110, 2336-2341, 2013
  79. Enders,JR et al. Towards Monitoring Real-Time Cellular Response Using an Integrated Microfluidics-MALDI/NESI-Ion Mobility-Mass Spectrometry Platform, IET Syst. Biol., 4, 416-427, 2010
  80. Kerr,TJ and McLean,JA. Peptide Quantitation Using Primary Amine Selective Metal Chelation Labels for Mass Spectrometry, Chem. Commun., 46, 5479-5481, 2010
  81. Mclean,JA, Fenn,LS, Enders,JR. Structurally Selective Imaging Mass Spectrometry by Imaging Ion Mobility-Mass Spectrometry. In: Mass Spectrometric Imaging:  History, Fundamentals and Protocols, Methods in Molecular Biology, Sweedler,JV and Rubakhin,SS, eds. Humana Press, New York, 363-383, 2010
  82. Fenn,LS and McLean,JA. Structural Resolution of Carbohydrate Positional and Structural Isomers Based on Gas-Phase Ion Mobility-Mass Spectrometry, Phys. Chem. Chem. Phys., 13, 2196-2205, 2011
  83. Schmidt,MD et al. Automated Refinement and Inference of Analytical Models for Metabolic Networks, Phys. Biol., 8, 055011, 2011
  84. Yang,R et al. External Control of the GAL Network in S. Cerevisiae:  A View From Control Theory, PloS. One., 6, e19353, 2011
  85. LeDuc,PR, Messner,WC, Wikswo,JP. How Do Control-Based Approaches Enter into Biology?, Annu. Rev. Biomed. Engr., 13, 369-396, 2011
  86. Gao,Y et al. A Versatile Valve-Enabled Microfluidic Cell Co-Culture Platform and Demonstration of Its Applications to Neurobiology and Cancer Biology, Biomed. Microdevices, 13, 539-548, 2011
  87. Warnement,MR et al. Quantum Dot Probes for Monitoring Dynamic Cellular Response:  Reporters of T Cell Activation, IEEE Trans. NanoBiosci., 5, 268-272, 2006
  88. Harkness,KM et al. Surface Fragmentation of Complexes From Thiolate Protected Gold Nanoparticles by Ion Mobility-Mass Spectrometry, Anal. Chem., 82, 3061-3066, 2010
  89. Harkness,KM et al. A Structural Mass Spectrometry Strategy for the Relative Quantitation of Ligands on Mixed Monolayer-Protected Gold Nanoparticles, Anal. Chem., 82, 9268-9274, 2010
  90. Dukes III,AD et al. Single-Nanocrystal Spectroscopy of White-Light-Emitting CdSe Nanocrystals, The Journal of Physical Chemistry A, 115, 4076-4081, 2011
  91. Wikswo,JP et al. Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-a-Chip Systems, IEEE Trans. Biomed. Eng., 60, 682-690, 2013
  92. Chumbler,NM et al. Clostridium Difficile Toxin B Causes Epithelial Cell Necrosis Through an Autoprocessing-Independent Mechanism, PLoS Pathogens, 8, Article e1003072, 2012
  93. Walker,GM et al. Effects of Flow and Diffusion on Chemotaxis Studies in a Microfabricated Gradient Generator, Lab Chip, 5, 611-618, 2005
  94. Sai,J et al. The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand Induced Activation of ERK, AKT and Chemotaxis in HL60 Cells, J. Biol. Chem., 281, 35931-35941, 2006
  95. Gorman,BR and Wikswo,JP. Characterization of Transport in Microfluidic Gradient Generators, Microfluid. Nanofluid., 4, 273-285, 2008
  96. Gruver,JS, Wikswo,JP, Chung,CY. 3'-Phosphoinositides Regulate the Coordination of Speed and Accuracy During Chemotaxis, Biophys. J., 95, 4057-4067, 2008
  97. Elzie,CA et al. Dynamic Localization of G Proteins in Dictyostelium Discoideum, J. Cell Sci., 122, 2597-2603, 2009
  98. Sai,J et al. Parallel Phosphatidylinositol 3-Kinase (PI3K)-Dependent and Src-Dependent Pathways Lead to CXCL8-Mediated Rac2 Activation and Chemotaxis, J. Biol. Chem., 283, 26538-26547, 2008
  99. Liu,Y et al. Microfluidic Switching System for Analyzing Chemotaxis Responses of Wortmannin-Inhibited HL-60 Cells, Biomed. Microdevices, 10, 499-507, 2008
  100. Rachakonda,G et al. Increased Cell Migration and Plasticity in Nrf2 Deficient Cancer Cell Lines, Oncogene, 29, 3703-3714, 2010
  101. Jowhar,D et al. Open Access Microfluidic Device for the Study of Cell Migration Diring Chemotaxis, Integr. Biol., 2, 648-658, 2010
  102. Ashby,W, Wikswo,JP, Zijlstra,A. Magnetically Attachable Stencils and the Non-Destructive Analytis of the Contribution Made by the Underlying Matrix to Cell Migration, Biomaterials, 33, 8189-8203, 2012
  103. Ashby,WJ and Zijlstra,A. Established and Novel Methods of Interrogating Two-Dimensional Cell Migration, Integr. Biol., 4, 1338-1350, 2012
  104. Ashby,WJ et al. Towards Scalable Complexity: Four Tools Spanning in Vitro to in Vivo Models of Cancer Migration, Clin. Exp. Metastas., 28, 256, 2011
  105. Addae-Mensah,KA et al. A Flexible, Quantum Dot-Labeled Cantilever Post Array for Studying Cellular Microforces, Sens. Act. A, 136, 385-397, 2007
  106. Addae-Mensah,KA and Wikswo,JP. Measurement Techniques for Cellular Biomechanics In Vitro, Exp. Biol. Med., 233, 792-809, 2008
  107. Addae-Mensah,KA, Reiserer,RS, Wikswo,JP. Poly(Vinyl Alcohol) As a Structure Release Layer for Microfabrication of Polymer Composite Structures, J. Micromech. Microeng., 17, N41-N46, 2007
  108. Addae-Mensah,KA et al. Cryogenic Etching of Silicon:  an Alternative Method for Fabrication of Vertical Microcantilever Master Molds, J. Microelectromech. S., 19, 64-74, 2010
  109. An,SS et al. Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix, Biochem. Biophys. Res. Commun., 382, 697-703, 2009
  110. Wang,W et al. Mobility of Protozoa Through Narrow Channels, Appl. Environ. Microbiol., 71, 4268-4637, 2005
  111. Wang,W et al. Protozoan Migration in Bent Microfluidic Channels, Appl. Environ. Microbiol., 74, 1945-1949, 2008
  112. Rocheleau,JV et al. Microfluidic Glucose Stimulation Reveals Limited Coordination of Intracellular Ca2+ Activity Oscillations in Pancreatic Islets, PNAS, 101, 12899-12903, 2004
  113. Rocheleau,JV and Piston,DW. Combining Microfluidics and Quantitative Fluorescence Microscopy to Examine Pancreatic Islet Molecular Physiology. In: Methods in Cell Biology, Biophysical Tools for Biologists, Correia,JJ and Detrich,HW, eds. Elsevier, 71-92, 2008
  114. Benninger,RKP et al. Gap Junction Coupling and Calcium Waves in the Pancreatic Islet, Biophys. J., 95, 5048-5061, 2008
  115. Easley,CJ et al. Rapid and Inexpensive Fabrication of Polymeric Microfluidic Devices Via Toner Transfer Masking, Lab Chip, 9, 1119-1127, 2009
  116. Georgescu,W et al. Model-Controlled Hydrodynamic Focusing to Generate Multiple Overlapping Gradients of Surface-Immobilized Proteins in Microfluidic Devices, Lab Chip, 8, 238-244, 2008
  117. Liu,Y et al. Microfabricated Scaffold-Guided Endothelial Morphogenesis in Three-Dimensional Culture, Biomed. Microdevices, 13, 837-846, 2011
  118. Faley,S et al. Microfluidic Platform for Real-Time Signaling Analysis of Multiple Single T Cells in Parallel, Lab Chip, 8, 1700-1712, 2008
  119. Faley,SL et al. Microfluidic Single Cell Arrays to Interrogate Signalling Dynamics of Individual, Patient-Derived Hematopoietic Stem Cells, Lab Chip, 9, 2659-2664, 2009
  120. Wlodkowic,D et al. Microfluidic Single-Cell Array Cytometry for the Analysis of Tumour Apoptosis, Anal. Chem., 81, 5517-5523, 2009
  121. Bornhop,DJ et al. Free-Solution, Label-Free Molecular Interactions Studied by Back-Scattering Interferometry, Science, 317, 1732-1736, 2007
  122. Vajandar,SK et al. SiO2-Coated Porous Anodic Alumina Membranes for High Flow Rate Electroosmotic Pumping, Nanotechnology, 18, 275705, 2007
  123. Seale,KT et al. Mirrored Pyramidal Wells for Simultaneous Mutiple Vantage Point Microscopy, J. Microsc., 232, Pt.1, 1-6, 2008
  124. Seale,K, Janetopoulos,C, Wikswo,J. Micro-Mirrors for Nanoscale Three-Dimensional Microscopy, Acs Nano, 3, 493-497, 2009
  125. Gould,PA et al. Rotary Planar Peristaltic Micropump, Lab Chip, Submitted, 2011
  126. Schaffer,DK et al. Milli-to-Micro:  Soft Lithography and Rapid Prototyping for Lab on a Well Plate, In Preparation, 2011
  127. Skandarajah,A et al. Quantifying Chemical Gradients in Geometrically Complex Microfluidic Devices:  Mathematical Modeling and Ratiometric Fluorescence Validation, In Preparation, 2011
  128. Baudenbacher,FJ, Wikswo,JP, Balcarcel,RR et al., Apparatus and Methods for Monitoring the Status of a Metabolically Active Cell, US Pat.No. 7,704,745 B2, Apr. 27, 2010
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