Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure

Experimental Biology and Medicine

Volumn 239, Issue 9, 2014, Pages 1225-1239

  Sung, Jong Hwan ^a   Srinivasan, Balaji ^b   Esch, Mandy Brigitte ^c   McLamb, William T ^b   Bernabini, Catia ^b   Shuler, Michael L ^c   Hickman, James J ^b,d  

^a Hong Ik University   (South Korea)

^b UNIVERSITY OF CENTRAL FLORIDA   (United States)

^c Cornell University   (United States)

^d UNIVERSITY OF CENTRAL FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

chemical analysis; electrical analysis; mechanical analysis; microfabrication; Microphysiological system; PBPK models

Indexed keywords

DIMETICONE; HEPTANOL; SPARFLOXACIN;

ARTICLE; ATOMIC FORCE MICROSCOPY; BASAL METABOLIC RATE; CELL INTERACTION; CHEMICAL ANALYSIS; CHEMICAL MODEL; CHEMICAL MODIFICATION; CULTURE MEDIUM; DISEASE MODEL; ELECTRIC RESISTANCE; EXPOSURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIGH THROUGHPUT SCREENING; HUMAN; ION MOBILITY SPECTROMETRY; LAB ON A CHIP; MECHANICAL STRESS; METABOLIC ACTIVITY ASSAY; MICROELECTROMECHANICAL SYSTEM; MICROFLUIDIC ANALYSIS; MICROFLUIDICS; MICROTECHNOLOGY; PHARMACODYNAMICS; PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING; TISSUE CULTURE TECHNIQUE; TISSUE ENGINEERING; TRANSENDOTHELIAL ELECTRICAL RESISTANCE; ANIMAL; BIOLOGICAL MODEL; DRUG SCREENING; ELECTRICAL ANALYSIS; EQUIPMENT; MECHANICAL ANALYSIS; METHODOLOGY; MICROPHYSIOLOGICAL SYSTEM; PBPK MODELS; PHARMACOKINETICS; REVIEW;

CHEMICAL ANALYSIS; ELECTRICAL ANALYSIS; MECHANICAL ANALYSIS; MICROFABRICATION; MICROPHYSIOLOGICAL SYSTEM; PBPK MODELS;

ANIMALS; DRUG EVALUATION, PRECLINICAL; HUMANS; LAB-ON-A-CHIP DEVICES; MODELS, BIOLOGICAL; PHARMACOKINETICS; TISSUE CULTURE TECHNIQUES;

EID: 84907014905     PISSN: 15353702     EISSN: 15353699     Source Type: Journal    
DOI: 10.1177/1535370214529397     Document Type: Article

References (139)

1. Lau YY,Chen YH,Liu TT,Li C,Cui X,White RE,Cheng KC.Evaluation of a novel in vitro Caco-2 hepatocyte hybrid system for predicting in vivo oral bioavailability.Drug Metab Dispos. 2004;32:937-42
2. Li AP,Bode C,Sakai Y.A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells.Chem Biol Interact. 2004;150:129-36
3. Lotito SB,Frei B.Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?.Free Radic Biol Med. 2006;41:1727-46
4. Sung JH,Esch MB,Prot JM,Long CJ,Smith A,Hickman JJ,Shuler ML.Microfabricated mammalian organ systems and their integration into models of whole animals and humans.Lab Chip. 2013;13:1201-12
5. Sung JH,Esch MB,Shuler ML.Integration of in silico and in vitro platforms for pharmacokinetic-pharmacodynamic modeling.Expert Opin Drug Metab Toxicol. 2010;6:1063-81
6. Huh D,Torisawa YS,Hamilton GA,Kim HJ,Ingber DE.Microengineered physiological biomimicry: organs-on-chips.Lab Chip. 2012;12:2156-64
7. Wikswo JP,Curtis EL,Eagleton ZE,Evans BC,Kole A,Hofmeister LH,Matloff WJ.Scaling and systems biology for integrating multiple organs-on-a-chip.Lab Chip. 2013;13:3496-511
8. Aarons L.Physiologically based pharmacokinetic modelling: a sound mechanistic basis is needed.Br J Clin Pharmacol. 2005;60:581-3
9. McCarley KD,Bunge AL.Physiologically relevant one-compartment pharmacokinetic models for skin. 1. Development Of models.J Pharm Sci. 1998;87:1264-1264
10. Czock D,Keller F,Rasche FM,Haussler U.Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.Clin Pharmacokinet. 2005;44:61-98
11. Himmelstein KJ,Lutz RJ.A review of the applications of physiologically based pharmacokinetic modeling.J Pharmacokinet Pharmacodyn. 1979;7:127-45
12. Davies B,Morris T.Physiological parameters in laboratory animals and humans.Pharm Res. 1993;10:1093-5.
13. van Midwoud PM,Verpoorte E,Groothuis GM.Microfluidic devices for in vitro studies on liver drug metabolism and toxicity.Integr Biol (Camb). 2011;3:509-21
14. Poulin P,Theil FP.Prediction of pharmacokinetics prior to in vivo studies. II. Generic physiologically based pharmacokinetic models of drug disposition.J Pharm Sci. 2002;91:1358-70
15. Benowitz N,Forsyth RP,Melmon KL,Rowland M.Lidocaine disposition kinetics in monkey and man. II. Effects of hemorrhage and sympathomimetic drug administration.Clin Pharmacol Ther. 1974;16:99-109
16. Aarons L.Population pharmacokinetics: theory and practice.Br J Clin Pharmacol. 1991;32:669-70
17. Nestorov I.Whole body pharmacokinetic models.Clin Pharmacokinet. 2003;42:883-908
18. Ritchie RH,Morgan DJ,Horowitz JD.Myocardial effect compartment modeling of metoprolol and sotalol: importance of myocardial subsite drug concentration.J Pharm Sci. 1998;87:177-82
19. Lobo ED,Balthasar JP.Pharmacokinetic-pharmacodynamic modeling of methotrexate-induced toxicity in mice.J Pharm Sci. 2003;92:1654-64
20. Mager DE,Wyska E,Jusko WJ.Diversity of mechanism-based pharmacodynamic models.Drug Metab Dispos. 2003;31:510-8
21. Sung JH,Dhiman A,Shuler ML.A combined pharmacokinetic-pharmacodynamic (PK-PD) model for tumor growth in the rat with UFT administration.J Pharm Sci. 2009;98:1885-904
22. Timchalk C,Nolan RJ,Mendrala AL,Dittenber DA,Brzak KA,Mattsson JL.A Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humans.Toxicol Sci. 2002;66:34-53
23. Timchalk C,Poet TS.Development of a physiologically based pharmacokinetic and pharmacodynamic model to determine dosimetry and cholinesterase inhibition for a binary mixture of chlorpyrifos and diazinon in the rat.Neurotoxicology. 2008;29:428-43
24. Derendorf H,Lesko LJ,Chaikin P,Colburn WA,Lee P,Miller R,Powell R,Rhodes G,Stanski D,Venitz J.Pharmacokinetic/pharmacodynamic modeling in drug research and development.J Clin Pharmacol. 2000;40:1399-418
25. Csajka C,Verotta D.Pharmacokinetic-pharmacodynamic modelling: history and perspectives.J Pharmacokinet Pharmacodyn. 2006;33:227-79
26. Agoram BM,Martin SW,van der Graaf PH.The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in translational research of biologics.Drug Discov Today. 2007;12:1018-24
27. Moraes C,Labuz JM,Leung BM,Inoue M,Chun TH,Takayama S.On being the right size: scaling effects in designing a human-on-a-chip.Integr Biol (Camb). 2013;5:1149-61
28. Reich PB,Tjoelker MG,Machado JL,Oleksyn J.Universal scaling of respiratory metabolism, size and nitrogen in plants.Nature. 2006;439:457-61
29. West GB,Woodruff WH,Brown JH.Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals.Proc Natl Acad Sci U S A. 2002;99:2473-8
30. Mazzei D,Guzzardi MA,Giusti S,Ahluwalia A.A low shear stress modular bioreactor for connected cell culture under high flow rates.Biotechnol Bioeng. 2010;106:127-37
31. Vozzi F,Heinrich JM,Bader A,Ahluwalia AD.Connected culture of murine hepatocytes and HUVEC in a multicompartmental bioreactor.Tissue Eng Part A. 2009;15:1291-9
32. Sin A,Chin KC,Jamil MF,Kostov Y,Rao G,Shuler ML.The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors.Biotechnol Prog. 2004;20:338-45
33. Sung JH,Shuler ML.A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs.Lab Chip. 2009;9:1385-94
34. Sung JH, Shuler ML. Pharmacokinetic-pharmacodynamic models on a chip. In: Nahmias Y, Sangeeta NB (eds) Methods in bioengineering: microdevices in biology and medicine. Boston, MA: Artech House, 2009.
35. Tatosian DA,Shuler ML.A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers.Biotechnol Bioeng. 2009;103:187-98
36. Oh KW,Lee K,Ahn B,Furlani EP.Design of pressure-driven microfluidic networks using electric circuit analogy.Lab Chip. 2012;12:515-45
37. Kim S,Lee H,Chung M,Jeon NL.Engineering of functional, perfusable 3D microvascular networks on a chip.Lab Chip. 2013;13:1489-500
38. Moya ML,Hsu YH,Lee AP,Hughes CC,George SC.In vitro perfused human capillary networks.Tissue Eng Part C Methods. 2013;19:730-7
39. Allen JW,Khetani SR,Bhatia SN.In vitro zonation and toxicity in a hepatocyte bioreactor.Toxicol Sci. 2005;84:110-9
40. Khetani SR,Bhatia SN.Microscale culture of human liver cells for drug development.Nat Biotechnol. 2008;26:120-6
41. Kim J,Hegde M,Jayaraman A.Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions.Lab Chip. 2010;10:43-50
42. Mahler GJ,Esch MB,Glahn RP,Shuler ML.Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity.Biotechnol Bioeng. 2009;104:193-205
43. Booth R,Kim H.Characterization of a microfluidic in vitro model of the blood-brain barrier (muBBB).Lab Chip. 2012;12:1784-92
44. Griep LM,Wolbers F,de Wagenaar B,ter Braak PM,Weksler BB,Romero IA,Couraud PO,Vermes I,van der Meer AD,van den Berg A.BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function.Biomed Microdevices. 2013;15:145-50
45. Prabhakarpandian B,Shen MC,Nichols JB,Mills IR,Sidoryk-Wegrzynowicz M,Aschner M,Pant K.SyM-BBB: a microfluidic blood brain barrier model.Lab Chip. 2013;13:1093-101
46. Miller C,George S,Niklason L.Developing a tissue-engineered model of the human bronchiole.J Tissue Eng Regen Med. 2010;4:619-27
47. Huh D,Matthews BD,Mammoto A,Montoya-Zavala M,Hsin HY,Ingber DE.Reconstituting organ-level lung functions on a chip.Science. 2010;328:1662-8
48. Jang KJ,Cho HS,Kang do H,Bae WG,Kwon TH,Suh KY.Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells.Integr Biol (Camb). 2011;3:134-41
49. Jang KJ,Mehr AP,Hamilton GA,McPartlin LA,Chung S,Suh KY,Ingber DE.Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment.Integr Biol (Camb). 2013;5:1119-29
50. Jang KJ,Suh KY.A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells.Lab Chip. 2010;10:36-42
51. Chen MB,Srigunapalan S,Wheeler AR,Simmons CA.A 3D microfluidic platform incorporating methacrylated gelatin hydrogels to study physiological cardiovascular cell-cell interactions.Lab Chip. 2013;13:2591-8
52. Natarajan A,Stancescu M,Dhir V,Armstrong C,Sommerhage F,Hickman JJ,Molnar P.Patterned cardiomyocytes on microelectrode arrays as a functional, high information content drug screening platform.Biomaterials. 2011;32:4267-74
53. Song JW,Cavnar SP,Walker AC,Luker KE,Gupta M,Tung YC,Luker GD,Takayama S.Microfluidic endothelium for studying the intravascular adhesion of metastatic breast cancer cells.PloS One. 2009;4:e5756-e5756
54. Hsu YH,Moya ML,Hughes CC,George SC,Lee AP.A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays.Lab Chip. 2013;13:2990-8
55. Zheng Y,Chen J,Craven M,Choi NW,Totorica S,Diaz-Santana A,Kermani P,Hempstead B,Fischbach-Teschl C,Lopez JA,Stroock AD.In vitro microvessels for the study of angiogenesis and thrombosis.Proc Natl Acad Sci U S A. 2012;109:9342-7
56. Chang H,Kim BJ,Kim YS,Suarez SS,Wu M.Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.PloS One. 2013;8:e60587-e60587
57. Huh D,Leslie DC,Matthews BD,Fraser JP,Jurek S,Hamilton GA,Thorneloe KS,McAlexander MA,Ingber DE.A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice.Sci Transl Med. 2012;4:159ra47-159ra47
58. Ploss A,Khetani SR,Jones CT,Syder AJ,Trehan K,Gaysinskaya VA,Mu K,Ritola K,Rice CM,Bhatia SN.Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures.Proc Natl Acad Sci U S A. 2010;107:3141-5
59. Moraes C,Mehta G,Lesher-Perez SC,Takayama S.Organs-on-a-chip: a focus on compartmentalized microdevices.Ann Biomed Eng. 2012;40:1211-27
60. Landersdorfer CB,Jusko WJ.Pharmacokinetic/pharmacodynamic modelling in diabetes mellitus.Clin Pharmacokinet. 2008;47:417-48
61. Stefek M,Karasu C.Eye lens in aging and diabetes: effect of quercetin.Rejuvenation Res. 2011;14:525-34
62. Siriwardhana N,Kalupahana NS,Cekanova M,LeMieux M,Greer B,Moustaid-Moussa N.Modulation of adipose tissue inflammation by bioactive food compounds.J Nutr Biochem. 2013;24:613-23
63. Manzano S,Williamson G.Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells.Mol Nutr Food Res. 2010;54:1773-80
64. Bardy G,Virsolvy A,Quignard JF,Ravier MA,Bertrand G,Dalle S,Cros G,Magous R,Richard S,Oiry C.Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.Br J Pharmacol. 2013;169:1102-13
65. Artursson P,Palm K,Luthman K.Caco-2 monolayers in experimental and theoretical predictions of drug transport.Adv Drug Deliv Rev. 2001;46:27-43
66. Lee MY,Kumar RA,Sukumaran SM,Hogg MG,Clark DS,Dordick JS.Three-dimensional cellular microarray for high-throughput toxicology assays.Proc Natl Acad Sci U S A. 2008;105:59-63
67. van Midwoud PM,Groothuis GM,Merema MT,Verpoorte E.Microfluidic biochip for the perifusion of precision-cut rat liver slices for metabolism and toxicology studies.Biotechnol Bioeng. 2010;105:184-94
68. van Midwoud PM,Merema MT,Verpoorte E,Groothuis GM.A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices.Lab Chip. 2010;10:2778-86
69. Viravaidya K,Sin A,Shuler ML.Development of a microscale cell culture analog to probe naphthalene toxicity.Biotechnol Prog. 2004;20:316-23
70. Sung JH,Kam C,Shuler ML.A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip.Lab Chip. 2010;10:446-55
71. Zhang C,Zhao Z,Abdul Rahim NA,van Noort D,Yu H.Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments.Lab Chip. 2009;9:3185-92
72. Iori E,Vinci B,Murphy E,Marescotti MC,Avogaro A,Ahluwalia A.Glucose and fatty acid metabolism in a 3 tissue in-vitro model challenged with normo- and hyperglycaemia.PloS One. 2012;7:e34704-e34704
73. Wagner I,Materne EM,Brincker S,Sussbier U,Fradrich C,Busek M,Sonntag F,Sakharov DA,Trushkin EV,Tonevitsky AG,Lauster R,Marx U.A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture.Lab Chip. 2013;13:3538-47
74. Choi JR,Sung JH,Shuler ML,Kim D.Investigation of portable in situ fluorescence optical detection for microfluidic 3D cell culture assays.Opt Lett. 2010;35:1374-6
75. Natarajan A,Molnar P,Sieverdes K,Jamshidi A,Hickman JJ.Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.Toxicol In Vitro. 2006;20:375-81
76. Alford PW,Feinberg AW,Sheehy SP,Parker KK.Biohybrid thin films for measuring contractility in engineered cardiovascular muscle.Biomaterials. 2010;31:3613-21
77. Herrmann KL,McCulloch AD,Omens JH.Glycated collagen cross-linking alters cardiac mechanics in volume-overload hypertrophy.Am J Physiol Heart Circ Physiol. 2003;284:H1277-84
78. Shimizu K,Fujita H,Nagamori E.Evaluation systems of generated forces of skeletal muscle cell-based bio-actuators.J Biosci Bioeng. 2013;115:115-21
79. Wilson K,Das M,Wahl KJ,Colton RJ,Hickman J.Measurement of contractile stress generated by cultured rat muscle on silicon cantilevers for toxin detection and muscle performance enhancement.PloS One. 2010;5:e11042-e11042
80. Fraticelli A,Josephson R,Danziger R,Lakatta E,Spurgeon H.Morphological and contractile characteristics of rat cardiac myocytes from maturation to senescence.Am J Physiol. 1989;257:H259-65
81. Tasche C,Meyhofer E,Brenner B.A force transducer for measuring mechanical properties of single cardiac myocytes.Am J Physiol. 1999;277:H2400-8
82. Shepherd N,Vornanen M,Isenberg G.Force measurements from voltage-clamped guinea pig ventricular myocytes.Am J Physiol. 1990;258:H452-9
83. Brandt PW,Colomo F,Piroddi N,Poggesi C,Tesi C.Force regulation by Ca2+ in skinned single cardiac myocytes of frog.Biophys J. 1998;74:1994-2004
84. Marganski WA,De Biase VM,Burgess ML,Dembo M.Demonstration of altered fibroblast contractile activity in hypertensive heart disease.Cardiovasc Res. 2003;60:547-56
85. Tanaka Y,Morishima K,Shimizu T,Kikuchi A,Yamato M,Okano T,Kitamori T.Demonstration of a PDMS-based bio-microactuator using cultured cardiomyocytes to drive polymer micropillars.Lab Chip. 2006;6:230-5
86. Lin G,Palmer RE,Pister KS,Roos KP.Miniature heart cell force transducer system implemented in MEMS technology.IEEE Trans Biomed Eng. 2001;48:996-1006
87. Kaneko T,Kojima K,Yasuda K.An on-chip cardiomyocyte cell network assay for stable drug screening regarding community effect of cell network size.Analyst. 2007;132:892-8
88. McCain ML,Sheehy SP,Grosberg A,Goss JA,Parker KK.Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip.Proc Natl Acad Sci U S A. 2013;110:9770-5
89. Vandenburgh H.High-content drug screening with engineered musculoskeletal tissues.Tissue Eng Part B Rev. 2010;16:55-64
90. Das M,Gregory CA,Molnar P,Riedel LM,Wilson K,Hickman JJ.A defined system to allow skeletal muscle differentiation and subsequent integration with silicon microstructures.Biomaterials. 2006;27:4374-80
91. Liao H,Zhou GQ.Development and progress of engineering of skeletal muscle tissue.Tissue Eng Part B Rev. 2009;15:319-31
92. Levenberg S,Rouwkema J,Macdonald M,Garfein ES,Kohane DS,Darland DC,Marini R,van Blitterswijk CA,Mulligan RC,D'Amore PA,Langer R.Engineering vascularized skeletal muscle tissue.Nat Biotechnol. 2005;23:879-84
93. Hinds S,Bian W,Dennis RG,Bursac N.The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle.Biomaterials. 2011;32:3575-83
94. Powell CA,Smiley BL,Mills J,Vandenburgh HH.Mechanical stimulation improves tissue-engineered human skeletal muscle.Am J Physiol Cell Physiol. 2002;283:C1557-65
95. Vandenburgh H,Shansky J,Benesch-Lee F,Barbata V,Reid J,Thorrez L,Valentini R,Crawford G.Drug-screening platform based on the contractility of tissue-engineered muscle.Muscle Nerve. 2008;37:438-47
96. Shimizu K,Sasaki H,Hida H,Fujita H,Obinata K,Shikida M,Nagamori E.Assembly of skeletal muscle cells on a Si-MEMS device and their generative force measurement.Biomed Microdevices. 2010;12:247-52
97. Tsukita S,Furuse M,Itoh M.Multifunctional strands in tight junctions.Nat Rev Mol Cell Biol. 2001;2:285-93
98. Fasano A,Shea-Donohue T.Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases.Nat Rev Gastroenterol Hepatol. 2005;2:416-22
99. Hawkins BT,Davis TP.The blood-brain barrier/neurovascular unit in health and disease.Pharmacol Rev. 2005;57:173-85
100. Daneman R,Zhou L,Kebede AA,Barres BA.Pericytes are required for blood-brain barrier integrity during embryogenesis.Nature. 2010;468:562-6
101. Rubas W,Cromwell ME,Shahrokh Z,Villagran J,Nguyen TN,Wellton M,Nguyen TH,Mrsny RJ.Flux measurements across Caco-2 monolayers may predict transport in human large intestinal tissue.J Pharm Sci. 1996;85:165-9
102. Douville NJ,Tung YC,Li R,Wang JD,El-Sayed ME,Takayama S.Fabrication of two-layered channel system with embedded electrodes to measure resistance across epithelial and endothelial barriers.Anal Chem. 2010;82:2505-11
103. Sun T,Swindle EJ,Collins JE,Holloway JA,Davies DE,Morgan H.On-chip epithelial barrier function assays using electrical impedance spectroscopy.Lab Chip. 2010;10:1611-7
104. Jimison LH,Tria SA,Khodagholy D,Gurfinkel M,Lanzarini E,Hama A,Malliaras GG,Owens RM.Measurement of barrier tissue integrity with an organic electrochemical transistor.Adv Mater. 2012;24:5919-23
105. Johnstone AF,Gross GW,Weiss DG,Schroeder OH,Gramowski A,Shafer TJ.Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century.Neurotoxicology. 2010;31:331-50
106. Jones IL,Livi P,Lewandowska MK,Fiscella M,Roscic B,Hierlemann A.The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics.Anal Bioanal Chem. 2011;399:2313-29
107. Asai Y,Tada M,Otsuji TG,Nakatsuji N.Combination of functional cardiomyocytes derived from human stem cells and a highly-efficient microelectrode array system: an ideal hybrid model assay for drug development.Curr Stem Cell Res Ther. 2010;5:227-32
108. Nam Y,Wheeler BC.In vitro microelectrode array technology and neural recordings.Crit Rev Biomed Eng. 2011;39:45-61
109. Morin F,Nishimura N,Griscom L,Lepioufle B,Fujita H,Takamura Y,Tamiya E.Constraining the connectivity of neuronal networks cultured on microelectrode arrays with microfluidic techniques: a step towards neuron-based functional chips.Biosens Bioelectron. 2006;21:1093-100.
110. Kanagasabapathi TT,Ciliberti D,Martinoia S,Wadman WJ,Decre MM.Dual-compartment neurofluidic system for electrophysiological measurements in physically segregated and functionally connected neuronal cell culture.Front Neuroeng. 2011;4:13-13
111. Braam SR,Tertoolen L,van de Stolpe A,Meyer T,Passier R,Mummery CL.Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes.Stem Cell Res. 2010;4:107-16
112. Caspi O,Itzhaki I,Kehat I,Gepstein A,Arbel G,Huber I,Satin J,Gepstein L.In vitro electrophysiological drug testing using human embryonic stem cell derived cardiomyocytes.Stem Cells Dev. 2009;18:161-72
113. Varghese K,Molnar P,Das M,Bhargava N,Lambert S,Kindy MS,Hickman JJ.A new target for amyloid beta toxicity validated by standard and high-throughput electrophysiology.PloS One. 2010;5:e8643-e8643
114. He M,Herr AE.Microfluidic polyacrylamide gel electrophoresis with in situ immunoblotting for native protein analysis.Anal Chem. 2009;81:8177-84
115. Zhang C,Xu J,Ma W,Zheng W.PCR microfluidic devices for DNA amplification.Biotechnol Adv. 2006;24:243-84
116. Roux A,Lison D,Junot C,Heilier JF.Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: a review.Clin Biochem. 2011;44:119-35
117. Wikswo JP,Block FE,Cliffel DE,Goodwin CR,Marasco CC,Markov DA,McLean DL,McLean JA,McKenzie JR,Reiserer RS,Samson PC,Schaffer DK,Seale KT,Sherrod SD.Engineering challenges for instrumenting and controlling integrated organ-on-chip systems.IEEE Trans Biomed Eng. 2013;60:682-90
118. Enders JR,Marasco CC,Kole A,Nguyen B,Sevugarajan S,Seale KT,Wikswo JP,McLean JA.Towards monitoring real-time cellular response using an integrated microfluidics-matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion mobility-mass spectrometry platform.IET Syst Biol. 2010;4:416-27
119. Yu H,Alexander CM,Beebe DJ.A plate reader-compatible microchannel array for cell biology assays.Lab Chip. 2007;7:388-91
120. Shuler ML,Esch MB.Body-on-a chip: using microfluidic systems to predict human responses to drugs.Pure Appl Chem. 2010;82:1635-45
121. Meyvantsson I,Warrick JW,Hayes S,Skoien A,Beebe DJ.Automated cell culture in high density tubeless microfluidic device arrays.Lab Chip. 2008;8:717-24
122. Faley SL,Copland M,Wlodkowic D,Kolch W,Seale KT,Wikswo JP,Cooper JM.Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells.Lab Chip. 2009;9:2659-64
123. Simmons CS,Petzold BC,Pruitt BL.Microsystems for biomimetic stimulation of cardiac cells.Lab Chip. 2012;12:3235-48
124. Oh TI,Sung JH,Tatosian DA,Shuler ML,Kim D.Real-time fluorescence detection of multiple microscale cell culture analog devices in situ.Cytometry A. 2007;71:857-65
125. Sung JH,Choi JR,Kim D,Shuler ML.Fluorescence optical detection in situ for real-time monitoring of cytochrome P450 enzymatic activity of liver cells in multiple microfluidic devices.Biotechnol Bioeng. 2009;104:516-25
126. Lee SR,Lee YT,Sawada K,Takao H,Ishida M.Development of a disposable glucose biosensor using electroless-plated Au/Ni/copper low electrical resistance electrodes.Biosens Bioelectron. 2008;24:410-4
127. Luo X,Davis JJ.Electrical biosensors and the label free detection of protein disease biomarkers.Chem Soc Rev. 2013;42:5944-62
128. Bellin M,Marchetto MC,Gage FH,Mummery CL.Induced pluripotent stem cells: the new patient?.Nat Rev Mol Cell Biol. 2012;13:713-26
129. Choucha-Snouber L,Aninat C,Grsicom L,Madalinski G,Brochot C,Poleni PE,Razan F,Guillouzo CG,Legallais C,Corlu A,Leclerc E.Investigation of ifosfamide nephrotoxicity induced in a liver-kidney co-culture biochip.Biotechnol Bioeng. 2013;110:597-608
130. van der Meer AD,van den Berg A.Organs-on-chips: breaking the in vitro impasse.Integr Biol (Camb). 2012;4:461-70
131. van der Valk J,Brunner D,De Smet K,Fex Svenningsen A,Honegger P,Knudsen LE,Lindl T,Noraberg J,Price A,Scarino ML,Gstraunthaler G.Optimization of chemically defined cell culture media–replacing fetal bovine serum in mammalian in vitro methods.Toxicol In Vitro. 2010;24:1053-63
132. Schaffner AE,Barker JL,Stenger DA,Hickman JJ.Investigation of the factors necessary for growth of hippocampal neurons in a defined system.J Neurosci Methods. 1995;62:111-9
133. Das M,Molnar P,Devaraj H,Poeta M,Hickman JJ.Electrophysiological and morphological characterization of rat embryonic motoneurons in a defined system.Biotechnol Prog. 2003;19:1756-61
134. Guo X,Das M,Rumsey J,Gonzalez M,Stancescu M,Hickman J.Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.Tissue Eng Part C Methods. 2010;16:1347-55
135. Smith AST,Long CJ,Pirozzi K,Hickman JJ.A functional system for high-content screening of neuromuscular junctions in vitro.Technology. 2013;1:1-12
136. Guo X,Gonzalez M,Stancescu M,Vandenburgh HH,Hickman JJ.Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.Biomaterials. 2011;32:9602-11
137. Davis H,Gonzalez M,Bhargava N,Stancescu M,Hickman JJ,Lambert S.Rat cortical oligodendrocyte-embryonic motoneuron co-culture: an axon-oligodendrocyte interaction model.J Biomater Tissue Eng. 2012;2:206-14
138. Levenberg S,Huang NF,Lavik E,Rogers AB,Itskovitz-Eldor J,Langer R.Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds.Proc Natl Acad Sci U S A. 2003;100:12741-6
139. Page H,Flood P,Reynaud E.Three-dimensional tissue cultures: current trends and beyond.Cell Tissue Res. 2013;352:123-31