1932

Abstract

Organs-on-chips (OOC) are widely seen as being the next generation in vitro models able to accurately recreate the biochemical-physical cues of the cellular microenvironment found in vivo. In addition, they make it possible to examine tissue-scale functional properties of multicellular systems dynamically and in a highly controlled manner. Here we summarize some of the most remarkable examples of OOC technology's ability to extract clinically relevant tissue-level information. The review is organized around the types of OOC outputs that can be measured from the cultured tissues and transferred to clinically meaningful information. First, the creation of functional tissues-on-chip is discussed, followed by the presentation of tissue-level readouts specific to OOC, such as morphological changes, vessel formation and function, tissue properties, and metabolic functions. In each case, the clinical relevance of the extracted information is highlighted.

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2020-06-12
2024-10-10
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Literature Cited

  1. 1. 
    Bhatia SN, Ingber DE. 2014. Microfluidic organs-on-chips. Nat. Biotechnol. 32:8760–72
    [Google Scholar]
  2. 2. 
    Marx U, Andersson TB, Bahinski A, Beilmann M, Beken S et al. 2016. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33:3272–321
    [Google Scholar]
  3. 3. 
    Wang YI, Carmona C, Hickman JJ, Shuler ML 2018. Multiorgan microphysiological systems for drug development: strategies, advances, and challenges. Adv. Healthc. Mater. 7:21701000
    [Google Scholar]
  4. 4. 
    Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE 2010. Reconstituting organ-level lung functions on a chip. Science 328:59861662–68
    [Google Scholar]
  5. 5. 
    Bichsel CA, Hall SRR, Schmid RA, Guenat OT, Geiser T 2015. Primary human lung pericytes support and stabilize in vitro perfusable microvessels. Tissue Eng. A 21:15–162166–76
    [Google Scholar]
  6. 6. 
    Barrile R, Van Der Meer AD, Park H, Fraser JP, Simic D et al. 2018. Organ-on-chip recapitulates thrombosis induced by an anti-CD154 monoclonal antibody: translational potential of advanced microengineered systems. Clin. Pharmacol. Ther. 104:61240–48
    [Google Scholar]
  7. 7. 
    Sung JH, Shuler ML. 2009. 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 9:101385–94
    [Google Scholar]
  8. 8. 
    Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC et al. 2014. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513:422–25
    [Google Scholar]
  9. 9. 
    Shi Y, Inoue H, Wu JC, Yamanaka S 2016. Induced pluripotent stem cell technology: a decade of progress. Nat. Rev. 16:2115–30
    [Google Scholar]
  10. 10. 
    Williams LA, Davis-Dusenbery BN, Eggan KC 2012. SnapShot: directed differentiation of pluripotent stem cells. Cell 149:1174.e1
    [Google Scholar]
  11. 11. 
    Price PJ. 2017. Best practices for media selection for mammalian cells. In Vitro Cell. Dev. Biol. 53:673–81
    [Google Scholar]
  12. 12. 
    Gauvin R, Mehmet R, Merryman WD, Khademhosseini A 2012. Hydrogels and microtechnologies for engineering the cellular microenvironment. Wires Nanomed. Nanobiotechnol. 4:3235–46
    [Google Scholar]
  13. 13. 
    da Silveira dos Santos AX, Liberali P 2019. From single cells to tissue self-organization. FEBS J 286:1495–513
    [Google Scholar]
  14. 14. 
    Wang Y, Ahmad AA, Sims CE, Magness ST, Allbritton NL 2014. In vitro generation of colonic epithelium from primary cells guided by microstructures. Lab Chip 14:91622–31
    [Google Scholar]
  15. 15. 
    Sieber S, Wirth L, Cavak N, Koenigsmark M, Marx U et al. 2018. Bone marrow-on-a-chip: Long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment. J. Tissue Eng. Regen. Med. 12:479–89
    [Google Scholar]
  16. 16. 
    Zamprogno P, Wüthrich S, Achenbach S, Stucki JD, Hobi N et al. 2019. Second-generation lung-on-a-chip array with a stretchable biological membrane. bioRxiv 608919. https://doi.org/10.1101/608919
    [Crossref]
  17. 17. 
    Zhang B, Montgomery M, Chamberlain MD, Ogawa S, Korolj A et al. 2016. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15:6669–78
    [Google Scholar]
  18. 18. 
    Sano E, Mori C, Nashimoto Y, Yokokawa R, Kotera H, Torisawa Y 2018. Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network. Biomicrofluidics 12:042204
    [Google Scholar]
  19. 19. 
    Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M et al. 2019. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat. Methods 16:255–62
    [Google Scholar]
  20. 20. 
    Schutgens F, Rookmaaker MB, Margaritis T, Rios A, Ammerlaan C et al. 2019. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat. Biotechnol. 37:303–13
    [Google Scholar]
  21. 21. 
    Park SE, Georgescu A, Huh D 2019. Organoids-on-a-chip. Science 364:960–65
    [Google Scholar]
  22. 22. 
    Takebe T, Zhang B, Radisic M 2017. Synergistic engineering: organoids meet organs-on-a-chip. Cell Stem Cell 21:3297–300
    [Google Scholar]
  23. 23. 
    David L, Dumitrascu DL. 2017. The bicentennial of the stethoscope: a reappraisal. Clujul Med 90:3361–63
    [Google Scholar]
  24. 24. 
    Huh D, Fujioka H, Tung Y-C, Futai N, Paine R et al. 2007. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. PNAS 104:4818886–91
    [Google Scholar]
  25. 25. 
    Edlow BL, Mareyam A, Horn A, Polimeni JR, Dylan M 2019. 7 Tesla MRI of the ex vivo human brain at 100 micron resolution. bioRxiv 649822. https://doi.org/10.1101/649822
    [Crossref]
  26. 26. 
    Bailey KE, Floren ML, Ovidio TJD, Lammers SR, Stenmark KR, Magin XCM 2019. Tissue-informed engineering strategies for modeling human pulmonary diseases. Am. J. Physiol. Lung Cell. Mol. Physiol. 316:L303–20
    [Google Scholar]
  27. 27. 
    Cai Y, Schrenk S, Goines J, Davis GE, Boscolo E 2019. Constitutive active mutant TIE2 induces enlarged vascular lumen formation with loss of apico-basal polarity and pericyte recruitment. Sci. Rep. 9:12352
    [Google Scholar]
  28. 28. 
    Haase K, Kamm RD. 2017. Advances in on-chip vascularization. Regen. Med. 12:3285–302
    [Google Scholar]
  29. 29. 
    Zhao H, Chappell JC. 2019. Microvascular bioengineering: a focus on pericytes. J. Biol. Eng. 13:26
    [Google Scholar]
  30. 30. 
    Soleimani S, Shamsi M, Ghazani AM, Modarres H, Valente K et al. 2018. Translational models of tumor angiogenesis: a nexus of in silico and in vitro models. Biotechnol. Adv. 36:880–93
    [Google Scholar]
  31. 31. 
    Ko J, Ahn J, Kim S, Lee Y, Lee J et al. 2019. Tumor spheroid-on-a-chip: a standardized microfluidic culture platform for investigating tumor angiogenesis. Lab Chip 19:2822–33
    [Google Scholar]
  32. 32. 
    Ko J, Lee Y, Lee S, Lee S, Jeon NL 2019. Human ocular angiogenesis-inspired vascular models on an injection-molded microfluidic chip. Adv. Healthc. Mater. 8:1900328
    [Google Scholar]
  33. 33. 
    Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S et al. 2012. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4:159ra147
    [Google Scholar]
  34. 34. 
    Kim DW, Zloza A, Broucek J, Schenkel JM, Ruby C et al. 2014. Interleukin-2 alters distribution of CD144 (VE-cadherin) in endothelial cells. J. Transl. Med. 12:113
    [Google Scholar]
  35. 35. 
    Jain A, Barrile R, van der Meer AD, Mammoto A, Mammoto T et al. 2017. A primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin. Pharmacol. Ther. 103:2332–40
    [Google Scholar]
  36. 36. 
    Zeinali S, Bichsel CA, Hobi N, Funke M, Marti TM et al. 2018. Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro. Angiogenesis 21:4861–71
    [Google Scholar]
  37. 37. 
    Bichsel CA, Wang L, Froment L, Berezowska S, Müller S et al. 2017. Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model. Sci. Rep. 7:10636
    [Google Scholar]
  38. 38. 
    Jiménez-Torres JA, Virumbrales-Muñoz M, Sung KE, Hee M, Abel EJ, Beebe DJ 2019. Patient-specific organotypic blood vessels as an in vitro model for anti-angiogenic drug response testing in renal cell carcinoma. EBioMedicine 42:408–19
    [Google Scholar]
  39. 39. 
    Garcia AN, Vogel SM, Komarova YA, Malik AB 2011. Permeability of endothelial barrier: cell culture and in vivo models. Methods Mol. Biol. 763:333–54
    [Google Scholar]
  40. 40. 
    van der Helm MW, Odijk M, Frimat J, van der Meer AD, Eijkel JCT et al. 2016. Direct quantification of transendothelial electrical resistance in organs-on-chips. Biosens. Bioelectron. 85:924–29
    [Google Scholar]
  41. 41. 
    Srinivasan B, Kolli AR, Esch MB, Abaci HE, Shuler ML, Hickman JJ 2015. TEER measurement techniques for in vitro barrier model systems. J. Lab. Autom. 20:2107–26
    [Google Scholar]
  42. 42. 
    Offeddu GS, Haase K, Gillrie MR, Li R, Morozova O et al. 2019. An on-chip model of protein paracellular and transcellular permeability in the microcirculation. Biomaterials 212:115–25
    [Google Scholar]
  43. 43. 
    Schnoor M. 2015. Endothelial actin-binding proteins and actin dynamics in leukocyte transendothelial migration. J. Immunol. 194:3535–41
    [Google Scholar]
  44. 44. 
    Strilic B, Offermanns S. 2017. Intravascular survival and extravasation of tumor cells. Cancer Cell 32:282–93
    [Google Scholar]
  45. 45. 
    Tang Y, Soroush F, Sun S, Liverani E, Langston JC et al. 2018. Protein kinase C-delta inhibition protects blood-brain barrier from sepsis-induced vascular damage. J. Neuroinflamm. 15:309
    [Google Scholar]
  46. 46. 
    Kim JJ, Ellett F, Thomas CN, Jalali F, Anderson RR et al. 2019. A microscale, full-thickness, human skin on a chip assay simulating neutrophil responses to skin infection and antibiotic treatments. Lab Chip 19:3094–103
    [Google Scholar]
  47. 47. 
    Menon NV, Tay HM, Pang KT, Dalan R, Wong SC et al. 2018. A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis. APL Bioeng 2:016103
    [Google Scholar]
  48. 48. 
    Bersini S, Miermont A, Pavesi A, Kamm RD, Thiery P et al. 2018. A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells. Oncotarget 9:9036110–25
    [Google Scholar]
  49. 49. 
    Boussommier-Calleja A, Atiyas Y, Haase K, Headley M, Lewis C, Kamm RD 2019. The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials 198:180–93
    [Google Scholar]
  50. 50. 
    Schwartz LH, Litière S, de Vries E, Ford R, Mandrekar S et al. 2016. RECIST 1.1 update and clarification: from the RECIST Committee. Eur. J. Cancer 62:132–37
    [Google Scholar]
  51. 51. 
    Hodi FS, Ballinger M, Lyons B, Soria JC, Nishino M et al. 2018. Immune-modified response evaluation criteria in solid tumors (imRECIST): refining guidelines to assess the clinical benefit of cancer immunotherapy. J. Clin. Oncol. 36:850–58
    [Google Scholar]
  52. 52. 
    Fidler IJ, Kripke ML. 2015. The challenge of targeting metastasis. Cancer Metastasis Rev 34:635–41
    [Google Scholar]
  53. 53. 
    Mallat RK, John CM, Kendrick DJ, Braun A 2017. The vascular endothelium: a regulator of arterial tone and interface for the immune system. Clin. Rev. Clin. Lab. Sci. 54:7–8458–70
    [Google Scholar]
  54. 54. 
    Günther A, Yasotharan S, Vagaon A, Lochovsky C, Pinto S et al. 2010. A microfluidic platform for probing small artery structure and function. Lab Chip 10:2341–49
    [Google Scholar]
  55. 55. 
    Ferguson-Myrthil N. 2012. Vasopressor use in adult patients. Cardiol. Rev. 20:3153–58
    [Google Scholar]
  56. 56. 
    Li Y, Wu Y, Liu Y, Deng Q, Mak M, Yang X 2019. Atmospheric nanoparticles affect vascular function using a 3D human vascularized organotypic chip. Nanoscale 11:15537–49
    [Google Scholar]
  57. 57. 
    Kim S, Takayama S. 2015. Organ-on-a-chip and the kidney. Kidney Res. Clin. Pract. 34:3165–69
    [Google Scholar]
  58. 58. 
    Wilmer MJ, Ng CP, Lanz HL, Vulto P, Suter-Dick L, Masereeuw R 2016. Kidney-on-a-chip technology for drug-induced nephrotoxicity screening. Trends Biotechnol 34:2156–70
    [Google Scholar]
  59. 59. 
    Bajaj P, Chowdhury SK, Yucha R, Kelly EJ, Xiao G 2018. Emerging kidney models to investigate metabolism, transport, and toxicity of drugs and xenobiotics. Drug Metab. Dispos. 46:1692–702
    [Google Scholar]
  60. 60. 
    Nieskens TTG, Wilmer MJ. 2016. Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction. Eur. J. Pharmacol. 790:46–56
    [Google Scholar]
  61. 61. 
    Zhou M, Zhang X, Wen X, Wu T, Wang W 2016. Development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy. Sci. Rep. 6:31771
    [Google Scholar]
  62. 62. 
    Musah S, Mammoto A, Ferrante TC, Jeanty SSF, Mammoto T et al. 2017. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat. Biomed. Eng. 1:0069
    [Google Scholar]
  63. 63. 
    Vormann MK, Gijzen L, Hutter S, Boot L, Nicolas A et al. 2018. Nephrotoxicity and kidney transport assessment on 3D perfused proximal tubules. AAPS J 20:90
    [Google Scholar]
  64. 64. 
    Maschmeyer I, Lorenz AK, Schimek K, Hasenberg T, Ramme AP et al. 2015. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15:2688–99
    [Google Scholar]
  65. 65. 
    Bein A, Shin W, Jalili-Firoozinezhad S, Park MH, Sontheimer-Phelps A et al. 2018. Microfluidic organ-on-a-chip models of human intestine. Cell. Mol. Gastron. Hepatol. 5:4659–68
    [Google Scholar]
  66. 66. 
    Wang Y, Kim R, Hinman SS, Zwarycz B, Magness ST, Allbritton NL 2018. Bioengineered systems and designer matrices that recapitulate. Cell. Mol. Gastron. Hepatol. 5:440–53
    [Google Scholar]
  67. 67. 
    Du Y, Khandekar G, Llewellyn J, Polacheck W, Chen C, Wells RG 2019. A bile duct-on-a-chip with organ-level functions. Hepatology https://doi.org/10.1002/hep.30918
    [Crossref] [Google Scholar]
  68. 68. 
    Nelson CM, Gleghorn JP, Pang M, Jaslove JM, Goodwin K et al. 2017. Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development. Development 144:4328–35
    [Google Scholar]
  69. 69. 
    Manfrin A, Tabata Y, Paquet ER, Vuaridel AR, Rivest FR et al. 2019. Engineered signaling centers for the spatially controlled patterning of human pluripotent stem cells. Nat. Methods 16:640–48
    [Google Scholar]
  70. 70. 
    Samal P, van Blitterswijk C, Truckenmüller R, Giselbrecht S 2019. Grow with the flow: when morphogenesis meets microfluidics. Adv. Mater. 31:1805764
    [Google Scholar]
  71. 71. 
    Chen CZC, Raghunath M. 2009. Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis-state of the art. Fibrogenesis Tissue Repair 2:7
    [Google Scholar]
  72. 72. 
    Xu X, Li Z, Cai L, Calve S, Neu CP 2016. Mapping the nonreciprocal micromechanics of individual cells and the surrounding matrix within living tissues. Sci. Rep. 6:24272
    [Google Scholar]
  73. 73. 
    Booth AJ, Hadley R, Cornett AM, Dreffs AA, Matthes SA et al. 2012. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am. J. Respir. Crit. Care Med. 186:9866–76
    [Google Scholar]
  74. 74. 
    Knudsen L, Ruppert C, Ochs M 2017. Tissue remodelling in pulmonary fibrosis. Cell Tissue Res 367:607–26
    [Google Scholar]
  75. 75. 
    Moeller A, Ask K, Warburton D, Gauldie J, Kolb M 2008. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis. ? Int. J. Biochem. Cell Biol. 40:3362–82
    [Google Scholar]
  76. 76. 
    Felder M, Trüeb B, Stucki AO, Borcard S, Daniel J 2019. Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip. Front. Bioeng. Biotechnol. 7:3
    [Google Scholar]
  77. 77. 
    Funke M, Geiser T. 2015. Idiopathic pulmonary fibrosis: the turning point is now. ! Swiss Med. Wkly. 145:w14139
    [Google Scholar]
  78. 78. 
    Gabbiani G. 2003. The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol. 200:500–3
    [Google Scholar]
  79. 79. 
    Kong M, Lee J, Yazdi IK, Miri AK, Lin Y et al. 2019. Cardiac fibrotic remodeling on a chip with dynamic mechanical stimulation. Adv. Healthc. Mater. 8:1801146
    [Google Scholar]
  80. 80. 
    Asmani M, Velumani S, Li Y, Wawrzyniak N, Chen Z et al. 2018. Fibrotic microtissue array to predict anti-fibrosis drug efficacy. Nat. Commun. 9:2066
    [Google Scholar]
  81. 81. 
    Ebinuma H, Saito H, Komuta M, Ojiro K, Wakabayashi K, Usui S 2011. Evaluation of liver fibrosis by transient elastography using acoustic radiation force impulse: comparison with Fibroscan. J. Gastroenterol. 46:1238–48
    [Google Scholar]
  82. 82. 
    Bulusu V, Prior N, Snaebjornsson M, Kuehne A, Sonnen K et al. 2017. Spatiotemporal analysis of a glycolytic activity gradient linked to mouse embryo mesoderm development. Dev. Cell 40:331–41
    [Google Scholar]
  83. 83. 
    Rinnerthaler M, Streubel MK, Bischof J, Richter K 2015. Skin aging, gene expression and calcium. Exp. Gerontol. 68:59–65
    [Google Scholar]
  84. 84. 
    Shin W, Hinojosa C, Ingber D, Kim HJ 2019. Human intestinal morphogenesis controlled by transepithelial morphogen gradient and flow-dependent physical cues in a microengineered gut-on-a-chip. iScience 15:391–406
    [Google Scholar]
  85. 85. 
    Jalili-Firoozinezhad S, Gazzaniga FS, Calamari EL, Camacho DM, Fadel CW et al. 2019. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat. Biomed. Eng. 3:520–31
    [Google Scholar]
  86. 86. 
    König M, Holzhütter HG, Berndt N 2013. Metabolic gradients as key regulators in zonation of tumor energy metabolism: a tissue-scale model-based study. Biotechnol. J. 8:1058–69
    [Google Scholar]
  87. 87. 
    Shin W, Wu A, Massidda MW, Foster C, Thomas N et al. 2019. A robust longitudinal co-culture of obligate anaerobic gut microbiome with human intestinal epithelium in an anoxic-oxic interface-on-a-chip. Front. Bioeng. Biotechnol. 7:13
    [Google Scholar]
  88. 88. 
    Soto-Gutierrez A, Gough A, Vernetti LA, Taylor DL, Monga SP 2017. Pre-clinical and clinical investigations of metabolic zonation in liver diseases: the potential of microphysiology systems. Exp. Biol. Med. 242:1605–16
    [Google Scholar]
  89. 89. 
    Gebhardt R, Matz-Soja M. 2014. Liver zonation: novel aspects of its regulation and its impact on homeostasis. World J. Gastroenterol. 20:268491–504
    [Google Scholar]
  90. 90. 
    Häussinger D, Lames W, Moorman A 1992. Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme 46:1–372–93
    [Google Scholar]
  91. 91. 
    Kang YB, Eo J, Mert S, Yarmush M, Usta B 2018. Metabolic patterning on a chip: towards in vitro liver zonation of primary rat and human hepatocytes. Sci. Rep 8:18951
    [Google Scholar]
  92. 92. 
    Lee-Montiel FT, George SM, Gough AH, Sharma AD, Wu J et al. 2017. Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems. Exp. Biol. Med. 242:1617–32
    [Google Scholar]
  93. 93. 
    Moya A, Ortega-Ribera M, Guimera X, Sowade E, Zea M et al. 2018. Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system. Lab Chip 18:2023–35
    [Google Scholar]
  94. 94. 
    Li X, George SM, Vernetti L, Gough AH, Taylor DL 2018. A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX. Lab Chip 18:2614–31
    [Google Scholar]
  95. 95. 
    Castiello FR, Heileman K, Tabrizian M 2016. Microfluidic perfusion systems for secretion fingerprint analysis of pancreatic islets: applications, challenges and opportunities. Lab Chip 16:409–31
    [Google Scholar]
  96. 96. 
    McConnell H, Rice P, Wada G, Owicki J, Parce W 1991. The microphysiometer biosensor. Curr. Opin. Struct. Biol. 1:4647–52
    [Google Scholar]
  97. 97. 
    Dishinger JF, Reid KR, Kennedy RT 2009. Quantitative monitoring of insulin secretion from microfluidic chip. Anal. Chem. 81:3119–27
    [Google Scholar]
  98. 98. 
    Gerasimov JY, Schaefer CS, Yang W, Grout RL, Lai RY 2013. Development of an electrochemical insulin sensor based on the insulin-linked polymorphic region. Biosens. Bioelectron. 42:62–68
    [Google Scholar]
  99. 99. 
    Lee J, So H, Jeon E 2008. Aptamers as molecular recognition elements for electrical nanobiosensors. Anal. Bioanal. Chem. 390:1023–32
    [Google Scholar]
  100. 100. 
    Zbinden A, Marzi J, Schlünder K, Probst C, Urbanczyk M et al. 2019. Non-invasive marker-independent high content analysis of a microphysiological human pancreas-on-a-chip model. Matrix Biol https://doi.org/10.1016/j.matbio.2019.06.008
    [Crossref] [Google Scholar]
  101. 101. 
    Marasco CC, Enders JR, Seale KT, Mclean JA, Wikswo JP 2015. Real-time cellular exometabolome analysis with a microfluidic-mass spectrometry platform. PLOS ONE 10:2e0117685
    [Google Scholar]
  102. 102. 
    La Cour JB, Generelli S, Barbe L, Guenat OT 2016. Low-cost disposable ALT electrochemical microsensors for in-vitro hepatotoxic assessment. Sens. Actuators B 228:360–65
    [Google Scholar]
  103. 103. 
    Bae S, Fang MZ, Rustgi V, Zarbl H, Androulakis I 2019. At the interface of lifestyle, behavior, and circadian rhythms: metabolic implications. Front. Nutr. 28: https://doi.org/10.3389/FNUT.2019.00132
    [Crossref] [Google Scholar]
  104. 104. 
    Cyr KJ, Avaldi OM, Wikswo JP 2017. Circadian hormone control in a human-on-a-chip: in vitro biology's ignored component?. Exp. Biol. Med. 242:1714–31
    [Google Scholar]
  105. 105. 
    Xiao S, Coppeta JR, Rogers HB, Isenberg BC, Zhu J et al. 2017. A microfluidic culture model of the reproductive tract and 28-day menstrual cycle. Nat. Commun. 8:14584
    [Google Scholar]
  106. 106. 
    Bauer S, Wennbe C, Kanebratt KP, Durieux I, Andersson S et al. 2017. Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci. Rep. 7:14620
    [Google Scholar]
  107. 107. 
    Maass C, Dallas M, Labarge ME, Shockley M, Geishecker E et al. 2018. Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies. Sci. Rep. 8:8015
    [Google Scholar]
  108. 108. 
    Meyer T, Tiburcy M, Zimmermann W 2019. Cardiac macrotissues-on-a-plate models for phenotypic drug screens. Adv. Drug Deliv. Rev. 140:93–100
    [Google Scholar]
  109. 109. 
    Fantuzzo JA, Hart RP, Zahn JD, Pang ZP 2019. Compartmentalized devices as tools for investigation of human brain network dynamics. Dev. Dyn. 248:65–77
    [Google Scholar]
  110. 110. 
    Frimat J, Luttge R. 2019. The need for physiological micro-nanofluidic systems of the brain. Front. Bioeng. Biotechnol. https://doi.org/10.3389/fbioe.2019.00100
    [Crossref] [Google Scholar]
  111. 111. 
    Esch EW, Bahniski A, Huh D 2015. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discov. 14:4248–60
    [Google Scholar]
  112. 112. 
    Selimović Š, Dokmeci MR, Khademhosseini A 2013. Organs-on-a-chip for drug discovery. Curr. Opin. Pharmacol. 13:5829–33
    [Google Scholar]
  113. 113. 
    Ronaldson-Bouchard K, Vunjak-Novakovic G. 2018. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell 22:3310–24
    [Google Scholar]
  114. 114. 
    Fabre KM, Livingston C, Tagle DA 2014. Organs-on-chips (microphysiological systems): tools to expedite efficacy and toxicity testing in human tissue. Exp. Biol. Med. 239:91073–77
    [Google Scholar]
  115. 115. 
    Ackermann T, Tardito S. 2019. Cell culture medium formulation and its implications in cancer metabolism. Trends Cancer 5:6329–32
    [Google Scholar]
  116. 116. 
    Peel S, Corrigan A, Ehrhardt B, Jang K, Caetano-Pinto P et al. 2019. Introducing an automated high content confocal imaging approach for Organs-on-Chips. Lab Chip 19:410–21
    [Google Scholar]
  117. 117. 
    Polat A, Hassan S, Yildirim I, Oliver LE, Mostafaei M et al. 2019. A miniaturized optical tomography platform for volumetric imaging of engineered living systems. Lab Chip 19:550–61
    [Google Scholar]
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