1932

Abstract

Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested.

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2021-07-27
2024-06-18
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Literature Cited

  1. 1. 
    Lippmann M. 2008. Environmental Toxicants: Human Exposures and Their Health Effects Hoboken, NJ: John Wiley & Sons. , 4th ed..
    [Google Scholar]
  2. 2. 
    World Health Organ 2018. Mycotoxins World Health Organ. Geneva: https://www.who.int/news-room/fact-sheets/detail/mycotoxins
    [Google Scholar]
  3. 3. 
    Darbre PD 2015. What are endocrine disruptors and where are they found?. Endocrine Disruption and Human Health, ed. PD Darbre3–26 Boston: Academic
    [Google Scholar]
  4. 4. 
    Romm A 2010. Breast cancer. Botanical Medicine for Women's Health A Romm, ML Hardy, S Mills 306–20 St. Louis, MO: Churchill Livingstone
    [Google Scholar]
  5. 5. 
    Bennetts HW, Underwood EJ, Shier FL. 1946. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust. Vet. J. 22:12–12
    [Google Scholar]
  6. 6. 
    Setchell KDR, Gosselin SJ, Welsh MB, Johnston JO, Balistreri WF et al. 1987. Dietary estrogens—a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology 93:2225–33
    [Google Scholar]
  7. 7. 
    Huang Y, Pan L, Xia X, Feng Y, Jiang C, Cui Y. 2008. Long-term effects of phytoestrogen daidzein on penile cavernosal structures in adult rats. Urology 72:1220–24
    [Google Scholar]
  8. 8. 
    Pan L, Xia X, Feng Y, Jiang C, Cui Y, Huang Y. 2008. Exposure of juvenile rats to the phytoestrogen daidzein impairs erectile function in a dose-related manner in adulthood. J. Androl. 29:155–62
    [Google Scholar]
  9. 9. 
    Maqbool F, Mostafalou S, Bahadar H, Abdollahi M. 2016. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms. Life Sci. 145:265–73
    [Google Scholar]
  10. 10. 
    Waring RH, Harris RM. 2005. Endocrine disruptors: A human risk?. Mol. Cell. Endocrinol. 244:12–9
    [Google Scholar]
  11. 11. 
    Cheng CY, Wong EWP, Lie PPY, Li MWM, Su L et al. 2011. Environmental toxicants and male reproductive function. Spermatogenesis 1:12–13
    [Google Scholar]
  12. 12. 
    Groff T. 2010. Bisphenol A: invisible pollution. Curr. Opin. Pediatr. 22:4524–29
    [Google Scholar]
  13. 13. 
    Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJR, Schoenfelder G. 2010. Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ. Health. Perspect. 118:81055–70
    [Google Scholar]
  14. 14. 
    Vandenberg LN, Maffini MV, Sonnenschein C, BS Rubin, Soto AM. 2009. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr. Rev. 30:175–95
    [Google Scholar]
  15. 15. 
    Li MWM, Mruk DD, Lee WM, Cheng CY. 2009. Disruption of the blood-testis barrier integrity by bisphenol A in vitro: Is this a suitable model for studying blood-testis barrier dynamics?. Int. J. Biochem. Cell. Biol. 41:112302–14
    [Google Scholar]
  16. 16. 
    Chapin RE, Adams J, Boekelheide K, Gray LE, Hayward SW et al. 2008. NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res. B Dev. Reprod. Toxicol. 83:3157–395
    [Google Scholar]
  17. 17. 
    Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A et al. 2007. In vitro molecular mechanisms of bisphenol A action. Reprod. Toxicol. 24:2178–98
    [Google Scholar]
  18. 18. 
    Hunt PA, Susiarjo M, Rubio C, Hassold TJ. 2009. The bisphenol A experience: a primer for the analysis of environmental effects on mammalian reproduction. Biol. Reprod. 81:5807–13
    [Google Scholar]
  19. 19. 
    Taylor JA, Welshons WV, Vom Saal FS 2008. No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24 h after administration in neonatal female mice. Reprod. Toxicol. 25:2169–76
    [Google Scholar]
  20. 20. 
    Gur S, Sikka SC 2018. Environmental risk factors related to male reproductive health in Turkish society. Bioenvironmental Issues Affecting Men's Reproductive and Sexual Health SC Sikka, WJG Hellstrom 41–52 Boston: Academic
    [Google Scholar]
  21. 21. 
    McLachlan JA. 2001. Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Endocr. Rev. 22:3319–41
    [Google Scholar]
  22. 22. 
    Schell LM, Gallo MV, Deane GD, Nelder KR, DeCaprio AP, Jacobs A. 2014. Relationships of polychlorinated biphenyls and dichlorodiphenyldichloroethylene (p,p′-DDE) with testosterone levels in adolescent males. Environ. Health. Perspect. 122:3304–9
    [Google Scholar]
  23. 23. 
    Calvert GM, Mehler LN, Alsop J, De Vries AL, Besbelli N 2010. Surveillance of pesticide-related illness and injury in humans. Hayes’ Handbook of Pesticide Toxicology R Krieger 1313–69 New York: Academic. , 3rd ed..
    [Google Scholar]
  24. 24. 
    Casida JE 2010. Pest toxicology: the primary mechanisms of pesticide action. Hayes’ Handbook of Pesticide Toxicology R Krieger 103–17 New York: Academic. , 3rd ed..
    [Google Scholar]
  25. 25. 
    Lock EA, Wilks MF. 2010. Paraquat. Hayes’ Handbook of Pesticide Toxicology R Krieger 1771–827 New York: Academic. , 3rd ed..
    [Google Scholar]
  26. 26. 
    Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. 1995. Persistent DDT metabolite p,p′-DDE is a potent androgen receptor antagonist. Nature 375:6532581–85
    [Google Scholar]
  27. 27. 
    Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J et al. 2011. Arsenic: toxicity, oxidative stress and human disease. J. Appl. Toxicol. 31:295–107
    [Google Scholar]
  28. 28. 
    Wolff MS, Buckley J, Engel SM, McConnell RS, Barr DB. 2017. Emerging exposures of developmental toxicants. Curr. Opin. Pediatr. 29:2218–24
    [Google Scholar]
  29. 29. 
    Ali A, Suhail M, Mathew S, Shah MA, Harakeh SM et al. 2016. Nanomaterial induced immune responses and cytotoxicity. J. Nanosci. Nanotechnol. 16:140–57
    [Google Scholar]
  30. 30. 
    Ema M, Gamo M, Honda K. 2016. Developmental toxicity of engineered nanomaterials in rodents. Toxicol. Appl. Pharm. 299:47–52
    [Google Scholar]
  31. 31. 
    Magaye R, Zhao J, Bowman L, Ding M. 2012. Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles. Exp. Ther. Med. 4:4551–61
    [Google Scholar]
  32. 32. 
    Luo Y-H, Chang LW, Lin P. 2015. Metal-based nanoparticles and the immune system: activation, inflammation, and potential applications. BioMed. Res. Int. 2015: 143720.
    [Google Scholar]
  33. 33. 
    Baughman RH, Zakhidov AA, de Heer WA. 2002. Carbon nanotubes: the route toward applications. Science 297:5582787–92
    [Google Scholar]
  34. 34. 
    Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH et al. 2008. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat. Nanotechnol. 3:7423–28
    [Google Scholar]
  35. 35. 
    Baker VA. 2001. Endocrine disruptors—testing strategies to assess human hazard. Toxicol. Vitro 15:4413–19
    [Google Scholar]
  36. 36. 
    Weissman A, Keefer J, Miagkov A, Sathyamoorthy M, Perschke S, Wang FL 2007. Cell-based screening assays. Comprehensive Medicinal Chemistry II JB Taylor, DJ Triggle 617–46 Oxford, UK: Elsevier
    [Google Scholar]
  37. 37. 
    Chen JJ, Budelsky AL. 2011. Prostaglandin D2 receptor CRTH2 antagonists for the treatment of inflammatory diseases. Prog. Med. Chem. 50:49–107
    [Google Scholar]
  38. 38. 
    Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Häggblad J et al. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138:3863–70
    [Google Scholar]
  39. 39. 
    Kuiper GGJM, Lemmen JG, Carlsson B, Corton JC, Safe SH et al. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 139:104252–63
    [Google Scholar]
  40. 40. 
    Wang J, Rahman MF, Duhart HM, Newport GD, Patterson TA et al. 2009. Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles. Neurotoxicology 30:6926–33
    [Google Scholar]
  41. 41. 
    Huang R, Southall N, Cho M-H, Xia M, Inglese J, Austin CP. 2008. Characterization of diversity in toxicity mechanism using in vitro cytotoxicity assays in quantitative high throughput screening. Chem. Res. Toxicol. 21:3659–67
    [Google Scholar]
  42. 42. 
    Comm. Predict.-Toxicol. Approaches Mil. Assess. Acute Expo., Comm. Toxicol., Board Environ. Stud. Toxicol., Board Life Sci., Div. Earth Life Stud., Natl. Acad. Sci. Eng. Med 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense Washington, DC: Natl. Acad. Press
    [Google Scholar]
  43. 43. 
    Kabadi PK, Vantangoli MM, Rodd AL, Leary E, Madnick SJ et al. 2015. Into the depths: techniques for in vitro three-dimensional microtissue visualization. BioTechniques 59:5279–86
    [Google Scholar]
  44. 44. 
    Lewinski N, Colvin V, Drezek R. 2008. Cytotoxicity of nanoparticles. Small 4:126–49
    [Google Scholar]
  45. 45. 
    Stone V, Johnston H, Schins RPF. 2009. Development of in vitro systems for nanotoxicology: methodological considerations. Crit. Rev. Toxicol. 39:7613–26
    [Google Scholar]
  46. 46. 
    Goode AE, Carter DAG, Motskin M, Pienaar IS, Chen S et al. 2015. High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells. Biomaterials 70:57–70
    [Google Scholar]
  47. 47. 
    Chan FK-M, Moriwaki K, De Rosa MJ. 2013. Detection of necrosis by release of lactate dehydrogenase (LDH) activity. Methods Mol. Biol. 979:65–70
    [Google Scholar]
  48. 48. 
    Kumar P, Nagarajan A, Uchil PD. 2018. Analysis of cell viability by the lactate dehydrogenase assay. Cold Spring. Harb. Protoc. 2018:6 https://doi.org/10.1101/pdb.prot095497
    [Crossref] [Google Scholar]
  49. 49. 
    Stoehr LC, Gonzalez E, Stampfl A, Casals E, Duschl A et al. 2011. Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells. Part. Fibre Toxicol. 8:36
    [Google Scholar]
  50. 50. 
    Gliga AR, Skoglund S, Odnevall Wallinder I, Fadeel B, Karlsson HL 2014. Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release. Part. Fibre Toxicol. 11:11
    [Google Scholar]
  51. 51. 
    Riss T, Niles A, Moravec R, Karassina N, Vidugiriene J 2004. Cytotoxicity assays: in vitro methods to measure dead cells. Assay Guidance Manual GS Sittampalam, A Grossman, K Brimacombe, M Arkin, D Auld et al. Bethesda, MD: Eli Lilly & Co./Natl. Cent. Adv. Transl. Sci.
    [Google Scholar]
  52. 52. 
    Farcal L, Andón FT, Cristo LD, Rotoli BM, Bussolati O et al. 2015. Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: first steps towards an intelligent testing strategy. PLOS ONE 10:5e0127174
    [Google Scholar]
  53. 53. 
    Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ. 2005. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol. Vitro 19:7975–83
    [Google Scholar]
  54. 54. 
    Mu Q, David CA, Galceran J, Rey-Castro C, Krzemiński Ł et al. 2014. Systematic investigation of the physicochemical factors that contribute to the toxicity of ZnO nanoparticles. Chem. Res. Toxicol. 27:4558–67
    [Google Scholar]
  55. 55. 
    Armand L, Tarantini A, Beal D, Biola-Clier M, Bobyk L et al. 2016. Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents. Nanotoxicology 10:7913–23
    [Google Scholar]
  56. 56. 
    Anguissola S, Garry D, Salvati A, O'Brien PJ, Dawson KA 2014. High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles. PLOS ONE 9:9e108025
    [Google Scholar]
  57. 57. 
    Shannahan JH, Podila R, Brown JM. 2015. A hyperspectral and toxicological analysis of protein corona impact on silver nanoparticle properties, intracellular modifications, and macrophage activation. Int. J. Nanomed. 10:6509–21
    [Google Scholar]
  58. 58. 
    Bhise NS, Ribas J, Manoharan V, Zhang YS, Polini A et al. 2014. Organ-on-a-chip platforms for studying drug delivery systems. J. Control. Release 190:82–93
    [Google Scholar]
  59. 59. 
    Miller MC, Mohrenweiser HW, Bell DA. 2001. Genetic variability in susceptibility and response to toxicants. Toxicol. Lett. 120:1–3269–80
    [Google Scholar]
  60. 60. 
    Jang K-J, Mehr AP, Hamilton GA, McPartlin LA, Chung S et al. 2013. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr. Biol. 5:91119–29
    [Google Scholar]
  61. 61. 
    Kratz SRA, Höll G, Schuller P, Ertl P, Rothbauer M. 2019. Latest trends in biosensing for microphysiological organs-on-a-chip and body-on-a-chip systems. Biosensors 9:3110
    [Google Scholar]
  62. 62. 
    Chitcholtan K, Asselin E, Parent S, Sykes PH, Evans JJ. 2013. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Exp. Cell Res. 319:75–87
    [Google Scholar]
  63. 63. 
    Bovard D, Sandoz A, Luettich K, Frentzel S, Iskandar A et al. 2018. A lung/liver-on-a-chip platform for acute and chronic toxicity studies. Lab Chip 18:243814–29
    [Google Scholar]
  64. 64. 
    van den Berg A, Mummery CL, Passier R, van der Meer AD. 2019. Personalised organs-on-chips: functional testing for precision medicine. Lab Chip 19:2198–205
    [Google Scholar]
  65. 65. 
    Wu Q, Liu J, Wang X, Feng L, Wu J et al. 2020. Organ-on-a-chip: recent breakthroughs and future prospects. BioMed. Eng. OnLine 19:19
    [Google Scholar]
  66. 66. 
    Hegde M, Jindal R, Bhushan A, Bale SS, McCarty WJ et al. 2014. Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform. Lab Chip 14:2033–39
    [Google Scholar]
  67. 67. 
    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]
  68. 68. 
    Sauer UG, Vogel S, Hess A, Kolle SN, Ma-Hock L et al. 2013. In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems. Toxicol. Vitro 27:1174–90
    [Google Scholar]
  69. 69. 
    Iavicoli I, Fontana L, Nordberg G. 2016. The effects of nanoparticles on the renal system. Crit. Rev. Toxicol. 46:6490–560
    [Google Scholar]
  70. 70. 
    Toh YC, Lim TC, Tai D, Xiao G, van Noor D et al. 2009. A microfluidic 3D hepatocyte chip for drug toxicity testing. Lab Chip 9:2026–35
    [Google Scholar]
  71. 71. 
    Zhao Y, Kankala RK, Wang S-B, Chen A-Z. 2019. Multi-organs-on-chips: towards long-term biomedical investigations. Molecules 24:4675
    [Google Scholar]
  72. 72. 
    Marsano A, Conficconi C, Lemme M, Occhetta P, Gaudiello E et al. 2016. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. Lab Chip 16:599–610
    [Google Scholar]
  73. 73. 
    Agrawal G, Aung A, Varghese S. 2017. Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury. Lab Chip 17:3447–61
    [Google Scholar]
  74. 74. 
    Sin A, Chin KC, Jamil MF, Kostov Y, Rao G, Shuler ML. 2004. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors. Biotechnol. Prog. 20:1338–45
    [Google Scholar]
  75. 75. 
    Yang J-W, Shen Y-C, Lin K-C, Cheng S-J, Chen S-L et al. 2020. Organ-on-a-chip: opportunities for assessing the toxicity of particulate matter. Front. Bioeng. Biotechnol. 8:519
    [Google Scholar]
  76. 76. 
    Satoh T, Sugiura S, Shin K, Onuki-Nagasaki R, Ishida S et al. 2017. A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic pressure-driven medium circulation platform. Lab Chip 18:1115–25
    [Google Scholar]
  77. 77. 
    McAleer CW, Long CJ, Elbrecht D, Sasserath T, Bridges LR et al. 2019. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci. Transl. Med. 11:497eaav1386
    [Google Scholar]
  78. 78. 
    Herland A, Maoz BM, Das D, Somayaji MR, Prantil-Baun R et al. 2020. Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips. Nat. Biomed. Eng. 4:4421–36
    [Google Scholar]
  79. 79. 
    Schimek K, Frentzel S, Luettich K, Bovard D, Rütschle I et al. 2020. Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies. Sci. Rep. 10:17865
    [Google Scholar]
  80. 80. 
    Novak R, Ingram M, Marquez S, Das D, Delahanty A et al. 2020. Robotic fluidic coupling and interrogation of multiple vascularized organ chips. Nat. Biomed. Eng. 4:4407–20
    [Google Scholar]
  81. 81. 
    Sticker D, Rothbauer M, Ehgartner J, Steininger C, Liske O et al. 2019. Oxygen management at the microscale: a functional biochip material with long-lasting and tunable oxygen scavenging properties for cell culture applications. ACS Appl. Mater. Interfaces 11:9730–39
    [Google Scholar]
  82. 82. 
    Büyüktiryaki S, Sümbelli Y, Keçili R, Hussain CM 2019. Lab-on-chip platforms for environmental analysis. Encyclopedia of Analytical Science P Worsfold, C Poole, A Townshend, M Miró 267–73 Oxford, UK: Academic. , 3rd ed..
    [Google Scholar]
  83. 83. 
    Olsavsky KM, Page JL, Johnson MC, Zarbl H, Strom SC et al. 2007. Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues. Toxicol. Appl. Pharmacol. 222:42–56
    [Google Scholar]
  84. 84. 
    Rodríguez-Antona C, Donato MT, Boobis A, Edwards RJ, Watts PS et al. 2002. Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells. Xenobiotica 32:505–20
    [Google Scholar]
  85. 85. 
    Pan C, Kumar C, Bohl S, Klingmueller U, Mann M. 2009. Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions. Mol. Cell. Proteom. 8:443–50
    [Google Scholar]
  86. 86. 
    Fu X, Wu X, Djekidel MN, Zhang Y. 2019. Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cells. Nat. Cell Biol. 21:835–44
    [Google Scholar]
  87. 87. 
    Narsinh KH, Plews J, Wu JC. 2011. Comparison of human induced pluripotent and embryonic stem cells: Fraternal or identical twins?. Mol. Ther. 19:635–38
    [Google Scholar]
  88. 88. 
    Ullah I, Subbarao RB, Rho GJ. 2015. Human mesenchymal stem cells—current trends and future prospective. Biosci. Rep. 35:2 e00191
    [Google Scholar]
  89. 89. 
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–72
    [Google Scholar]
  90. 90. 
    Xia M, Huang R, Witt KL, Southall N, Fostel J et al. 2008. Compound cytotoxicity profiling using quantitative high-throughput screening. Environ. Health. Perspect. 116:3284–91
    [Google Scholar]
  91. 91. 
    Ahadian S, Civitarese R, Bannerman D, Mohammadi MH, Lu R et al. 2018. Organ-on-a-chip platforms: a convergence of advanced materials, cells, and microscale technologies. Adv. Healthc. Mater. 7:21700506
    [Google Scholar]
  92. 92. 
    Dong R, Liu Y, Mou L, Deng J, Jiang X. 2019. Microfluidics-based biomaterials and biodevices. Adv. Mater. 31:451805033
    [Google Scholar]
  93. 93. 
    He Y, Lu F. 2016. Development of synthetic and natural materials for tissue engineering applications using adipose stem cells. Stem Cells Int 2016:5786257
    [Google Scholar]
  94. 94. 
    Huang HC, Chang YJ, Chen WC, Harn HIC, Tang MJ et al. 2013. Enhancement of renal epithelial cell functions through microfluidic-based coculture with adipose-derived stem cells. Tissue Eng. A 19:2024–34
    [Google Scholar]
  95. 95. 
    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]
  96. 96. 
    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. 15:669–78
    [Google Scholar]
  97. 97. 
    Shirosaki Y, Hirai M, Hayakawa S, Fujii E, Lopes MA et al. 2015. Preparation and in vitro cytocompatibility of chitosan–siloxane hybrid hydrogels. J. Biomed. Mater. Res. A 103:289–99
    [Google Scholar]
  98. 98. 
    Bhattacharjee N, Parra-Cabrera C, Kim YT, Kuo AP, Folch A. 2018. Desktop-stereolithography 3D-printing of a poly(dimethylsiloxane)-based material with Sylgard-184 properties. Adv. Mater. 30:1800001
    [Google Scholar]
  99. 99. 
    Liu Y, Zhang L, Wu W, Zhao M, Wang W. 2016. Restraining non-specific adsorption of protein using Parylene C-caulked polydimethylsiloxane. Biomicrofluidics 10:2024126
    [Google Scholar]
  100. 100. 
    Lee PJ, Hung PJ, Lee LP. 2007. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol. Bioeng. 97:1340–46
    [Google Scholar]
  101. 101. 
    Taylor AM, Dieterich DC, Ito HT, Kim SA, Schuman EM. 2010. Microfluidic local perfusion chambers for the visualization and manipulation of synapses. Neuron 66:57–68
    [Google Scholar]
  102. 102. 
    Yum K, Hong SG, Healy KE, Lee LP. 2014. Physiologically relevant organs on chips. Biotechnol. J. 9:116–27
    [Google Scholar]
  103. 103. 
    Bhatia SN, Yarmush ML, Toner M. 1997. Controlling cell interactions by micropatterning in co-cultures: hepatocytes and 3T3 fibroblasts. J. Biomed. Mater. Res. 34:189–99
    [Google Scholar]
  104. 104. 
    Kaarj K, Yoon J-Y. 2019. Methods of delivering mechanical stimuli to organ-on-a-chip. Micromachines 10:10700
    [Google Scholar]
  105. 105. 
    Stucki JD, Hobi N, Galimov A, Stucki AO, Schneider-Daum N et al. 2018. Medium throughput breathing human primary cell alveolus-on-chip model. Sci. Rep. 8:14359
    [Google Scholar]
  106. 106. 
    Torisawa Y, Mosadegh B, Bersano-Begey T, Steele JM, Luker KE et al. 2010. Microfluidic platform for chemotaxis in gradients formed by CXCL12 source-sink cells. Integr. Biol. 2:680–86
    [Google Scholar]
  107. 107. 
    Zhang Q, Beirne S, Shu K, Esrafilzadeh D, Huang XF et al. 2018. Electrical stimulation with a conductive polymer promotes neurite outgrowth and synaptogenesis in primary cortical neurons in 3D. Sci. Rep. 8:9855
    [Google Scholar]
  108. 108. 
    Ahadian S, Ostrovidov S, Hosseini V, Kaji H, Ramalingam M et al. 2013. Electrical stimulation as a biomimicry tool for regulating muscle cell behavior. Organogenesis 9:87–92
    [Google Scholar]
  109. 109. 
    Kim HJ, Li H, Collins JJ, Ingber DE 2016. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. PNAS 113:E7–15
    [Google Scholar]
  110. 110. 
    Lee H, Kim DS, Ha SK, Choi I, Lee JM et al. 2017. A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic–pharmacodynamic (PK–PD) model. Biotechnol. Bioeng. 114:432–43
    [Google Scholar]
  111. 111. 
    Negus SS, Banks ML. 2018. Pharmacokinetic–pharmacodynamic (PKPD) analysis with drug discrimination. Curr. Top. Behav. Neurosci. 39:245–59
    [Google Scholar]
  112. 112. 
    Guerrero YA, Desai D, Sullivan C, Kindt E, Spilker ME et al. 2020. A microfluidic perfusion platform for in vitro analysis of drug pharmacokinetic-pharmacodynamic (PK-PD) relationships. AAPS J 22:53
    [Google Scholar]
  113. 113. 
    Shinha K, Nihei W, Ono T, Nakazato R, Kimura H. 2020. A pharmacokinetic–pharmacodynamic model based on multi-organ-on-a-chip for drug–drug interaction studies. Biomicrofluidics 14:044108
    [Google Scholar]
  114. 114. 
    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]
  115. 115. 
    Odijk M, van der Meer AD, Levner D, Kim HJ, van der Helm MW et al. 2015. Measuring direct current trans-epithelial electrical resistance in organ-on-a-chip microsystems. Lab Chip 15:745–52
    [Google Scholar]
  116. 116. 
    Mori N, Morimoto Y, Takeuchi S. 2018. Transendothelial electrical resistance (TEER) measurement system of 3D tubular vascular channel. IEEE Micro Electro Mech. Syst. 2018:322–25
    [Google Scholar]
  117. 117. 
    Brown AM, Renaud Y, Ross C, Hansen M, Mongrain I et al. 2014. Development of a broad-based ADME panel for use in pharmacogenomic studies. Pharmacogenomics 15:1185–95
    [Google Scholar]
  118. 118. 
    Rodrigues D, Rowland A. 2019. From endogenous compounds as biomarkers to plasma-derived nanovesicles as liquid biopsy; Has the golden age of translational pharmacokinetics-absorption, distribution, metabolism, excretion-drug–drug interaction science finally arrived?. Clin. Pharmacol. Ther. 105:1407–20
    [Google Scholar]
  119. 119. 
    Yoshida K, Guo C, Sane R. 2018. Quantitative prediction of OATP-mediated drug-drug interactions with model-based analysis of endogenous biomarker kinetics. CPT Pharmacometr. Syst. Pharmacol. 7:517–24
    [Google Scholar]
  120. 120. 
    Li X, Tian T. 2018. Recent advances in an organ-on-a-chip: biomarker analysis and applications. Anal. Methods 10:263122–30
    [Google Scholar]
  121. 121. 
    Veal EA, Day AM, Morgan BA. 2007. Hydrogen peroxide sensing and signaling. Mol. Cell 26:11–14
    [Google Scholar]
  122. 122. 
    Kilic T, Navaee F, Stradolini F, Renaud P, Carrara S 2018. Organs-on-chip monitoring: sensors and other strategies. Microphysiol. Syst. 2:5
    [Google Scholar]
  123. 123. 
    Bang S, Jeong S, Choi N, Kim HN. 2019. Brain-on-a-chip: a history of development and future perspective. Biomicrofluidics 13:5051301
    [Google Scholar]
  124. 124. 
    Motallebnejad P, Thomas A, Swisher SL, Azarin SM. 2019. An isogenic hiPSC-derived BBB-on-a-chip. Biomicrofluidics 13:6064119
    [Google Scholar]
  125. 125. 
    Lee SR, Hyung S, Bang S, Lee Y, Ko J et al. 2019. Modeling neural circuit, blood-brain barrier, and myelination on a microfluidic 96 well plate. Biofabrication 11:035013
    [Google Scholar]
  126. 126. 
    Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR et al. 2017. Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci. Rep. 7:142296
    [Google Scholar]
  127. 127. 
    McCuskey RS. 2008. The hepatic microvascular system in health and its response to toxicants. Anat. Rec. 291:6661–71
    [Google Scholar]
  128. 128. 
    Zuchowska A, Kwapiszewska K, Chudy M, Dybko A, Brzozka Z. 2017. Studies of anticancer drug cytotoxicity based on long-term HepG2 spheroid culture in a microfluidic system. Electrophoresis 38:81206–16
    [Google Scholar]
  129. 129. 
    Deng J, Zhang X, Chen Z, Luo Y, Lu Y et al. 2019. A cell lines derived microfluidic liver model for investigation of hepatotoxicity induced by drug-drug interaction. Biomicrofluidics 13:2024101
    [Google Scholar]
  130. 130. 
    de Mello CPP, Carmona-Moran C, McAleer CW, Perez J, Coln EA et al. 2020. Microphysiological heart–liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery. Lab Chip 20:749–59
    [Google Scholar]
  131. 131. 
    Cong Y, Han X, Wang Y, Chen Z, Lu Y et al. 2020. Drug toxicity evaluation based on organ-on-a-chip technology. Micromachines 11:4381
    [Google Scholar]
  132. 132. 
    Yin L, Du G, Zhang B, Zhang H, Yin R et al. 2020. Efficient drug screening and nephrotoxicity assessment on co-culture microfluidic kidney chip. Sci. Rep. 10:16568
    [Google Scholar]
  133. 133. 
    Sakolish C, Chen Z, Dalaijamts C, Mitra K, Liu Y et al. 2020. Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling. Toxicol. Vitro 63:104752
    [Google Scholar]
  134. 134. 
    Suter-Dick L, Mauch L, Ramp D, Caj M, Vormann MK et al. 2018. Combining extracellular miRNA determination with microfluidic 3D cell cultures for the assessment of nephrotoxicity: a proof of concept study. AAPS J 20:586
    [Google Scholar]
  135. 135. 
    Tian H, Pang J, Qin K, Yuan W, Kong J et al. 2020. A novel tissue-based liver–kidney-on-a-chip can mimic liver tropism of extracellular vesicles derived from breast cancer cells. Biotechnol. J. 15:1900107
    [Google Scholar]
  136. 136. 
    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. Gastroenter. 5:4659–68
    [Google Scholar]
  137. 137. 
    Poceviciute R, Ismagilov RF. 2019. Human-gut-microbiome on a chip. Nat. Biomed. Eng. 3:7500–1
    [Google Scholar]
  138. 138. 
    Kasendra M, Luc R, Yin J, Manatakis DV, Kulkarni G et al. 2020. Duodenum intestine-chip for preclinical drug assessment in a human relevant model. eLife 9:e50135
    [Google Scholar]
  139. 139. 
    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. 3:7520–31
    [Google Scholar]
  140. 140. 
    Jeong K, Yu YJ, You JY, Rhee WJ, Kim JA. 2020. Exosome-mediated microRNA-497 delivery for anti-cancer therapy in a microfluidic 3D lung cancer model. Lab Chip 20:3548–57
    [Google Scholar]
  141. 141. 
    Frost TS, Jiang L, Zohar Y. 2020. Pharmacokinetic analysis of epithelial/endothelial cell barriers in microfluidic bilayer devices with an air-liquid interface. Micromachines 11:5536
    [Google Scholar]
  142. 142. 
    Skardal A, Aleman J, Forsythe S, Rajan S, Murphy S et al. 2020. Drug compound screening in single and integrated multi-organoid body-on-a-chip systems. Biofabrication 12:025017
    [Google Scholar]
  143. 143. 
    Lukács B, Bajza Á, Kocsis D, Csorba A, Antal I et al. 2019. Skin-on-a-chip device for ex vivo monitoring of transdermal delivery of drugs—design, fabrication, and testing. Pharmaceutics 11:9445
    [Google Scholar]
  144. 144. 
    Alexander F, Eggert S, Wiest J. 2018. Skin-on-a-chip: transepithelial electrical resistance and extracellular acidification measurements through an automated air-liquid interface. Genes 9:2114
    [Google Scholar]
  145. 145. 
    Schimek K, Hsu HH, Boehme M, Kornet JJ, Marx U et al. 2018. Bioengineering of a full-thickness skin equivalent in a 96-well insert format for substance permeation studies and organ-on-a-chip applications. Bioengineering 5:43
    [Google Scholar]
  146. 146. 
    Bavli D, Prill S, Ezra E, Levy G, Cohen M et al. 2016. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. PNAS 113:16E2231–40
    [Google Scholar]
  147. 147. 
    Liu L, Koo Y, Russell T, Gay E, Li Y, Yun Y. 2020. Three-dimensional brain-on-chip model using human iPSC-derived GABAergic neurons and astrocytes: butyrylcholinesterase post-treatment for acute malathion exposure. PLOS ONE 15:3e0230335
    [Google Scholar]
  148. 148. 
    Wang Y, Wang L, Zhu Y, Qin J. 2018. Human brain organoid-on-a-chip to model prenatal nicotine exposure. Lab Chip 18:6851–60
    [Google Scholar]
  149. 149. 
    Santbergen MJC, van der Zande M, Gerssen A, Bouwmeester H, Nielen MWF. 2020. Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies. Anal. Bioanal. Chem. 412:51111–22
    [Google Scholar]
  150. 150. 
    Kim K, Jeon HM, Choi KC, Sung GY. 2020. Testing the effectiveness of Curcuma longa leaf extract on a skin equivalent using a pumpless skin-on-a-chip model. Int. J. Mol. Sci. 21:113898
    [Google Scholar]
  151. 151. 
    Kafi MA, Kim T-H, An JH, Choi J-W. 2011. Electrochemical cell-based chip for the detection of toxic effects of bisphenol-A on neuroblastoma cells. Biosens. Bioelectron. 26:73371–75
    [Google Scholar]
  152. 152. 
    Li Z, Jiang L, Tao T, Su W, Guo Y et al. 2017. Assessment of cadmium-induced nephrotoxicity using a kidney-on-a-chip device. Toxicol. Res. 6:3372–80
    [Google Scholar]
  153. 153. 
    Zhang M, Xu C, Jiang L, Qin J. 2018. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol. Res. 7:61048–60
    [Google Scholar]
  154. 154. 
    Elias-Kirma S, Artzy-Schnirman A, Das P, Heller-Algazi M, Korin N, Sznitman J. 2020. In situ-like aerosol inhalation exposure for cytotoxicity assessment using airway-on-chips platforms. Front. Bioeng. Biotechnol. 8:91
    [Google Scholar]
  155. 155. 
    Chang S-Y, Weber EJ, Sidorenko VS, Chapron A, Yeung CK et al. 2017. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2:22e95978
    [Google Scholar]
  156. 156. 
    Theobald J, Ghanem A, Wallisch P, Banaeiyan AA, Andrade-Navarro MA et al. 2018. Liver-kidney-on-chip to study toxicity of drug metabolites. ACS Biomater. Sci. Eng. 4:178–89
    [Google Scholar]
  157. 157. 
    Meghani N, Kim KH, Kim SH, Lee SH, Choi KH. 2020. Evaluation and live monitoring of pH-responsive HSA-ZnO nanoparticles using a lung-on-a-chip model. Arch. Pharm. Res. 43:5503–13
    [Google Scholar]
  158. 158. 
    Yoon J-Y 2016. Introduction. Introduction to Biosensors: From Electric Circuits to Immunosensors J-Y Yoon 1–15 Cham, Switz: Springer Int.
    [Google Scholar]
  159. 159. 
    Shintu L, Baudoin R, Navratil V, Prot JM, Pontoizeau C et al. 2012. Metabolomics-on-a-chip and predictive systems toxicology in microfluidic bioartificial organs. Anal. Chem. 84:1840–48
    [Google Scholar]
  160. 160. 
    Zhang F, Liu W, Zhou S, Jiang L, Wang K, Wei Y et al. 2020. Investigation of environmental pollutant-induced lung inflammation and injury in a 3D coculture-based microfluidic pulmonary alveolus system. Anal. Chem. 92:7200–8
    [Google Scholar]
  161. 161. 
    Liu F, Bing T, Shangguan D, Zhao M, Shao N. 2016. Ratiometric fluorescent biosensing of hydrogen peroxide and hydroxyl radical in living cells with lysozyme-silver nanoclusters: lysozyme as stabilizing ligand and fluorescence signal unit. Anal. Chem. 88:2110631–38
    [Google Scholar]
  162. 162. 
    Dhara K, Mahapatra DR. 2019. Recent advances in electrochemical nonenzymatic hydrogen peroxide sensors based on nanomaterials: a review. J. Mater. Sci. 54:1912319–57
    [Google Scholar]
  163. 163. 
    Prill S, Jaeger MS, Duschl C. 2014. Long-term microfluidic glucose and lactate monitoring in hepatic cell culture. Biomicrofluidics 8:3034102
    [Google Scholar]
  164. 164. 
    Soucy JR, Bindas AJ, Koppes AN, Koppes RA 2019. Instrumented microphysiological systems for real-time measurement and manipulation of cellular electrochemical processes. iScience 21:521–48
    [Google Scholar]
  165. 165. 
    Pemberton RM, Cox T, Tuffin R, Drago GA, Griffiths J et al. 2014. Fabrication and evaluation of a micro(bio)sensor array chip for multiple parallel measurements of important cell biomarkers. Sensors 14:1120519–32
    [Google Scholar]
  166. 166. 
    Bernhardt G, Distèche A, Jaenicke R, Koch B, Lüdemann H-D, Stetter K-O. 1988. Effect of carbon dioxide and hydrostatic pressure on the pH of culture media and the growth of methanogens at elevated temperature. Appl. Microbiol. Biotechnol. 28:2176–81
    [Google Scholar]
  167. 167. 
    Kieninger J, Weltin A, Flamm H, Urban GA. 2018. Microsensor systems for cell metabolism—from 2D culture to organ-on-chip. Lab Chip 18:91274–91
    [Google Scholar]
  168. 168. 
    Asphahani F, Zhang M. 2007. Cellular impedance biosensors for drug screening and toxin detection. Analyst 132:9835–41
    [Google Scholar]
  169. 169. 
    Heileman K, Daoud J, Tabrizian M. 2013. Dielectric spectroscopy as a viable biosensing tool for cell and tissue characterization and analysis. Biosens. Bioelectron. 49:348–59
    [Google Scholar]
  170. 170. 
    Asif A, Kim KH, Jabbar F, Kim S, Choi KH. 2020. Real-time sensors for live monitoring of disease and drug analysis in microfluidic model of proximal tubule. Microfluid. Nanofluid. 24:643
    [Google Scholar]
  171. 171. 
    Zhao Y, Rafatian N, Wang EY, Feric NT, Lai BFL et al. 2020. Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform. Matrix Biol 85–86:189–204
    [Google Scholar]
  172. 172. 
    D'Costa K, Kosic M, Lam A, Moradipour A, Zhao Y, Radisic M 2020. Biomaterials and culture systems for development of organoid and organ-on-a-chip models. Ann. Biomed. Eng. 48:72002–27
    [Google Scholar]
  173. 173. 
    Vriend J, Peters JGP, Nieskens TTG, Škovroňová R, Blaimschein N et al. 2020. Flow stimulates drug transport in a human kidney proximal tubule-on-a-chip independent of primary cilia. Biochim. Biophys. Acta 1864:1129433
    [Google Scholar]
  174. 174. 
    Beekers I, van Rooij T, Verweij MD, Versluis M, de Jong N et al. 2018. Acoustic characterization of a vessel-on-a-chip microfluidic system for ultrasound-mediated drug delivery. IEEE Trans. Ultrason. Ferroelect. Freq. Contr. 65:4570–81
    [Google Scholar]
  175. 175. 
    Lin A, Sved Skottvoll F, Rayner S, Pedersen-Bjergaard S, Sullivan G et al. 2020. 3D cell culture models and organ-on-a-chip: meet separation science and mass spectrometry. Electrophoresis 41:1–256–64
    [Google Scholar]
  176. 176. 
    Kimura H, Ikeda T, Nakayama H, Sakai Y, Fujii T. 2015. An on-chip small intestine-liver model for pharmacokinetic studies. J. Lab. Autom. 20:3265–73
    [Google Scholar]
  177. 177. 
    Kimura H, Sakai Y, Fujii T. 2018. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab. Pharmacokinet. 33:143–48
    [Google Scholar]
  178. 178. 
    Jin Y, Kim J, Lee JS, Min S, Kim S et al. 2018. Vascularized liver organoids generated using induced hepatic tissue and dynamic liver-specific microenvironment as a drug testing platform. Adv. Funct. Mater. 28:371801954
    [Google Scholar]
  179. 179. 
    Zhang YS, Aleman J, Shin SR, Kilic T, Kim D et al. 2017. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. PNAS 114:12E2293–302
    [Google Scholar]
  180. 180. 
    Achberger K, Probst C, Haderspeck J, Bolz S, Rogal J et al. 2019. Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. eLife 8:e46188
    [Google Scholar]
  181. 181. 
    Bücheler M, Wirz C, Schütz A, Bootz F. 2002. Tissue engineering of human salivary gland organoids. Acta Oto-Laryngol 122:5541–45
    [Google Scholar]
  182. 182. 
    Sung JH, Shuler ML. 2009. A micro cell culture analog (μCCA) 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]
  183. 183. 
    Misun PM, Rothe J, Schmid YRF, Hierlemann A, Frey O. 2016. Multi-analyte biosensor interface for real-time monitoring of 3D microtissue spheroids in hanging-drop networks. Microsys. Nanoeng. 2:116022
    [Google Scholar]
  184. 184. 
    Rivera KR, Pozdin VA, Young AT, Erb PD, Wisniewski NA et al. 2019. Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems. Biosens. Bioelectron. 123:131–40
    [Google Scholar]
  185. 185. 
    Mousavi Shaegh SA, De Ferrari F, Zhang YS, Nabavinia M, Mohammad NB et al. 2016. A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices. Biomicrofluidics 10:4044111
    [Google Scholar]
  186. 186. 
    Kalmykov A, Huang C, Bliley J, Shiwarski D, Tashman J et al. 2019. Organ-on-e-chip: three-dimensional self-rolled biosensor array for electrical interrogations of human electrogenic spheroids. Sci. Adv. 5:8eaax0729
    [Google Scholar]
  187. 187. 
    Henry OYF, Villenave R, Cronce M, Leineweber W, Benz M, Ingber DE. 2017. Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function. Lab Chip 17:132264–71
    [Google Scholar]
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