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Multi-organ on a chip for personalized precision medicine

Published online by Cambridge University Press:  13 August 2018

Vivekanandan Palaninathan Open the ORCID record for Vivekanandan Palaninathan [Opens in a new window] ,
Vimal Kumar ,
Toru Maekawa ,
Dorian Liepmann ,
Ramasamy Paulmurugan ,
Jairam R. Eswara ,
Pulickel M. Ajayan ,
Shine Augustine ,
Bansi D. Malhotra  and
Sowmya Viswanathan
...Show all authors
Vivekanandan Palaninathan
Affiliation:
Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
Vimal Kumar
Affiliation:
Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
Toru Maekawa
Affiliation:
Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
Dorian Liepmann
Affiliation:
Department of Bioengineering, University of California, Berkeley, CA, USA
Ramasamy Paulmurugan
Affiliation:
Department of Radiology, Cellular Pathway Imaging Laboratory, Stanford University School of Medicine, 3155 Porter Drive, Suite 2236, Palo Alto, CA 94304, USA
Jairam R. Eswara
Affiliation:
Brigham and Women's Hospital, Division of Urology, 75 Francis Street, Boston, Massachusetts 02115, USA
Pulickel M. Ajayan
Affiliation:
Department of Materials Science and Nanoengineering, Rice University, Houston, TX 77005, USA
Shine Augustine
Affiliation:
Department of Biotechnology, Delhi Technological University, Main Bawana Road, Delhi 110042, India
Bansi D. Malhotra
Affiliation:
Department of Biotechnology, Delhi Technological University, Main Bawana Road, Delhi 110042, India
Sowmya Viswanathan
Affiliation:
Newton-Wellesley Hospital, Newton, MA 02462, USA
Venkatesan Renugopalakrishnan*
Affiliation:
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA
D. Sakthi Kumar*
Affiliation:
Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
*
Address all correspondence to D. Sakthi Kumar and V. Renugoplakrishnan at sakthi@toyo.jp and v.renugopalakrishnan@northeastern.edu
Address all correspondence to D. Sakthi Kumar and V. Renugoplakrishnan at sakthi@toyo.jp and v.renugopalakrishnan@northeastern.edu
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Abstract

The inefficiencies of the current pipeline from discovery to clinical approval of drugs demand a surrogate method to indicate adverse drug reactions, e.g. liver damage. Organ-on-chip (OOC) models would be an ideal, rapid, and human-specific alternate, which would render animal testing obsolete. The ground-breaking ability of OOCs and Multi-OOC constructs is the accurate simulation of the in vivo conditions of human organs leading to precise drug screens for cytotoxicity and/or drug efficacy at a faster pace and lesser cost. Here we discuss the innovation, architecture, and the progress of OOCs towards human body-on-a-chip.

Type
2D Nanomaterials for Healthcare and Lab-on-a-Chip Devices Prospective Articles
Information
MRS Communications , Volume 8 , Issue 3 , September 2018 , pp. 652 - 667
Copyright
Copyright © Materials Research Society 2018 

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Footnotes

This paper is dedicated to Suraj Renugopalakrishnan.

References

1.Kang, W., McNaughton, R.L., and Espinosa, H.D.: Micro- and nanoscale technologies for delivery into adherent cells. Trends Biotechnol. 34, 665 (2016).Google Scholar
2.Zhang, B. and Radisic, M.: Organ-on-a-chip devices advance to market. Lab. Chip 17, 2395 (2017).Google Scholar
3.Baker, M.: Tissue models: a living system on a chip. Nature 471, 661 (2011).Google Scholar
4.Greenman, J.: Looking to the future of organs-on-chip. Future. Sci. OA. 3, FSO205 (2017).Google Scholar
5.Shamir, E.R. and Ewald, A.J.: Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol. 15, 647 (2014).Google Scholar
6.Huh, D., Hamilton, G.A., and Ingber, D.E.: From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745 (2011).Google Scholar
7.Mroue, R., and Bissell, M.J.: Three-dimensional cultures of mouse mammary epithelial cells. Methods Mol. Biol. 945, 221 (2013).Google Scholar
8.Duval, K., Grover, H., Han, L.H., Mou, Y., Pegoraro, A.F., Fredberg, J., and Chen, Z.: Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda) 32, 266 (2017).Google Scholar
9.Huh, D., Kim, H.J., Fraser, J.P., Shea, D.E., Khan, M., Bahinski, A., Hamilton, G.A., and Ingber, D.E.: Microfabrication of human organs-on-chips. Nat. Protoc. 8, 2135 (2013).Google Scholar
10.Moraes, C., Mehta, G., Lesher-Perez, S.C., and Takayama, S.: Organs-on-a-chip: a focus on compartmentalized microdevices. Ann. Biomed. Eng. 40, 1211 (2012).Google Scholar
11.Wagner, I., Materne, E.M., Brincker, S., Sussbier, U., Fradrich, C., Busek, M., Sonntag, F., Sakharov, D.A., Trushkin, E.V., Tonevitsky, A.G., Lauster, R., and 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 13, 3538 (2013).Google Scholar
12.Halldorsson, S., Lucumi, E., Gomez-Sjoberg, R., and Fleming, R.M.T.: Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices. Biosens. Bioelectron. 63, 218 (2015).Google Scholar
13.Meyvantsson, I., and Beebe, D.J.: Cell culture models in microfluidic systems. Annu. Rev. Anal. Chem. (Palo Alto Calif.) 1, 423 (2008).Google Scholar
14.Whitesides, G.M.: The origins and the future of microfluidics. Nature 442, 368 (2006).Google Scholar
15.Gauvin, R. and Khademhosseini, A.: Microscale technologies and modular approaches for tissue engineering: moving toward the fabrication of complex functional structures. ACS Nano. 5, 4258 (2011).Google Scholar
16.Khademhosseini, A., Langer, R., Borenstein, J., and Vacanti, J.P.: Microscale technologies for tissue engineering and biology. Proc. Natl. Acad. Sci. USA 103, 2480 (2006).Google Scholar
17.Liedl, T., Hogberg, B., Tytell, J., Ingber, D.E., and Shih, W.M.: Self-assembly of three-dimensional prestressed tensegrity structures from DNA. Nat. Nanotechnol. 5, 520 (2010).Google Scholar
18.Mammoto, T. and Ingber, D.E.: Mechanical control of tissue and organ development. Development 137, 1407 (2010).Google Scholar
19.Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., and Ingber, D.E.: Reconstituting organ-level lung functions on a chip. Science 328, 1662 (2010).Google Scholar
20.van Duinen, V., Trietsch, S.J., Joore, J., Vulto, P., and Hankemeier, T.: Microfluidic 3D cell culture: from tools to tissue models. Curr. Opin. Biotechnol. 35, 118 (2015).Google Scholar
21.Bhatia, S.N. and Ingber, D.E.: Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760 (2014).Google Scholar
22.Carraro, A., Hsu, W.M., Kulig, K.M., Cheung, W.S., Miller, M.L., Weinberg, E.J., Swart, E.F., Kaazempur-Mofrad, M., Borenstein, J.T., Vacanti, J.P., and Neville, C.: In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed. Microdevices 10, 795 (2008).Google Scholar
23.Khetani, S.R. and Bhatia, S.N.: Microscale culture of human liver cells for drug development. Nat. Biotechnol. 26, 120 (2008).Google Scholar
24.Rennert, K., Steinborn, S., Groger, M., Ungerbock, B., Jank, A.M., Ehgartner, J., Nietzsche, S., Dinger, J., Kiehntopf, M., Funke, H., Peters, F.T., Lupp, A., Gartner, C., Mayr, T., Bauer, M., Huber, O., and Mosig, A.S.: A microfluidically perfused three dimensional human liver model. Biomaterials 71, 119 (2015).Google Scholar
25.Knowlton, S. and Tasoglu, S.: A bioprinted liver-on-a-chip for drug screening applications. Trends Biotechnol. 34, 681 (2016).Google Scholar
26.Huh, D.D.: A human breathing lung-on-a-chip. Ann. Am. Thorac. Soc. 12(Suppl. 1), S42 (2015).Google Scholar
27.Benam, K.H., Villenave, R., Lucchesi, C., Varone, A., Hubeau, C., Lee, H.H., Alves, S.E., Salmon, M., Ferrante, T.C., Weaver, J.C., Bahinski, A., Hamilton, G.A., and Ingber, D.E.: Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat. Methods 13, 151 (2016).Google Scholar
28.Jang, K.J. and Suh, K.Y.: A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab. Chip 10, 36 (2010).Google Scholar
29.Musah, S., Mammoto, A., Ferrante, T.C., Jeanty, S.S.F., Hirano-Kobayashi, M., Mammoto, T., Roberts, K., Chung, S., Novak, R., Ingram, M., Fatanat-Didar, T., Koshy, S., Weaver, J.C., Church, G.M., and Ingber, D.E.: Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat. Biomed. Eng. 1, 0069 (2017).Google Scholar
30.Jang, K.J., Mehr, A.P., Hamilton, G.A., McPartlin, L.A., Chung, S., Suh, K.Y., and Ingber, D.E.: Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr. Biol. (Camb) 5, 1119 (2013).Google Scholar
31.Kim, H.J., Huh, D., Hamilton, G., and Ingber, D.E.: Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab. Chip 12, 2165 (2012).Google Scholar
32.Kasendra, M., Tovaglieri, A., Sontheimer-Phelps, A., Jalili-Firoozinezhad, S., Bein, A., Chalkiadaki, A., Scholl, W., Zhang, C., Rickner, H., Richmond, C.A., Li, H., Breault, D.T., and Ingber, D.E.: Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids. Sci. Rep. 8, 2871 (2018).Google Scholar
33.Shim, K.Y., Lee, D., Han, J., Nguyen, N.T., Park, S., and Sung, J.H.: Microfluidic gut-on-a-chip with three-dimensional villi structure. Biomed. Microdevices 19, 37 (2017).Google Scholar
34.Puleo, C.M., McIntosh Ambrose, W., Takezawa, T., Elisseeff, J., and Wang, T.H.: Integration and application of vitrified collagen in multilayered microfluidic devices for corneal microtissue culture. Lab. Chip 9, 3221 (2009).Google Scholar
35.Dodson, K.H., Echevarria, F.D., Li, D., Sappington, R.M., and Edd, J.F.: Retina-on-a-chip: a microfluidic platform for point access signaling studies. Biomed. Microdevices 17, 114 (2015).Google Scholar
36.Estlack, Z., Bennet, D., Reid, T., and Kim, J.: Microengineered biomimetic ocular models for ophthalmological drug development. Lab. Chip 17, 1539 (2017).Google Scholar
37.Wang, Y., Wang, L., Zhu, Y., and Qin, J.: Human brain organoid-on-a-chip to model prenatal nicotine exposure. Lab. Chip 18, 851 (2018).Google Scholar
38.Wufuer, M., Lee, G., Hur, W., Jeon, B., Kim, B.J., Choi, T.H., and Lee, S.: Skin-on-a-chip model simulating inflammation, edema and drug-based treatment. Sci. Rep. 6, 37471 (2016).Google Scholar
39.Mori, N., Morimoto, Y., and Takeuchi, S.: Skin integrated with perfusable vascular channels on a chip. Biomaterials 116, 48 (2017).Google Scholar
40.Jusoh, N., Oh, S., Kim, S., Kim, J., and Jeon, N.L.: Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix. Lab. Chip 15, 3984 (2015).Google Scholar
41.Torisawa, Y.S., Spina, C.S., Mammoto, T., Mammoto, A., Weaver, J.C., Tat, T., Collins, J.J., and Ingber, D.E.: Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat. Methods 11, 663 (2014).Google Scholar
42.Qian, F., Huang, C., Lin, Y.D., Ivanovskaya, A.N., O'Hara, T.J., Booth, R.H., Creek, C.J., Enright, H.A., Soscia, D.A., Belle, A.M., Liao, R., Lightstone, F.C., Kulp, K.S., and Wheeler, E.K.: Simultaneous electrical recording of cardiac electrophysiology and contraction on chip. Lab. Chip 17, 1732 (2017).Google Scholar
43.Ahadian, S., Civitarese, R., Bannerman, D., Mohammadi, M.H., Lu, R., Wang, E., Davenport-Huyer, L., Lai, B., Zhang, B., Zhao, Y., Mandla, S., Korolj, A., and Radisic, M.: Organ-on-A-chip platforms: a convergence of advanced materials, cells, and microscale technologies. Adv. Healthc. Mater. 7, 1700506 (2018).Google Scholar
44.Reardon, S.: Biodefence researchers seek ‘Homo chippiens’. Nature 518, 2 (2015).Google Scholar
45.Lee, S.H., Ha, S.K., Choi, I., Choi, N., Park, T.H., and Sung, J.H.: Microtechnology-based organ systems and whole-body models for drug screening. Biotechnol. J. 11, 746 (2016).Google Scholar
46.Rogal, J., Probst, C., and Loskill, P.: Integration concepts for multi-organ chips: how to maintain flexibility?! Future. Sci. OA. 3, FSO180 (2017).Google Scholar
47.Tsamandouras, N., Chen, W.L.K., Edington, C.D., Stokes, C.L., Griffith, L.G., and Cirit, M.: Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. AAPS J. 19, 1499 (2017).Google Scholar
48.Skardal, A., Murphy, S.V., Devarasetty, M., Mead, I., Kang, H.W., Seol, Y.J., Shrike Zhang, Y., Shin, S.R., Zhao, L., Aleman, J., Hall, A.R., Shupe, T.D., Kleensang, A., Dokmeci, M.R., Jin Lee, S., Jackson, J.D., Yoo, J.J., Hartung, T., Khademhosseini, A., Soker, S., Bishop, C.E., and Atala, A.: Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci. Rep. 7, 8837 (2017).Google Scholar
49.Maschmeyer, I., Lorenz, A.K., Schimek, K., Hasenberg, T., Ramme, A.P., Hubner, J., Lindner, M., Drewell, C., Bauer, S., Thomas, A., Sambo, N.S., Sonntag, F., Lauster, R., and Marx, U.: A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab. Chip 15, 2688 (2015).Google Scholar
50.Oleaga, C., Bernabini, C., Smith, A.S., Srinivasan, B., Jackson, M., McLamb, W., Platt, V., Bridges, R., Cai, Y., Santhanam, N., Berry, B., Najjar, S., Akanda, N., Guo, X., Martin, C., Ekman, G., Esch, M.B., Langer, J., Ouedraogo, G., Cotovio, J., Breton, L., Shuler, M.L., and Hickman, J.J.: Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci. Rep. 6, 20030 (2016).Google Scholar
51.Edington, C.D., Chen, W.L.K., Geishecker, E., Kassis, T., Soenksen, L.R., Bhushan, B.M., Freake, D., Kirschner, J., Maass, C., Tsamandouras, N., Valdez, J., Cook, C.D., Parent, T., Snyder, S., Yu, J., Suter, E., Shockley, M., Velazquez, J., Velazquez, J.J., Stockdale, L., Papps, J.P., Lee, I., Vann, N., Gamboa, M., LaBarge, M.E., Zhong, Z., Wang, X., Boyer, L.A., Lauffenburger, D.A., Carrier, R.L., Communal, C., Tannenbaum, S.R., Stokes, C.L., Hughes, D.J., Rohatgi, G., Trumper, D.L., Cirit, M., and Griffith, L.G.: Interconnected microphysiological systems for quantitative biology and pharmacology studies. Sci. Rep. 8, 4530 (2018).Google Scholar
52.Materne, E.M., Maschmeyer, I., Lorenz, A.K., Horland, R., Schimek, K.M., Busek, M., Sonntag, F., Lauster, R., and Marx, U.: The multi-organ chip--a microfluidic platform for long-term multi-tissue coculture. J. Vis. Exp. 98, e52526 (2015).Google Scholar
53.Ewart, L., Dehne, E.M., Fabre, K., Gibbs, S., Hickman, J., Hornberg, E., Ingelman-Sundberg, M., Jang, K.J., Jones, D.R., Lauschke, V.M., Marx, U., Mettetal, J.T., Pointon, A., Williams, D., Zimmermann, W.H., and Newham, P.: Application of microphysiological systems to enhance safety assessment in drug discovery. Annu. Rev. Pharmacol. Toxicol. 58, 65 (2018).Google Scholar
54.Kaushik, G., Leijten, J., and Khademhosseini, A.: Concise review: organ engineering: design, technology, and integration. Stem Cells 35, 51 (2017).Google Scholar
55.Low, L.A. and Tagle, D.A.: Microphysiological systems (“Organs-on-Chips”) for drug efficacy and toxicity testing. Clin. Transl. Sci. 10, 237 (2017).Google Scholar
56.Shuler, M.L., Ghanem, A., Quick, D., Wong, M.C., and Miller, P.: A self-regulating cell culture analog device to mimic animal and human toxicological responses. Biotechnol. Bioeng. 52, 45 (1996).Google Scholar
57.Sin, A., Baxter, G.T., and Shuler, M.L.: Animal on a chip: a microscale cell culture analog device for evaluating toxicological and pharmacological profiles. Microfluidics BioMEMS Proc. SPIE 4560 (2001).Google Scholar
58.Clerc, S. and Villien, M.: Organs-on-chips: small market and gigantic promise, 2017.Google Scholar
59.Borba, M., Castelletti, C.H.M., Filho, J.L.L., and Martins, D.B.G.: Point-of-care devices: the next frontier in personalized chemotherapy. Future. Sci. OA. 3, FSO219 (2017).Google Scholar
60.Syedmoradi, L., Daneshpour, M., Alvandipour, M., Gomez, F.A., Hajghassem, H., and Omidfar, K.: Point of care testing: the impact of nanotechnology. Biosens. Bioelectron. 87, 373 (2017).Google Scholar
61.Mabey, D., Peeling, R.W., Ustianowski, A., and Perkins, M.D.: Diagnostics for the developing world. Nat. Rev. Microbiol. 2, 231 (2004).Google Scholar
62.Groger, M., Dinger, J., Kiehntopf, M., Peters, F.T., Rauen, U., and Mosig, A.S.: Preservation of cell structure, metabolism, and biotransformation activity of liver-on-chip organ models by hypothermic storage. Adv. Healthc. Mater. 7, 1700616 (2018).Google Scholar
63.Beckwitt, C.H., Clark, A.M., Wheeler, S., Taylor, D.L., Stolz, D.B., Griffith, L., and Wells, A.: Liver ‘organ on a chip’. Exp. Cell Res. 363, 15 (2018).Google Scholar
64.Prot, J.M., Aninat, C., Griscom, L., Razan, F., Brochot, C., Guillouzo, C.G., Legallais, C., Corlu, A., and Leclerc, E.: Improvement of HepG2/C3a cell functions in a microfluidic biochip. Biotechnol. Bioeng. 108, 1704 (2011).Google Scholar
65.Lauschke, V.M., Hendriks, D.F., Bell, C.C., Andersson, T.B., and Ingelman-Sundberg, M.: Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates. Chem. Res. Toxicol. 29, 1936 (2016).Google Scholar
66.Bell, C.C., Lauschke, V.M., Vorrink, S.U., Palmgren, H., Duffin, R., Andersson, T.B., and Ingelman-Sundberg, M.: Transcriptional, Functional, and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells, and three-dimensional human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury. Drug Metab. Dispos. 45, 419 (2017).Google Scholar
67.Bhise, N.S., Manoharan, V., Massa, S., Tamayol, A., Ghaderi, M., Miscuglio, M., Lang, Q., Shrike Zhang, Y., Shin, S.R., Calzone, G., Annabi, N., Shupe, T.D., Bishop, C.E., Atala, A., Dokmeci, M.R., and Khademhosseini, A.: A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication 8, 014101 (2016).Google Scholar
68.Wang, L., Tao, T., Su, W., Yu, H., Yu, Y., and Qin, J.: A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice. Lab. Chip 17, 1749 (2017).Google Scholar
69.Heileman, K., Daoud, J., Hasilo, C., Gasparrini, M., Paraskevas, S., and Tabrizian, M.: Microfluidic platform for assessing pancreatic islet functionality through dielectric spectroscopy. Biomicrofluidics 9, 044125 (2015).Google Scholar
70.Ashammakhi, N., Elkhammas, E.A., and Hasan, A.: Glomerulus-on-a-chip. Life Up. Transplantation 101, e343 (2017).Google Scholar
71.Anil Kumar, P., Welsh, G.I., Saleem, M.A., and Menon, R.K.: Molecular and cellular events mediating glomerular podocyte dysfunction and depletion in diabetes mellitus. Front Endocrinol. (Lausanne) 5, 151 (2014).Google Scholar
72.Zhou, M., Zhang, X., Wen, X., Wu, T., Wang, W., Yang, M., Wang, J., Fang, M., Lin, B., and Lin, H.: Development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy. Sci. Rep. 6, 31771 (2016).Google Scholar
73.Nguyen, D.T., van Noort, D., Jeong, I.K., and Park, S.: Endocrine system on chip for a diabetes treatment model. Biofabrication. 9, 015021 (2017).Google Scholar
74.Roder, P.V., Wu, B., Liu, Y., and Han, W.: Pancreatic regulation of glucose homeostasis. Exp. Mol. Med. 48, e219 (2016).Google Scholar
75.Carlson, A.L., Mullen, D.M., and Bergenstal, R.M.: Clinical use of continuous glucose monitoring in adults with type 2 diabetes. Diabetes Technol. Ther. 19, S4 (2017).Google Scholar
76.Viswanathan, S., Narayanan, T.N., Aran, K., Fink, K.D., Paredes, J., Ajayan, P.M., Filipek, S., Miszta, P., Tekin, H.C., Inci, F., Demirci, U., Li, P., Bolotin, K.I., Liepmann, D., and Renugopalakrishanan, V.: Graphene–protein field effect biosensors: glucose sensing. Mater. Today 18, 513 (2015).Google Scholar
77.Grosberg, A., Alford, P.W., McCain, M.L., and Parker, K.K.: Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. Lab. Chip 11, 4165 (2011).Google Scholar
78.McCain, M.L., Sheehy, S.P., Grosberg, A., Goss, J.A., and Parker, K.K.: Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip. Proc. Natl. Acad. Sci. U. S. A. 110, 9770 (2013).Google Scholar
79.Xiao, Y., Zhang, B., Liu, H., Miklas, J.W., Gagliardi, M., Pahnke, A., Thavandiran, N., Sun, Y., Simmons, C., Keller, G., and Radisic, M.: Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac bundle. Lab. Chip 14, 869 (2014).Google Scholar
80.Mathur, A., Loskill, P., Shao, K., Huebsch, N., Hong, S., Marcus, S.G., Marks, N., Mandegar, M., Conklin, B.R., Lee, L.P., and Healy, K.E.: Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 5, 8883 (2015).Google Scholar
81.Marsano, A., Conficconi, C., Lemme, M., Occhetta, P., Gaudiello, E., Votta, E., Cerino, G., Redaelli, A., and Rasponi, M.: Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. Lab. Chip 16, 599 (2016).Google Scholar
82.Liu, Y.C., Lee, I.C., and Lei, K.F.: Toward the development of an artificial brain on a micropatterned and material-regulated biochip by guiding and promoting the differentiation and neurite outgrowth of neural stem/progenitor cells. ACS Appl. Mater. Interfaces 10, 5269 (2018).Google Scholar
83.van der Helm, M.W., van der Meer, A.D., Eijkel, J.C., van den Berg, A., and Segerink, L.I.: Microfluidic organ-on-chip technology for blood-brain barrier research. Tissue. Barriers. 4, e1142493 (2016).Google Scholar
84.Lee, J.M., Kim, J.E., Borana, J., Chung, B.H., and Chung, B.G.: Dual-micropillar-based microfluidic platform for single embryonic stem cell-derived neuronal differentiation. Electrophoresis 34, 1931 (2013).Google Scholar
85.Bang, S., Na, S., Jang, J.M., Kim, J., and Jeon, N.L.: Engineering-aligned 3D neural circuit in microfluidic device. Adv. Healthc. Mater. 5, 159 (2016).Google Scholar
86.Park, J., Lee, B.K., Jeong, G.S., Hyun, J.K., Lee, C.J., and Lee, S.H.: Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease. Lab. Chip 15, 141 (2015).Google Scholar
87.Kimura, H., Ikeda, T., Nakayama, H., Sakai, Y., and Fujii, T.: An on-chip small intestine-liver model for pharmacokinetic studies. J. Lab. Autom. 20, 265 (2015).Google Scholar
88.Xiao, S., Coppeta, J.R., Rogers, H.B., Isenberg, B.C., Zhu, J., Olalekan, S.A., McKinnon, K.E., Dokic, D., Rashedi, A.S., Haisenleder, D.J., Malpani, S.S., Arnold-Murray, C.A., Chen, K., Jiang, M., Bai, L., Nguyen, C.T., Zhang, J., Laronda, M.M., Hope, T.J., Maniar, K.P., Pavone, M.E., Avram, M.J., Sefton, E.C., Getsios, S., Burdette, J.E., Kim, J.J., Borenstein, J.T., and Woodruff, T.K.: A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat. Commun. 8, 14584 (2017).Google Scholar
89.Bauer, S., Wennberg Huldt, C., Kanebratt, K.P., Durieux, I., Gunne, D., Andersson, S., Ewart, L., Haynes, W.G., Maschmeyer, I., Winter, A., Ammala, C., Marx, U., and Andersson, T.B.: Publisher correction: functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci. Rep. 8, 1672 (2018).Google Scholar
90.Mohammed, M.I., Haswell, S., and Gibson, I.: Lab-on-a-chip or Chip-in-a-lab: challenges of commercialization lost in translation. Procedia Technol. 20, 54 (2015).Google Scholar
91.Low, L.A. and Tagle, D.A.: Organs-on-chips: progress, challenges, and future directions. Exp. Biol. Med. (Maywood) 242, 1573 (2017).Google Scholar
92.Tasciotti, E., Cabrera, F.J., Evangelopoulos, M., Martinez, J.O., Thekkedath, U.R., Kloc, M., Ghobrial, R.M., Li, X.C., Grattoni, A., and Ferrari, M.: The emerging role of nanotechnology in cell and organ transplantation. Transplantation 100, 1629 (2016).Google Scholar
93.Balijepalli, A. and Sivaramakrishan, V.: Organs-on-chips: research and commercial perspectives. Drug Discov. Today 22, 397 (2017).Google Scholar
94.Nawroth, J., Rogal, J., Weiss, M., Brucker, S.Y., and Loskill, P.: Organ-on-a-chip systems for women's health applications. Adv. Healthc. Mater. 7, 1700550 (2018).Google Scholar