Organ-on-a-chip devices have enabled major breakthroughs in biomedical research, but they have yet to be successfully translated to the pharmaceutical industry. Traditional microfluidic devices rely on irreversible bonding techniques to seal fluidic channels, which limit their accessibility and automation and can be labour-intensive to operate. New and more versatile chip designs are urgently needed to enable industrial applications and to support complex, 3D cell cultures. Clamps allow microdevices to be opened and closed before, after and during operation, such that cells can be directly accessed whenever needed. This versatility facilitates the incorporation of more physiologically relevant 3D in vitro models, including organoids, and allows a wider range of on-chip and off-chip biochemical assays. This Review describes the current trend from irreversible chip bonding to innovative, reversible fastening techniques. We introduce the concept of Lock-and-Play devices as emerging tools that can provide a leak-tight seal in a single step for high-throughput applications. Finally, we analyse the applications in which Lock-and-Play devices are likely to have the biggest impact for the drug development industry.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 per month
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
DiMasi, J. A., Grabowski, H. G. & Hansen, R. W. Innovation in the pharmaceutical industry: new estimates of R&D costs. J. Health Econ. 47, 20–33 (2016).
Mullard, A. Parsing clinical success rates. Nat. Rev. Drug Discov. 15, 447 (2016).
Skardal, A., Aleman, J., Forsythe, S., Rajan, S. & Murphy, S. Drug compound screening in single and integrated multi-organoid body- on-a-chip systems. Biofabrication 12, 025017 (2020).
Skardal, A. et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci. Rep. 7, 8837 (2017).
Mcaleer, C. W. et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci. Transl. Med. 11, eaav1386 (2019).
Zhang, B. & Radisic, M. Organ-on-A-chip devices advance to market. Lab Chip 17, 2395–2420 (2017).
QY Research. Global Organ-On-Chip Market Insights, Forecast to 2025 (QY Research, 2019).
Franzen, N. et al. Impact of organ-on-a-chip technology on pharmaceutical R&D costs. Drug Discov. Today 24, 1720–1724 (2019).
Willyard, C. Channeling chip power: Tissue chips are being put to the test by industry. Nat. Med. 23, 138–140 (2017).
Horejs, C. Organ chips, organoids and the animal testing conundrum. Nat. Rev. Mater. 6, 372–373 (2021).
Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug Discov. 20, 345–361 (2021).
Schuster, B. et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat. Commun. 11, 5271 (2020).
Abhyankar, V. V., Wu, M., Koh, C.-Y. & Hatch, A. V. A reversibly sealed, easy access, modular (SEAM) microfluidic architecture to establish in vitro tissue interfaces. PLoS ONE 11, e0156341 (2016).
Ma, L. D. et al. Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe: in situ perfusion culture of 3D hepatic spheroids. Lab Chip 18, 2547–2562 (2018).
Anwar, K., Han, T. & Kim, S. M. Sensors and Actuators B : Chemical Reversible sealing techniques for microdevice applications. Sens. Actuators B Chem. 153, 301–311 (2011).
Herland, A. et al. Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips. Nat. Biomed. Eng. 4, 421–436 (2020).
Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010).
Park, T. E. et al. Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies. Nat. Commun. 10, 2621 (2019).
Jang, K. J. et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr. Biol. 5, 1119–1129 (2013).
Kim, S. et al. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication 8, 015021 (2016).
Sun, X. & Nunes, S. S. Biowire platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Methods 101, 21–26 (2016).
Nunes, S. S. et al. Biowire: A platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat. Methods 10, 781–787 (2013).
Esch, E. W., Bahinski, A. & Huh, D. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discov. 14, 248–260 (2015).
Schimek, K. et al. Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies. Sci. Rep. 10, 7865 (2020).
Sharifi, F. et al. A foreign body response-on-a-chip platform. Adv. Healthc. Mater. 8, e1801425 (2019).
Kulthong, K. et al. Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners. RSC Adv. 8, 32440–32453 (2018).
McDonald, J. C. et al. Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21, 27–40 (2000).
Chen, Q., Li, G. & Nie, Y. Investigation and improvement of reversible microfluidic devices based on glass–PDMS–glass sandwich configuration. Microfluid. Nanofluid. 16, 83–90 (2014).
Thompson, C. S. & Abate, A. R. Adhesive-based bonding technique for PDMS microfluidic devices. Lab Chip 13, 632–635 (2013).
Cao, H. H. et al. Reversible bonding by dimethyl-methylphenylmethoxy siloxane-Based stamping technique for reusable poly(dimethylsiloxane) microfluidic chip. Micro Nano Lett. 10, 229–232 (2015).
Shiroma, L. S. et al. Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices. Sci. Rep. 6, 26032 (2016).
Pitingolo, G., Riaud, A., Nastruzzi, C. & Taly, V. Tunable and reversible gelatin-based bonding for microfluidic cell culture. Adv. Eng. Mater. 21, 1900145 (2019).
Dekker, S. et al. Standardized and modular microfluidic platform for fast Lab on Chip system development. Sens. Actuators B Chem. 272, 468–478 (2018).
Tkachenko, E., Gutierrez, E., Ginsberg, M. H. & Groisman, A. An easy to assemble microfluidic perfusion device with a magnetic clamp. Lab Chip 9, 1085–1095 (2009).
Agarwal, A. Microfluidic heart on a chip for higher throughput pharmacological studies. Lab Chip 21, 3599–3608 (2013).
Esch, M. B., Ueno, H., Applegate, R. & Shuler, M. L. Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue. Lab Chip 16, 2719–2729 (2016).
Wang, Y. I., Abaci, H. E. & Shuler, M. L. Microfluidic blood–brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol. Bioeng. 114, 184–194 (2017).
Satoh, T. et al. A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic pressure-driven medium circulation platform. Lab Chip 18, 115–125 (2018).
Domansky, K. et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10, 51–58 (2010).
Schaff, U. Y. et al. Vascular mimetics based on microfluidics for imaging the leukocyte-endothelial inflammatory response. Lab Chip 7, 448–456 (2007).
Crozatier, C. et al. Microfluidic modulus for convenient cell culture and screening experiments. Microelectron. Eng. 84, 1694–1697 (2007).
Tsou, J. et al. Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. Microcirculation 15, 311–323 (2008).
Le Berre, M., Crozatier, C., Velve Casquillas, G. & Chen, Y. Reversible assembling of microfluidic devices by aspiration. Microelectron. Eng. 83, 1284–1287 (2006).
Khademhosseini, A. et al. Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays. Lab Chip 5, 1380–1386 (2005).
Rafat, M., Raad, D. R., Rowat, A. C. & Auguste, D. T. Fabrication of reversibly adhesive fluidic devices using magnetism. Lab Chip 9, 3016–3019 (2009).
Pitingolo, G., Nizard, P., Riaud, A. & Taly, V. Beyond the on/off chip trade-off: A reversibly sealed microfluidic platform for 3D tumor microtissue analysis. Sens. Actuators B Chem. 274, 393–401 (2018).
Rasponi, M. et al. Reliable magnetic reversible assembly of complex microfluidic devices: Fabrication, characterization, and biological validation. Microfluid. Nanofluidics 10, 1097–1107 (2011).
Tsao, C. W. & Lee, Y. P. Magnetic microparticle-polydimethylsiloxane composite for reversible microchannel bonding. Sci. Technol. Adv. Mater. 17, 2–11 (2016).
Shah, P. et al. A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat. Commun. 7, 11535 (2016).
Zhang, Y. S. Modular multi-organ-on-chips platform with physicochemical sensor integration. Proc. 2017 IEEE 60th Int. Midwest Symp. Circuits Syst. https://doi.org/10.1109/MWSCAS.2017.8052865 (2017).
Vittayarukskul, K. & Lee, A. P. A truly Lego® -like modular microfluidics platform. J. Micromech. Microeng. 27, 035004 (2017).
Xie, X., Maharjan, S., Liu, S., Zhang, Y. S. & Livermore, C. A modular, reconfigurable microfabricated assembly platform for microfluidic transport and multitype cell culture and drug testing. Micromachines 11, 2 (2020).
Collins, S. D. & Smith, R. L. Fluidic interconnects for modular assembly of chemical microsystems. Sens. Actuators B Chem. 49, 40–45 (1998).
van Meer, B. J. et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem. Biophys. Res. Commun. 482, 323–328 (2017).
Owens, C. E. & Hart, A. J. High-precision modular microfluidics by micromilling of interlocking injection-molded blocks. Lab Chip 18, 890–901 (2018).
Gomez, Y., Navarro-Tableros, V., Tetta, C., Camussi, G. & Brizzi, M. F. A versatile model of microfluidic perifusion system for the evaluation of C-peptide secretion profiles: Comparison between human pancreatic islets and HLSC-derived islet-like structures. Biomedicines 8, 26 (2020).
Lenguito, G. et al. Resealable, optically accessible, PDMS-free fluidic platform for ex vivo interrogation of pancreatic islets. Lab Chip 17, 772–781 (2017).
Li, X., George, S. M., Vernetti, L., Gough, A. H. & Taylor, D. L. 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, 2614–2631 (2018).
Paydar, O. H. et al. Characterization of 3D-printed microfluidic chip interconnects with integrated O-rings. Sens. Actuators, A Phys. 205, 199–203 (2014).
Shanti, A. et al. Multi-compartment 3D-cultured organ-on-a-chip: towards a biomimetic lymph node for drug development. Pharmaceutics 12, 464 (2020).
Pampaloni, F., Reynaud, E. G. & Stelzer, E. H. K. The third dimension bridges the gap between cell culture and live tissue. Nat. Rev. Mol. Cell Biol. 8, 839–845 (2007).
Park, J. et al. 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, 141–150 (2015).
Kasendra, M. et al. Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids. Sci. Rep. 8, 2871 (2018).
Kim, H. J., Li, H., Collins, J. J. & Ingber, D. E. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc. Natl Acad. Sci. USA 113, E7–E15 (2016).
Novak, R. et al. A robotic platform for fluidically-linked human body-on-chips experimentation. Nat. Biomed. Eng. 4, 407–420 (2020).
Takahashi, Y. et al. 3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells. Biosci. Rep. 35, e00208 (2015).
Bell, C. C. et al. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci. Rep. 6, 25187 (2016).
Moshksayan, K. et al. Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture. Sens. Actuators B Chem. 263, 151–176 (2018).
Bavli, D. et al. Real-time monitoring of metabolic function in liver-onchip microdevices tracks the dynamics of Mitochondrial dysfunction. Proc. Natl Acad. Sci. USA 113, 2231–2240 (2016).
Spence, J. R. et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105–110 (2011).
Nakano, T. et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10, 771–785 (2012).
Takebe, T. et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481–484 (2013).
Lancaster, M. A. et al. Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 35, 659–666 (2017).
Homan, K. A. et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat. Methods 16, 255–262 (2019).
Takebe, T., Zhang, B. & Radisic, M. Synergistic engineering: organoids meet organs-on-a-chip. Cell Stem Cell 21, 297–300 (2017).
Park, S. E., Georgescu, A. & Huh, D. Organoids-on-a-chip. Science 965, 837–842 (2019).
Kakni, P. et al. Intestinal organoid culture in polymer film-based microwell arrays. Adv. Biosyst. 4, 2000126 (2020).
Wong, A. P., Perez-Castillejos, R., Christopher Love, J. & Whitesides, G. M. Partitioning microfluidic channels with hydrogel to construct tunable 3-D cellular microenvironments. Biomaterials 29, 1853–1861 (2008).
Mota, C., Camarero-Espinosa, S., Baker, M. B., Wieringa, P. & Moroni, L. Bioprinting: from tissue and organ development to in vitro models. Chem. Rev. 120, 10547–10607 (2020).
Brassard, J. A., Nikolaev, M., Hübscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22–29 (2021).
Grigoryan, B. et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science 364, 458–464 (2019).
Bhise, N. S. et al. A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication 8, 14101 (2016).
Zhang, Y. S. et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials 110, 45–59 (2016).
Skardal, A., Shupe, T. & Atala, A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov. Today 21, 1399–1411 (2016).
Zhang, Y. S. et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc. Natl Acad. Sci. USA 114, 2293–2302 (2017).
Schimek, K. et al. Integrating biological vasculature into a multi-organ-chip microsystem. Lab Chip 13, 3588–3598 (2013).
Sung, J. H. & Shuler, M. L. A micro cell culture analog (CCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 9, 1385–1394 (2009).
Baert, Y. et al. A multi-organ-chip co-culture of liver and testis equivalents: A first step toward a systemic male reprotoxicity model. Hum. Reprod. 35, 1029–1044 (2020).
Lin, N. et al. Repeated dose multi-drug testing using a microfluidic chip-based coculture of human liver and kidney proximal tubules equivalents. Sci. Rep. 10, 8879 (2020).
Chramiec, A. et al. Integrated human organ-on-a-chip model for predictive studies of anti-tumor drug efficacy and cardiac safety. Lab Chip 20, 4357–4372 (2020).
Ronaldson-Bouchard, K. et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat. Biomed. Eng. 6, 351–371 (2022).
O’Reilly, L. P., Luke, C. J., Perlmutter, D. H., Silverman, G. A. & Pak, S. C. C. elegans in high-throughput drug discovery. Adv. Drug Deliv. Rev. 69–70, 247–253 (2014).
Mondal, S. & Ben-Yakar, A. in Organ-on-a-chip: Engineered Microenvironments for Safety and Efficacy Testing Ch. 11, 363–390 (Academic Press, 2019).
Westhoff, J. H. et al. Development of an automated imaging pipeline for the analysis of the zebrafish larval kidney. PLoS ONE 8, e82137 (2013).
Peravali, R. et al. Automated feature detection and imaging for high-resolution screening of zebrafish embryos. Biotechniques 50, 319–324 (2011).
Hulme, S. E. et al. Lifespan-on-a-chip: microfluidic chambers for performing lifelong observation of C. elegans. Lab Chip 10, 589–597 (2010).
Hulme, S. E., Shevkoplyas, S. S., Apfeld, J., Fontana, W. & Whitesides, G. M. A microfabricated array of clamps for immobilizing and imaging C. elegans. Lab Chip 7, 1515–1523 (2007).
Dong, L. et al. C . elegans immobilization using deformable microfluidics for in vivo studies of early embryogenesis and intestinal microbiota. in 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS) 616–619 (IEEE, 2017).
Mondal, S. et al. Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model. Nat. Commun. 7, 13023 (2016).
Nghe, P. et al. Microfabricated polyacrylamide devices for the controlled culture of growing cells and developing organisms. PLoS ONE 8, e75537 (2013).
Patra, B., Peng, C. C., Liao, W. H., Lee, C. H. & Tung, Y. C. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device. Sci. Rep. 6, 21061 (2016).
Kim, H. J., Huh, D., Hamilton, G. & Ingber, D. E. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12, 2165–2174 (2012).
Buchanan, B. C. & Yoon, J. Y. Microscopic imaging methods for organ-on-a-chip platforms. Micromachines 13, 328 (2022).
Smith, A. S. T. et al. Utilization of microscale silicon cantilevers to assess cellular contractile function in vitro. J. Vis. Exp. 92, e51866 (2014).
Sasserath, T. et al. Differential monocyte actuation in a three-organ functional innate immune system-on-a-chip. Adv. Sci. 7, 2000323 (2020).
Chin, H., Gillissen, J. J. J., Miyako, E. & Cho, N.-J. Microfluidic liquid cell chamber for scanning probe microscopy measurement application Microfluidic liquid cell chamber for scanning probe microscopy measurement application. Rev. Sci. Instrum. 90, 046105 (2019).
Gottwald, E. et al. Characterization of a chip-based bioreactor for three-dimensional cell cultivation via magnetic resonance imaging. Z. Med. Phys. 23, 102–110 (2013).
Miller, P. G. & Shuler, M. L. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol. Bioeng. 113, 2213–2227 (2016).
Miller, P. G., Chen, C. Y., Wang, Y. I., Gao, E. & Shuler, M. L. Multiorgan microfluidic platform with breathable lung chamber for inhalation or intravenous drug screening and development. Biotechnol. Bioeng. 117, 486–497 (2020).
Esch, M. B., Mahler, G. J., Stokol, T. & Shuler, M. L. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 14, 3081–3092 (2014).
Sakolish, C. M. & Mahler, G. J. A novel microfluidic device to model the human proximal tubule and glomerulus. RSC Adv 7, 4216–4225 (2017).
Nguyen, T. et al. Robust chemical bonding of PMMA microfluidic devices to porous PETE membranes for reliable cytotoxicity testing of drugs. Lab Chip 19, 3706–3713 (2019).
Su, X. et al. Microfluidic cell culture and its application in high throughput drug screening: cardiotoxicity assay for hERG channels. J. Biomol. Screen 16, 101–111 (2011).
Tsamandouras, N. et al. Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. AAPS J. 19, 1499–1512 (2017).
Edington, C. D. et al. Interconnected microphysiological systems for quantitative biology and pharmacology studies. Sci. Rep. 8, 4530 (2018).
Yang, C. Z., Yaniger, S. I., Jordan, V. C., Klein, D. J. & Bittner, G. D. Most plastic products release estrogenic chemicals: A potential health problem that can be solved. Environ. Health Perspect. 119, 989–996 (2011).
Burshtein, N., Chan, S. T., Toda-Peters, K., Shen, A. Q. & Haward, S. J. 3D-printed glass microfluidics for fluid dynamics and rheology. Curr. Opin. Colloid Interface Sci. 43, 1–14 (2019).
Campbell, S. B. et al. Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater. Sci. Eng. 7, 2880–2899 (2021).
Leung, C. M. et al. A guide to the organ-on-a-chip. Nat. Rev. Methods Primers 2, 33 (2022).
Konda, A., Taylor, J. M., Stoller, M. A. & Morin, S. A. Reconfigurable microfluidic systems with reversible seals compatible with 2D and 3D surfaces of arbitrary chemical composition. Lab Chip 15, 2009–2017 (2015).
Pereiro, I., Khartchenko, A. F., Petrini, L. & Kaigala, G. V. Nip the bubble in the bud: a guide to avoid gas nucleation in microfluidics. Lab Chip 19, 2296–2314 (2019).
Wevers, N. R. et al. High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform. Sci. Rep. 6, 38856 (2016).
Novak, R. et al. Robotic fluidic coupling and interrogation of multiple vascularized organ chips. Nat. Biomed. Eng. 4, 407–420 (2020).
Cao, X. et al. A tumor-on-a-chip system with bioprinted blood and lymphatic vessel pair. Adv. Funct. Mater. 29, 1807173 (2019).
Pires de Mello, C. et al. Microphysiological heart-liver body-on-a-chip system with skin mimic for evaluating topical drug delivery. Lab Chip 20, 749–759 (2020).
Oleaga, C. et al. Long-term electrical and mechanical function monitoring of a human-on-a-chip system. Adv. Funct. Mater. 29, 1805792 (2019).
Chen, W. L. K. et al. Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk. Biotechnol. Bioeng. 114, 2648–2659 (2017).
Wang, X., Cirit, M., Wishnok, J. S., Griffith, L. G. & Tannenbaum, S. R. Analysis of an integrated human multiorgan microphysiological system for combined tolcapone metabolism and brain metabolomics. Anal. Chem. 91, 8667–8675 (2019).
Esch, M. B., Mahler, G. J., Stokol, T. & Shuler, M. L. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 14, 3081–3092 (2014).
Moya, A. et al. Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system. Lab Chip 18, 2023–2035 (2018).
Maoz, B. M. et al. A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. Nat. Biotechnol. 36, 865–877 (2018).
Sung, J. H., Kam, C. & Shuler, M. L. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10, 446–455 (2010).
Qu, Y. et al. A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity. Biomaterials 155, 41–53 (2018).
Ong, L. J. Y. et al. A 3D printed microfluidic perfusion device for multicellular spheroid cultures. Biofabrication 9, 045005 (2017).
Hu, N. et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc. Natl Acad. Sci. USA 114, E2293–E2302 (2017).
Lamberti, A. et al. Microfluidic sealing and housing system for innovative dye-sensitized solar cell architecture. Microelectron. Eng. 88, 2308–2310 (2011).
Gang, A., Haustein, N., Baraban, L. & Cuniberti, G. Multifunctional reversibly sealable microfluidic devices for patterned material deposition approaches. RSC Adv. 5, 11806–11811 (2015).
This study was financially supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement number 825745.
S.G. is founder and shareholder of 300MICRONS GmbH. D.J.T.C. and L.M. declare no competing interests.
Peer review information
Nature Reviews Materials thanks Yi-Chin Toh, Louis Ong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Teixeira Carvalho, D.J., Moroni, L. & Giselbrecht, S. Clamping strategies for organ-on-a-chip devices. Nat Rev Mater 8, 147–164 (2023). https://doi.org/10.1038/s41578-022-00523-z