Micro Total Bioassay System for Ingested Substances: Assessment of Intestinal Absorption, Hepatic Metabolism, and Bioactivity
Abstract
Oral medicines and food constituents are absorbed in the intestine and metabolized in the liver, after which they exhibit their activity toward a target tissue. Micromodels of human tissues were developed to mimic these processes and bioactivities. By integrating the micromodels, we realized a micro total bioassay system for oral substances; this system comprised a microintestine, microliver, and the target components. The microchip was composed of a slide glass and polydimethylsiloxane (PDMS) sheets with microchannels fabricated by photolithography. Caco-2 cells were cultured in the intestine component, and HepG2 cells, in the liver component. The human breast carcinoma MCF-7 cells were cultured in the target component, and the activities of anticancer agents and estrogen-like substances were successfully assayed. By using this system, the overall properties of the ingested cyclophosphamide, epirubicin, 17-β estradiol, and soy isoflavone, i.e., their intestinal absorption, hepatic metabolism, and bioactivity toward target cells, could be assayed with operative ease. Further, the assay time and cell consumption were reduced compared to those in conventional in vitro bioassay systems.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a breast cancer/liver microenvironment chip, breast cancer cells cultured in the tumor microenvironment have higher vascular porosity and tumor microenvironment permeability than blood vessels in healthy liver microenvironment.
“Compared with blood vessels in the healthy liver microenvironment, breast cancer cells cultured in the microenvironment of this model have higher vascular porosity and tumor microenvironment permeability.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [220]
Cites
Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane)
Duffy, D. C., McDonald, J. C., Schueller, O. J. A., & Whitesides, G. M. (1998) · Analytical Chemistry · doi:10.1021/ac980656z · Cited by 5,301 · see citing works
O'Brien, J., Wilson, I., Orton, T., & Pognan, F. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01606.x · Cited by 3,446 · see citing works
Poly(dimethylsiloxane) as a Material for Fabricating Microfluidic Devices
McDonald, J. C., & Whitesides, G. M. (2002) · Accounts of Chemical Research · doi:10.1021/ar010110q · Cited by 2,458 · see citing works
Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A
Green, S., Walter, P., Kumar, V., Krust, A., Bornert, J., Argos, P., & Chambon, P. (1986) · Nature · doi:10.1038/320134a0 · Cited by 2,320 · see citing works
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA..
Morito, K., HIROSE, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T., Ogawa, S., Inoue, S., Muramatsu, M., & Masamune, Y. (2001) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.24.351 · Cited by 615 · see citing works
Caco-2 Cell Monolayers as a Model for Drug Transport Across the Intestinal Mucosa
Hilgers, A. R., Conradi, R. A., & Burton, P. S. (1990) · Pharmaceutical Research · doi:10.1023/a:1015937605100 · Cited by 587 · see citing works
High-aspect-ratio, ultrathick, negative-tone near-UV photoresist and its applications for MEMS
Lorenz, H., Despont, M., Fahrni, N., Brügger, J., Vettiger, P., & Renaud, P. (1998) · Sensors and Actuators A Physical · doi:10.1016/s0924-4247(98)80055-1 · Cited by 573 · see citing works
Chang, T. K. H., Weber, G. F., Crespi, C. L., & Waxman, D. J. (1993) · PubMed · Cited by 545 · see citing works
Patterning cells and their environments using multiple laminar fluid flows in capillary networks
Takayama, S., McDonald, J. C., Ostuni, E., Liang, M. N., Kenis, P. J. A., Ismagilov, R. F., & Whitesides, G. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5545 · Cited by 529 · see citing works
Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., & Zhu, B. T. (2003) · Endocrinology · doi:10.1210/en.2003-0192 · Cited by 457 · see citing works
Cell Culture in 3-Dimensional Microfluidic Structure of PDMS (polydimethylsiloxane)
Leclerc, É., Sakai, Y., & Fujii, T. (2003) · Biomedical Microdevices · doi:10.1023/a:1024583026925 · Cited by 325 · see citing works
Electroosmotic pumping and electrophoretic separations for miniaturized chemical analysis systems
Manz, A., Effenhauser, C. S., Burggraf, N., Harrison, D. J., Seiler, K., & Fluri, K. (1994) · Journal of Micromechanics and Microengineering · doi:10.1088/0960-1317/4/4/010 · Cited by 277 · see citing works
Response of human breast cancer cells to heat shock and chemotherapeutic drugs.
Ciocca, D. R., Fuqua, S. A. W., Lock-Lim, S., Toft, D. O., Welch, W. J., & McGuire, W. L. (1992) · PubMed · Cited by 243 · see citing works
Selective Chemical Treatment of Cellular Microdomains Using Multiple Laminar Streams
Takayama, S., Ostuni, E., LeDuc, P. R., Naruse, K., Ingber, D. E., & Whitesides, G. M. (2003) · Chemistry & Biology · doi:10.1016/s1074-5521(03)00019-x · Cited by 210 · see citing works
Li, A. P., Reith, M. K., Rasmussen, A., Gorski, J. C., Hall, S. D., Xu, L., Kaminski, D. L., & Cheng, L. K. (1997) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(97)00071-9 · Cited by 172 · see citing works
A microfluidic system to evaluate intestinal absorption
Imura, Y., Asano, Y., Sato, K., & Yoshimura, E. (2009) · Analytical Sciences · doi:10.2116/analsci.25.1403 · Cited by 159 · see citing works
Self-citationYoshitomi, S., Ikemoto, K., Takahashi, J., Miki, H., Namba, M., & Asahi, S. (2001) · Toxicology in Vitro · doi:10.1016/s0887-2333(01)00011-x · Cited by 112 · see citing works
Alsenz, J., & Haenel, E. (2003) · Pharmaceutical Research · doi:10.1023/b:pham.0000008043.71001.43 · Cited by 110 · see citing works
Development of a Microchip-Based Bioassay System Using Cultured Cells
Goto, M., Sato, K., Murakami, A., Tokeshi, M., & Kitamori, T. (2005) · Analytical Chemistry · doi:10.1021/ac040165g · Cited by 104 · see citing works
Self-citationMarino, A. M., Yarde, M., Patel, H., Chong, S., & Balimane, P. V. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.03.008 · Cited by 101 · see citing works
Drahushuk, A. T., McGarrigle, B. P., Tai, H.-L., Kitareewan, S., Goldstein, J. A., & Olson, J. R. (1996) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1996.0236 · Cited by 62 · see citing works
Decreased plasma half-life of cyclophosphamide during repeated high-dose administration
Graham, M. I., Shaw, I. C., Souhami, R. L., Sidau, B., Harper, P., & McLean, A. E. M. (1983) · Cancer Chemotherapy and Pharmacology · doi:10.1007/bf00255760 · Cited by 53 · see citing works
Worboys, P. D., Bradbury, A., & Houston, J. B. (1995) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)06550-x · Cited by 50 · see citing works
Tokuyama, T., Fujii, S., Sato, K., Abo, M., & Ōkubo, A. (2005) · Analytical Chemistry · doi:10.1021/ac048288o · Cited by 46 · see citing works
Self-citationCell culture and life support system for microbioreactor and bioassay
Tanaka, Y., Sato, K., Yamato, M., Okano, T., & Kitamori, T. (2005) · Journal of Chromatography A · doi:10.1016/j.chroma.2005.06.053 · Cited by 35 · see citing works
Self-citationDavidsson, R., Boketoft, Å., Bristulf, J., Kotarsky, K., Olde, B., Owman, C., Bengtsson, M., Laurell, T., & Emnéus, J. (2004) · Analytical Chemistry · doi:10.1021/ac035249o · Cited by 33 · see citing works
Modulations of Food-derived Substances on Intestinal Permeability in Caco-2 Cell Monolayers
KONISHI, Y. (2003) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.67.2297 · Cited by 30 · see citing works
Estrogen response element-independent regulation of gene expression by genistein in intestinal cells
Hua, P., Tsai, W.-J., & Kuo, S. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(03)00075-7 · Cited by 22 · see citing works
Visvikis, A., Goergen, J., Oster, T., Bagrel, D., Wellman, M., Marc, A., Engasser, J., & Siest, G. (1990) · Clinica Chimica Acta · doi:10.1016/0009-8981(90)90023-l · Cited by 17 · see citing works
Yamamoto, D., Tanaka, K., Nakai, K., Baden, T., Inoue, K., Yamamoto, C., Takemoto, H., Kamato, K., Hirata, H., Morikawa, S., et al. (2002) · Breast Cancer Research and Treatment · doi:10.1023/a:1014940632674 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
From 3D cell culture to organs-on-chips
Huh, D., Hamilton, G. A., & Ingber, D. E. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.09.005 · Cited by 1,834 · see citing works
Organs-on-chips at the frontiers of drug discovery
Esch, E. W., Bahinski, A., & Huh, D. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4539 · Cited by 1,185 · see citing works
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184 · see citing works
Microengineered physiological biomimicry: Organs-on-Chips
Huh, D., Torisawa, Y., Hamilton, G. A., Kim, H. J., & Ingber, D. E. (2012) · Lab on a Chip · doi:10.1039/c2lc40089h · Cited by 667 · see citing works
Wagner, I., Materne, E.-M., Brincker, S., Süßbier, U., Frädrich, C., Busek, M., Sonntag, F., Sakharov, D. A., Trushkin, E. V., Tonevitsky, A. G., et al. (2013) · Lab on a Chip · doi:10.1039/c3lc50234a · Cited by 476 · see citing works
Organ/body-on-a-chip based on microfluidic technology for drug discovery
Kimura, H., Sakai, Y., & Fujii, T. (2018) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2017.11.003 · Cited by 435 · see citing works
Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis
Frey, O., Misun, P. M., Fluri, D. A., Hengstler, J. G., & Hierlemann, A. R. (2014) · Nature Communications · doi:10.1038/ncomms5250 · Cited by 382 · see citing works
Biomimetic tissues on a chip for drug discovery
Ghaemmaghami, A. M., Hancock, M. J., Harrington, H., Kaji, H., & Khademhosseini, A. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2011.10.029 · Cited by 359 · see citing works
Organs-on-chips: breaking the in vitro impasse
van der Meer, A. D., & van den Berg, A. (2012) · Integrative Biology · doi:10.1039/c2ib00176d · Cited by 309 · see citing works
Marx, U. (2016) · ALTEX · doi:10.14573/altex.1603161 · Cited by 295 · see citing works
Recent advances in microfluidic technologies for cell-to-cell interaction studies
Rothbauer, M., Zirath, H., & Ertl, P. (2018) · Lab on a Chip · doi:10.1039/c7lc00815e · Cited by 277 · see citing works
Micro and nanoscale technologies in oral drug delivery
Ahadian, S., Finbloom, J. A., Mofidfar, M., Di̇ltemi̇z, S. E., Nasrollahi, F., Davoodi, E., Hosseini, V., Mylonaki, I., Sangabathuni, S., Montazerian, H., et al. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.012 · Cited by 271 · see citing works
Micro Total Analysis Systems for Cell Biology and Biochemical Assays
Kovarik, M. L., Gach, P. C., Ornoff, D. M., Wang, Y., Balowski, J., Farrag, L., & Allbritton, N. L. (2011) · Analytical Chemistry · doi:10.1021/ac202611x · Cited by 268 · see citing works
The relevance and potential roles of microphysiological systems in biology and medicine
Wikswo, J. P. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214542068 · Cited by 248 · see citing works
Tumor-on-a-chip: from bioinspired design to biomedical application
Liu, X., Fang, J., Huang, S., Wu, X., Xie, X., Wang, J., Liu, F., Zhang, M., Peng, Z., & Hu, N. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00277-8 · Cited by 246 · see citing works
Design and demonstration of a pumpless 14 compartment microphysiological system
Miller, P. G., & Shuler, M. L. (2016) · Biotechnology and Bioengineering · doi:10.1002/bit.25989 · Cited by 235 · see citing works
Lauschke, V. M., Hendriks, D. F. G., Bell, C. C., Andersson, T. B., & Ingelman-Sundberg, M. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00150 · Cited by 226 · see citing works
Sung, J. H., Esch, M. B., Prot, J. M., Long, C. J., Smith, A. S. T., Hickman, J. J., & Shuler, M. L. (2013) · Lab on a Chip · doi:10.1039/c3lc41017j · Cited by 232 · see citing works
Organs-on-a-chip: a new tool for drug discovery
Polini, A., Prodanov, L., Bhise, N. S., Manoharan, V., Dokmeci, M. R., & Khademhosseini, A. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.886562 · Cited by 223 · see citing works
Maschmeyer, I., Hasenberg, T., Jaenicke, A., Lindner, M., Lorenz, A., Zech, J., Garbe, L., Sonntag, F., Hayden, P. J., Ayehunie, S., et al. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.03.002 · Cited by 220 · see citing works
Advances and Current Challenges in Intestinal in vitro Model Engineering: A Digest
Costa, J. S., & Ahluwalia, A. D. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00144 · Cited by 193 · see citing works
Microfluidic titer plate for stratified 3D cell culture
Trietsch, S. J., Israëls, G. D., Joore, J., Hankemeier, T., & Vulto, P. (2013) · Lab on a Chip · doi:10.1039/c3lc50210d · Cited by 189 · see citing works
Baker, M. (2011) · Nature · doi:10.1038/471661a · Cited by 188 · see citing works
Microfluidic Gut-liver chip for reproducing the first pass metabolism
Choe, A., Ha, S. K., Choi, I., Choi, N., & Sung, J. H. (2017) · Biomedical Microdevices · doi:10.1007/s10544-016-0143-2 · Cited by 188 · see citing works
Satoh, T., Sugiura, S., Shin, K., Onuki-Nagasaki, R., Ishida, S., Kikuchi, K., Kakiki, M., & Kanamori, T. (2018) · Lab on a Chip · doi:10.1039/c7lc00952f · Cited by 181 · see citing works
Marx, U., Walles, H., Hoffmann, S., Lindner, G., Horland, R., Sonntag, F., Klotzbach, U., Sakharov, D. A., Tonevitsky, A., & Lauster, R. (2012) · Alternatives to Laboratory Animals · doi:10.1177/026119291204000504 · Cited by 174 · see citing works
Human-on-chip for therapy development and fundamental science
Luni, C., Serena, E., & Elvassore, N. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2013.08.015 · Cited by 169 · see citing works
Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges
Wang, Y. I., Carmona, C., Hickman, J. J., & Shuler, M. L. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201701000 · Cited by 168 · see citing works
Microfluidic cell culture models for tissue engineering
Inamdar, N. K., & Borenstein, J. T. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.05.512 · Cited by 162 · see citing works
Liver-Kidney-on-Chip To Study Toxicity of Drug Metabolites
Theobald, J., Ghanem, A., Wallisch, P., Banaeiyan, A. A., Andrade-Navarro, M. A., Taškova, K., Haltmeier, M., Kurtz, A., Becker, H., Reuter, S., et al. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00417 · Cited by 157 · see citing works
Biochemical analysis on microfluidic chips
Wu, J., He, Z., Chen, Q., & Lin, J. (2016) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2016.03.013 · Cited by 151 · see citing works
Shao, Y., & Fu, J. (2013) · Advanced Materials · doi:10.1002/adma.201304431 · Cited by 148 · see citing works
Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations
Zhao, Y., Kankala, R. K., Wang, S., & Chen, A. (2019) · Molecules · doi:10.3390/molecules24040675 · Cited by 136 · see citing works
An On-Chip Small Intestine–Liver Model for Pharmacokinetic Studies
Kimura, H., Ikeda, T., Nakayama, H., Sakai, Y., & Fujii, T. (2015) · SLAS Technology · doi:10.1177/2211068214557812 · Cited by 136 · see citing works
Organ‐on‐a‐Chip Technology for Reproducing Multiorgan Physiology
Lee, S. H., & Sung, J. H. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700419 · Cited by 128 · see citing works
3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis
Kim, J.-Y., Fluri, D. A., Marchan, R., Boonen, K., Mohanty, S., Singh, P., Hammad, S., Landuyt, B., Hengstler, J. G., Kelm, J. M., et al. (2015) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2015.01.003 · Cited by 126 · see citing works
Jackson, E., & Lu, H. (2016) · Integrative Biology · doi:10.1039/c6ib00039h · Cited by 125 · see citing works
Yu, F., Deng, R., Tong, W. H., Li, H., Ng, C. W., IslamBadhan, A., Iliescu, C., & Yu, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-13848-5 · Cited by 125 · see citing works
Gut-on-chip: Recreating human intestine in vitro
Xiang, Y., Wen, H., Yu, Y., Li, M., Fu, X., & Huang, S. (2020) · Journal of Tissue Engineering · doi:10.1177/2041731420965318 · Cited by 120 · see citing works
Gut-on-a-chip models for dissecting the gut microbiology and physiology
Valiei, A., Aminian-Dehkordi, J., & Mofrad, M. R. K. (2023) · APL Bioengineering · doi:10.1063/5.0126541 · Cited by 117 · see citing works
An Overview of Organs-on-Chips Based on Deep Learning
Li, J., Chen, J., Bai, H., Wang, H., Hao, S., Ding, Y., Peng, B., Zhang, J., Li, L., & Huang, W. (2022) · Research · doi:10.34133/2022/9869518 · Cited by 113 · see citing works
Journey of organ on a chip technology and its role in future healthcare scenario
Singh, D., Mathur, A. K., Arora, S., Roy, S., & Mahindroo, N. (2022) · Applied Surface Science Advances · doi:10.1016/j.apsadv.2022.100246 · Cited by 113 · see citing works
Approaching the in vitro clinical trial: engineering organs on chips
Capulli, A. K., Tian, K., Mehandru, N., Bukhta, A., Choudhury, S. F., Suchyta, M., & Parker, K. K. (2014) · Lab on a Chip · doi:10.1039/c4lc00276h · Cited by 111 · see citing works
Dehne, E., Tonevitsky, A., & Marx, U. (2013) · Lab on a Chip · doi:10.1039/c3lc50240f · Cited by 108 · see citing works
Recent developments in microfluidic devices for in vitro cell culture for cell-biology research
Gao, D., Liu, H., Jiang, Y., Lin, J., Gao, D., Liu, H., & Jiang, Y. (2012) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2012.02.008 · Cited by 95 · see citing works
Michel, T., Halabalaki, M., & Skaltsounis, A. (2013) · Planta Medica · doi:10.1055/s-0032-1328300 · Cited by 89 · see citing works
Barriers-on-chips: Measurement of barrier function of tissues in organs-on-chips
Arık, Y. B., van der Helm, M. W., Odijk, M., Segerink, L. I., Passier, R. C., van den Berg, A., & van der Meer, A. D. (2018) · Biomicrofluidics · doi:10.1063/1.5023041 · Cited by 85 · see citing works
Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review
Kashaninejad, N., Nikmaneshi, M., Moghadas, H., Kiyoumarsi Oskouei, A., Rismanian, M., Barisam, M., Saidi, M., & Firoozabadi, B. (2016) · Micromachines · doi:10.3390/mi7080130 · Cited by 79 · see citing works
Organ on Chip Technology to Model Cancer Growth and Metastasis
Imparato, G., Urciuolo, F., & Netti, P. A. (2022) · Bioengineering · doi:10.3390/bioengineering9010028 · Cited by 76 · see citing works
Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications
Morsink, M., Willemen, N., Leijten, J., Bansal, R., & Shin, S. (2020) · Micromachines · doi:10.3390/mi11090849 · Cited by 73 · see citing works
Exploring Living Multicellular Organisms, Organs, and Tissues Using Microfluidic Systems
Sivagnanam, V., & Gijs, M. A. M. (2013) · Chemical Reviews · doi:10.1021/cr200432q · Cited by 72 · see citing works
Kim, J., Fluri, D. A., Kelm, J. M., Hierlemann, A. R., & Frey, O. (2014) · SLAS TECHNOLOGY · doi:10.1177/2211068214564056 · Cited by 71 · see citing works
de Haan, P., Ianovska, M. A., Mathwig, K., van Lieshout, G. A. A., Triantis, V., Bouwmeester, H., & Verpoorte, E. M. J. (2019) · Lab on a Chip · doi:10.1039/c8lc01080c · Cited by 71 · see citing works
Imura, Y., Yoshimura, E., & Sato, K. (2012) · Analytical Sciences · doi:10.2116/analsci.28.197 · Cited by 70 · see citing works
Self-citationZhang, J., Wu, J., Li, H., Chen, Q., & Lin, J. (2015) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2015.01.013 · Cited by 70 · see citing works
In Vitro Immune Organs-on-Chip for Drug Development: A Review
Shanti, A., Teo, J. C. M., & Stefanini, C. (2018) · Pharmaceutics · doi:10.3390/pharmaceutics10040278 · Cited by 68 · see citing works
High-Content Assessment of Cardiac Function Using Heart-on-a-Chip Devices as Drug Screening Model
Conant, G., Lai, B. F. L., Lu, R. X. Z., Korolj, A., Wang, E. Y., & Radisic, M. (2017) · Stem Cell Reviews and Reports · doi:10.1007/s12015-017-9736-2 · Cited by 67 · see citing works
Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies
Kozalak, G., Bütün, İ., Toyran, E., & Koşar, A. (2023) · Pharmaceuticals · doi:10.3390/ph16010111 · Cited by 60 · see citing works
Patterned superhydrophobic surfaces to process and characterize biomaterials and 3D cell culture
Neto, A. I., Levkin, P. A., & Mano, J. F. (2018) · Materials Horizons · doi:10.1039/c7mh00877e · Cited by 59 · see citing works
Glass-based organ-on-a-chip device for restricting small molecular absorption
Hirama, H., Satoh, T., Sugiura, S., Shin, K., Onuki-Nagasaki, R., Kanamori, T., & Inoue, T. (2018) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2018.10.019 · Cited by 59 · see citing works
Youhanna, S. C., Kemas, A. M., Preiss, L. C., Zhou, Y., Shen, J. X., Cakal, S. D., Paqualini, F. S., Goparaju, S. K., Shafagh, R. Z., Lind, J. U., et al. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000238 · Cited by 57 · see citing works
Onfroy-Roy, L., Hamel, D., Foncy, J., Malaquin, L., & Ferrand, A. (2020) · Cells · doi:10.3390/cells9122629 · Cited by 55 · see citing works
Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction
Jin, H., Xue, Z., Liu, J., Ma, B., Yang, J., & Lei, L. (2024) · Biomaterials Research · doi:10.34133/bmr.0016 · Cited by 53 · see citing works
Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip
Li, Z., Guo, Y., Yu, Y., Xu, C., Xu, H. M., & Qin, J. (2016) · Integrative Biology · doi:10.1039/c6ib00162a · Cited by 53 · see citing works
Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs
Sung, J. H. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1908996 · Cited by 53 · see citing works
Intestine-on-a-chip: Next level in vitro research model of the human intestine
Donkers, J. M., Amirabadi, H. E., & van de Steeg, E. (2020) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2020.11.002 · Cited by 52 · see citing works
Pancreas-on-a-Chip Technology for Transplantation Applications
Abadpour, S., Aizenshtadt, A., Olsen, P. A., Shoji, K., Wilson, S., Krauss, S., & Scholz, H. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01357-1 · Cited by 36 · see citing works
Cancer-on-a-chip for precision cancer medicine
Liu, L., Wang, H., Chen, R., Song, Y., Wei, W., Baek, D. S. H., Gillin, M., Kurabayashi, K., & Chen, W. (2025) · Lab on a Chip · doi:10.1039/d4lc01043d · Cited by 47 · see citing works
Miniaturized pre-clinical cancer models as research and diagnostic tools
Håkanson, M., Cukierman, E., & Charnley, M. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.11.010 · Cited by 45 · see citing works
Pharmacokinetic and pharmacodynamic insights from microfluidic intestine-on-a-chip models
Lee, S. H., Choi, N., & Sung, J. H. (2019) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2019.1700950 · Cited by 44 · see citing works
Microfluidic based human-on-a-chip: A revolutionary technology in scientific research
Syama, S., & Mohanan, P. V. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.02.049 · Cited by 44 · see citing works
Fernández‐Costa, J. M., Ortega, M. A., Rodríguez‐Comas, J., López‐Muñoz, G. A., Yeste, J., Mangas‐Florencio, L., Fernandez‐González, M., Martin‐Lasierra, E., Tejedera‐Villafranca, A., & Ramón‐Azcón, J. (2022) · Advanced Materials Technologies · doi:10.1002/admt.202200873 · Cited by 42 · see citing works
Recent Advances in Gut‐ and Gut–Organ‐Axis‐on‐a‐Chip Models
Kim, R., & Sung, J. H. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202302777 · Cited by 42 · see citing works
Tetsuka, K., Ohbuchi, M., & Tabata, K. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.05.010 · Cited by 41 · see citing works
Models of the Gut for Analyzing the Impact of Food and Drugs
Fois, C. A. M., Le, T. Y. L., Schindeler, A., Naficy, S., McClure, D. D., Read, M. N., Valtchev, P., Khademhosseini, A., & Dehghani, F. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201900968 · Cited by 41 · see citing works
Technological tools and strategies for culturing human gut microbiota in engineered in vitro models
Sardelli, L., Perottoni, S., Tunesi, M., Boeri, L., Fusco, F., Petrini, P., Albani, D., & Giordano, C. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27816 · Cited by 41 · see citing works
Signore, M. A., Pascali, C. D., Giampetruzzi, L., Siciliano, P. A., & Francioso, L. N. (2021) · Sensing and Bio-Sensing Research · doi:10.1016/j.sbsr.2021.100443 · Cited by 41 · see citing works
Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems
Kang, T., & Kim, H. (2016) · Micromachines · doi:10.3390/mi7070107 · Cited by 40 · see citing works
Gastrointestinal microphysiological systems
Blutt, S. E., Broughman, J. R., Zou, W. Y., Zeng, X., Karandikar, U. C., In, J., Zachos, N. C., Kovbasnjuk, O. N., Donowitz, M., & Estes, M. K. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217710638 · Cited by 40 · see citing works
Hou, Y., Ai, X., Zhao, L., Gao, Z., Wang, Y., Lu, Y., Tu, P., & Jiang, Y. (2020) · Lab on a Chip · doi:10.1039/d0lc00288g · Cited by 38 · see citing works
Wang, H., Li, X., Shi, P., You, X., & Zhao, G. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101079 · Cited by 36 · see citing works
An on-chip intestine-liver model for multiple drugs absorption and metabolism behavior simulation
Jie, M., Lin, H., He, Z., Liu, H., Li, H., & Lin, J. (2017) · Science China Chemistry · doi:10.1007/s11426-017-9167-0 · Cited by 34 · see citing works
Phytoestrogens: The current state of research emphasizing breast pathophysiology
Senthilkumar, H. A., Fata, J. E., & Kennelly, E. J. (2018) · Phytotherapy Research · doi:10.1002/ptr.6115 · Cited by 34 · see citing works
Liver-on-a-chip platform to study anticancer effect of statin and its metabolites
Chen, P.-Y., Hsieh, M.-J., Liao, Y.-H., Lin, Y.-C., & Hou, Y. (2020) · Biochemical Engineering Journal · doi:10.1016/j.bej.2020.107831 · Cited by 33 · see citing works
Sakharov, D. A., Maltseva, D. V., Knyazev, E. N., Nikulin, S. V., Poloznikov, A. A., Shilin, S. A., Baranova, A. V., Tsypina, I. M., & Tonevitsky, A. (2019) · BMC Systems Biology · doi:10.1186/s12918-019-0686-y · Cited by 31 · see citing works
Hughes, D. J., Kostrzewski, T. M., & Sceats, E. L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217708976 · Cited by 31 · see citing works
Advances of microfluidic intestine-on-a-chip for analyzing anti-inflammation of food
Liang, D., Su, W., & Tan, M. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1875395 · Cited by 27 · see citing works
Development of cell metabolite analysis on microfluidic platform
Lin, L., & Lin, J. (2015) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2015.09.003 · Cited by 27 · see citing works
Microfluidics for nano-pathophysiology
Sato, K., Sasaki, N., Svahn, H. A., & Satō, K. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.08.009 · Cited by 27 · see citing works
Self-citationImura, Y., Yoshimura, E., & Sato, K. (2012) · Analytical Chemistry · doi:10.1021/ac302938q · Cited by 25 · see citing works
Self-citationTowards better models and mechanistic biomarkers for drug-induced gastrointestinal injury
Carr, D. F., Ayehunie, S., Davies, A., Duckworth, C. A., French, S., Hall, N., Hussain, S. A., Mellor, H. R., Norris, A. M., Park, B. K., et al. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.01.002 · Cited by 25 · see citing works
Microtechnology‐based organ systems and whole‐body models for drug screening
Lee, S. H., Ha, S. K., Choi, I., Choi, N., Park, T. H., & Sung, J. H. (2016) · Biotechnology Journal · doi:10.1002/biot.201500551 · Cited by 24 · see citing works
Docci, L., Parrott, N. J., Krähenbühl, S., & Fowler, S. M. (2019) · SLAS DISCOVERY · doi:10.1177/2472555219831407 · Cited by 24 · see citing works
Gao, X., Tanaka, Y., Sugii, Y., Mawatari, K., & Kitamori, T. (2011) · Analytical Sciences · doi:10.2116/analsci.27.907 · Cited by 23 · see citing works
Wu, J., Jie, M., Dong, X., Qi, H., & Lin, J. (2016) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.7643 · Cited by 22 · see citing works
Microtechnology-based in vitro models: Mimicking liver function and pathophysiology
Lee, S. Y., Kim, D., Sung, J. H., & Sung, J. H. (2021) · APL Bioengineering · doi:10.1063/5.0061896 · Cited by 21 · see citing works
Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms
Yahya, W. N. W., Kadri, N. A., & Ibrahim, F. (2014) · Sensors · doi:10.3390/s140711714 · Cited by 21 · see citing works
In vitro three-dimensional models in cancer research: a review
Imparato, G., Urciuolo, F., & Netti, P. A. (2015) · International Materials Reviews · doi:10.1179/1743280415y.0000000003 · Cited by 20 · see citing works
Lacombe, J., Soldevila, M., & Zenhausern, F. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.07.019 · Cited by 20 · see citing works
Biomaterials and bioengineering to guide tissue morphogenesis in epithelial organoids
Jeon, E. Y., Sorrells, L., & Abaci, H. E. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1038277 · Cited by 19 · see citing works
- Authors
- Imura, Y., Sato, K., & Yoshimura, E.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Sato, Kiichi
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-11-23
- Volume
- 82
- Issue
- 24
- Pages
- 9983-9988
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W2089859139
- Cited by
- 172
- References
- 30
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 21 · 2019: 16 · 2018: 9 · 2017: 19 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 10 · 2012: 10
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- RIKEN
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
- Keywords
- intestinal absorption, hepatic metabolism, oral drug absorption, Caco-2 cells, HepG2 cells, MCF-7 cells, anticancer agents, cyclophosphamide, epirubicin, estradiol, soy isoflavones, microfluidics, PDMS microchannel, in vitro bioassay
- MeSH terms
- Antineoplastic Agents, Cyclophosphamide, Estradiol, Humans, Intestinal Absorption, Isoflavones, Liver, Models, Biological, Epirubicin, Cell Line, Tumor, Microchip Analytical Procedures, Lab-On-A-Chip Devices
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review