Multi-channel 3-D cell culture device integrated on a silicon chip for anticancer drug sensitivity test
Abstract
A novel three-dimensional cell culture system was constructed with an array of cell panels (4 x 5) in a silicon chip, together with multi-channel drug containers. Human breast cancer (MCF-7) cells were embedded in a collagen-gel matrix and entrapped in a pyramidal-shaped silicon hole. Each cell panel can be isolated by a channel composed of a microfluid part and a reservoir. A cell panel was exposed to 200 mm KCN for 2 days to demonstrate that each cell panel could be independently evaluated under various stimulation conditions. Based on the cellular respiration activity, the proliferation behavior was continuously monitored on the silicon-based cell array for 5 days using scanning electrochemical microscopy (SECM). The cells entrapped in the device (3-D culture) proliferated normally, and the proliferation rate was lower than that of cells grown in a monolayer cell culture (2-D culture). The effects of three anticancer drugs measured simultaneously on the cell chip were in good agreement with those obtained by a conventional colorimetric assay. Our results suggest that the silicon-based device for 3D culture is appropriate for a chemosensitivity assay involving multi-chemical stimulation.
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?
Other researchers have used 3D cell-based electrochemical biosensors to quantify cancer cell resistance to drug compounds and to study cancer cell proliferation in the presence of anticancer drugs.
“Other researchers have used 3D cell-based electrochemical biosensors to quantify cancer cell resistance to drug compounds 78,95 and to study cancer cell proliferation in the presence of anticancer drugs. 94”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [94]
Anticancer drug screening has been an important application for 3D cell culture biosensors because biosensor-based assays enable multiplex analysis of different drugs and/or cancer cells.
“Anticancer drug screening has been an important application for 3D cell culture biosensors because the biosensor-based assays enable multiplex analysis of different drugs and/or cancer cells. 94”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [94]
Cites
Patterning proteins and cells using soft lithography
Kane, R. S. (1999) · Biomaterials · doi:10.1016/s0142-9612(99)00165-9 · Cited by 1,492 · see citing works
Weaver, V. M., Petersen, O. W., Wang, F., Larabell, C. A., Briand, P., Damsky, C., & Bissell, M. J. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.1.231 · Cited by 1,483 · see citing works
Abbott, A. (2003) · Nature · doi:10.1038/424870a · Cited by 1,237 · see citing works
Cell interactions with three-dimensional matrices
Cukierman, E., Pankov, R. G., & Yamada, K. M. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00364-2 · Cited by 889 · see citing works
Polymer microstructures formed by moulding in capillaries
Kim, E., Xia, Y., & Whitesides, G. M. (1995) · Nature · doi:10.1038/376581a0 · Cited by 878 · see citing works
Weaver, V. M., Lelièvre, S. A., Lakins, J. N., Chrenek, M. A., Jones, J., Giancotti, F. G., Werb, Z., & Bissell, M. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00125-3 · Cited by 794 · see citing works
A morphological biosensor for mammalian cells
Giæver, I., & Keese, C. R. (1993) · Nature · doi:10.1038/366591a0 · Cited by 775 · see citing works
Patterned Delivery of Immunoglobulins to Surfaces Using Microfluidic Networks
Delamarche, E., Bernard, A., Schmid, H., et al. (1997) · Science · doi:10.1126/science.276.5313.779 · Cited by 678 · see citing works
The cytosensor microphysiometer: biological applications of silicon technology
McConnell, H. M., Owicki, J. C., Parce, J. W., Miller, D., Baxter, G. T., Wada, H., & Pitchford, S. C. (1992) · Science · doi:10.1126/science.1329199 · Cited by 622 · see citing works
Modeling tissue-specific signaling and organ function in three dimensions
Schmeichel, K. L., & Bissell, M. J. (2003) · Journal of Cell Science · doi:10.1242/jcs.00503 · Cited by 583 · see citing works
Recent advances in biologically sensitive field-effect transistors (BioFETs)
Schöning, M. J., & Poghossian, A. (2002) · The Analyst · doi:10.1039/b204444g · Cited by 566 · see citing works
Integration of Cell Culture and Microfabrication Technology
Park, T., & Shuler, M. (2003) · Biotechnology progress (Print) · doi:10.1021/bp020143k · Cited by 495 · see citing works
Development and Application of Cell-Based Biosensors
Pancrazio, J. J., Whelan, J., Borkholder, D. A., Ma, W., & Stenger, D. A. (1999) · Annals of Biomedical Engineering · doi:10.1114/1.225 · Cited by 391 · see citing works
Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures
Ehret, R., Baumann, W., Brischwein, M., et al. (1997) · Biosensors and Bioelectronics · doi:10.1016/0956-5663(96)89087-7 · Cited by 388 · see citing works
Engineering cellular microenvironments to improve cell-based drug testing
Bhadriraju, K., & Chen, C. S. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02273-0 · Cited by 355 · see citing works
Using electroactive substrates to pattern the attachment of two different cell populations
Yousaf, M. N., Houseman, B. T., & Mrksich, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.101112898 · Cited by 351 · see citing works
Bousse, L. J. (1996) · Sensors and Actuators B Chemical · doi:10.1016/s0925-4005(96)01906-5 · Cited by 345 · see citing works
Taking the Study of Cancer Cell Survival to a New Dimension
Jacks, T., & Weinberg, R. A. (2002) · Cell · doi:10.1016/s0092-8674(02)01229-1 · Cited by 302 · see citing works
Stenger, D. A., Georger, J. H., Dulcey, C. S., Hickman, J. J., Rudolph, A. S., Nielsen, T. B., McCort, S. M., & Calvert, J. M. (1992) · Journal of the American Chemical Society · doi:10.1021/ja00048a013 · Cited by 297 · see citing works
Zeck, G., & Fromherz, P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181348698 · Cited by 290 · see citing works
Yang, J., Richards, J. O., Bowman, P. R. T., et al. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.7.3401 · Cited by 283 · see citing works
Detection of physiologically active compounds using cell-based biosensors
Stenger, D. A., Gross, G. W., Keefer, E. W., Shaffer, K. M., Andreadis, J. D., Ma, W., & Pancrazio, J. J. (2001) · Trends in biotechnology · doi:10.1016/s0167-7799(01)01690-0 · Cited by 196 · see citing works
Layer-by-layer microfluidics for biomimetic three-dimensional structures
Tan, W., & Desai, T. A. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2003.08.021 · Cited by 193 · see citing works
Oxygen Consumption of Single Bovine Embryos Probed by Scanning Electrochemical Microscopy
Shiku, H., Shiraishi, T., Ohya, H., et al. (2001) · Analytical Chemistry · doi:10.1021/ac010339j · Cited by 192 · see citing works
Self-citationQuantitative analysis of vascular endothelial growth factor in primary breast cancer
Toi, M., Kondo, S., Suzuki, H., Yamamoto, Y., Inada, K., Imazawa, T., Taniguchi, T., & Tominaga, T. (1996) · Cancer · doi:10.1002/(sici)1097-0142(19960315)77:6 · Cited by 192 · see citing works
Cytosensor® Microphysiometer: technology and recent applications
Hafner, F. (2000) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(00)00069-5 · Cited by 179 · see citing works
Potential of the histoculture drug-response assay to contribute to cancer patient survival.
Kubota, T., Sasano, N., Abe, O., et al. (1995) · PubMed · Cited by 148 · see citing works
Functional cellular assays with multiparametric silicon sensor chips
Brischwein, M., Motrescu, E. R., Cabala, E., Otto, A. M., Grothe, H., & Wolf, B. A. (2003) · Lab on a Chip · doi:10.1039/b308888j · Cited by 134 · see citing works
Nishizawa, M., Takoh, K., & Matsue, T. (2002) · Langmuir · doi:10.1021/la011576k · Cited by 119 · see citing works
Self-citationScanning electrochemical microscopy of living cells
Liu, B., Cheng, W., Rotenberg, S. A., et al. (2001) · Journal of Electroanalytical Chemistry · doi:10.1016/s0022-0728(00)00436-8 · Cited by 103 · see citing works
Microelectrochemical Approach to Induce Local Cell Adhesion and Growth on Substrates
Kaji, H., Kanada, M., Oyamatsu, D., et al. (2003) · Langmuir · doi:10.1021/la035537f · Cited by 101 · see citing works
Monitoring of cellular signalling and metabolism with modular sensor-technique
Wolf, B. A., Brischwein, M., Baumann, W., et al. (1998) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(97)00136-x · Cited by 95 · see citing works
Torisawa, Y., Kaya, T., Takii, Y., Oyamatsu, D., Nishizawa, M., & Matsue, T. (2003) · Analytical Chemistry · doi:10.1021/ac026317u · Cited by 94 · see citing works
Self-citationFactors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures.
Miller, B. E., Miller, F. R., & Heppner, G. H. (1985) · PubMed · Cited by 88 · see citing works
Kaya, T., Torisawa, Y., Oyamatsu, D., Nishizawa, M., & Matsue, T. (2003) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(03)00083-6 · Cited by 88 · see citing works
Self-citationTakamura, Y., Kobayashi, H., Taguchi, T., Motomura, K., Inaji, H., & Noguchi, S. (2002) · International Journal of Cancer · doi:10.1002/ijc.10208 · Cited by 84 · see citing works
Immobilization of neural cells in three-dimensional matrices for biosensor applications
O’Connor, S. M., Andreadis, J. D., Shaffer, K. M., Ma, W., Pancrazio, J. J., & Stenger, D. A. (2000) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(99)00055-x · Cited by 81 · see citing works
High-throughput cell analysis using multiplexed array technologies
Beske, O. E., & Goldbard, S. B. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02388-7 · Cited by 67 · see citing works
Kobayashi, H., Higashiyama, M., Minamigawa, K., et al. (2001) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.2001.tb01083.x · Cited by 62 · see citing works
Lorenzelli, L., Margesin, B., Sergio Martinoia, A., Tedesco, M., & Valle, M. (2003) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(03)00040-x · Cited by 56 · see citing works
Approach to a multiparametric sensor-chip-based tumor chemosensitivity assay
Henning, T. D., Brischwein, M., Baumann, W., et al. (2001) · Anti-Cancer Drugs · doi:10.1097/00001813-200101000-00004 · Cited by 49 · see citing works
Cooke, D., & O’Kennedy, R. J. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4274 · Cited by 43 · see citing works
Proliferation assay on a silicon chip applicable for tumors extirpated from mammalians
Torisawa, Y., Shiku, H., Kasai, S., Nishizawa, M., & Matsue, T. (2003) · International Journal of Cancer · doi:10.1002/ijc.11693 · Cited by 33 · see citing works
Self-citationSaikawa, Y., Kubota, T., Furukawa, T., et al. (1994) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1994.tb02426.x · Cited by 32 · see citing works
Pharmacological characterization of micropatterned cardiac myocytes
Kaji, H., Takii, Y., Nishizawa, M., et al. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00275-8 · Cited by 31 · see citing works
Self-citationEkelund, S., Nygren, P., & Larsson, R. L. (1998) · Anti-Cancer Drugs · doi:10.1097/00001813-199807000-00003 · Cited by 27 · see citing works
Metzger, R., Deglmann, C. J., Hoerrlein, S., et al. (2001) · Toxicology · doi:10.1016/s0300-483x(01)00440-1 · Cited by 24 · see citing works
Koezuka, M., KONDO, N., Kobayashi, H., et al. (1993) · International Journal of Oncology · doi:10.3892/ijo.2.6.953 · Cited by 21 · see citing works
Kondo, T., Do, T. K., Kubota, T., et al. (2000) · PubMed · Cited by 21 · see citing works
THE CYTOSENSOR™-MICROPHYSIOMETER
Metzger, R. (1994) · Elsevier eBooks · doi:10.1016/b978-0-7506-1845-8.50084-3 · Cited by 20 · see citing works
Yamaue, H., Tanimura, H., Nobuji, K. O. N. O., et al. (2003) · PubMed · Cited by 12 · see citing works
Sinha, D. K., & White, C. J. (1988) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02629086 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Microfluidic cell culture systems for drug research
Wu, M.-H., Huang, S.-B., & Lee, G.-B. (2010) · Lab on a Chip · doi:10.1039/b921695b · Cited by 432 · see citing works
A novel 3D mammalian cell perfusion-culture system in microfluidic channels
Toh, Y.-C., Zhang, C., Zhang, J., Khong, Y. M., Chang, S., Samper, V. D., van Noort, D., Hutmacher, D. W., & Yu, H. (2007) · Lab on a Chip · doi:10.1039/b614872g · Cited by 414 · see citing works
A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip
Torisawa, Y.-S., Takagi, A., Nashimoto, Y., Yasukawa, T., Shiku, H., & Matsue, T. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2006.08.054 · Cited by 176 · see citing works
Self-citationLei, K. F., Wu, M.-H., Hsu, C.-W., & Chen, Y.-D. (2014) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2013.07.031 · Cited by 111 · 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
Whole-cell biochips for bio-sensing: integration of live cells and inanimate surfaces
Ben-Yoav, H., Melamed, S., Freeman, A., Shacham-Diamand, Y., & Belkin, S. (2011) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2010.532767 · Cited by 52 · see citing works
Wu, M.-H., Chang, Y.-H., Liu, Y.-T., Chen, Y.-M., Wang, S.-S., Wang, H.-Y., Lai, C.-S., & Pan, T.-M. (2011) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2010.11.027 · Cited by 42 · see citing works
Microfluidic Biopsy Trapping Device for the Real-Time Monitoring of Tumor Microenvironment
Holton, A. B., Sinatra, F. L., Kreahling, J., Conway, A. J., Landis, D. A., & Altiok, S. (2017) · PLOS ONE · doi:10.1371/journal.pone.0169797 · Cited by 35 · see citing works
- Authors
- Torisawa, Y.-S., Shiku, H., Yasukawa, T., Nishizawa, M., & Matsue, T.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Shiku, Hitoshi
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 26
- Issue
- 14
- Pages
- 2165-2172
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2049493146
- Cited by
- 124
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 10 · 2012: 6
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- 3D cell culture, anticancer drug sensitivity, chemosensitivity assay, MCF-7 cells, collagen gel, silicon micropillars, cell proliferation monitoring, scanning electrochemical microscopy, cellular respiration
- MeSH terms
- Antineoplastic Agents, Breast Neoplasms, Cell Survival, Drug Screening Assays, Antitumor, Electrochemistry, Equipment Design, Humans, Silicon, Biosensing Techniques, Cell Culture Techniques, Equipment Failure Analysis, Microscopy, Scanning Probe, Cell Line, Tumor, Microfluidic Analytical Techniques, Cell Proliferation
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
