Real-time and non-invasive impedimetric monitoring of cell proliferation and chemosensitivity in a perfusion 3D cell culture microfluidic chip
Abstract
A perfusion three-dimensional (3D) cell culture microfluidic chip has been developed for real-time and non-invasive impedimetric monitoring of cell proliferation and chemosensitivity. In this study, human oral cancer cells (OEC-M1) were encapsulated in 3D agarose scaffold and cultured in a miniaturized chamber under perfusion of tested substance. This setting provides a more in vitro physiologically relevant microenvironment to better mimic the complex in vivo microenvironment. A pair of vertical electrodes was embedded at the opposite sidewalls of the culture chamber for the on-site impedance measurement. Cell density in the 3D construct was shown to be proportional to the impedance magnitude of the entire construct. Therefore, perfusion 3D cell culture was performed for up to 5 days and cell proliferation can be monitored by the impedimetric analysis. Moreover, real-time impedimetric monitoring of cell viability under the perfusion of anti-cancer drug in different concentrations was conducted and the impedance magnitude was directly correlated with the cell viability. From the confirmation of the endpoint cell viability assays, a concentration-dependent effect was shown; however, the response of cell viability during the drug treatment was able to be traced by the impedance measurement. The experimental results showed that cell proliferation and chemosensitivity in 3D cell culture format can be monitored by impedance measurement. This microfluidic chip has a high potential to develop a powerful analytical platform for cancer research.
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2D and 3D cell cultures are suitable for exploring cellular responses to drugs, toxins, and biomaterials.
“Although 2D and 3D cell cultures are suitable for exploring cellular responses to drugs, toxins, and biomaterials, 77 only 3D cultures exhibit a hierarchical structure and cellular heterogeneity that can closely mimic in vivo cell morphology and function (proliferation, differentiation, gene expression, etc.), 78,79 cell-cell interactions, and diffusion barriers.”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [77]
3D models can better replicate intrinsic physiological conditions and in vivo cellular responses to external stimuli compared to the 2D monolayer.
“Therefore, 3D models can better replicate intrinsic physiological conditions and in vivo cellular responses to external stimuli compared to the 2D monolayer. 77,78,80-82”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [77]
Cites
The third dimension bridges the gap between cell culture and live tissue
Pampaloni, F., Reynaud, E. G., & Stelzer, E. H. K. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2236 · Cited by 2,817 · see citing works
Benya, P. D., & Shaffer, J. D. (1982) · Cell · doi:10.1016/0092-8674(82)90027-7 · Cited by 2,284 · see citing works
Abbott, A. (2003) · Nature · doi:10.1038/424870a · Cited by 1,237 · see citing works
Dielectric and electronic properties of biological materials
Pethig, R. (1979) · Cited by 702 · see citing works
Dielectric and Electronic Properties of Biological Materials
Willis, M. (1980) · Biochemical Education · doi:10.1016/0307-4412(80)90102-8 · Cited by 462 · see citing works
Nanoscaled interdigitated electrode arrays for biochemical sensors
Gerwen, P. V., Laureyn, W., Laureys, W., et al. (1998) · Sensors and Actuators B Chemical · doi:10.1016/s0925-4005(98)00128-2 · Cited by 394 · 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
Interdigitated array microelectrodes based impedance biosensors for detection of bacterial cells
Varshney, M., & Li, Y. (2008) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2008.10.001 · Cited by 366 · see citing works
3D cell culture opens new dimensions in cell-based assays
Justice, B. A., Badr, N. A., & Felder, R. A. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.11.006 · Cited by 340 · see citing works
Yang, L., Li, Y., Griffis, C. L., et al. (2003) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2003.10.009 · Cited by 303 · see citing works
Hoemann, C. D., Sun, J., Chrzanowski, V., et al. (2002) · Analytical Biochemistry · doi:10.1006/abio.2001.5436 · Cited by 160 · see citing works
Torisawa, Y.-S., Shiku, H., Yasukawa, T., Nishizawa, M., & Matsue, T. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2004.05.028 · Cited by 124 · see citing works
Impedance studies of bio-behavior and chemosensitivity of cancer cells by micro-electrode arrays
Liu, Q., Yu, J., Xiao, L., Tang, J. C. O., Zhang, Y., Wang, P., & Yang, M. (2008) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2008.07.044 · Cited by 119 · see citing works
Wu, M., Urban, J. P. G., Cui, Z., & Cui, Z. F. (2006) · Biomedical Microdevices · doi:10.1007/s10544-006-9597-y · Cited by 107 · see citing works
Self-citationImpedance measurement for real time detection of neuronal cell death
Diemert, S., Dolga, A. M., Tobaben, S., Grohm, J., Pfeifer, S., Öxler, E.-M., & Culmsee, C. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2011.09.012 · Cited by 98 · see citing works
Ma, K.-S., Zhou, H., Zoval, J. V., et al. (2005) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2005.04.038 · Cited by 85 · see citing works
Mishra, N. N., Retterer, S. T., Zieziulewicz, T. J., et al. (2005) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2005.01.011 · Cited by 76 · see citing works
Label-free and reversible immunosensor based upon an ac impedance interrogation protocol
Grant, S., Davis, F., Law, K. A., et al. (2005) · Analytica Chimica Acta · doi:10.1016/j.aca.2005.01.003 · Cited by 68 · see citing works
Cui, Z., Xu, X., Trainor, N. B., Triffitt, J. T., Urban, J., & Tirlapur, U. K. (2007) · Toxicology in Vitro · doi:10.1016/j.tiv.2007.05.015 · Cited by 65 · see citing works
Saum, A. G. E., Cumming, R. H., & Rowell, F. J. (1998) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(97)00129-2 · Cited by 64 · see citing works
Biomarkers for simplifying HTS 3D cell culture platforms for drug discovery: the case for cytokines
Lai, Y., Asthana, A., & Kisaalita, W. S. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.01.009 · Cited by 43 · 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
Self-citationThakur, M., Mergel, K., Weng, A., et al. (2012) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2012.03.024 · Cited by 41 · see citing works
Wu, M., & Kuo, C.-Y. (2010) · Biomedical Microdevices · doi:10.1007/s10544-010-9478-2 · Cited by 23 · see citing works
Self-citationLei, K. F. (2011) · Measurement Science and Technology · doi:10.1088/0957-0233/22/10/105802 · Cited by 18 · see citing works
Self-citationLei, K. F., Wu, M.-H., Hsu, C.-W., & Chen, Y.-D. (2012) · International Journal of Electrochemical Science · doi:10.1016/s1452-3981(23)16588-6 · Cited by 12 · see citing works
Self-citationLei, K. F., Wu, M., Hsu, C., & Lin, C.-Y. (2012) · International Journal of Electrochemical Science · doi:10.1016/s1452-3981(23)18036-9 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
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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
Is it time to start transitioning from 2D to 3D cell culture?
Jensen, C., & Teng, Y. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00033 · Cited by 1,640 · see citing works
Hydrogels as artificial matrices for cell seeding in microfluidic devices
Akther, F., Little, P., Li, Z., Nguyen, N.-T., & Ta, H. T. (2020) · RSC Advances · doi:10.1039/d0ra08566a · Cited by 127 · see citing works
Engineering fiber anisotropy within natural collagen hydrogels
Ahmed, A., Joshi, I. M., Mansouri, M., Ahamed, N. N. N., Hsu, M.-C., Gaborski, T. R., & Abhyankar, V. V. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00036.2021 · Cited by 41 · see citing works
- Authors
- Lei, K. F., Wu, M.-H., Hsu, C.-W., & Chen, Y.-D.
- Affiliations
- Chang Gung University (TW)
- Corresponding author
- Lei, Kin Fong
- Venue
- Biosensors and Bioelectronics
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 51
- Pages
- 16-21
- ISSN
- 0956-5663 (ISSN-L)
- OpenAlex
- W1995746991
- Cited by
- 111
- References
- 27
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 3 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 12 · 2014: 9 · 2013: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biosensors and Bioelectronics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- cell proliferation, chemosensitivity, microfluidics, oral cancer cells, cell viability, anticancer drug response, impedance measurement, anticancer drug screening
- MeSH terms
- Antineoplastic Agents, Cell Survival, Drug Screening Assays, Antitumor, Equipment Design, Humans, Mouth Neoplasms, Sepharose, Biosensing Techniques, Electric Impedance, Cell Culture Techniques, Cell Line, Tumor, Microfluidic Analytical Techniques, Cell Proliferation, Tissue Scaffolds
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