Real-time and non-invasive impedimetric monitoring of cell proliferation and chemosensitivity in a perfusion 3D cell culture microfluidic chip.
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.
Graduate Institute of Medical Mechatronics, Chang Gung University, Taoyuan, Taiwan ROC; Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan ROC. Electronic address: kflei@mail.cgu.edu.tw.
Kin Fong
KF
Lei
Min-Hsien
MH
Wu
Che-Wei
CW
Hsu
Yi-Dao
YD
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology; D015374:Biosensing Techniques / Q000295:instrumentation; D018929:Cell Culture Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation*; D017097:Electric Impedance; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009062:Mouth Neoplasms / Q000188:drug therapy; D012685:Sepharose / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry
D000970:Antineoplastic Agents; D012685:Sepharose
Cell culture; Cell proliferation; Chemosensitivity; Impedance measurement; Microfluidic chip