title: High-density microfluidic arrays for cell cytotoxicity analysis.
abstract: In this paper, we report on the development of a multilayer elastomeric microfluidic array platform for the high-throughput cell cytotoxicity screening of mammalian cell lines. Microfluidic channels in the platform for cell seeding are orthogonal to channels for toxin exposure, and within each channel intersection is a circular chamber with cell-trapping sieves. Integrated, pneumatically-actuated elastomeric valves within the device isolate the microchannel array within the device into parallel rows and columns for cell seeding and toxin exposure. As a demonstration of the multiplexing capability of the platform, a microfluidic array containing 576 chambers was used to screen three cell types (BALB/3T3, HeLa, and bovine endothelial cells) against a panel of five toxins (digitonin, saponin, CoCl(2), NiCl(2), acrolein). Evaluation of on-chip cell morphology and viability was carried out using fluorescence microscopy, with outcomes comparable to microtiter plate cytotoxicity assays. Using this scalable platform, cell seeding and toxin exposure can be carried out within a single microfluidic device in a multiplexed format, enabling high-density parallel cytotoxicity screening while minimizing reagent consumption.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kim
authors.forename: Manuel
authors.initials: M
authors.lastname: Marquez
authors.forename: Todd
authors.initials: T
authors.lastname: Thorsen
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D041702:BALB 3T3 Cells / Q000187:drug effects / Q000648:ultrastructure; D002417:Cattle; D003035:Cobalt / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000502:physiology; D004072:Digitonin / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D004867:Equipment Design; D006367:HeLa Cells / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D009532:Nickel / Q000633:toxicity*; D012503:Saponins / Q000633:toxicity*; D013997:Time Factors
chemical_list: D012503:Saponins; D003035:Cobalt; C022838:nickel chloride; D000171:Acrolein; D009532:Nickel; C018021:cobaltous chloride; D004072:Digitonin