Microfluidic tissue model for live cell screening.
We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue-like culture and high-throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 microm wide cell culture pocket, an artificial endothelial barrier with 2 microm pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over 1 week in a solid tumor-like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for "flow cell" based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow-through biochemistry. Each fluidically independent tissue unit contained approximately 500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti-cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384-well dish for up to 5 days of continuous drug exposure.
Lee
Philip J
PJ
CellASIC Corporation, 2551 Merced St., San Leandro, California 94577, USA. pjlee@cellasic.com
Gaige
Terry A
TA
Ghorashian
Navid
N
Hung
Paul J
PJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D001671:Biochemistry / Q000379:methods; D001709:Biotechnology / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D006367:HeLa Cells; D006801:Humans; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D013997:Time Factors
D000970:Antineoplastic Agents