Microfluidic single-cell array cytometry for the analysis of tumor apoptosis.
Limitations imposed by conventional analytical technologies for cell biology, such as flow cytometry or microplate imaging, are often prohibitive for the kinetic analysis of single-cell responses to therapeutic compounds. In this paper, we describe the application of a microfluidic array to the real-time screening of anticancer drugs against arrays of single cells. The microfluidic platform comprises an array of micromechanical traps, designed to passively corral individual nonadherent cells. This platform, fabricated in the biologically compatible elastomer poly(dimethylsiloxane), PDMS, enables hydrodynamic trapping of cells in low shear stress zones, enabling time-lapse studies of nonadherent hematopoietic cells. Results indicate that these live-cell, microfluidic microarrays can be readily applied to kinetic analysis of investigational anticancer agents in hematopoietic cancer cells, providing new opportunities for automated microarray cytometry and higher-throughput screening. We also demonstrate the ability to quantify on-chip the anticancer drug induced apoptosis. Specifically, we show that with small numbers of trapped cells (approximately 300) under careful serial observation we can achieve results with only slightly greater statistical spread than can be obtained with single-pass flow cytometer measurements of 15,000-30,000 cells.
Wlodkowic
Donald
D
The Bioelectronics Research Centre, Department of Electronics and Electrical Engineering, University of Glasgow, G12 8LT, United Kingdom.
Faley
Shannon
S
Zagnoni
Michele
M
Wikswo
John P
JP
Cooper
Jonathan M
JM
D000970:Antineoplastic Agents / Q000032:analysis* / Q000633:toxicity; D017209:Apoptosis; D045744:Cell Line, Tumor; D005434:Flow Cytometry / Q000379:methods*; D018922:HL-60 Cells; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism; D009930:Organic Chemicals / Q000737:chemistry; D013194:Staining and Labeling; D046888:Tissue Array Analysis / Q000379:methods*
D000970:Antineoplastic Agents; D009930:Organic Chemicals; C402795:SYTOX Green