Article

Microvalve-assisted patterning platform for measuring cellular dynamics based on 3D cell culture.

Department of Bio and Brain Engineering, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Korea.
Biotechnology and Bioengineering (impact factor: 3.95). 06/2008; 101(5):1005-13. DOI:10.1002/bit.21962 pp.1005-13
Source: PubMed

ABSTRACT A microfluidic platform to satisfy both 3D cell culture and cell-based assay is required for credible assay results and improved assay concept in drug discovery. In this article, we demonstrate a microvalve-assisted patterning (MAP) platform to provide a new method for investigating cellular dynamics by generating a linear concentration gradient of a drug as well as to realize 3D cell culture in a microenvironment. The MAP platform was fabricated by multilayer soft lithography and several microvalves made it possible to pattern a cell-matrix (scaffold) and to exchange media solutions without breaking cell-matrix structure in a microchannel. This approach provides not only exact fluids control, bubble removal, and stable solution exchange in a microchannel, but also reliable scaffold fabrication and 3D cell culture. In this study, hepatotoxicity tests with human hepatocellular liver carcinoma cells (HepG2) were also performed in real-time monitoring where cell morphologies exposed to different drug concentrations were observed at a time. Compared to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, the MAP platform could be used to reduce drug amount and assay time for cell-based assays as much as 10 and 3 times, respectively.

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Keywords

3 times
 
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
 
3D cell culture
 
assay concept
 
assay time
 
bubble removal
 
cell-based assay
 
cell-based assays
 
cellular dynamics
 
credible assay results
 
different drug concentrations
 
drug amount
 
drug discovery
 
exchange media solutions
 
hepatotoxicity tests
 
human hepatocellular liver carcinoma cells
 
MAP platform
 
microvalve-assisted patterning
 
multilayer soft lithography
 
reliable scaffold fabrication
 

Minseok S Kim