A dielectrophoresis-based cellular microarray microfluidic system for anticancer drug screenings
Date Issued
2010
Date
2010
Author(s)
Hsiung, Lo-Chang
Abstract
With low efficiency of chemotherapy for some patients, there is a need for predicting the outcome of a treatment by performing in vitro cellular drug screenings. To predict drug responses, cellular microarray－a powerful tool for high throughput screening－has been used to meet the need.
Here, this thesis presents a dielectrophoresis (DEP)-based cellular microarray perfusion system for anticancer drug screenings. A collagen-coated planar interdigitated ring electrode (PIRE) array utilizing positive dielectrophoresis to pattern cells uniformly is put forth. Furthermore, a functional integration of a concentration gradient generator (CGG) and an anti-crosstalk valve (ACV) is presented to generate a linear concentration gradient of drug without unwanted crosstalk of drug concentrations for a stable drug perfusion. Besides, a tailor-made configuration was designed to keep the pressure inside chip higher than ambient pressure which served to provide a bubble-free culture environment.
Results suggest that the proposed system provides a viable microfluidic culture environment for drug screenings. Cell patterning on a PIRE showed that cells were patterned within minutes with good uniformity (for a 6×6 PIRE array: 48 ± 6 cells per PIRE; for a 1×3 array: 92 ± 5 cells per PIRE). Cell viability test revealed healthy patterned cells after 24-hour culture. Furthermore, quantification of fluorescence intensity of living cells showed an acceptable reproducibility of cell viability among PIREs (mean normalized intensity per PIRE was 1 ± 0.138). Moreover, observations of patterned cells during 24-hour drug perfusion showed good correlation between cell viability and drug concentration, and no statistical significance in dose responses between the microfluidic system and 96-well plates. Besides, bubble elimination in a PDMS chip showed the relationship between the time for bubble elimination and the associate bubble sizes was linear.
The DEP-based cellular microarray perfusion system should benefit applications desiring uniform cellular patterning, and supplement microfluidic perfusion approach for building up a correlation to in vivo drug responses for improving efficacy of chemotherapy.
Subjects
dielectrophoresis
cell patterning
cellular Microarray
bubble elimination
perfusion culture system
concentration gradient generator
PDMS valve
SDGs
Type
thesis
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