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Cost-Efficient Transcriptomic-Based Drug Screening

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A robust high-throughput sandwich cell-based drug screening platform.

Shufang Zhang¹, Wenhao Tong, Baixue Zheng

¹Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.

|October 26, 2010

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We developed a high-throughput platform using sandwiched hepatocytes for drug toxicity testing. This robust system improves drug sensitivity and reduces variability in hepatotoxicity screening.

Area of Science:

Hepatology
Drug Development
Biotechnology

Background:

Early-stage hepatotoxicity evaluation is crucial for pharmaceutical development.
Sandwiched hepatocytes offer a stable in-vitro model for drug testing.
Existing models face challenges in maintaining cell function and throughput.

Purpose of the Study:

To develop a robust, high-throughput hepatotoxicity testing platform.
To enhance cellular function and mass transfer for drug screening.
To improve drug sensitivity and reduce variability in toxicity responses.

Main Methods:

Utilized a galactosylated microfabricated membrane sandwich for hepatocyte culture.
Employed a perfusion bioreactor to maintain long-term cell function and mass transfer.

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Optimized bioreactor design and flow rate using computational fluid dynamics and experiments.

Transferred cultured hepatocytes to 96-well plates for robotic liquid handling.

Main Results:

Hepatocytes maintained 3D morphology, urea production, and cytochrome P450 activity for 14 days.
The platform demonstrated improved drug sensitivity in hepatotoxicity testing.
Low variability in responses was observed across different culture dates.
The system supports robust high-throughput screening of drug candidates.

Conclusions:

The developed platform provides a reliable method for early-stage hepatotoxicity evaluation.
This high-throughput system enhances drug screening efficiency and accuracy.
The platform facilitates the identification of safer drug candidates in pharmaceutical development.