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Microwell bioreactor system for cell-based high throughput proliferation and cytotoxicity assays

Paper ID Volume ID Publish Year Pages File Format Full-Text
34850 45052 2013 11 PDF Available
Title
Microwell bioreactor system for cell-based high throughput proliferation and cytotoxicity assays
Abstract

Cell-based high throughput proliferation and cytotoxicity assays are increasingly used in drug screening and bioprocess development. However, online monitoring of cell proliferation, pH, and dissolved oxygen (DO) has been a challenge in 3D cell-based assays. In this work, a 40-microwell bioreactor (40-MBR) system was developed from a 384-well plate for real-time, noninvasive monitoring of pH, DO, and cell proliferation in 3D microenvironments. Chinese hamster ovary (CHO) and MCF-07 breast cancer cells cultured in 40-MBR confirmed that the 40-MBR was capable of simultaneously monitoring DO and cell proliferation based on culture fluorescence and pH by measuring the absorbance of phenol red. Cytotoxicity studies of sodium butyrate on CHO cells demonstrated that 40-MBR with dynamic background fluorescence correction gave more reliable and highly reproducible growth kinetic data compared to conventional multiwells with static background correction. Furthermore, the dosage effects of two new anticancer drug candidates, 5,7-dihydroxy-2-(4-hydroxyphenyl)-8-[(E)-2-phenylethenyl]-3,4-dihydro-2H-1-benzopyran-4-one (DH-8P-DB) and 5,7-dihydroxy-2-(4-hydroxyphenyl)-6-[(E)-2-phenylethenyl]-3,4-dihydro-2H-1-benzopyran-4-one (DH-6P-DB), on HT-29 colon cancer cells were assessed using the 40-MBR, and the results indicated that DH-6P-DB would be a more potent drug in treating colon cancer than DH-8P-DB. These studies demonstrated that 40-MBR could serve as a high throughput platform for screening potential cancer drugs in early-stage drug discovery.

► We report a novel 40-microwell bioreactor (40-MBR) for cell-based high throughput screening. ► This 40-MBR allows online monitoring of pH, DO, and cell proliferation in 3D microenvironments. ► Cell responses to drugs can be assessed with highly reproducible growth kinetic data. ► This provides a high throughput screening of cytotoxicity for early-stage drug discovery.

Keywords
Cell-based high throughput screening; Cytotoxicity assay; Drug discovery; Microwell bioreactor; Proliferation
First Page Preview
Microwell bioreactor system for cell-based high throughput proliferation and cytotoxicity assays
Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 48, Issue 1, January 2013, Pages 78–88
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering