Cancer drug screening with an on-chip multi-drug dispenser in digital microfluidics. Issue 24 (11th November 2021)

• Record Type: Journal Article
• Authors: Zhai, Jiao; Li, Caiwei; Li, Haoran; Yi, Shuhong; Yang, Ning; Miao, Kai; Deng, Chuxia; Jia, Yanwei; Mak, Pui-In; Martins, Rui P.
• Is Part Of: Lab on a chip. Volume 21:Issue 24(2021)
• Page Start: 4749
• Page End: 4759
• Publication Date: 2021-11-11
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d1lc00895a
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : A digital microfluidic system with an innovative control structure and chip design to generate concentrations that span three to four orders of magnitude for single or multi-drug dispensing was developed. Abstract : Microfluidics has been the most promising platform for drug screening with a limited number of cells. However, convenient on-chip preparation of a wide range of drug concentrations remains a large challenge and has restricted wide acceptance of microfluidics in precision medicine. In this paper, we report a digital microfluidic system with an innovative control structure and chip design for on-chip drug dispensing to generate concentrations that span three to four orders of magnitude, enabling single drug or combinatorial multi-drug screening with simple electronic control. Specifically, we utilize droplet ejection from a drug drop sitting on a special electrode, named a drug dispenser, under high-voltage pulse actuation to deliver the desired amount of drugs to be picked up by a cell suspension drop driven by low-voltage sine wave actuation. Our proof-of-principle validation for this technique as a convenient single and multi-drug screening involved testing of the drug toxicity of two chemotherapeutics, cisplatin (Cis) and epirubicin (EP), towards MDA-MB-231 breast cancer cells and MCF-10A normal breast cells. The results are consistent with those screened based on traditional 96-well plates. These findings demonstrate the reliability of the drug screening system with an on-chip drug dispenser. This system with fewer cancer cells, less drug consumption, a small footprint, and high scalability with regard to concentration could pave the way for drug screening on biopsied primary tumor cells for precision medicine or any concentration-related research.