High‐Throughput Screening of Cell Transfection Enhancers Using Miniaturized Droplet Microarrays. Issue 3 (11th February 2020)

• Record Type: Journal Article
• Authors: Liu, Yanxi; Tronser, Tina; Peravali, Ravindra; Reischl, Markus; Levkin, Pavel A.
• Is Part Of: Advanced biosystems. Volume 4:Issue 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-11
• Subjects: droplet microarrays -- drugs -- high‐throughput screening -- miniaturization -- transfection; Biological systems -- Periodicals; Biotechnology -- Periodicals; Bioengineering -- Periodicals; Biomedical engineering -- Periodicals; Biological Science Disciplines; Periodicals; Periodicals; 660.6
• DOI: 10.1002/adbi.201900257
• Languages: English
• ISSNs: 2366-7478

Abstract

Abstract: DNA delivery is a powerful research tool for biological research and clinical therapies. However, many nonviral transfection reagents have relatively low transfection efficiency. It is hypothesized that by treating cells with small molecules, the transfection efficiency can be improved. However, in order to identify such transfection‐enhancing molecules, thousands of molecules must be tested. Current high‐throughput screening (HTS) technologies based on microtiter plates are not suitable for such screenings due to the prohibitively high costs of reagents and operation. Here, the use of the droplet microarray (DMA) platform to screen 774 FDA‐approved drugs with CHO‐K1, Jurkat and HEK293T cells is reported. The volume of individual aqueous compartments is 20 nL, requiring 0.84 mL of cell suspension and 200 pmoles of each drug (total 0.02 moles) to perform the screening. Thus, the requirement for cells and reagents is 2500 times less than that for the same experiment performed in 384‐well plates. The results reveal the potential of the DMA platform as a more cost‐effective and less labor‐intensive approach to HTS. Furthermore, an increase (approximately two‐ to fivefold) in transfection efficiency is achieved by treating cells with some molecules. This study clearly demonstrates the potential of the DMA platform for miniaturization of biochemical and cellular HTS. Abstract : Here, the droplet microarray platform is used to screen 774 Food and Drug Administration‐approved drugs in a total of 42 000 individual cell transfection experiments using 2500 times less reagents than in microtiter plates. The screening identifies a number of molecules that can enhance transfection efficiency several times in difficult‐to‐transfect cells.