An Automated Single-Cell Droplet-Digital Microfluidic Platform for Monoclonal Antibody Discovery

被引:5
作者
Ahmadi, Fatemeh [1 ,2 ]
Tran, Hao [1 ]
Letourneau, Natasha [3 ]
Little, Samuel R. [1 ,2 ]
Fortin, Annie [4 ]
Moraitis, Anna N. [4 ]
Shih, Steve C. C. [1 ,2 ,3 ]
机构
[1] Concordia Univ, Dept Elect & Comp Engn, 1455 Maisonneuve Blvd West, Montreal, PQ H3G 1M8, Canada
[2] Concordia Univ, Ctr Appl Synthet Biol, 7141 Sherbrooke St West, Montreal, PQ H4B 1R6, Canada
[3] Concordia Univ, Dept Biol, 7141 Sherbrooke St West, Montreal, PQ H4B 1R6, Canada
[4] Natl Res Council Canada, Human Hlth Therapeut Res Ctr, Montreal, PQ H4P 2R2, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
antibody discovery; deterministic co-encapsulation; droplet-based microfluidics; droplet operations; CHIP; MANIPULATION; ARRAY; SELECTION; MICROPARTICLES; ENCAPSULATION; EXCHANGE; RELEASE; SYSTEM;
D O I
10.1002/smll.202308950
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Monoclonal antibody (mAb) discovery plays a prominent role in diagnostic and therapeutic applications. Droplet microfluidics has become a standard technology for high-throughput screening of antibody-producing cells due to high droplet single-cell confinement frequency and rapid analysis and sorting of the cells of interest with their secreted mAbs. In this work, a new method is described for on-demand co-encapsulation of cells that eliminates the difficulties associated with washing in between consecutive steps inside the droplets and enables the washing and addition of fresh media. The new platform identifies hybridoma cells that are expressing antibodies of interest using antibody-characterization assays to find the best-performing or rare-cell antibody candidates. A new microfluidic method for antibody screening that allows for deterministic encapsulation of two cells and for frequent washes with minimal losses in the droplet. This new method is powered by droplet-digital microfluidics, which combines droplet-in-flow techniques with digital microfluidic for the generation and the manipulation of droplets. image
引用
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页数:13
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