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Mass Activated Droplet Sorting (MADS) Enables High‐Throughput Screening of Enzymatic Reactions at Nanoliter Scale
Author(s) -
HollandMoritz Daniel A.,
Wismer Michael K.,
Mann Benjamin F.,
Farasat Iman,
Devine Paul,
Guetschow Erik D.,
Mangion Ian,
Welch Christopher J.,
Moore Jeffrey C.,
Sun Shuwen,
Kennedy Robert T.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201913203
Subject(s) - sorting , microfluidics , throughput , sort , mass spectrometry , microreactor , computer science , chemistry , high throughput screening , nanotechnology , biological system , chromatography , materials science , biochemistry , biology , algorithm , information retrieval , catalysis , telecommunications , wireless
Microfluidic droplet sorting enables the high‐throughput screening and selection of water‐in‐oil microreactors at speeds and volumes unparalleled by traditional well‐plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for high‐throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESI‐MS). Droplets are split, one portion is analyzed by ESI‐MS, and the second portion is sorted based on the MS result. Throughput of 0.7 samples s −1 is achieved with 98 % accuracy using a self‐correcting and adaptive sorting algorithm. We use the system to screen ≈15 000 samples in 6 h and demonstrate its utility by sorting 25 nL droplets containing transaminase expressed in vitro. Label‐free ESI‐MS droplet screening expands the toolbox for droplet detection and recovery, improving the applicability of droplet sorting to protein engineering, drug discovery, and diagnostic workflows.