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Integrated, Continuous Emulsion Creamer
Automated and reproducible sample handling is a key requirement for high-throughput compound screening and currently demands heavy reliance on expensive robotics in screening centers. Integrated droplet microfluidic screening processors are poised to replace robotic automation by miniaturizing bioch...
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Published in: | Analytical chemistry (Washington) 2017-12, Vol.89 (24), p.13227-13234 |
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container_title | Analytical chemistry (Washington) |
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creator | Cochrane, Wesley G Hackler, Amber L Cavett, Valerie J Price, Alexander K Paegel, Brian M |
description | Automated and reproducible sample handling is a key requirement for high-throughput compound screening and currently demands heavy reliance on expensive robotics in screening centers. Integrated droplet microfluidic screening processors are poised to replace robotic automation by miniaturizing biochemical reactions to the droplet scale. These processors must generate, incubate, and sort droplets for continuous droplet screening, passively handling millions of droplets with complete uniformity, especially during the key step of sample incubation. Here, we disclose an integrated microfluidic emulsion creamer that packs (“creams”) assay droplets by draining away excess oil through microfabricated drain channels. The drained oil coflows with creamed emulsion and then reintroduces the oil to disperse the droplets at the circuit terminus for analysis. Creamed emulsion assay incubation time dispersion was 1.7%, 3-fold less than other reported incubators. The integrated, continuous emulsion creamer (ICEcreamer) was used to miniaturize and optimize measurements of various enzymatic activities (phosphodiesterase, kinase, bacterial translation) under multiple- and single-turnover conditions. Combining the ICEcreamer with current integrated microfluidic DNA-encoded library bead processors eliminates potentially cumbersome instrumentation engineering challenges and is compatible with assays of diverse target class activities commonly investigated in drug discovery. |
doi_str_mv | 10.1021/acs.analchem.7b03070 |
format | article |
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Integrated droplet microfluidic screening processors are poised to replace robotic automation by miniaturizing biochemical reactions to the droplet scale. These processors must generate, incubate, and sort droplets for continuous droplet screening, passively handling millions of droplets with complete uniformity, especially during the key step of sample incubation. Here, we disclose an integrated microfluidic emulsion creamer that packs (“creams”) assay droplets by draining away excess oil through microfabricated drain channels. The drained oil coflows with creamed emulsion and then reintroduces the oil to disperse the droplets at the circuit terminus for analysis. Creamed emulsion assay incubation time dispersion was 1.7%, 3-fold less than other reported incubators. The integrated, continuous emulsion creamer (ICEcreamer) was used to miniaturize and optimize measurements of various enzymatic activities (phosphodiesterase, kinase, bacterial translation) under multiple- and single-turnover conditions. Combining the ICEcreamer with current integrated microfluidic DNA-encoded library bead processors eliminates potentially cumbersome instrumentation engineering challenges and is compatible with assays of diverse target class activities commonly investigated in drug discovery.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.7b03070</identifier><identifier>PMID: 29124927</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Assaying ; Automation ; Chemistry ; Coding ; Deoxyribonucleic acid ; Dispersion ; DNA ; Drainage channels ; Droplets ; Drug discovery ; Enzymatic activity ; Enzymes ; Incubation ; Incubators ; Instrumentation ; Kinases ; Microfluidics ; Miniaturization ; Oil ; Phosphodiesterase ; Processors ; Robotics ; Screening</subject><ispartof>Analytical chemistry (Washington), 2017-12, Vol.89 (24), p.13227-13234</ispartof><rights>Copyright © 2017 American Chemical Society</rights><rights>Copyright American Chemical Society Dec 19, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a514t-792ebd9799a0f023499f8d967fba0571a3c472019cb7ef69d0d06835621c78473</citedby><cites>FETCH-LOGICAL-a514t-792ebd9799a0f023499f8d967fba0571a3c472019cb7ef69d0d06835621c78473</cites><orcidid>0000-0002-6531-6693</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29124927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cochrane, Wesley G</creatorcontrib><creatorcontrib>Hackler, Amber L</creatorcontrib><creatorcontrib>Cavett, Valerie J</creatorcontrib><creatorcontrib>Price, Alexander K</creatorcontrib><creatorcontrib>Paegel, Brian M</creatorcontrib><title>Integrated, Continuous Emulsion Creamer</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. 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The integrated, continuous emulsion creamer (ICEcreamer) was used to miniaturize and optimize measurements of various enzymatic activities (phosphodiesterase, kinase, bacterial translation) under multiple- and single-turnover conditions. 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The drained oil coflows with creamed emulsion and then reintroduces the oil to disperse the droplets at the circuit terminus for analysis. Creamed emulsion assay incubation time dispersion was 1.7%, 3-fold less than other reported incubators. The integrated, continuous emulsion creamer (ICEcreamer) was used to miniaturize and optimize measurements of various enzymatic activities (phosphodiesterase, kinase, bacterial translation) under multiple- and single-turnover conditions. 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source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
subjects | Assaying Automation Chemistry Coding Deoxyribonucleic acid Dispersion DNA Drainage channels Droplets Drug discovery Enzymatic activity Enzymes Incubation Incubators Instrumentation Kinases Microfluidics Miniaturization Oil Phosphodiesterase Processors Robotics Screening |
title | Integrated, Continuous Emulsion Creamer |
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