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Microfluidic SlipChip device for multistep multiplexed biochemistry on a nanoliter scale

Zhukov, Dmitriy V. and Khorosheva, Eugenia M. and Khazaei, Tahmineh and Du, Wenbin and Selck, David A. and Shishkin, Alexander A. and Ismagilov, Rustem F. (2019) Microfluidic SlipChip device for multistep multiplexed biochemistry on a nanoliter scale. Lab on a Chip, 19 (19). pp. 3200-3211. ISSN 1473-0197.

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We have developed a multistep microfluidic device that expands the current SlipChip capabilities by enabling multiple steps of droplet merging and multiplexing. Harnessing the interfacial energy between carrier and sample phases, this manually operated device accurately meters nanoliter volumes of reagents and transfers them into on-device reaction wells. Judiciously shaped microfeatures and surface-energy traps merge droplets in a parallel fashion. Wells can be tuned for different volumetric capacities and reagent types, including for pre-spotted reagents that allow for unique identification of original well contents even after their contents are pooled. We demonstrate the functionality of the multistep SlipChip by performing RNA transcript barcoding on-device for synthetic spiked-in standards and for biologically derived samples. This technology is a good candidate for a wide range of biological applications that require multiplexing of multistep reactions in nanoliter volumes, including single-cell analyses.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Zhukov, Dmitriy V.0000-0002-4834-3147
Khorosheva, Eugenia M.0000-0003-3620-4884
Khazaei, Tahmineh0000-0002-4743-2383
Du, Wenbin0000-0002-7401-1410
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:© 2019 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. The article was received on 06 Jun 2019, accepted on 29 Jul 2019 and first published on 23 Aug 2019. Data availability: Any data not in the ESI will be made available upon request to the corresponding author. Conflicts of interest: This paper is the subject of a patent application filed by Caltech. R. F. I. has a financial interest in Talis Biomedical Corp. This research was supported in part by a seed grant from the Donna & Benjamin M. Rosen Bioengineering Center (Caltech), an NSF Graduate Research Fellowship [DGE-1144469] to D. V. Z., a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship [PGSD3-438474-2013] to T. K., an NIH Director's Pioneer Award [DP50D012190], an Achievement Rewards for College Scientists (ARCS) fellowship to D. A. S., and an NIH NRSA [5T32GM07616NSF] to D. A. S. We thank Andres Collazo at Caltech's Beckman Institute Biological Imaging Facility for imaging advice, and Igor Antoshechkin at Caltech's Millard and Muriel Jacobs Genetics and Genomics Laboratory for cDNA library sequencing. We also thank Mitchell Guttman for advice on total transcriptome sequencing, Mario Blanco and Jacob Barlow for helpful consultations on sequencing data processing, Erik B. Jue for helpful advice on 3D rendering of devices in CAD, and Natasha Shelby for contributions to writing and editing this manuscript.
Group:Rosen Bioengineering Center
Funding AgencyGrant Number
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NSF Graduate Research FellowshipDGE-1144469
Natural Sciences and Engineering Research Council of Canada (NSERC)PGSD3-438474-2013
NIH Predoctoral Fellowship5T32GM07616NSF
Issue or Number:19
Record Number:CaltechAUTHORS:20190823-090755927
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98147
Deposited By: Tony Diaz
Deposited On:23 Aug 2019 16:24
Last Modified:03 Mar 2020 19:00

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