Oil-mediated high-throughput generation and sorting of water-in-water droplets

Lang Nan; Yang Cao; Shuai Yuan; Ho Cheung Shum

doi:10.1038/s41378-020-0180-0

Oil-mediated high-throughput generation and sorting of water-in-water droplets

Lang Nan
, Yang Cao
, Shuai Yuan
, Ho Cheung Shum^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

37 Citations (Scopus)

18 Downloads (CityUHK Scholars)

Abstract

Aqueous two-phase system (ATPS) droplets have demonstrated superior compatibility over conventional water-in-oil droplets for various biological assays. However, the ultralow interfacial tension hampers efficient and stable droplet generation, limiting further development and more extensive use of such approaches. Here, we present a simple strategy to employ oil as a transient medium for ATPS droplet generation. Two methods based on passive flow focusing and active pico-injection are demonstrated to generate water-water-oil double emulsions, achieving a high generation frequency of ~2.4 kHz. Through evaporation of the oil to break the double emulsions, the aqueous core can be released to form uniform-sized water-in-water droplets. Moreover, this technique can be used to fabricate aqueous microgels, and the introduction of the oil medium enables integration of droplet sorting to produce single-cell-laden hydrogels with a harvest rate of over 90%. We believe that the demonstrated high-throughput generation and sorting of ATPS droplets represent an important tool to advance droplet-based tissue engineering and single-cell analyses. © 2020, The Author(s).

Original language	English
Article number	70
Journal	Microsystems and Nanoengineering
Volume	6
Issue number	1
Online published	7 Sept 2020
DOIs	https://doi.org/10.1038/s41378-020-0180-0
Publication status	Published - 2020
Externally published	Yes

Bibliographical note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Funding

This work was supported by the General Research Fund (Nos. 17307919, 17329516, 17304017, 17305518, and 17306315) and the Research Impact Fund (No. R7072-18) from the Research Grants Council of Hong Kong, Excellent Young Scientists Fund (Hong Kong and Macau) (21922816) from the National Natural Science Foundation of China (NSFC) as well as the Seed Fund for Basic Research (Nos. 201811149241, 201711159249, and 201611159205), the Seed Fund for Translational and Applied Research (No. 201711160016) and Platform Technology Funding from the University of Hong Kong. We thank Prof. Maria Li Lung from HKU’s Department of Clinical Oncology for providing the KYSE-150 cell samples, Ph.D. candidate Yage Zhang for the assistance in cell culture, and Dr. Youchuang Chao for the discussion of ATPS solution preparation.

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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title = "Oil-mediated high-throughput generation and sorting of water-in-water droplets",

abstract = "Aqueous two-phase system (ATPS) droplets have demonstrated superior compatibility over conventional water-in-oil droplets for various biological assays. However, the ultralow interfacial tension hampers efficient and stable droplet generation, limiting further development and more extensive use of such approaches. Here, we present a simple strategy to employ oil as a transient medium for ATPS droplet generation. Two methods based on passive flow focusing and active pico-injection are demonstrated to generate water-water-oil double emulsions, achieving a high generation frequency of \textasciitilde{}2.4 kHz. Through evaporation of the oil to break the double emulsions, the aqueous core can be released to form uniform-sized water-in-water droplets. Moreover, this technique can be used to fabricate aqueous microgels, and the introduction of the oil medium enables integration of droplet sorting to produce single-cell-laden hydrogels with a harvest rate of over 90\%. We believe that the demonstrated high-throughput generation and sorting of ATPS droplets represent an important tool to advance droplet-based tissue engineering and single-cell analyses. {\textcopyright} 2020, The Author(s).",

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AU - Nan, Lang

AU - Cao, Yang

AU - Yuan, Shuai

AU - Shum, Ho Cheung

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PY - 2020

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N2 - Aqueous two-phase system (ATPS) droplets have demonstrated superior compatibility over conventional water-in-oil droplets for various biological assays. However, the ultralow interfacial tension hampers efficient and stable droplet generation, limiting further development and more extensive use of such approaches. Here, we present a simple strategy to employ oil as a transient medium for ATPS droplet generation. Two methods based on passive flow focusing and active pico-injection are demonstrated to generate water-water-oil double emulsions, achieving a high generation frequency of ~2.4 kHz. Through evaporation of the oil to break the double emulsions, the aqueous core can be released to form uniform-sized water-in-water droplets. Moreover, this technique can be used to fabricate aqueous microgels, and the introduction of the oil medium enables integration of droplet sorting to produce single-cell-laden hydrogels with a harvest rate of over 90%. We believe that the demonstrated high-throughput generation and sorting of ATPS droplets represent an important tool to advance droplet-based tissue engineering and single-cell analyses. © 2020, The Author(s).

AB - Aqueous two-phase system (ATPS) droplets have demonstrated superior compatibility over conventional water-in-oil droplets for various biological assays. However, the ultralow interfacial tension hampers efficient and stable droplet generation, limiting further development and more extensive use of such approaches. Here, we present a simple strategy to employ oil as a transient medium for ATPS droplet generation. Two methods based on passive flow focusing and active pico-injection are demonstrated to generate water-water-oil double emulsions, achieving a high generation frequency of ~2.4 kHz. Through evaporation of the oil to break the double emulsions, the aqueous core can be released to form uniform-sized water-in-water droplets. Moreover, this technique can be used to fabricate aqueous microgels, and the introduction of the oil medium enables integration of droplet sorting to produce single-cell-laden hydrogels with a harvest rate of over 90%. We believe that the demonstrated high-throughput generation and sorting of ATPS droplets represent an important tool to advance droplet-based tissue engineering and single-cell analyses. © 2020, The Author(s).

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DO - 10.1038/s41378-020-0180-0

M3 - RGC 21 - Publication in refereed journal

C2 - 34567680

SN - 2055-7434

VL - 6

JO - Microsystems and Nanoengineering

JF - Microsystems and Nanoengineering

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Oil-mediated high-throughput generation and sorting of water-in-water droplets

Abstract

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