Rapid switching and durable on-chip spark-cavitation-bubble cell sorter

Abstract Precise and high-speed sorting of individual target cells from heterogeneous populations plays an imperative role in cell research. Although the conventional fluorescence-activated cell sorter (FACS) is capable of rapid and accurate cell sorting, it occupies a large volume of the instrument...

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Main Authors: Zeheng Jiao, Yong Han, Jingjing Zhao, Zixi Chao, Attila Tárnok, Zheng You
Format: Article
Language:English
Published: Nature Publishing Group 2022-05-01
Series:Microsystems & Nanoengineering
Online Access:https://doi.org/10.1038/s41378-022-00382-2
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author Zeheng Jiao
Yong Han
Jingjing Zhao
Zixi Chao
Attila Tárnok
Zheng You
author_facet Zeheng Jiao
Yong Han
Jingjing Zhao
Zixi Chao
Attila Tárnok
Zheng You
author_sort Zeheng Jiao
collection DOAJ
description Abstract Precise and high-speed sorting of individual target cells from heterogeneous populations plays an imperative role in cell research. Although the conventional fluorescence-activated cell sorter (FACS) is capable of rapid and accurate cell sorting, it occupies a large volume of the instrument and inherently brings in aerosol generation as well as cross-contamination among samples. The sorting completed in a fully enclosed and disposable microfluidic chip has the potential to eliminate the above concerns. However, current microfluidic cell sorters are hindered by the high complexities of the fabrication procedure and the off-chip setup. In this paper, a spark-cavitation-bubble-based fluorescence-activated cell sorter is developed to perform fast and accurate sorting in a microfluidic chip. It features a simple structure and an easy operation. This microfluidic sorter comprises a positive electrode of platinum and a negative electrode of tungsten, which are placed on the side of the main channel. By applying a high-voltage discharge on the pair of electrodes, a single spark cavitation bubble is created to deflect the target particle into the downstream collection channel. The sorter has a short switching time of 150 μs and a long lifespan of more than 100 million workable actions. In addition, a novel control strategy is proposed to dynamically adjust the discharge time to stabilize the size of the cavitation bubble for continuous sorting. The dynamic control of continuously triggering the sorter, the optimal delay time between fluorescence detection and cell sorting, and a theoretical model to predict the ideal sorting recovery and purity are studied to improve and evaluate the sorter performance. The experiments demonstrate that the sorting rate of target particles achieves 1200 eps, the total analysis throughput is up to 10,000 eps, the particles sorted at 4000 eps exhibit a purity greater than 80% and a recovery rate greater than 90%, and the sorting effect on the viability of HeLa cells is negligible.
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spelling doaj.art-b0e1bd46d81944248a5472ba96d5aa5f2022-12-22T02:34:22ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342022-05-018111010.1038/s41378-022-00382-2Rapid switching and durable on-chip spark-cavitation-bubble cell sorterZeheng Jiao0Yong Han1Jingjing Zhao2Zixi Chao3Attila Tárnok4Zheng You5State Key Laboratory of Precision Measurement Technology and Instrument, Tsinghua UniversityState Key Laboratory of Precision Measurement Technology and Instrument, Tsinghua UniversityDepartment of Structural Biology, Stanford University, School of MedicineState Key Laboratory of Precision Measurement Technology and Instrument, Tsinghua UniversityDepartment of Precision Instrument, Tsinghua UniversityState Key Laboratory of Precision Measurement Technology and Instrument, Tsinghua UniversityAbstract Precise and high-speed sorting of individual target cells from heterogeneous populations plays an imperative role in cell research. Although the conventional fluorescence-activated cell sorter (FACS) is capable of rapid and accurate cell sorting, it occupies a large volume of the instrument and inherently brings in aerosol generation as well as cross-contamination among samples. The sorting completed in a fully enclosed and disposable microfluidic chip has the potential to eliminate the above concerns. However, current microfluidic cell sorters are hindered by the high complexities of the fabrication procedure and the off-chip setup. In this paper, a spark-cavitation-bubble-based fluorescence-activated cell sorter is developed to perform fast and accurate sorting in a microfluidic chip. It features a simple structure and an easy operation. This microfluidic sorter comprises a positive electrode of platinum and a negative electrode of tungsten, which are placed on the side of the main channel. By applying a high-voltage discharge on the pair of electrodes, a single spark cavitation bubble is created to deflect the target particle into the downstream collection channel. The sorter has a short switching time of 150 μs and a long lifespan of more than 100 million workable actions. In addition, a novel control strategy is proposed to dynamically adjust the discharge time to stabilize the size of the cavitation bubble for continuous sorting. The dynamic control of continuously triggering the sorter, the optimal delay time between fluorescence detection and cell sorting, and a theoretical model to predict the ideal sorting recovery and purity are studied to improve and evaluate the sorter performance. The experiments demonstrate that the sorting rate of target particles achieves 1200 eps, the total analysis throughput is up to 10,000 eps, the particles sorted at 4000 eps exhibit a purity greater than 80% and a recovery rate greater than 90%, and the sorting effect on the viability of HeLa cells is negligible.https://doi.org/10.1038/s41378-022-00382-2
spellingShingle Zeheng Jiao
Yong Han
Jingjing Zhao
Zixi Chao
Attila Tárnok
Zheng You
Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
Microsystems & Nanoengineering
title Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
title_full Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
title_fullStr Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
title_full_unstemmed Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
title_short Rapid switching and durable on-chip spark-cavitation-bubble cell sorter
title_sort rapid switching and durable on chip spark cavitation bubble cell sorter
url https://doi.org/10.1038/s41378-022-00382-2
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AT zixichao rapidswitchinganddurableonchipsparkcavitationbubblecellsorter
AT attilatarnok rapidswitchinganddurableonchipsparkcavitationbubblecellsorter
AT zhengyou rapidswitchinganddurableonchipsparkcavitationbubblecellsorter