Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities

Byunghoon Kang; Seungmin Han; Hye Young Son; Byeonggeol Mun; Moo Kwang Shin; Yuna Choi; Jongjin Park; Jeong Ki Min; Daewon Park; Eun Kyung Lim; Yong Min Huh; Seungjoo Haam

doi:10.1016/j.bios.2021.113576

Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities

Byunghoon Kang, Seungmin Han, Hye Young Son, Byeonggeol Mun, Moo Kwang Shin, Yuna Choi, Jongjin Park, Jeong Ki Min, Daewon Park, Eun Kyung Lim, Yong Min Huh, Seungjoo Haam

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 10⁷ cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.

Original language	English
Article number	113576
Journal	Biosensors and Bioelectronics
Volume	194
DOIs	https://doi.org/10.1016/j.bios.2021.113576
Publication status	Published - 2021 Dec 15

Bibliographical note

Funding Information:
This research was supported by National R&D Programs through National Research Foundation (NRF) of Korea funded by Ministry of Science and ICT (MSIT) of Korea ( NRF-2017M3A9G5083322 , NRF-2018M3A9E2022819 , NRF-2018M3A9E2022821 , and NRF-2021M3E5E3080379 ), Global Frontier Program through Center for BioNano Health-Guard funded by MSIT of Korea ( HGUARD_2014M3A6B2060507 ), the Nano Material Technology Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017M3A7B4041798 ), Technology Development Program for Biological Hazards Management in Indoor Air through Korea Environment Industry & Technology Institute (KEITI) funded by Ministry of Environment (ME) of Korea ( 2021003370003 ), Industrial Technology Alchemist Program of the Ministry of Trade, Industry, and Energy (MOTIE) of Korea ( 20012435 ) and KRIBB Research Initiative Program ( 1711134038 and 1711134081 ).

Publisher Copyright:
© 2021

All Science Journal Classification (ASJC) codes

Biotechnology
Biophysics
Biomedical Engineering
Electrochemistry

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10.1016/j.bios.2021.113576

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Kang, B., Han, S., Son, H. Y., Mun, B., Shin, M. K., Choi, Y., Park, J., Min, J. K., Park, D., Lim, E. K., Huh, Y. M., & Haam, S. (2021). Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities. Biosensors and Bioelectronics, 194, [113576]. https://doi.org/10.1016/j.bios.2021.113576

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title = "Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities",

abstract = "Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 107 cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.",

author = "Byunghoon Kang and Seungmin Han and Son, {Hye Young} and Byeonggeol Mun and Shin, {Moo Kwang} and Yuna Choi and Jongjin Park and Min, {Jeong Ki} and Daewon Park and Lim, {Eun Kyung} and Huh, {Yong Min} and Seungjoo Haam",

note = "Funding Information: This research was supported by National R&D Programs through National Research Foundation (NRF) of Korea funded by Ministry of Science and ICT (MSIT) of Korea ( NRF-2017M3A9G5083322 , NRF-2018M3A9E2022819 , NRF-2018M3A9E2022821 , and NRF-2021M3E5E3080379 ), Global Frontier Program through Center for BioNano Health-Guard funded by MSIT of Korea ( HGUARD_2014M3A6B2060507 ), the Nano Material Technology Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017M3A7B4041798 ), Technology Development Program for Biological Hazards Management in Indoor Air through Korea Environment Industry & Technology Institute (KEITI) funded by Ministry of Environment (ME) of Korea ( 2021003370003 ), Industrial Technology Alchemist Program of the Ministry of Trade, Industry, and Energy (MOTIE) of Korea ( 20012435 ) and KRIBB Research Initiative Program ( 1711134038 and 1711134081 ). Publisher Copyright: {\textcopyright} 2021",

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doi = "10.1016/j.bios.2021.113576",

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T1 - Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities

AU - Kang, Byunghoon

AU - Han, Seungmin

AU - Son, Hye Young

AU - Mun, Byeonggeol

AU - Shin, Moo Kwang

AU - Choi, Yuna

AU - Park, Jongjin

AU - Min, Jeong Ki

AU - Park, Daewon

AU - Lim, Eun Kyung

AU - Huh, Yong Min

AU - Haam, Seungjoo

N1 - Funding Information: This research was supported by National R&D Programs through National Research Foundation (NRF) of Korea funded by Ministry of Science and ICT (MSIT) of Korea ( NRF-2017M3A9G5083322 , NRF-2018M3A9E2022819 , NRF-2018M3A9E2022821 , and NRF-2021M3E5E3080379 ), Global Frontier Program through Center for BioNano Health-Guard funded by MSIT of Korea ( HGUARD_2014M3A6B2060507 ), the Nano Material Technology Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017M3A7B4041798 ), Technology Development Program for Biological Hazards Management in Indoor Air through Korea Environment Industry & Technology Institute (KEITI) funded by Ministry of Environment (ME) of Korea ( 2021003370003 ), Industrial Technology Alchemist Program of the Ministry of Trade, Industry, and Energy (MOTIE) of Korea ( 20012435 ) and KRIBB Research Initiative Program ( 1711134038 and 1711134081 ). Publisher Copyright: © 2021

PY - 2021/12/15

Y1 - 2021/12/15

N2 - Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 107 cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.

AB - Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 107 cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.

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Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities

Abstract

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