Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells
The separation of peripheral blood mononuclear cells (PBMCs) into constituent blood cell types is a vital step to obtain immune cells for autologous cell therapies. The ability to separate PBMCs using label-free microfluidic techniques, based on differences in biomechanical properties, can have a nu...
Gespeichert in:
Veröffentlicht in: | Biomicrofluidics 2023-09, Vol.17 (5), p.054102 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 5 |
container_start_page | 054102 |
container_title | Biomicrofluidics |
container_volume | 17 |
creator | Raj, Abhishek Ramirez, Katily Young, Katherine M. Stone, Nicholas Shankles, Peter Ali, Mehdia Nadeem Rajab Compton, Anthony Malik Lam, Wilbur Alexeev, Alexander Sulchek, Todd |
description | The separation of peripheral blood mononuclear cells (PBMCs) into constituent blood cell types is a vital step to obtain immune cells for autologous cell therapies. The ability to separate PBMCs using label-free microfluidic techniques, based on differences in biomechanical properties, can have a number of benefits over other conventional techniques, including lower cost, ease of use, and avoidance of animal-derived labeling antibodies. Here, we report a microfluidic device that uses compressive diagonal ridges to separate PBMCs into highly pure samples of viable and functional lymphocytes. The technique utilizes the differences in the biophysical properties of PBMC sub-populations to direct the lymphocytes and monocytes into separate outlets. The biophysical properties of the monocytes and lymphocytes from healthy donors were first characterized using atomic force microscopy. Lymphocytes were found to be significantly stiffer than monocytes, with a mean cell stiffness of 1495 and 931 Pa, respectively. The differences in biophysical properties resulted in distinct trajectories through the microchannel terminating at different outlets, resulting in a lymphocyte sample with purity and viability both greater than 96% with no effect on the cells’ ability to produce interferon gamma, a cytokine crucial for innate and adaptive immunity. |
doi_str_mv | 10.1063/5.0161047 |
format | Article |
fullrecord | <record><control><sourceid>proquest_scita</sourceid><recordid>TN_cdi_proquest_miscellaneous_2868119499</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2868119499</sourcerecordid><originalsourceid>FETCH-LOGICAL-c404t-44f02a0cc6eab331854ec12b7a70ed9dda2eb6a2729694319dd451f97946268c3</originalsourceid><addsrcrecordid>eNp9kc1rFTEUxQex2Fpd-A9IwI0KU_M9k1WR4kfhQTe6DpnMjS8lk4zJTOH99-b1PUt10dW93Pw4nJzTNG8IviBYsk_iAhNJMO-eNWdEMdoSLPrnj_bT5mUptxgL0lH6ojllXcckJuqsiRszQGhdBkCTtzm5sPrRW-RLCmbxKaLkkFuj3e8mIBNHdOfNEACF3TRvk90tUJDLaUIzZD9vIVdsCCmNaEoxxdUGMBlZCKG8ak6cCQVeH-d58_Prlx9X39vNzbfrq8-b1nLMl5Zzh6nB1kowA2OkFxwsoUNnOgyjGkdDYZCGdlRJxRmpFy6IU53iksresvPm8qA7r8MEo4W4VFd6zn4yeaeT8frfl-i3-le60zUtQqhQVeH9USGn3yuURU--7P9gIqS1aNrLnhDF1R599x96m9Zcw7qnJBGCUVqpDweqhlxKBvfghmC9r1ELfayxsm8f238g__ZWgY8HoFi_3Nf0hNof1Namxg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2866155322</pqid></control><display><type>article</type><title>Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells</title><source>AIP Journals Complete</source><source>PubMed Central</source><creator>Raj, Abhishek ; Ramirez, Katily ; Young, Katherine M. ; Stone, Nicholas ; Shankles, Peter ; Ali, Mehdia Nadeem Rajab ; Compton, Anthony Malik ; Lam, Wilbur ; Alexeev, Alexander ; Sulchek, Todd</creator><creatorcontrib>Raj, Abhishek ; Ramirez, Katily ; Young, Katherine M. ; Stone, Nicholas ; Shankles, Peter ; Ali, Mehdia Nadeem Rajab ; Compton, Anthony Malik ; Lam, Wilbur ; Alexeev, Alexander ; Sulchek, Todd</creatorcontrib><description>The separation of peripheral blood mononuclear cells (PBMCs) into constituent blood cell types is a vital step to obtain immune cells for autologous cell therapies. The ability to separate PBMCs using label-free microfluidic techniques, based on differences in biomechanical properties, can have a number of benefits over other conventional techniques, including lower cost, ease of use, and avoidance of animal-derived labeling antibodies. Here, we report a microfluidic device that uses compressive diagonal ridges to separate PBMCs into highly pure samples of viable and functional lymphocytes. The technique utilizes the differences in the biophysical properties of PBMC sub-populations to direct the lymphocytes and monocytes into separate outlets. The biophysical properties of the monocytes and lymphocytes from healthy donors were first characterized using atomic force microscopy. Lymphocytes were found to be significantly stiffer than monocytes, with a mean cell stiffness of 1495 and 931 Pa, respectively. The differences in biophysical properties resulted in distinct trajectories through the microchannel terminating at different outlets, resulting in a lymphocyte sample with purity and viability both greater than 96% with no effect on the cells’ ability to produce interferon gamma, a cytokine crucial for innate and adaptive immunity.</description><identifier>ISSN: 1932-1058</identifier><identifier>EISSN: 1932-1058</identifier><identifier>DOI: 10.1063/5.0161047</identifier><identifier>PMID: 37736019</identifier><identifier>CODEN: BIOMGB</identifier><language>eng</language><publisher>United States: American Institute of Physics</publisher><subject>Antibodies ; Biomechanics ; Blood ; Blood cells ; Immune system ; Labels ; Lymphocytes ; Microchannels ; Microfluidic devices ; Regular</subject><ispartof>Biomicrofluidics, 2023-09, Vol.17 (5), p.054102</ispartof><rights>Author(s)</rights><rights>2023 Author(s).</rights><rights>2023 Author(s). Published under an exclusive license by AIP Publishing.</rights><rights>2023 Author(s). 2023 Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-44f02a0cc6eab331854ec12b7a70ed9dda2eb6a2729694319dd451f97946268c3</citedby><cites>FETCH-LOGICAL-c404t-44f02a0cc6eab331854ec12b7a70ed9dda2eb6a2729694319dd451f97946268c3</cites><orcidid>0000-0003-4196-6293 ; 0000-0002-4677-6440 ; 0000-0001-6567-3335 ; 0000-0001-5276-3219 ; 0000-0002-8692-8779 ; 0009-0003-6251-6280 ; 0000-0002-8285-0003 ; 0000-0002-0325-7990 ; 0000-0002-2779-8345 ; 0009-0009-3374-5475</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511259/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://pubs.aip.org/bmf/article-lookup/doi/10.1063/5.0161047$$EHTML$$P50$$Gscitation$$H</linktohtml><link.rule.ids>230,314,723,776,780,790,881,4498,27901,27902,53766,53768,76126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37736019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raj, Abhishek</creatorcontrib><creatorcontrib>Ramirez, Katily</creatorcontrib><creatorcontrib>Young, Katherine M.</creatorcontrib><creatorcontrib>Stone, Nicholas</creatorcontrib><creatorcontrib>Shankles, Peter</creatorcontrib><creatorcontrib>Ali, Mehdia Nadeem Rajab</creatorcontrib><creatorcontrib>Compton, Anthony Malik</creatorcontrib><creatorcontrib>Lam, Wilbur</creatorcontrib><creatorcontrib>Alexeev, Alexander</creatorcontrib><creatorcontrib>Sulchek, Todd</creatorcontrib><title>Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells</title><title>Biomicrofluidics</title><addtitle>Biomicrofluidics</addtitle><description>The separation of peripheral blood mononuclear cells (PBMCs) into constituent blood cell types is a vital step to obtain immune cells for autologous cell therapies. The ability to separate PBMCs using label-free microfluidic techniques, based on differences in biomechanical properties, can have a number of benefits over other conventional techniques, including lower cost, ease of use, and avoidance of animal-derived labeling antibodies. Here, we report a microfluidic device that uses compressive diagonal ridges to separate PBMCs into highly pure samples of viable and functional lymphocytes. The technique utilizes the differences in the biophysical properties of PBMC sub-populations to direct the lymphocytes and monocytes into separate outlets. The biophysical properties of the monocytes and lymphocytes from healthy donors were first characterized using atomic force microscopy. Lymphocytes were found to be significantly stiffer than monocytes, with a mean cell stiffness of 1495 and 931 Pa, respectively. The differences in biophysical properties resulted in distinct trajectories through the microchannel terminating at different outlets, resulting in a lymphocyte sample with purity and viability both greater than 96% with no effect on the cells’ ability to produce interferon gamma, a cytokine crucial for innate and adaptive immunity.</description><subject>Antibodies</subject><subject>Biomechanics</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Immune system</subject><subject>Labels</subject><subject>Lymphocytes</subject><subject>Microchannels</subject><subject>Microfluidic devices</subject><subject>Regular</subject><issn>1932-1058</issn><issn>1932-1058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kc1rFTEUxQex2Fpd-A9IwI0KU_M9k1WR4kfhQTe6DpnMjS8lk4zJTOH99-b1PUt10dW93Pw4nJzTNG8IviBYsk_iAhNJMO-eNWdEMdoSLPrnj_bT5mUptxgL0lH6ojllXcckJuqsiRszQGhdBkCTtzm5sPrRW-RLCmbxKaLkkFuj3e8mIBNHdOfNEACF3TRvk90tUJDLaUIzZD9vIVdsCCmNaEoxxdUGMBlZCKG8ak6cCQVeH-d58_Prlx9X39vNzbfrq8-b1nLMl5Zzh6nB1kowA2OkFxwsoUNnOgyjGkdDYZCGdlRJxRmpFy6IU53iksresvPm8qA7r8MEo4W4VFd6zn4yeaeT8frfl-i3-le60zUtQqhQVeH9USGn3yuURU--7P9gIqS1aNrLnhDF1R599x96m9Zcw7qnJBGCUVqpDweqhlxKBvfghmC9r1ELfayxsm8f238g__ZWgY8HoFi_3Nf0hNof1Namxg</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>Raj, Abhishek</creator><creator>Ramirez, Katily</creator><creator>Young, Katherine M.</creator><creator>Stone, Nicholas</creator><creator>Shankles, Peter</creator><creator>Ali, Mehdia Nadeem Rajab</creator><creator>Compton, Anthony Malik</creator><creator>Lam, Wilbur</creator><creator>Alexeev, Alexander</creator><creator>Sulchek, Todd</creator><general>American Institute of Physics</general><general>AIP Publishing LLC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>H8D</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4196-6293</orcidid><orcidid>https://orcid.org/0000-0002-4677-6440</orcidid><orcidid>https://orcid.org/0000-0001-6567-3335</orcidid><orcidid>https://orcid.org/0000-0001-5276-3219</orcidid><orcidid>https://orcid.org/0000-0002-8692-8779</orcidid><orcidid>https://orcid.org/0009-0003-6251-6280</orcidid><orcidid>https://orcid.org/0000-0002-8285-0003</orcidid><orcidid>https://orcid.org/0000-0002-0325-7990</orcidid><orcidid>https://orcid.org/0000-0002-2779-8345</orcidid><orcidid>https://orcid.org/0009-0009-3374-5475</orcidid></search><sort><creationdate>20230901</creationdate><title>Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells</title><author>Raj, Abhishek ; Ramirez, Katily ; Young, Katherine M. ; Stone, Nicholas ; Shankles, Peter ; Ali, Mehdia Nadeem Rajab ; Compton, Anthony Malik ; Lam, Wilbur ; Alexeev, Alexander ; Sulchek, Todd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-44f02a0cc6eab331854ec12b7a70ed9dda2eb6a2729694319dd451f97946268c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antibodies</topic><topic>Biomechanics</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Immune system</topic><topic>Labels</topic><topic>Lymphocytes</topic><topic>Microchannels</topic><topic>Microfluidic devices</topic><topic>Regular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raj, Abhishek</creatorcontrib><creatorcontrib>Ramirez, Katily</creatorcontrib><creatorcontrib>Young, Katherine M.</creatorcontrib><creatorcontrib>Stone, Nicholas</creatorcontrib><creatorcontrib>Shankles, Peter</creatorcontrib><creatorcontrib>Ali, Mehdia Nadeem Rajab</creatorcontrib><creatorcontrib>Compton, Anthony Malik</creatorcontrib><creatorcontrib>Lam, Wilbur</creatorcontrib><creatorcontrib>Alexeev, Alexander</creatorcontrib><creatorcontrib>Sulchek, Todd</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Aerospace Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomicrofluidics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raj, Abhishek</au><au>Ramirez, Katily</au><au>Young, Katherine M.</au><au>Stone, Nicholas</au><au>Shankles, Peter</au><au>Ali, Mehdia Nadeem Rajab</au><au>Compton, Anthony Malik</au><au>Lam, Wilbur</au><au>Alexeev, Alexander</au><au>Sulchek, Todd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells</atitle><jtitle>Biomicrofluidics</jtitle><addtitle>Biomicrofluidics</addtitle><date>2023-09-01</date><risdate>2023</risdate><volume>17</volume><issue>5</issue><spage>054102</spage><pages>054102-</pages><issn>1932-1058</issn><eissn>1932-1058</eissn><coden>BIOMGB</coden><abstract>The separation of peripheral blood mononuclear cells (PBMCs) into constituent blood cell types is a vital step to obtain immune cells for autologous cell therapies. The ability to separate PBMCs using label-free microfluidic techniques, based on differences in biomechanical properties, can have a number of benefits over other conventional techniques, including lower cost, ease of use, and avoidance of animal-derived labeling antibodies. Here, we report a microfluidic device that uses compressive diagonal ridges to separate PBMCs into highly pure samples of viable and functional lymphocytes. The technique utilizes the differences in the biophysical properties of PBMC sub-populations to direct the lymphocytes and monocytes into separate outlets. The biophysical properties of the monocytes and lymphocytes from healthy donors were first characterized using atomic force microscopy. Lymphocytes were found to be significantly stiffer than monocytes, with a mean cell stiffness of 1495 and 931 Pa, respectively. The differences in biophysical properties resulted in distinct trajectories through the microchannel terminating at different outlets, resulting in a lymphocyte sample with purity and viability both greater than 96% with no effect on the cells’ ability to produce interferon gamma, a cytokine crucial for innate and adaptive immunity.</abstract><cop>United States</cop><pub>American Institute of Physics</pub><pmid>37736019</pmid><doi>10.1063/5.0161047</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4196-6293</orcidid><orcidid>https://orcid.org/0000-0002-4677-6440</orcidid><orcidid>https://orcid.org/0000-0001-6567-3335</orcidid><orcidid>https://orcid.org/0000-0001-5276-3219</orcidid><orcidid>https://orcid.org/0000-0002-8692-8779</orcidid><orcidid>https://orcid.org/0009-0003-6251-6280</orcidid><orcidid>https://orcid.org/0000-0002-8285-0003</orcidid><orcidid>https://orcid.org/0000-0002-0325-7990</orcidid><orcidid>https://orcid.org/0000-0002-2779-8345</orcidid><orcidid>https://orcid.org/0009-0009-3374-5475</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-1058 |
ispartof | Biomicrofluidics, 2023-09, Vol.17 (5), p.054102 |
issn | 1932-1058 1932-1058 |
language | eng |
recordid | cdi_proquest_miscellaneous_2868119499 |
source | AIP Journals Complete; PubMed Central |
subjects | Antibodies Biomechanics Blood Blood cells Immune system Labels Lymphocytes Microchannels Microfluidic devices Regular |
title | Label-free microfluidic isolation of functional and viable lymphocytes from peripheral blood mononuclear cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T05%3A29%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_scita&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Label-free%20microfluidic%20isolation%20of%20functional%20and%20viable%20lymphocytes%20from%20peripheral%20blood%20mononuclear%20cells&rft.jtitle=Biomicrofluidics&rft.au=Raj,%20Abhishek&rft.date=2023-09-01&rft.volume=17&rft.issue=5&rft.spage=054102&rft.pages=054102-&rft.issn=1932-1058&rft.eissn=1932-1058&rft.coden=BIOMGB&rft_id=info:doi/10.1063/5.0161047&rft_dat=%3Cproquest_scita%3E2868119499%3C/proquest_scita%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2866155322&rft_id=info:pmid/37736019&rfr_iscdi=true |