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Flow radiocytometry using droplet optofluidics
Flow-based cytometry methods are widely used to analyze heterogeneous cell populations. However, their use for small molecule studies remains limited due to bulky fluorescent labels that often interfere with biochemical activity in cells. In contrast, radiotracers require minimal modification of the...
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Published in: | Biosensors & bioelectronics 2021-12, Vol.194, p.113565-113565, Article 113565 |
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creator | Ha, Byunghang Kim, Tae Jin Moon, Ejung Giaccia, Amato J. Pratx, Guillem |
description | Flow-based cytometry methods are widely used to analyze heterogeneous cell populations. However, their use for small molecule studies remains limited due to bulky fluorescent labels that often interfere with biochemical activity in cells. In contrast, radiotracers require minimal modification of their target molecules and can track biochemical processes with negligible interference and high specificity. Here, we introduce flow radiocytometry (FRCM) that broadens the scope of current cytometry methods to include beta-emitting radiotracers as probes for single cell studies. FRCM uses droplet microfluidics and radiofluorogenesis to translate the radioactivity of single cells into a fluorescent signal that is then read out using a high-throughput optofluidic device. As a proof of concept, we quantitated [18F]fluorodeoxyglucose radiotracer uptake in single human breast cancer cells and successfully assessed the metabolic flux of glucose and its heterogeneity at the cellular level. We believe FRCM has potential applications ranging from analytical assays for cancer and other diseases to development of small-molecule drugs.
•We developed flow radiocytometry to measure radiotracer uptake in single cells with high throughput.•An optimized radiofluorogenesis process converts radioactivity into fluorescence with minimal crosstalk between drops.•Using the method, we assessed the metabolic flux of glucose and its heterogeneity in different cell samples. |
doi_str_mv | 10.1016/j.bios.2021.113565 |
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•We developed flow radiocytometry to measure radiotracer uptake in single cells with high throughput.•An optimized radiofluorogenesis process converts radioactivity into fluorescence with minimal crosstalk between drops.•Using the method, we assessed the metabolic flux of glucose and its heterogeneity in different cell samples.</description><identifier>ISSN: 0956-5663</identifier><identifier>EISSN: 1873-4235</identifier><identifier>DOI: 10.1016/j.bios.2021.113565</identifier><identifier>PMID: 34492500</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Biological Assay ; Biosensing Techniques ; Droplet microfluidics ; Flow Cytometry ; Fluorodeoxyglucose ; Humans ; Microfluidics ; Optofluidics ; Physical Phenomena ; Radiochemistry ; Radiofluorogenesis ; Single-cell analysis</subject><ispartof>Biosensors & bioelectronics, 2021-12, Vol.194, p.113565-113565, Article 113565</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-6b64facdaf90ab0d15a6db3cdcfd993a0c4283aa7c9097eeeeefb38306a108c13</citedby><cites>FETCH-LOGICAL-c455t-6b64facdaf90ab0d15a6db3cdcfd993a0c4283aa7c9097eeeeefb38306a108c13</cites><orcidid>0000-0002-0247-6470 ; 0000-0002-4491-4627</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34492500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ha, Byunghang</creatorcontrib><creatorcontrib>Kim, Tae Jin</creatorcontrib><creatorcontrib>Moon, Ejung</creatorcontrib><creatorcontrib>Giaccia, Amato J.</creatorcontrib><creatorcontrib>Pratx, Guillem</creatorcontrib><title>Flow radiocytometry using droplet optofluidics</title><title>Biosensors & bioelectronics</title><addtitle>Biosens Bioelectron</addtitle><description>Flow-based cytometry methods are widely used to analyze heterogeneous cell populations. However, their use for small molecule studies remains limited due to bulky fluorescent labels that often interfere with biochemical activity in cells. In contrast, radiotracers require minimal modification of their target molecules and can track biochemical processes with negligible interference and high specificity. Here, we introduce flow radiocytometry (FRCM) that broadens the scope of current cytometry methods to include beta-emitting radiotracers as probes for single cell studies. FRCM uses droplet microfluidics and radiofluorogenesis to translate the radioactivity of single cells into a fluorescent signal that is then read out using a high-throughput optofluidic device. As a proof of concept, we quantitated [18F]fluorodeoxyglucose radiotracer uptake in single human breast cancer cells and successfully assessed the metabolic flux of glucose and its heterogeneity at the cellular level. We believe FRCM has potential applications ranging from analytical assays for cancer and other diseases to development of small-molecule drugs.
•We developed flow radiocytometry to measure radiotracer uptake in single cells with high throughput.•An optimized radiofluorogenesis process converts radioactivity into fluorescence with minimal crosstalk between drops.•Using the method, we assessed the metabolic flux of glucose and its heterogeneity in different cell samples.</description><subject>Biological Assay</subject><subject>Biosensing Techniques</subject><subject>Droplet microfluidics</subject><subject>Flow Cytometry</subject><subject>Fluorodeoxyglucose</subject><subject>Humans</subject><subject>Microfluidics</subject><subject>Optofluidics</subject><subject>Physical Phenomena</subject><subject>Radiochemistry</subject><subject>Radiofluorogenesis</subject><subject>Single-cell analysis</subject><issn>0956-5663</issn><issn>1873-4235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kEFLwzAUx4Mobk6_gAfZ0UvrS9OkDYggw6kw8KLnkCbpzGibmbSTfXtbqkMvvss7vN_7v8cPoUsMMQbMbjZxYV2IE0hwjDGhjB6hKc4zEqUJocdoCpyyiDJGJugshA0AZJjDKZqQNOUJBZiieFm5z7mX2jq1b11tWr-fd8E267n2bluZdu62rSurzmqrwjk6KWUVzMV3n6G35cPr4ilavTw-L-5XkUopbSNWsLSUSsuSgyxAYyqZLojSqtScEwkqTXIiZaY48MwMVRYkJ8AkhlxhMkN3Y-62K2qjlWlaLyux9baWfi-ctOLvpLHvYu12IqcEOCF9wPV3gHcfnQmtqG1QpqpkY1wXREIzIBnGLO_RZESVdyF4Ux7OYBCDaLERg2gxiBaj6H7p6veDh5Ufsz1wOwKm17SzxougrGmU0dYb1Qrt7H_5X2QNkVY</recordid><startdate>20211215</startdate><enddate>20211215</enddate><creator>Ha, Byunghang</creator><creator>Kim, Tae Jin</creator><creator>Moon, Ejung</creator><creator>Giaccia, Amato J.</creator><creator>Pratx, Guillem</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0247-6470</orcidid><orcidid>https://orcid.org/0000-0002-4491-4627</orcidid></search><sort><creationdate>20211215</creationdate><title>Flow radiocytometry using droplet optofluidics</title><author>Ha, Byunghang ; Kim, Tae Jin ; Moon, Ejung ; Giaccia, Amato J. ; Pratx, Guillem</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-6b64facdaf90ab0d15a6db3cdcfd993a0c4283aa7c9097eeeeefb38306a108c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biological Assay</topic><topic>Biosensing Techniques</topic><topic>Droplet microfluidics</topic><topic>Flow Cytometry</topic><topic>Fluorodeoxyglucose</topic><topic>Humans</topic><topic>Microfluidics</topic><topic>Optofluidics</topic><topic>Physical Phenomena</topic><topic>Radiochemistry</topic><topic>Radiofluorogenesis</topic><topic>Single-cell analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ha, Byunghang</creatorcontrib><creatorcontrib>Kim, Tae Jin</creatorcontrib><creatorcontrib>Moon, Ejung</creatorcontrib><creatorcontrib>Giaccia, Amato J.</creatorcontrib><creatorcontrib>Pratx, Guillem</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biosensors & bioelectronics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ha, Byunghang</au><au>Kim, Tae Jin</au><au>Moon, Ejung</au><au>Giaccia, Amato J.</au><au>Pratx, Guillem</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flow radiocytometry using droplet optofluidics</atitle><jtitle>Biosensors & bioelectronics</jtitle><addtitle>Biosens Bioelectron</addtitle><date>2021-12-15</date><risdate>2021</risdate><volume>194</volume><spage>113565</spage><epage>113565</epage><pages>113565-113565</pages><artnum>113565</artnum><issn>0956-5663</issn><eissn>1873-4235</eissn><abstract>Flow-based cytometry methods are widely used to analyze heterogeneous cell populations. However, their use for small molecule studies remains limited due to bulky fluorescent labels that often interfere with biochemical activity in cells. In contrast, radiotracers require minimal modification of their target molecules and can track biochemical processes with negligible interference and high specificity. Here, we introduce flow radiocytometry (FRCM) that broadens the scope of current cytometry methods to include beta-emitting radiotracers as probes for single cell studies. FRCM uses droplet microfluidics and radiofluorogenesis to translate the radioactivity of single cells into a fluorescent signal that is then read out using a high-throughput optofluidic device. As a proof of concept, we quantitated [18F]fluorodeoxyglucose radiotracer uptake in single human breast cancer cells and successfully assessed the metabolic flux of glucose and its heterogeneity at the cellular level. We believe FRCM has potential applications ranging from analytical assays for cancer and other diseases to development of small-molecule drugs.
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subjects | Biological Assay Biosensing Techniques Droplet microfluidics Flow Cytometry Fluorodeoxyglucose Humans Microfluidics Optofluidics Physical Phenomena Radiochemistry Radiofluorogenesis Single-cell analysis |
title | Flow radiocytometry using droplet optofluidics |
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