High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics
The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (
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| Veröffentlicht in: | Biosensors & bioelectronics 2024-09, Vol.259, p.116411, Article 116411 |
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| container_title | Biosensors & bioelectronics |
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| creator | Zhu, Zhixian Zhang, Yixuan Zhang, Wenjun Tang, Dezhi Zhang, Song Wang, Lei Zou, Xiaoping Ni, Zhonghua Zhang, Shu Lv, Ying Xiang, Nan |
| description | The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 ( |
| doi_str_mv | 10.1016/j.bios.2024.116411 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3060384580</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0956566324004160</els_id><sourcerecordid>3060384580</sourcerecordid><originalsourceid>FETCH-LOGICAL-c307t-4db5b1f622b90efc49a2370ab2e5d6555b2ab080e19a912c376081abb3eb4cff3</originalsourceid><addsrcrecordid>eNp9kU2O1DAQhSMEYpqBC7BAXrJJ45_ESSQ2oxYwSCOxgbVlO5WkWokdbKelORR3xKEHlqz8ZL_6ylWvKN4yemSUyQ_no0Efj5zy6siYrBh7VhxY24iy4qJ-XhxoV8uyllLcFK9iPFNKG9bRl8WNaJuWyU4eil_3OE5lmoLfxmndEgEX0E4LuET8QFYfkp7JBZzfIrEY7DbrhG4kaVt8IBbmOZIhqylz5kcSwUVMeAHSox6djxh3zumOdWVXOhj1n8dVOxsga0tslhDyTcLcNJIt7nh0EBLm1gva4Id5wx5tfF28GPQc4c3TeVv8-Pzp--m-fPj25evp7qG0gjaprHpTGzZIzk1HYbBVp7loqDYc6l7WdW24NrSlwDrdMW5FI2nLtDECTGWHQdwW76_cNfifG8SkFoz7rNpBXoQSVFLRVnVLs5VfrfmbMQYY1Bpw0eFRMar2mNRZ7TGpPSZ1jSkXvXvib2aB_l_J31yy4ePVAHnKC0JQ0eb1WOgxgE2q9_g__m-Ev6i2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3060384580</pqid></control><display><type>article</type><title>High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Zhu, Zhixian ; Zhang, Yixuan ; Zhang, Wenjun ; Tang, Dezhi ; Zhang, Song ; Wang, Lei ; Zou, Xiaoping ; Ni, Zhonghua ; Zhang, Shu ; Lv, Ying ; Xiang, Nan</creator><creatorcontrib>Zhu, Zhixian ; Zhang, Yixuan ; Zhang, Wenjun ; Tang, Dezhi ; Zhang, Song ; Wang, Lei ; Zou, Xiaoping ; Ni, Zhonghua ; Zhang, Shu ; Lv, Ying ; Xiang, Nan</creatorcontrib><description>The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.</description><identifier>ISSN: 0956-5663</identifier><identifier>ISSN: 1873-4235</identifier><identifier>EISSN: 1873-4235</identifier><identifier>DOI: 10.1016/j.bios.2024.116411</identifier><identifier>PMID: 38781696</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Biomarkers, Tumor - blood ; Biosensing Techniques - instrumentation ; CA-19-9 Antigen - blood ; Circulating tumor cell ; Female ; Humans ; Inertial microfluidics ; Liquid Biopsy - methods ; Male ; Microfluidic Analytical Techniques - instrumentation ; Microfluidics - methods ; Middle Aged ; Neoplastic Cells, Circulating - pathology ; Pancreatic cancer ; Pancreatic Neoplasms - blood ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - pathology ; Portal Vein ; Portal venous system ; Tumor-proximal liquid biopsy</subject><ispartof>Biosensors & bioelectronics, 2024-09, Vol.259, p.116411, Article 116411</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c307t-4db5b1f622b90efc49a2370ab2e5d6555b2ab080e19a912c376081abb3eb4cff3</cites><orcidid>0000-0001-9803-4783</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bios.2024.116411$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38781696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Zhixian</creatorcontrib><creatorcontrib>Zhang, Yixuan</creatorcontrib><creatorcontrib>Zhang, Wenjun</creatorcontrib><creatorcontrib>Tang, Dezhi</creatorcontrib><creatorcontrib>Zhang, Song</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Zou, Xiaoping</creatorcontrib><creatorcontrib>Ni, Zhonghua</creatorcontrib><creatorcontrib>Zhang, Shu</creatorcontrib><creatorcontrib>Lv, Ying</creatorcontrib><creatorcontrib>Xiang, Nan</creatorcontrib><title>High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics</title><title>Biosensors & bioelectronics</title><addtitle>Biosens Bioelectron</addtitle><description>The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.</description><subject>Biomarkers, Tumor - blood</subject><subject>Biosensing Techniques - instrumentation</subject><subject>CA-19-9 Antigen - blood</subject><subject>Circulating tumor cell</subject><subject>Female</subject><subject>Humans</subject><subject>Inertial microfluidics</subject><subject>Liquid Biopsy - methods</subject><subject>Male</subject><subject>Microfluidic Analytical Techniques - instrumentation</subject><subject>Microfluidics - methods</subject><subject>Middle Aged</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - blood</subject><subject>Pancreatic Neoplasms - diagnosis</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Portal Vein</subject><subject>Portal venous system</subject><subject>Tumor-proximal liquid biopsy</subject><issn>0956-5663</issn><issn>1873-4235</issn><issn>1873-4235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2O1DAQhSMEYpqBC7BAXrJJ45_ESSQ2oxYwSCOxgbVlO5WkWokdbKelORR3xKEHlqz8ZL_6ylWvKN4yemSUyQ_no0Efj5zy6siYrBh7VhxY24iy4qJ-XhxoV8uyllLcFK9iPFNKG9bRl8WNaJuWyU4eil_3OE5lmoLfxmndEgEX0E4LuET8QFYfkp7JBZzfIrEY7DbrhG4kaVt8IBbmOZIhqylz5kcSwUVMeAHSox6djxh3zumOdWVXOhj1n8dVOxsga0tslhDyTcLcNJIt7nh0EBLm1gva4Id5wx5tfF28GPQc4c3TeVv8-Pzp--m-fPj25evp7qG0gjaprHpTGzZIzk1HYbBVp7loqDYc6l7WdW24NrSlwDrdMW5FI2nLtDECTGWHQdwW76_cNfifG8SkFoz7rNpBXoQSVFLRVnVLs5VfrfmbMQYY1Bpw0eFRMar2mNRZ7TGpPSZ1jSkXvXvib2aB_l_J31yy4ePVAHnKC0JQ0eb1WOgxgE2q9_g__m-Ev6i2</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Zhu, Zhixian</creator><creator>Zhang, Yixuan</creator><creator>Zhang, Wenjun</creator><creator>Tang, Dezhi</creator><creator>Zhang, Song</creator><creator>Wang, Lei</creator><creator>Zou, Xiaoping</creator><creator>Ni, Zhonghua</creator><creator>Zhang, Shu</creator><creator>Lv, Ying</creator><creator>Xiang, Nan</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><orcidid>https://orcid.org/0000-0001-9803-4783</orcidid></search><sort><creationdate>20240901</creationdate><title>High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics</title><author>Zhu, Zhixian ; Zhang, Yixuan ; Zhang, Wenjun ; Tang, Dezhi ; Zhang, Song ; Wang, Lei ; Zou, Xiaoping ; Ni, Zhonghua ; Zhang, Shu ; Lv, Ying ; Xiang, Nan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c307t-4db5b1f622b90efc49a2370ab2e5d6555b2ab080e19a912c376081abb3eb4cff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomarkers, Tumor - blood</topic><topic>Biosensing Techniques - instrumentation</topic><topic>CA-19-9 Antigen - blood</topic><topic>Circulating tumor cell</topic><topic>Female</topic><topic>Humans</topic><topic>Inertial microfluidics</topic><topic>Liquid Biopsy - methods</topic><topic>Male</topic><topic>Microfluidic Analytical Techniques - instrumentation</topic><topic>Microfluidics - methods</topic><topic>Middle Aged</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - blood</topic><topic>Pancreatic Neoplasms - diagnosis</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Portal Vein</topic><topic>Portal venous system</topic><topic>Tumor-proximal liquid biopsy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Zhixian</creatorcontrib><creatorcontrib>Zhang, Yixuan</creatorcontrib><creatorcontrib>Zhang, Wenjun</creatorcontrib><creatorcontrib>Tang, Dezhi</creatorcontrib><creatorcontrib>Zhang, Song</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Zou, Xiaoping</creatorcontrib><creatorcontrib>Ni, Zhonghua</creatorcontrib><creatorcontrib>Zhang, Shu</creatorcontrib><creatorcontrib>Lv, Ying</creatorcontrib><creatorcontrib>Xiang, Nan</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><jtitle>Biosensors & bioelectronics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Zhixian</au><au>Zhang, Yixuan</au><au>Zhang, Wenjun</au><au>Tang, Dezhi</au><au>Zhang, Song</au><au>Wang, Lei</au><au>Zou, Xiaoping</au><au>Ni, Zhonghua</au><au>Zhang, Shu</au><au>Lv, Ying</au><au>Xiang, Nan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics</atitle><jtitle>Biosensors & bioelectronics</jtitle><addtitle>Biosens Bioelectron</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>259</volume><spage>116411</spage><pages>116411-</pages><artnum>116411</artnum><issn>0956-5663</issn><issn>1873-4235</issn><eissn>1873-4235</eissn><abstract>The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>38781696</pmid><doi>10.1016/j.bios.2024.116411</doi><orcidid>https://orcid.org/0000-0001-9803-4783</orcidid></addata></record> |
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| subjects | Biomarkers, Tumor - blood Biosensing Techniques - instrumentation CA-19-9 Antigen - blood Circulating tumor cell Female Humans Inertial microfluidics Liquid Biopsy - methods Male Microfluidic Analytical Techniques - instrumentation Microfluidics - methods Middle Aged Neoplastic Cells, Circulating - pathology Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - pathology Portal Vein Portal venous system Tumor-proximal liquid biopsy |
| title | High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics |
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