Fully printed prothrombin time sensor for point-of-care testing
With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumber...
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Veröffentlicht in: | Biosensors & bioelectronics 2021-01, Vol.172, p.112770-112770, Article 112770 |
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creator | Williams, Nicholas X. Carroll, Brittani Noyce, Steven G. Hobbie, Hansel Alex Joh, Daniel Y. Rogers, Joseph G. Franklin, Aaron D. |
description | With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20–100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.
•Developed the first fully printed, low-cost, point-of-care test to measure PT/INR.•Overturned the previous findings that PT can be measured with a DC signal.•Demonstrated the first printed and the first flexible PT/INR device.•Created a comparison between clotting times and impedance curves of chicken and human blood, helping to normalize the PT sensing field towards a single testing sequence.•Created a low-cost, facile, impedimetric coagulometer for at-home PT/INR testing. |
doi_str_mv | 10.1016/j.bios.2020.112770 |
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•Developed the first fully printed, low-cost, point-of-care test to measure PT/INR.•Overturned the previous findings that PT can be measured with a DC signal.•Demonstrated the first printed and the first flexible PT/INR device.•Created a comparison between clotting times and impedance curves of chicken and human blood, helping to normalize the PT sensing field towards a single testing sequence.•Created a low-cost, facile, impedimetric coagulometer for at-home PT/INR testing.</description><identifier>ISSN: 0956-5663</identifier><identifier>EISSN: 1873-4235</identifier><identifier>DOI: 10.1016/j.bios.2020.112770</identifier><identifier>PMID: 33157410</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Biosensing Techniques ; Coagulation ; Humans ; Impedance ; Metal Nanoparticles ; Nanotubes, Carbon ; POCT ; Point-of-care ; Point-of-Care Systems ; Point-of-Care Testing ; Printed electronics ; Prothrombin Time ; PT/INR ; Quality of Life ; Silver</subject><ispartof>Biosensors & bioelectronics, 2021-01, Vol.172, p.112770-112770, Article 112770</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-c7378a266b8bcd91a325e8fa6e21b300cacc1f04419f955d7e2a25c7ff1c42f93</citedby><cites>FETCH-LOGICAL-c521t-c7378a266b8bcd91a325e8fa6e21b300cacc1f04419f955d7e2a25c7ff1c42f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bios.2020.112770$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33157410$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Williams, Nicholas X.</creatorcontrib><creatorcontrib>Carroll, Brittani</creatorcontrib><creatorcontrib>Noyce, Steven G.</creatorcontrib><creatorcontrib>Hobbie, Hansel Alex</creatorcontrib><creatorcontrib>Joh, Daniel Y.</creatorcontrib><creatorcontrib>Rogers, Joseph G.</creatorcontrib><creatorcontrib>Franklin, Aaron D.</creatorcontrib><title>Fully printed prothrombin time sensor for point-of-care testing</title><title>Biosensors & bioelectronics</title><addtitle>Biosens Bioelectron</addtitle><description>With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20–100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.
•Developed the first fully printed, low-cost, point-of-care test to measure PT/INR.•Overturned the previous findings that PT can be measured with a DC signal.•Demonstrated the first printed and the first flexible PT/INR device.•Created a comparison between clotting times and impedance curves of chicken and human blood, helping to normalize the PT sensing field towards a single testing sequence.•Created a low-cost, facile, impedimetric coagulometer for at-home PT/INR testing.</description><subject>Biosensing Techniques</subject><subject>Coagulation</subject><subject>Humans</subject><subject>Impedance</subject><subject>Metal Nanoparticles</subject><subject>Nanotubes, Carbon</subject><subject>POCT</subject><subject>Point-of-care</subject><subject>Point-of-Care Systems</subject><subject>Point-of-Care Testing</subject><subject>Printed electronics</subject><subject>Prothrombin Time</subject><subject>PT/INR</subject><subject>Quality of Life</subject><subject>Silver</subject><issn>0956-5663</issn><issn>1873-4235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1KxDAURoMoOo6-gAvp0k3H3KRpWhBFxD8Q3Og6pOmNZmibMekM-PZmmFF04yJcSM798nEIOQE6Awrl-XzWOB9njLJ0AUxKukMmUEmeF4yLXTKhtShzUZb8gBzGOKeUSqjpPjngHIQsgE7I1d2y6z6zRXDDiG2afnwPvm_ckI2uxyziEH3IbDoLn5jc29zogNmIcXTD2xHZs7qLeLydU_J6d_ty85A_Pd8_3lw_5UYwGHMjuaw0K8umakxbg-ZMYGV1iQwaTqnRxoClRQG1rYVoJTLNhJHWgimYrfmUXG5yF8umx9bgMAbdqdS71-FTee3U35fBvas3v1KyphwKkQLOtgHBfyxTedW7aLDr9IB-GRUrRCVZCUATyjaoCT7GgPbnG6BqbV7N1dq8WptXG_Np6fR3wZ-Vb9UJuNgAmDStHAYVjcPBYOsCmlG13v2X_wWbZpYB</recordid><startdate>20210115</startdate><enddate>20210115</enddate><creator>Williams, Nicholas X.</creator><creator>Carroll, Brittani</creator><creator>Noyce, Steven G.</creator><creator>Hobbie, Hansel Alex</creator><creator>Joh, Daniel Y.</creator><creator>Rogers, Joseph G.</creator><creator>Franklin, Aaron D.</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></search><sort><creationdate>20210115</creationdate><title>Fully printed prothrombin time sensor for point-of-care testing</title><author>Williams, Nicholas X. ; Carroll, Brittani ; Noyce, Steven G. ; Hobbie, Hansel Alex ; Joh, Daniel Y. ; Rogers, Joseph G. ; Franklin, Aaron D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-c7378a266b8bcd91a325e8fa6e21b300cacc1f04419f955d7e2a25c7ff1c42f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biosensing Techniques</topic><topic>Coagulation</topic><topic>Humans</topic><topic>Impedance</topic><topic>Metal Nanoparticles</topic><topic>Nanotubes, Carbon</topic><topic>POCT</topic><topic>Point-of-care</topic><topic>Point-of-Care Systems</topic><topic>Point-of-Care Testing</topic><topic>Printed electronics</topic><topic>Prothrombin Time</topic><topic>PT/INR</topic><topic>Quality of Life</topic><topic>Silver</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williams, Nicholas X.</creatorcontrib><creatorcontrib>Carroll, Brittani</creatorcontrib><creatorcontrib>Noyce, Steven G.</creatorcontrib><creatorcontrib>Hobbie, Hansel Alex</creatorcontrib><creatorcontrib>Joh, Daniel Y.</creatorcontrib><creatorcontrib>Rogers, Joseph G.</creatorcontrib><creatorcontrib>Franklin, Aaron D.</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>Williams, Nicholas X.</au><au>Carroll, Brittani</au><au>Noyce, Steven G.</au><au>Hobbie, Hansel Alex</au><au>Joh, Daniel Y.</au><au>Rogers, Joseph G.</au><au>Franklin, Aaron D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fully printed prothrombin time sensor for point-of-care testing</atitle><jtitle>Biosensors & bioelectronics</jtitle><addtitle>Biosens Bioelectron</addtitle><date>2021-01-15</date><risdate>2021</risdate><volume>172</volume><spage>112770</spage><epage>112770</epage><pages>112770-112770</pages><artnum>112770</artnum><issn>0956-5663</issn><eissn>1873-4235</eissn><abstract>With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20–100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.
•Developed the first fully printed, low-cost, point-of-care test to measure PT/INR.•Overturned the previous findings that PT can be measured with a DC signal.•Demonstrated the first printed and the first flexible PT/INR device.•Created a comparison between clotting times and impedance curves of chicken and human blood, helping to normalize the PT sensing field towards a single testing sequence.•Created a low-cost, facile, impedimetric coagulometer for at-home PT/INR testing.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>33157410</pmid><doi>10.1016/j.bios.2020.112770</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biosensing Techniques Coagulation Humans Impedance Metal Nanoparticles Nanotubes, Carbon POCT Point-of-care Point-of-Care Systems Point-of-Care Testing Printed electronics Prothrombin Time PT/INR Quality of Life Silver |
title | Fully printed prothrombin time sensor for point-of-care testing |
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