Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications
Microfluidic concentration gradient generators are useful in drug testing, drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfl...
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Veröffentlicht in: | Biomicrofluidics 2022-12, Vol.16 (6), p.064103 |
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creator | Yadav, Shital Tawade, Pratik Bachal, Ketaki Rakshe, Makrand A. Pundlik, Yash Gandhi, Prasanna S. Majumder, Abhijit |
description | Microfluidic concentration gradient generators are useful in drug testing, drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele–Shaw cell (MLHSC). Using the shaped ceramic structure as the template, μCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug—curcumin—using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of μCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilized to achieve a broad range of concentration gradient to be used for various biological and non-biological applications. |
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However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele–Shaw cell (MLHSC). Using the shaped ceramic structure as the template, μCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug—curcumin—using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of μCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilized to achieve a broad range of concentration gradient to be used for various biological and non-biological applications.</description><identifier>ISSN: 1932-1058</identifier><identifier>EISSN: 1932-1058</identifier><identifier>DOI: 10.1063/5.0126616</identifier><identifier>PMID: 36483022</identifier><identifier>CODEN: BIOMGB</identifier><language>eng</language><publisher>United States: American Institute of Physics</publisher><subject>Ceramics ; Concentration gradient ; Drug testing ; Finite element method ; Flow velocity ; Fluorescein ; Mesh generation ; Microfluidics ; Photolithography ; Regular ; Taylor instability</subject><ispartof>Biomicrofluidics, 2022-12, Vol.16 (6), p.064103</ispartof><rights>Author(s)</rights><rights>2022 Author(s).</rights><rights>2022 Author(s). 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However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele–Shaw cell (MLHSC). Using the shaped ceramic structure as the template, μCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug—curcumin—using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of μCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilized to achieve a broad range of concentration gradient to be used for various biological and non-biological applications.</description><subject>Ceramics</subject><subject>Concentration gradient</subject><subject>Drug testing</subject><subject>Finite element method</subject><subject>Flow velocity</subject><subject>Fluorescein</subject><subject>Mesh generation</subject><subject>Microfluidics</subject><subject>Photolithography</subject><subject>Regular</subject><subject>Taylor instability</subject><issn>1932-1058</issn><issn>1932-1058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU9rFTEUxYNYbH268AvIgBsVpt4kM5k3G0GKfwoFF-o63JfcmaZkJmOSKfjtTX3P2gq6CAncXw7nnsPYMw6nHJR8054CF0px9YCd8F6KmkO7fXjnfcwep3QF0PJOiEfsWKpmK0GIE4ZfDHrceao8xpFqjITVROmyTjmuJq-RbDU5E8PgV2edqcaI1tGcq5FmiphDrIZybFzHKlPKbh4rXBbvDGYX5vSEHQ3oEz093Bv27cP7r2ef6ovPH8_P3l3UpgGZa0HQiaGBZmslGmGkwc72A5Do5A5AmFZtW-yHvml2ijcS0XCBEoiXT5ZIbtjbve6y7iaypliM6PUS3YTxhw7o9P3J7C71GK513wklSlQb9vIgEMP3tWyiJ5cMeY8zhTVp0bVSchAdL-iLv9CrsMa5rFeoRinZgYBCvdpTJb2UIg23Zjjom-J0qw_FFfb5Xfe35O-mCvB6DyTj8q9k_6v2T_g6xD-gXuwgfwJ4O7C3</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Yadav, Shital</creator><creator>Tawade, Pratik</creator><creator>Bachal, Ketaki</creator><creator>Rakshe, Makrand A.</creator><creator>Pundlik, Yash</creator><creator>Gandhi, Prasanna S.</creator><creator>Majumder, Abhijit</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/0000-0002-0695-3967</orcidid><orcidid>https://orcid.org/0000-0002-2099-6429</orcidid><orcidid>https://orcid.org/0000-0003-2267-2695</orcidid><orcidid>https://orcid.org/0000-0002-2442-4823</orcidid><orcidid>https://orcid.org/0000-0001-8642-8822</orcidid></search><sort><creationdate>20221201</creationdate><title>Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications</title><author>Yadav, Shital ; Tawade, Pratik ; Bachal, Ketaki ; Rakshe, Makrand A. ; Pundlik, Yash ; Gandhi, Prasanna S. ; Majumder, Abhijit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-2e072f4048d3ac2c3ca7d9f0e273b002c5685a9f944b6143aac12a30e1f40dee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Ceramics</topic><topic>Concentration gradient</topic><topic>Drug testing</topic><topic>Finite element method</topic><topic>Flow velocity</topic><topic>Fluorescein</topic><topic>Mesh generation</topic><topic>Microfluidics</topic><topic>Photolithography</topic><topic>Regular</topic><topic>Taylor instability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yadav, Shital</creatorcontrib><creatorcontrib>Tawade, Pratik</creatorcontrib><creatorcontrib>Bachal, Ketaki</creatorcontrib><creatorcontrib>Rakshe, Makrand A.</creatorcontrib><creatorcontrib>Pundlik, Yash</creatorcontrib><creatorcontrib>Gandhi, Prasanna S.</creatorcontrib><creatorcontrib>Majumder, Abhijit</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>Yadav, Shital</au><au>Tawade, Pratik</au><au>Bachal, Ketaki</au><au>Rakshe, Makrand A.</au><au>Pundlik, Yash</au><au>Gandhi, Prasanna S.</au><au>Majumder, Abhijit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications</atitle><jtitle>Biomicrofluidics</jtitle><addtitle>Biomicrofluidics</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>16</volume><issue>6</issue><spage>064103</spage><pages>064103-</pages><issn>1932-1058</issn><eissn>1932-1058</eissn><coden>BIOMGB</coden><abstract>Microfluidic concentration gradient generators are useful in drug testing, drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele–Shaw cell (MLHSC). Using the shaped ceramic structure as the template, μCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug—curcumin—using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of μCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. 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subjects | Ceramics Concentration gradient Drug testing Finite element method Flow velocity Fluorescein Mesh generation Microfluidics Photolithography Regular Taylor instability |
title | Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications |
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