Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes
Adverse cardiac events are a major cause of late-stage drug development withdrawals. Improved in vitro systems for predicting cardiotoxicity are of great interest to prevent these events and to reduce the expenses involved in the introduction of cardiac drugs into the marketplace. Interdigitated ele...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-10-01
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| Series: | Biosensors |
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| Online Access: | http://www.mdpi.com/2079-6374/8/4/88 |
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| author | Cacie Hart Avra Kundu Kowsik Kumar Sreekanth J. Varma Jayan Thomas Swaminathan Rajaraman |
| author_facet | Cacie Hart Avra Kundu Kowsik Kumar Sreekanth J. Varma Jayan Thomas Swaminathan Rajaraman |
| author_sort | Cacie Hart |
| collection | DOAJ |
| description | Adverse cardiac events are a major cause of late-stage drug development withdrawals. Improved in vitro systems for predicting cardiotoxicity are of great interest to prevent these events and to reduce the expenses involved in the introduction of cardiac drugs into the marketplace. Interdigitated electrodes (IDEs) affixed with a culture well provide a simple, suitable solution for in vitro analysis of cells because of their high sensitivity, ease of fabrication, and label-free, nondestructive analysis. Culturing human pluripotent stem cell differentiated cardiomyocytes onto these IDEs allows for the use of the IDE–cell combination in predictive toxicity assays. IDEs with smaller interdigitated distances allow for greater sensitivity, but typically require cleanroom fabrication. In this communication, we report the definition of a simple IDE geometry on a printed nanostructured substrate, demonstrate a Cellular Index (CI) increase from 0 to 7.7 for human cardiomyocytes, and a decrease in CI from 2.3 to 1 with increased concentration of the model drug, norepinephrine. The nanostructuring results in an increased sensitivity of our 1 mm pitch IDEs when compared to traditionally fabricated IDEs with a pitch of 10 μm (100 times larger electrode gap). The entire nanostructured IDE (nIDE) is fabricated and assembled in a rapid nanofabrication environment, thus allowing for iterative design changes and robust fabrication of devices. |
| first_indexed | 2024-12-14T14:08:57Z |
| format | Article |
| id | doaj.art-69607b0139db440295413e36c42ee376 |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-12-14T14:08:57Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-69607b0139db440295413e36c42ee3762022-12-21T22:58:23ZengMDPI AGBiosensors2079-63742018-10-01848810.3390/bios8040088bios8040088Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated CardiomyocytesCacie Hart0Avra Kundu1Kowsik Kumar2Sreekanth J. Varma3Jayan Thomas4Swaminathan Rajaraman5Department of Materials Science & Engineering, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USADepartment of Materials Science & Engineering, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USADepartment of Materials Science & Engineering, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USADepartment of Materials Science & Engineering, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USAAdverse cardiac events are a major cause of late-stage drug development withdrawals. Improved in vitro systems for predicting cardiotoxicity are of great interest to prevent these events and to reduce the expenses involved in the introduction of cardiac drugs into the marketplace. Interdigitated electrodes (IDEs) affixed with a culture well provide a simple, suitable solution for in vitro analysis of cells because of their high sensitivity, ease of fabrication, and label-free, nondestructive analysis. Culturing human pluripotent stem cell differentiated cardiomyocytes onto these IDEs allows for the use of the IDE–cell combination in predictive toxicity assays. IDEs with smaller interdigitated distances allow for greater sensitivity, but typically require cleanroom fabrication. In this communication, we report the definition of a simple IDE geometry on a printed nanostructured substrate, demonstrate a Cellular Index (CI) increase from 0 to 7.7 for human cardiomyocytes, and a decrease in CI from 2.3 to 1 with increased concentration of the model drug, norepinephrine. The nanostructuring results in an increased sensitivity of our 1 mm pitch IDEs when compared to traditionally fabricated IDEs with a pitch of 10 μm (100 times larger electrode gap). The entire nanostructured IDE (nIDE) is fabricated and assembled in a rapid nanofabrication environment, thus allowing for iterative design changes and robust fabrication of devices.http://www.mdpi.com/2079-6374/8/4/88nanostructured Interdigitated Electrodesshadow maskcardiomyocytesin vitro cellular analysis |
| spellingShingle | Cacie Hart Avra Kundu Kowsik Kumar Sreekanth J. Varma Jayan Thomas Swaminathan Rajaraman Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes Biosensors nanostructured Interdigitated Electrodes shadow mask cardiomyocytes in vitro cellular analysis |
| title | Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes |
| title_full | Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes |
| title_fullStr | Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes |
| title_full_unstemmed | Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes |
| title_short | Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes |
| title_sort | rapid nanofabrication of nanostructured interdigitated electrodes nides for long term in vitro analysis of human induced pluripotent stem cell differentiated cardiomyocytes |
| topic | nanostructured Interdigitated Electrodes shadow mask cardiomyocytes in vitro cellular analysis |
| url | http://www.mdpi.com/2079-6374/8/4/88 |
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