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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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Autores principales: Hart, Cacie, Kundu, Avra, Kumar, Kowsik, Varma, Sreekanth J., Thomas, Jayan, Rajaraman, Swaminathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315475/
https://www.ncbi.nlm.nih.gov/pubmed/30314279
http://dx.doi.org/10.3390/bios8040088
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author Hart, Cacie
Kundu, Avra
Kumar, Kowsik
Varma, Sreekanth J.
Thomas, Jayan
Rajaraman, Swaminathan
author_facet Hart, Cacie
Kundu, Avra
Kumar, Kowsik
Varma, Sreekanth J.
Thomas, Jayan
Rajaraman, Swaminathan
author_sort Hart, Cacie
collection PubMed
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.
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spelling pubmed-63154752019-01-09 Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes Hart, Cacie Kundu, Avra Kumar, Kowsik Varma, Sreekanth J. Thomas, Jayan Rajaraman, Swaminathan Biosensors (Basel) Communication 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. MDPI 2018-10-11 /pmc/articles/PMC6315475/ /pubmed/30314279 http://dx.doi.org/10.3390/bios8040088 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Hart, Cacie
Kundu, Avra
Kumar, Kowsik
Varma, Sreekanth J.
Thomas, Jayan
Rajaraman, Swaminathan
Rapid Nanofabrication of Nanostructured Interdigitated Electrodes (nIDEs) for Long-Term In Vitro Analysis of Human Induced Pluripotent Stem Cell Differentiated Cardiomyocytes
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 Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315475/
https://www.ncbi.nlm.nih.gov/pubmed/30314279
http://dx.doi.org/10.3390/bios8040088
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