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Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells
Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only avail...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007481/ https://www.ncbi.nlm.nih.gov/pubmed/27581736 http://dx.doi.org/10.1038/srep32505 |
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author | Ramirez, Lisa Herschkowitz, Jason I. Wang, Jun |
author_facet | Ramirez, Lisa Herschkowitz, Jason I. Wang, Jun |
author_sort | Ramirez, Lisa |
collection | PubMed |
description | Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don’t have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future. |
format | Online Article Text |
id | pubmed-5007481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50074812016-09-07 Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells Ramirez, Lisa Herschkowitz, Jason I. Wang, Jun Sci Rep Article Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don’t have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future. Nature Publishing Group 2016-09-01 /pmc/articles/PMC5007481/ /pubmed/27581736 http://dx.doi.org/10.1038/srep32505 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ramirez, Lisa Herschkowitz, Jason I. Wang, Jun Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title | Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title_full | Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title_fullStr | Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title_full_unstemmed | Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title_short | Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells |
title_sort | stand-sit microchip for high-throughput, multiplexed analysis of single cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007481/ https://www.ncbi.nlm.nih.gov/pubmed/27581736 http://dx.doi.org/10.1038/srep32505 |
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