Microfluidic active loading of single cells enables analysis of complex clinical specimens
A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2019
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| Online Access: | http://hdl.handle.net/1721.1/120941 https://orcid.org/0000-0002-8541-0919 https://orcid.org/0000-0001-9939-764X https://orcid.org/0000-0002-5702-8667 https://orcid.org/0000-0002-6417-1007 https://orcid.org/0000-0001-5223-9433 |
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| author | Malinowski, Seth W. Touat, Mehdi Ligon, Keith L. Calistri, Nicholas L Kimmerling, Robert John Stevens, Mark M. Olcum, Selim A. Manalis, Scott R |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Malinowski, Seth W. Touat, Mehdi Ligon, Keith L. Calistri, Nicholas L Kimmerling, Robert John Stevens, Mark M. Olcum, Selim A. Manalis, Scott R |
| author_sort | Malinowski, Seth W. |
| collection | MIT |
| description | A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris. |
| first_indexed | 2024-09-23T10:05:29Z |
| format | Article |
| id | mit-1721.1/120941 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:05:29Z |
| publishDate | 2019 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1209412022-09-30T18:53:40Z Microfluidic active loading of single cells enables analysis of complex clinical specimens Malinowski, Seth W. Touat, Mehdi Ligon, Keith L. Calistri, Nicholas L Kimmerling, Robert John Stevens, Mark M. Olcum, Selim A. Manalis, Scott R Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Koch Institute for Integrative Cancer Research at MIT Calistri, Nicholas L Kimmerling, Robert John Stevens, Mark M. Olcum, Selim A. Manalis, Scott R A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris. National Cancer Institute (U.S.) (R01 CA170592) National Cancer Institute (U.S.) (R33 CA191143) National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051) Bridge Project 2019-03-12T20:09:26Z 2019-03-12T20:09:26Z 2018-11 2019-03-04T14:40:52Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/120941 Calistri, Nicholas L., Robert J. Kimmerling, Seth W. Malinowski, Mehdi Touat, Mark M. Stevens, Selim Olcum, Keith L. Ligon, and Scott R. Manalis. “Microfluidic Active Loading of Single Cells Enables Analysis of Complex Clinical Specimens.” Nature Communications 9, no. 1 (November 14, 2018). © 2018 The Authors https://orcid.org/0000-0002-8541-0919 https://orcid.org/0000-0001-9939-764X https://orcid.org/0000-0002-5702-8667 https://orcid.org/0000-0002-6417-1007 https://orcid.org/0000-0001-5223-9433 http://dx.doi.org/10.1038/s41467-018-07283-x Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Malinowski, Seth W. Touat, Mehdi Ligon, Keith L. Calistri, Nicholas L Kimmerling, Robert John Stevens, Mark M. Olcum, Selim A. Manalis, Scott R Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title | Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title_full | Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title_fullStr | Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title_full_unstemmed | Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title_short | Microfluidic active loading of single cells enables analysis of complex clinical specimens |
| title_sort | microfluidic active loading of single cells enables analysis of complex clinical specimens |
| url | http://hdl.handle.net/1721.1/120941 https://orcid.org/0000-0002-8541-0919 https://orcid.org/0000-0001-9939-764X https://orcid.org/0000-0002-5702-8667 https://orcid.org/0000-0002-6417-1007 https://orcid.org/0000-0001-5223-9433 |
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