Deformability-based cell selection with downstream immunofluorescence analysis
Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspen...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Royal Society of Chemistry (RSC)
2018
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| Online Access: | http://hdl.handle.net/1721.1/117695 https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5223-9433 |
| _version_ | 1811002338779856896 |
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| author | Shaw Bagnall, Josephine Byun, Sangwon Miyamoto, David T. Maheswaran, Shyamala Stott, Shannon L. Toner, Mehmet Kang, Joon Ho Manalis, Scott R |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Shaw Bagnall, Josephine Byun, Sangwon Miyamoto, David T. Maheswaran, Shyamala Stott, Shannon L. Toner, Mehmet Kang, Joon Ho Manalis, Scott R |
| author_sort | Shaw Bagnall, Josephine |
| collection | MIT |
| description | Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspended microchannel resonator (SMR), which can measure biophysical characteristics of a single cell based on the sensor's record of its buoyant mass as well as its precise position while it traverses through a constricted microfluidic channel. The measurement provides information regarding the amount of time a cell takes to pass through a constriction (passage time), as related to the cell's deformability and surface friction, as well as the particular manner in which it passes through. In the method presented here, cells of interest are determined based on passage time, and are collected off-chip for downstream immunofluorescence imaging. The biophysical single-cell SMR measurement can then be correlated to the molecular expression of the collected cell. This proof-of-principle is demonstrated by sorting and collecting tumor cells from cell line-spiked blood samples as well as a metastatic prostate cancer patient blood sample, identifying them by their surface protein expression and relating them to distinct SMR signal trajectories. |
| first_indexed | 2024-09-23T15:46:57Z |
| format | Article |
| id | mit-1721.1/117695 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:46:57Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry (RSC) |
| record_format | dspace |
| spelling | mit-1721.1/1176952022-09-29T16:07:24Z Deformability-based cell selection with downstream immunofluorescence analysis Shaw Bagnall, Josephine Byun, Sangwon Miyamoto, David T. Maheswaran, Shyamala Stott, Shannon L. Toner, Mehmet Kang, Joon Ho Manalis, Scott R Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Physics Koch Institute for Integrative Cancer Research at MIT Kang, Joon Ho Manalis, Scott R Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspended microchannel resonator (SMR), which can measure biophysical characteristics of a single cell based on the sensor's record of its buoyant mass as well as its precise position while it traverses through a constricted microfluidic channel. The measurement provides information regarding the amount of time a cell takes to pass through a constriction (passage time), as related to the cell's deformability and surface friction, as well as the particular manner in which it passes through. In the method presented here, cells of interest are determined based on passage time, and are collected off-chip for downstream immunofluorescence imaging. The biophysical single-cell SMR measurement can then be correlated to the molecular expression of the collected cell. This proof-of-principle is demonstrated by sorting and collecting tumor cells from cell line-spiked blood samples as well as a metastatic prostate cancer patient blood sample, identifying them by their surface protein expression and relating them to distinct SMR signal trajectories. National Cancer Institute (U.S.) (Grant P30-CA14051) 2018-09-10T19:39:31Z 2018-09-10T19:39:31Z 2016-03 2015-11 2018-09-10T15:46:07Z Article http://purl.org/eprint/type/JournalArticle 1757-9694 1757-9708 http://hdl.handle.net/1721.1/117695 Shaw Bagnall, Josephine et al. “Deformability-Based Cell Selection with Downstream Immunofluorescence Analysis.” Integrative Biology 8, 5 (March 2016): 654–664 © 2016 The Royal Society of Chemistry https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5223-9433 http://dx.doi.org/10.1039/C5IB00284B Integrative Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society of Chemistry (RSC) PMC |
| spellingShingle | Shaw Bagnall, Josephine Byun, Sangwon Miyamoto, David T. Maheswaran, Shyamala Stott, Shannon L. Toner, Mehmet Kang, Joon Ho Manalis, Scott R Deformability-based cell selection with downstream immunofluorescence analysis |
| title | Deformability-based cell selection with downstream immunofluorescence analysis |
| title_full | Deformability-based cell selection with downstream immunofluorescence analysis |
| title_fullStr | Deformability-based cell selection with downstream immunofluorescence analysis |
| title_full_unstemmed | Deformability-based cell selection with downstream immunofluorescence analysis |
| title_short | Deformability-based cell selection with downstream immunofluorescence analysis |
| title_sort | deformability based cell selection with downstream immunofluorescence analysis |
| url | http://hdl.handle.net/1721.1/117695 https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5223-9433 |
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