Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps

Emily S Park, Simon P Duffy, Kerryn Matthews, Richard R Ang, Tilman Todenhofer, Hamidreza Abdi, Arun Azad, Jenny Bazov, Kim N Chi, Peter Colin Black, Hongshen Ma

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch(R) system. The RCT mechanism was able to capture >/=5 CTCs in 18/22 (82 ) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found >/=5 CTCs in 9/22 (41 ) patients with a mean count of 25. The 10x improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.
Original languageEnglish
Pages (from-to)2278-2286
Number of pages9
JournalLab on a Chip
Volume15
Issue number10
DOIs
Publication statusPublished - 2015
Externally publishedYes

Cite this

Park, Emily S ; Duffy, Simon P ; Matthews, Kerryn ; Ang, Richard R ; Todenhofer, Tilman ; Abdi, Hamidreza ; Azad, Arun ; Bazov, Jenny ; Chi, Kim N ; Black, Peter Colin ; Ma, Hongshen. / Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps. In: Lab on a Chip. 2015 ; Vol. 15, No. 10. pp. 2278-2286.
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abstract = "The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch(R) system. The RCT mechanism was able to capture >/=5 CTCs in 18/22 (82 ) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found >/=5 CTCs in 9/22 (41 ) patients with a mean count of 25. The 10x improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.",
author = "Park, {Emily S} and Duffy, {Simon P} and Kerryn Matthews and Ang, {Richard R} and Tilman Todenhofer and Hamidreza Abdi and Arun Azad and Jenny Bazov and Chi, {Kim N} and Black, {Peter Colin} and Hongshen Ma",
year = "2015",
doi = "10.1039/c5lc00226e",
language = "English",
volume = "15",
pages = "2278--2286",
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Park, ES, Duffy, SP, Matthews, K, Ang, RR, Todenhofer, T, Abdi, H, Azad, A, Bazov, J, Chi, KN, Black, PC & Ma, H 2015, 'Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps' Lab on a Chip, vol. 15, no. 10, pp. 2278-2286. https://doi.org/10.1039/c5lc00226e

Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps. / Park, Emily S; Duffy, Simon P; Matthews, Kerryn; Ang, Richard R; Todenhofer, Tilman; Abdi, Hamidreza; Azad, Arun; Bazov, Jenny; Chi, Kim N; Black, Peter Colin; Ma, Hongshen.

In: Lab on a Chip, Vol. 15, No. 10, 2015, p. 2278-2286.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps

AU - Park, Emily S

AU - Duffy, Simon P

AU - Matthews, Kerryn

AU - Ang, Richard R

AU - Todenhofer, Tilman

AU - Abdi, Hamidreza

AU - Azad, Arun

AU - Bazov, Jenny

AU - Chi, Kim N

AU - Black, Peter Colin

AU - Ma, Hongshen

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N2 - The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch(R) system. The RCT mechanism was able to capture >/=5 CTCs in 18/22 (82 ) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found >/=5 CTCs in 9/22 (41 ) patients with a mean count of 25. The 10x improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.

AB - The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch(R) system. The RCT mechanism was able to capture >/=5 CTCs in 18/22 (82 ) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found >/=5 CTCs in 9/22 (41 ) patients with a mean count of 25. The 10x improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.

U2 - 10.1039/c5lc00226e

DO - 10.1039/c5lc00226e

M3 - Article

VL - 15

SP - 2278

EP - 2286

JO - Lab on a Chip

JF - Lab on a Chip

SN - 1473-0197

IS - 10

ER -