Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells

Ramdane A. Harouaka, Ming Da Zhou, Yin-Ting Yeh, Waleed J. Khan, Avisnata Das, Xin Liu, Christine C. Christ, David T. Dicker, Tara S. Baney, Jussuf T. Kaifi, Chandra Belani, Cristina Truica, Wafik S. El-Deiry, Jeffrey P. Allerton, Siyang Zheng

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. methods: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. results: The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples. conclusions: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.

Original languageEnglish (US)
Pages (from-to)323-333
Number of pages11
JournalClinical Chemistry
Volume60
Issue number2
DOIs
StatePublished - Feb 1 2014

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Circulating Neoplastic Cells
Tumors
Cells
Throughput
Equipment and Supplies
Blood
Neoplasms
Microfiltration
Flexible structures
Tumor Biomarkers
Blood Volume
Colorectal Neoplasms
Lung Neoplasms
Leukocytes
Breast Neoplasms
Neoplasm Metastasis
Antigens
Incidence

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Harouaka, Ramdane A. ; Zhou, Ming Da ; Yeh, Yin-Ting ; Khan, Waleed J. ; Das, Avisnata ; Liu, Xin ; Christ, Christine C. ; Dicker, David T. ; Baney, Tara S. ; Kaifi, Jussuf T. ; Belani, Chandra ; Truica, Cristina ; El-Deiry, Wafik S. ; Allerton, Jeffrey P. ; Zheng, Siyang. / Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells. In: Clinical Chemistry. 2014 ; Vol. 60, No. 2. pp. 323-333.
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title = "Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells",
abstract = "Background: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. methods: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. results: The FMSA device enriched tumor cells with 90{\%} capture efficiency, higher than 104 enrichment, and better than 80{\%} viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76{\%}) compared to 4 out of 18 (approximately 22{\%}) detected with the commercial CellSearch{\circledR} system. There was no incidence of clogging in over 100 tested fresh whole blood samples. conclusions: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.",
author = "Harouaka, {Ramdane A.} and Zhou, {Ming Da} and Yin-Ting Yeh and Khan, {Waleed J.} and Avisnata Das and Xin Liu and Christ, {Christine C.} and Dicker, {David T.} and Baney, {Tara S.} and Kaifi, {Jussuf T.} and Chandra Belani and Cristina Truica and El-Deiry, {Wafik S.} and Allerton, {Jeffrey P.} and Siyang Zheng",
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doi = "10.1373/clinchem.2013.206805",
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Harouaka, RA, Zhou, MD, Yeh, Y-T, Khan, WJ, Das, A, Liu, X, Christ, CC, Dicker, DT, Baney, TS, Kaifi, JT, Belani, C, Truica, C, El-Deiry, WS, Allerton, JP & Zheng, S 2014, 'Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells', Clinical Chemistry, vol. 60, no. 2, pp. 323-333. https://doi.org/10.1373/clinchem.2013.206805

Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells. / Harouaka, Ramdane A.; Zhou, Ming Da; Yeh, Yin-Ting; Khan, Waleed J.; Das, Avisnata; Liu, Xin; Christ, Christine C.; Dicker, David T.; Baney, Tara S.; Kaifi, Jussuf T.; Belani, Chandra; Truica, Cristina; El-Deiry, Wafik S.; Allerton, Jeffrey P.; Zheng, Siyang.

In: Clinical Chemistry, Vol. 60, No. 2, 01.02.2014, p. 323-333.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells

AU - Harouaka, Ramdane A.

AU - Zhou, Ming Da

AU - Yeh, Yin-Ting

AU - Khan, Waleed J.

AU - Das, Avisnata

AU - Liu, Xin

AU - Christ, Christine C.

AU - Dicker, David T.

AU - Baney, Tara S.

AU - Kaifi, Jussuf T.

AU - Belani, Chandra

AU - Truica, Cristina

AU - El-Deiry, Wafik S.

AU - Allerton, Jeffrey P.

AU - Zheng, Siyang

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. methods: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. results: The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples. conclusions: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.

AB - Background: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. methods: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. results: The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples. conclusions: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.

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