Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells

Author:

Harouaka Ramdane A12,Zhou Ming-Da12,Yeh Yin-Ting12,Khan Waleed J12,Das Avisnata3,Liu Xin3,Christ Christine C3,Dicker David T3,Baney Tara S2,Kaifi Jussuf T4,Belani Chandra P3,Truica Cristina I3,El-Deiry Wafik S3,Allerton Jeffrey P2,Zheng Si-Yang13

Affiliation:

1. Micro & Nano Integrated Biosystem (MINIBio) Laboratory, Department of Biomedical Engineering and Materials Research Institute, Pennsylvania State University, University Park, PA

2. Penn State Hershey Cancer Institute, State College, PA

3. Penn State Hershey Cancer Institute, Hershey, PA

4. Division of Surgical Oncology, Penn State Milton S. Hershey Medical Center, Hershey, PA

Abstract

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.

Funder

Penn State Hershey Cancer Institute

National Cancer Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

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