Abstract
Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison. Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients. This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
MeSH Terms
Cell Line, Tumor
Dimethylpolysiloxanes
Hemofiltration/instrumentation
Humans
Membranes, Artificial
Microfluidic Analytical Techniques/instrumentation
Neoplasms/blood,pathology
Neoplastic Cells, Circulating/pathology
Polymers
Xylenes
Chemicals
Dimethylpolysiloxanes
Membranes, Artificial
Polymers
Xylenes
parylene
baysilon
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lin Henry K
Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Zheng Siyang
Williams Anthony J
Balic Marija
Groshen Susan
Scher Howard I
Fleisher Martin
Stadler Walter
Datar Ram H
Tai Yu-Chong
Cote Richard J
References (18)
18 references, click to expand
-
Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer.
Clin Cancer Res. 2007 Apr 1;13(7):2023-9
PMID: 17404082
-
Cancer micrometastases.
Nat Rev Clin Oncol. 2009 Jun;6(6):339-51
PMID: 19399023
-
Isolation of rare circulating tumour cells in cancer patients by microchip technology.
Nature. 2007 Dec 20;450(7173):1235-9
PMID: 18097410
-
Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data.
Lancet Oncol. 2009 Mar;10(3):233-9
PMID: 19213602
-
Circulating tumor cells (CTC) detection: clinical impact and future directions.
Cancer Lett. 2007 Aug 18;253(2):180-204
PMID: 17314005
-
Detection and measurement of occult disease for the prognosis of solid tumors.
J Clin Oncol. 2003 Jul 1;21(13):2609-15
PMID: 12829682
-
Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood.
Cytometry. 2002 Dec 1;49(4):150-8
PMID: 12454978
-
Frequent EpCam protein expression in human carcinomas.
Hum Pathol. 2004 Jan;35(1):122-8
PMID: 14745734
-
Detection of mutations in EGFR in circulating lung-cancer cells.
N Engl J Med. 2008 Jul 24;359(4):366-77
PMID: 18596266
-
Separation of human breast cancer cells from blood by differential dielectric affinity.
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):860-4
PMID: 7846067
-
Circulating tumor cells, disease progression, and survival in metastatic breast cancer.
N Engl J Med. 2004 Aug 19;351(8):781-91
PMID: 15317891
-
Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.
Clin Cancer Res. 2008 Oct 1;14(19):6302-9
PMID: 18829513
-
The size of small cell lung carcinoma cells. Ratio to lymphocytes and correlation with specimen size and crush artifact.
Anal Quant Cytol Histol. 1992 Feb;14(1):32-4
PMID: 1313679
-
Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells.
J Chromatogr A. 2007 Aug 31;1162(2):154-61
PMID: 17561026
-
Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation.
Exp Hematol. 2004 Oct;32(10):891-904
PMID: 15504544
-
Rationale for adjuvant chemotherapy.
Cancer. 1977 Jun;39(6 Suppl):2875-82
PMID: 141322
-
Circulating tumor cells in patients with breast cancer dormancy.
Clin Cancer Res. 2004 Dec 15;10(24):8152-62
PMID: 15623589
-
Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells.
Am J Pathol. 2000 Jan;156(1):57-63
PMID: 10623654