Isolation of rare circulating tumour cells in cancer patients by microchip technology

Abstract

Viable tumour-derived epithelial cells — or circulating tumour cells (CTCs) — are found in peripheral blood from cancer patients, and are the probable origin of intractable metastatic disease. The isolation of such cells from cancer patients has been proven to be very difficult, primarily due to their exceedingly low numbers in peripheral blood. Now a microfluidic platform 'CTC-chip' has been developed, capable of selective, efficient separation of CTCs from the blood of cancer patients. This new tool could be used in the detection and diagnosis of cancers, and to monitor an individual patient's response to therapy. A microfluidic platform that is capable of efficiently and selectively separating viable circulating tumour cells (CTCs) from peripheral blood samples has been developed. Low levels of CTCs in the peripheral blood of patients with various cancers were identified, and it was shown that this device could be used to monitor an individual patient's response to anti-cancer therapy. Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease1,2,3,4. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers5,6,7,8. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity9. Here we describe the development of a unique microfluidic platform (the ‘CTC-chip’) capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5–1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer10.