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 disease. 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 cancers. 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 purity. 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 cancer.