A microfluidic platform called the CTC-chip was developed to efficiently and selectively isolate viable circulating tumour cells (CTCs) from peripheral blood samples. The CTC-chip uses antibody-coated microposts to capture CTCs under controlled flow conditions, without requiring pre-labelling or processing of the samples. The device successfully isolated CTCs from the blood of patients with metastatic lung, prostate, pancreatic, breast, and colon cancer in 115 of 116 samples (99%), with CTC counts ranging from 5 to 1,281 per ml and approximately 50% purity. It also isolated CTCs in 7 of 7 patients with early-stage prostate cancer. The CTC-chip demonstrated high sensitivity and specificity, allowing for the monitoring of 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. The CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in cancer patients, with broad implications for cancer biology research and clinical management, including detection, diagnosis, and monitoring of cancer. CTCs are rare, comprising as few as one cell per 10^9 hematologic cells in the blood of patients with metastatic cancer, making their isolation a significant technical challenge. Microfluidic lab-on-a-chip devices offer unique opportunities for cell sorting and rare-cell detection. However, they have shown limited capability to deal with the cellular and fluid complexity of large volumes of whole blood. The CTC-chip, a microfluidic device, can efficiently and reproducibly isolate CTCs from the blood of patients with common epithelial tumours. The CTC-chip consists of an array of microposts functionalized with anti-epithelial-cell-adhesion-molecule (EpCAM) antibodies, which specifically capture CTCs from unfractionated blood. The efficiency of cell capture on the CTC-chip is determined by flow velocity and shear force. The device was optimized using theoretical analyses and simulations, resulting in a CTC-chip containing an array of 78,000 microposts within a 970 mm² surface. The CTC-chip was tested with various cancer cell lines and showed high capture efficiency, with T-24 cells with relatively low EpCAM expression being captured as efficiently as high-level antigen-expressing cells. The CTC-chip was also tested with whole blood samples from healthy donors and cancer patients, showing high capture efficiency and no requirement for blood-sample pre-processing. The CTC-chip was used to identify and enumerate CTCs in cancer patients, with the majority of patients having metastatic disease. The average volume of blood analysed was 2.7 ml per sample.A microfluidic platform called the CTC-chip was developed to efficiently and selectively isolate viable circulating tumour cells (CTCs) from peripheral blood samples. The CTC-chip uses antibody-coated microposts to capture CTCs under controlled flow conditions, without requiring pre-labelling or processing of the samples. The device successfully isolated CTCs from the blood of patients with metastatic lung, prostate, pancreatic, breast, and colon cancer in 115 of 116 samples (99%), with CTC counts ranging from 5 to 1,281 per ml and approximately 50% purity. It also isolated CTCs in 7 of 7 patients with early-stage prostate cancer. The CTC-chip demonstrated high sensitivity and specificity, allowing for the monitoring of 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. The CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in cancer patients, with broad implications for cancer biology research and clinical management, including detection, diagnosis, and monitoring of cancer. CTCs are rare, comprising as few as one cell per 10^9 hematologic cells in the blood of patients with metastatic cancer, making their isolation a significant technical challenge. Microfluidic lab-on-a-chip devices offer unique opportunities for cell sorting and rare-cell detection. However, they have shown limited capability to deal with the cellular and fluid complexity of large volumes of whole blood. The CTC-chip, a microfluidic device, can efficiently and reproducibly isolate CTCs from the blood of patients with common epithelial tumours. The CTC-chip consists of an array of microposts functionalized with anti-epithelial-cell-adhesion-molecule (EpCAM) antibodies, which specifically capture CTCs from unfractionated blood. The efficiency of cell capture on the CTC-chip is determined by flow velocity and shear force. The device was optimized using theoretical analyses and simulations, resulting in a CTC-chip containing an array of 78,000 microposts within a 970 mm² surface. The CTC-chip was tested with various cancer cell lines and showed high capture efficiency, with T-24 cells with relatively low EpCAM expression being captured as efficiently as high-level antigen-expressing cells. The CTC-chip was also tested with whole blood samples from healthy donors and cancer patients, showing high capture efficiency and no requirement for blood-sample pre-processing. The CTC-chip was used to identify and enumerate CTCs in cancer patients, with the majority of patients having metastatic disease. The average volume of blood analysed was 2.7 ml per sample.