Live circulating tumour cells selection on digitized self-assembled cell array (Digi-saca) chip by in-parallel/in-situ image analysis, cell capture, and cultivation

Cancer is one of the major and most deadly diseases of mankind. With present technologies, early detection and prevention of cancer disease is still a major bottleneck. Circulating Tumor Cells (CTC) is one of the cancer biomarkers for the diagnosis of metastasis. However, there is an urgent need to improve the turn around time of CTC detection from a small sample volume in order to promote its clinical implications. This paper highlights Digi-SACA, an automated workflow to capture CTCs from the whole blood on self-assembled cell array chips. The gravity force and lateral driving force based microfluidic chip drive the mononuclear blood cells from 4 ml of samples to form a monolayer without any external fluid control equipment. The subsequent immunostaining and automated image acquisition, image processing, CTC enumeration, and CTC harvest can be completed within 4 h. The sensitivity of Digi-SACA chip is 1 in ten million leukocytes which is very promising for early detection of the CTC. In a small pilot study series, the Digi-SACA chip is able to detect of the mean of 14.4 CTCs from 4 ml of blood in 10 clinical samples from patients with breast cancer, while mean of 17.6 CTCs were measured from the same sample set with IsoFlux™ platform from 4 ml of blood. We have also demonstrated the efficiency of our technique to pick CTC with glass micropipettes for standard cell culture growth up to 11–15 days. Overall, our study represents the liability of the Digi-SACA system in CTCs enumeration, detection, and isolation against the state-of-the-art.