Abstract
The separation of circulating tumor cells (CTCs) from the peripheral blood is an important issue that has been highlighted because of their high clinical potential. However, techniques that depend solely on tumor-specific surface molecules or just the larger size of CTCs are limited by tumor heterogeneity. Here, we present a slanted weir microfluidic device that utilizes the size and deformability of CTCs to separate them from the unprocessed whole blood. By testing its ability using a highly invasive breast cancer cell line, our device achieved a 97% separation efficiency, while showing an 8-log depletion of erythrocytes and 5.6-log depletion of leukocytes. We also developed an image analysis tool that was able to characterize the various morphologies and differing deformability of the separating cells. From the results, we believe our system possesses a high potential for liquid biopsy, aiding future cancer research.
Highlights
Circulating tumor cells (CTCs) are cells that are shed from the primary tumor, in the early stage of tumor formation and growth, that circulate through the bloodstream forming secondary tumors on distant organs
From the videos provided by the image analysis tool, we found the hemocytes being dragged to the separation outlet along in fibrin clot or in the skewed flow stream formed by large thrombus, microemboli, or bubbles (Figure S5)
We have developed and demonstrated the slanted weir microfluidic device that was able to efficiently separate tumor cells, with minimized contamination from hemocytes
Summary
Circulating tumor cells (CTCs) are cells that are shed from the primary tumor, in the early stage of tumor formation and growth, that circulate through the bloodstream forming secondary tumors on distant organs. They are very rare in the bloodstream; a single tumor cell could be surrounded by a billion background blood cells. Once properly separated from a patient, CTCs can provide a variety of crucial information regarding cancer and its metastasis [1]. The number of CTCs can be utilized in early detection, and in the prognosis of cancer and real-time monitoring of the effectiveness of therapy [2,3]. When viable CTCs are retrieved with a high purity, their molecular characterization can assist therapeutic selection and scheme to realize personalized treatments for the patient [1,2,3].
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