Integrated Micro Nanotechnology for Sensitive Detection of Cancer Cells in Circulation

Circulating tumor cells (CTCs) are shed from the primary tumor into the peripheral blood. CTCs are emerging as important biomarkers with high clinical relevance. Enumeration of CTCs may have several clinical uses, including determination of prognosis in patients with established malignancy, or even detection of previously undiagnosed cancer.  However, due to the limitation of sensitivity and specificity of current technologies for CTC isolation, the full potential of CTCs has yet to be realized. Emerging microfluidic technologies are promising for isolating CTCs with a high yield; however, these platforms often have three-dimensional structures, thus lacking the advantages of traditional planar surface and limiting further characterization and expansion of cells on the chip. Here we describe a new approach to more effectively isolate CTCs incorporating the nanomaterial, graphene oxide (GO). Using self-assembly of GO on a patterned gold surface, we create islands of nano-arms for sensitive CTC capture without the aid of three dimensional posts or structures. The capture is truly planar and we demonstrate the isolation of cells with high sensitivity even at low frequency of target cells (75.22% ±29.46 at 5 cells/mL spiked in blood). This 2D planar GO-chip provides a maximum recovery rate of 95% and a stable mean capture efficiency of 82% up to 3 mL/hr sample processing rate. The cells are specifically captured on the planar islands of nano-arms and are able to proliferate after capture when placed in culture conditions in the chip. We further show that the GO-chip is able to capture CTCs from blood samples collected from pancreatic, breast and lung cancer patients. In summary, we present here a novel integrated nano microfluidic technology using GO for sensitive planar capture of CTCs.