Clinical available circulating tumor cell assay based on tetra(4-aminophenyl) porphyrin mediated reduced graphene oxide field effect transistor

Abstract

Circulating tumor cell (CTC) assay is one of the emerging “liquid biopsy” for cancer's diagnostic, an easy-to-operate and state-of-the-art CTC sensor is the imperative need of clinical medical laboratory. A label-free and solid-state sensor for clinical sample's CTC detection based on an aptamer (AS1411) functionalized graphene field effect transistor (GFET) by using tetra(4-aminophenyl) porphyrin mediated reduced graphene oxide as the channel material. Objects are CTCs of A549, MDA-MB-231, HeLa and HUVEC (as a control) in buffer solutions and EDTA anti-coagulant whole blood samples, as well as the anti-coagulant clinical blood samples from 49 breast cancer patients and 5 healthy persons. The sensitivities for CTCs in the range of 10 - 106 cells/ml are 3.14, 3.32, 2.60%/log10(cells/ml) for A549 (R2 = 0.97), MDA-MB-231 (R2 = 0.96) and HeLa (R2 = 0.98), respectively. Meanwhile, the selectivity for CTCs is also confirmed by the low sensitivity and R2 for HUVEC which are −0.13%/log10(cells/ml) and 0.50. Furthermore, whole blood interference is found to make the sensing range narrow. At last, their applications in grading clinical blood samples are found to be in agreements with the parallel diagnostic conclusions of these patients, samples of adenofibroma and effect of chemotherapy can also be identified. The aptamer specific, directly electronic CTC detection is accomplished by the proposed GFET based CTC sensor, it can provide a novel analytical technique for cancers' clinical assay.