Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells

Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients. Over the past decade, a series of NanoVelcro CTC Assays has been demonstrated for exploring the full potential of CTCs as a clinical biomarker, including CTC enumeration, phenotyping, genotyping and expression profiling.

Conceptual illustration of three generations of the NanoVelcro CTC Assays
developed by the UCLA team to achieve different clinical utilities

1^st-Gen NanoVelcro Chip [9, 80], composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. In conjunction with the use of the laser capture microdissection (LCM) technique, 2^nd-gen NanoVelcro-LMD technology [16, 81, 82], was developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping. By grafting thermoresponsive polymer brushes onto SiNS, 3^rd-gen Thermoresponsive NanoVelcro CTC Chips [83, 84] were developed for purification of CTCs via capture and release of CTCs at 37°C and 4°C, respectively. The surface-grafted polymer brushes were responsible for altering the accessibility of the capture agent on NanoVelcro substrates, allowing for rapid CTC purification with desired viability and molecular integrity.