Flow Rate Independent Multiscale Liquid Biopsy for Precision Oncology

TL;DR

This paper introduces a scalable, flow rate independent liquid biopsy device that efficiently captures circulating tumor cells, demonstrating high sensitivity and specificity for cancer detection and therapy response prediction.

Contribution

The authors develop a novel mesh-based enrichment device that maintains high capture efficiency across flow rates, improving upon existing affinity-based liquid biopsy methods.

Findings

Achieved over 75% capture efficiency between 50-200 uL/min flow rates.

Demonstrated 96% sensitivity and 100% specificity in detecting CTCs in patient blood samples.

Successfully identified potential responders to immunotherapy and HER2-positive breast cancer cases.

Abstract

Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management, but typically suffer from low throughput, relative complexity and post-processing limitations. Here we address these issues simultaneously by decoupling and independently optimizing the nano-, micro- and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate, as demonstrated with constant capture efficiencies, above 75% between 50-200 uL/min. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. We demonstrate its post processing capacity with the identification of potential responders to immune checkpoint inhibition therapy and the detection of HER2 positive breast cancer. The results compare well with other assays, including clinical standards. This suggests that our approach, which overcomes major limitations associated with affinity-based liquid biopsies, could help improve cancer management.