Immunoaffinity-based liquid biopsies of circulating tumour 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 optimising the nano-,
micro- and macro-scales of a CTC enrichment device that is both simple to
fabricate and operate. At its core is a scalable macroscale mesh with optimised
micropores, nano-functionalised with antibodies against cell surface proteins.
Unlike other affinity-based liquid biopsies, optimum capture can be achieved
independently of the 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. To demonstrate its post-processing
capabilities, we used immunofluorescence labelling to identify PD-L1+ CTCs in
36% of patients (n=33) as potential responders to immune checkpoint inhibition
therapy. Finally, our device achieved an 80% positive match in the
identification of HER2+ breast cancer (n=26) compared to clinical standard FISH
on solid biopsy. The results suggest that our approach, which overcomes major
limitations previously associated with affinity-based liquid biopsies, could
provide a versatile tool to improve cancer management.Comment: 21 pages, 5 figures (+ supplementary materials: 11 pages, 10 figures