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, nanofunctionalised 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 µL min-1. 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.