Click conjugation using discrete polyketones enables dual anchoring of antibodies and nanowires for exosome profiling

Targeted molecular capture from complex biological fluids remains a critical challenge in extracellular vesicle (EV) analysis. Here we develop a nanowire-based microfluidic platform functionalized via a single-step click conjugation using N-hydroxysuccinimide-functionalized polyketones (pKNHSs) with discrete chain lengths. Tetrameric pKNHS enabled efficient and stable antibody immobilization on ZnO nanowires while minimizing non-specific adsorption. This chemically defined interface facilitated the selective capture of EVs from both cultured cells and serum, preserving membrane proteins and encapsulated miRNAs. Using antibody-modified nanowires, we identified distinct miRNA signatures associated with specific membrane markers in serum samples from patients with high-grade serous ovarian carcinoma. These results highlight the ability of discrete, chain-engineered polyketones to enable robust and tunable bioconjugation chemistry. The discrete-length polymer design also offers a generalizable strategy for precision surface engineering. Our approach offers a modular strategy for EV enrichment and molecular profiling with potential applications in liquid biopsy and precision diagnostics.