Aptamer‐Signatured Nanoparticle Protein Corona for Size‐Dependent Fluorescent Barcoding Diagnosis

Abstract Cancer‐specific nanoparticl protein corona (NPC) opens a new avenue for biomarker discovery and diagnosis. However, the simultaneous detection of multiplex protein biomarkers from NPC is very challenging owing to ultra‐low abundance and limited detection probes. Here, an aptamer‐signatured NPC (ASNC)‐based size‐dependent fluorescence barcode is developed for flow cytometry profiling (FBFC) sensing platform to diagnose hepatocellular carcinoma (HCC). First, HCC‐specific NPC is obtained from incubating magnetic nanoparticles with clinical serum samples. A 12‐aptamer panel is incubated with NPC for the assembly of ASNC. Six aptamers are selected from the preliminary profiling of 30 HCC and healthy controls, resulting in ASNC for subsequent multiplex detection. To achieve simultaneous and orthogonal detection in one pot, advantage of the size‐dependent fluorescent microbeads are taken to profile the signature aptamers eluted from NPC via flow cytometry‐distinguishable barcodes. With 84 clinical HCC and healthy serum samples, a diagnostic accuracy of 94.12%, have attained which is higher than other single biomarkers or any combinations. Overall, by transferring protein biomarkers to ASNC, a simultaneous and multiplex ASNC‐based FBFC platform have developed which holds immense potential in facile and precise cancer diagnosis.