Multifunctional nanoprobe-enhanced capillary immunoassay: A sensitive dual mode SERS-photothermal biosensor for prostate cancer diagnosis.

The prostate cancer Enzyme-Linked Immunosorbent Assay (ELISA) diagnostic kit in serum facilitates effective screening and monitoring of prostate cancer. However, it has limitations such as complex procedures, low sensitivity, single-signal readout, and susceptibility to inactivation. In this study, we developed a sensitive dual mode biosensor for prostate cancer diagnosis, combining a multifunctional nanoprobe with capillary enzyme-linked immunosorbent assay (CLISA). The capillary, modified with capture antibodies, acts as a swab, integrating in situ trace sampling and the detection process, thereby eliminating the separation between sampling and detection in conventional ELISA. A multifunctional labeling biosensor was developed using a polydopamine (PDA) coating strategy with gold-platinum nanostars (AuNs@Pt) as the core. This newly designed biosensor simultaneously exhibits peroxidase-like activity and SERS (surface-enhanced Raman Spectroscopy) enhancement effect, meanwhile demonstrating excellent photothermal conversion efficiency up to 74.51 %. Furthermore, the PDA coating serves as a physical barrier that effectively inhibits oxidative deactivation of the metal nanoprobes, ensuring long-term stability of the biosensor. Under optimal conditions, the integrated nanoprobe-enhanced CLISA biosensor successfully achieved sensitive and specific detection of prostate specific antigen (PSA). The detection limit of the SERS mode is 0.07 pg/mL, while the detection limit of the photothermal mode is 0.1 pg/mL, which are both much more sensitive than the detection limit of the ELISA diagnostic kit (3.5 pg/mL). Based on a double-blind study involving serum samples from 11 prostate cancer patients and 11 healthy donors, the proposed biosensor demonstrated the ability to well identify prostate cancer serum samples. This biosensor does not require complicated procedures, making it potential for at-home prostate cancer screening.