Construction of a sensitive SWCNTs integrated SPR biosensor for detecting PD-L1+ exosomes based on Fe3O4@TiO2 specific enrichment and signal amplification.

Programmed cell death-ligand 1 positive (PD-L1+) exosomes play a crucial role in the realm of cancer diagnosis and treatment. Nevertheless, due to the intricate nature of biological specimens, coupled with the heterogeneity, low refractive index (RI), and scant surface coverage density of exosomes, traditional surface plasmon resonance (SPR) sensors still do not meet clinical detection requirements. This study utilizes the exceptional electrical and optical attributes of single-walled carbon nanotubes (SWCNTs) as the substrate for SPR sensing, thereby markedly enhancing sensitivity. Furthermore, sp2 hybridized SWCNTs have the ability to load specific recognition elements. Additionally, through the coordination interaction of Ti with phosphate groups and the ferromagnetism of Fe3O4, efficient exosomes isolation and enrichment in complex samples are achievable with the aid of an external magnetic field. Owing to the high-quality and high-RI of Fe3O4@TiO2, the response signal experiences amplification, thus further improving the performance of the SPR biosensor. The linear range of the SPR biosensor constructed by this method is 1.0 × 103 to 1.0 × 107 particles/mL, with a limit of detection (LOD) of 31.9 particles/mL. In the analysis of clinical serum samples, cancer patients can be differentiated from healthy individuals with an Area Under Curve (AUC) of 0.9835. This study not only establishes a novel platform for exosomes direct detection but also offers new perspectives for the sensitive detection of other biomarkers.

Ti3C2Tx MXene -facilitated non-selective trapping effect: Efficient SERS detection of exosomal PD-L1.

Biosensors developed through a sandwich approach have demonstrated favorable detection performance for exosomal programmed cell death 1 ligand 1 (ExoPD-L1) detection. However, the reported PD-L1 antibodies, peptides, and aptamers utilized in these biosensors typically bind to the extracellular region, with overlapping binding sites that severely constrain the fabrication of biosensors. In this study, we present a simple approach to specifically identify and analyze ExoPD-L1 through the non-selective trapping effect of Ti3C2TX (X=-O, -F, -OH) MXene on exosomes via the formation of Ti-O-P complexation, and the selective capture of peptide-functionalized Au@MPBA (4-Mercaptophenylboronic acid) @SiO2 surface enhanced Raman scattering (SERS) tags on ExoPD-L1. The biosensor delivered a both hypersensitive and reliable performance in exosome detection with a low limit of detection (20.74 particles/mL) in the linear range of 102 to 5×106 particles/mL. Furthermore, the biosensor demonstrated excellent stability and interference resistance in detecting ExoPD-L1 in clinical serum samples, enabling the easy differentiation of breast cancer patients from healthy controls. This work provides new insights into the design of biosensors for exosome detection and can serve as a replicable template for sandwich immunoassay detection for other types of sensors, including but not limited to SERS.