Rapid and Scalable Preparation of Highly Uniform, Atomically Thin MSe2 (M = Ti, Nb, Ta) Nanosheets as Ultra-Sensitive SERS Substrates for Lateral Flow Immunoassay

Abstract

Surface-enhanced Raman scattering (SERS) substrates based on 2D semimetallic materials have emerged as novel detecting platforms for detecting at the single-molecule level due to the high charge transfer efficiency between the layered materials and analytes. However, current methods such as chemical vapor deposition (CVD) or liquid-phase exfoliation face significant challenges in simultaneously achieving high yield and low defect density in preparing layered materials, which often leads to compromises in SERS efficiency or sensitivity, thereby limiting large-scale applications. Herein, an improved electrochemical cathodic exfoliation (ECE) protocol, developed through recent advancements, is employed to produce highly uniform and solution-processable TiSe₂, NbSe₂, and TaSe₂ monolayers with over 95% yield in 120 min. The SERS sensitivity (10⁻¹⁶ M for Rhodamine 6G) of 2D materials from ECE rivals that of CVD-prepared monolayers due to their low defect density. Using NbSe₂ as the SERS substrate, matrix metalloproteinase-9 in tear fluid is detected across 0.01 to 100 ng mL⁻¹, outperforming conventional enzyme-linked immunosorbent assay methods that typically detect at 1 ng mL⁻¹. The scalability of the modified ECE process not only facilitates its integration into lateral flow immunoassays but also paves the way for bridging the gap between practical applications and highly sensitive SERS detection using 2D materials.