Competitive effect-derived surface-enhanced Raman scattering for analysis of glutathione based on a gold...

Glutathione (GSH) plays a pivotal role in maintaining intracellular redox potential and regulating cellular signaling pathways. As a central antioxidant in human cells, its concentration not only reflects the cellular capacity to counteract oxidative stress but is also closely associated with overall physiological homeostasis and the progression of various pathologies. This strong physiological correlation underscores the pressing need to develop a reliable, rapid, and straightforward method for high-throughput GSH analysis. Therefore, there is a significant and growing demand for the development of a simple, easy-to-fabricate, highly efficient, and robust platform that enables accurate monitoring of GSH.

In this study, we present a rapid and high-efficient biosensing platform for GSH detection, leveraging the competitive binding interaction between GSH-Hg²⁺ coordination and T-Hg²⁺-T base pairing. This GSH biosensor was fabricated through the sequential assembly of gold nanotriangles (AuNTs), DNA1, Hg²⁺, DNA2, gold nanoparticles (AuNPs), and 4-mercaptobenzoic acid (4Mbn) onto a glass nanocapillary, yielding an integrated nanocapillary-AuNTs-DNA1-Hg²⁺-DNA2-AuNPs-4Mbn biosensor system. Coupled with surface-enhanced Raman scattering (SERS) techniques, this platform enables quantitative GSH detection over a wide concentration range from 10^-9 to 10^-3 M, achieving a detection limit as low as 10^-9 M. Furthermore, This GSH biosensor demonstrated outstanding selectivity toward GSH against potential interferents including glycine, glutamic acid, leucine, lysine, and cysteine owing to the stronger interactions between GSH and Hg²⁺ than the other amino acids, resulting in a significant decrease of Raman scattering intensity at 2225.2 cm^-1.

This innovative system enables efficient and rapid detection of GSH through a rationally designed competitive mechanism between GSH-Hg²⁺ coordination and T-Hg²⁺-T base pairing, allowing selective and quantitative analysis. The proposed platform establishes a versatile foundation for biomolecule monitoring via SERS-integrated nanocapillary technology, while also inspiring the future development of advanced nanofluidic devices.