Multiplex Cellular Microenvironment Detection Based on Surface-Enhanced Raman Scattering Patch

Abstract

Monitoring cellular microenvironment is of vital significance to study cell process, reveal pathological state, and predict early disease. Herein, a surface-enhanced Raman scattering (SERS) patch is proposed to sense the hydrogen peroxide (H₂O₂) concentration and pH variation of extracellular microenvironment in a multiplex manner. Scale-up and ordered gold nanorods (AuNRs) assembly is introduced by interfacial assembly and absorption transferring on the flexible polydimethylsiloxane (PDMS) film, providing the patch with great SERS enhancement for biosensing. The modification of H₂O₂-responsive and pH-susceptive Raman reporter molecule endows the SERS patch with high sensitivity to multiple analytes, and the construction of multivariate curve resolution (MCR) analysis facilitates the quantification of H₂O₂ and pH value in spite of the characteristic peaks overlap. Furthermore, the SERS patch is used to compare the extracellular microenvironments of different living cells. Results demonstrate that highly migratory cells (i.e., MDA-MB-231) secreted more H₂O₂ under phorbol 12-myristate 13-acetate (PMA) stimulation, and the extracellular microenvironment is more acidic than the cells with weak migration ability (i.e., MCF-7), revealing the relationship between cell migration and microenvironment. The strategy integrates H₂O₂ detection and pH determination in one patch, which may offer an approach for novel multiplex biosensor and cell migration investigation.