Label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering using a microfluidic chip

Surface-enhanced Raman scattering (SERS), owing to its high sensitivity based on localized surface plasmon resonance of nanostructured metals, is recently attracting much attention to be used for biotechnology, such as cell imaging and tumor therapy. On the other hand, the trace detection of bio-molecules with large molecular weight is still challenging because the troublesome treatment of SERS substrate using coupling or cross-linking agents is required. In this paper, we apply liquid interface assisted SERS (LI-SERS) method, which provides unique features of collection and self-immobilization of analyte molecules on the SERS substrate, to realize the label-free trace detection of bio-molecules with detection limits of pM similar to fM. Specifically, deoxyribonucleic acid (DNA) discrimination and quantitative detection of beta-Amyloid (A beta) in trace-concentration are demonstrated to illustrate the ultrahigh sensitivity and versatility of the LI-SERS method. The results suggest LI-SERS is promising for the early-stage diagnosis of diseases such as virus infection and Alzheimer's disease.