Trace detection of bio-molecules with large molecular weight using surface-enhanced Raman scattering (SERS) method 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 ~ fM. Specifically, DNA discrimination and quantitative detection of β-Amyloid (Aβ) in trace-concentration are demonstrated to illustrate the ultrahigh sensitivity and versatility of the LI-SERS method.
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