Label-Free SERS Quantum Semiconductor Probe for Molecular-Level and in Vitro Cellular Detection: A Noble-Metal-Free Methodology

Abstract

Accurate in vitro molecular-level analysis is an essential step prior to in vivo and clinical application for early diagnosis and cancer treatment. Among the diagnostic techniques, surface-enhanced Raman scattering (SERS) biosensing has shown growing potential due to its noninvasive and real-time characterization of the biomolecules. However, the application of SERS biosensing is mostly limited to the plasmonic noble metals, in the form of either nanoparticles or tips and substrates (fixed probe), on which surface plasmon resonance (SPR) is the prominent enhancement principle. The semiconductor quantum particles have been explored in several optoelectronics applications, but have never been reported to be exploited as a means of surface-enhanced Raman scattering (SERS) for molecular-level and intracellular sensing. Here, we report on the new generation of noble-metal-free SERS probe; Si@SiO₂ quantum probe (Si@SiO₂ Q-probe) whose affinity to functional groups not only imitates a self-driven labeling attribution that enables charge transfer (CT) as an augmented enhancement principle but also its mobile nature in miniaturized scale facilitates endocytosis for in situ live cell biosensing. Moreover, a significant enhancement factor of 10⁶ of rhodamine 6G (R6G) and 10⁷ of glutathione (GSH) at ∼5 × 10^-12 pM concentration has been achieved that is comparable to inherently plasmonic noble metals. Our results showed a capability of the Si@SiO₂ Q-probe to unveil the "biochemical fingerprint" of substantial components of mammalian and cancerous cervical cells, which leads to diagnosis of cervical cancer. These unique attributions of the Si@SiO₂ Q-probe can provide better insight into cell mutation and malignancy.