Ultrasensitive surface enhanced Raman scattering nanomotors : for location predicable biochemical detection, single-cell bioanalysis, and controllable biochemical release and real-time detection

Abstract

Localized surface plasmon resonance resulting from the concerted oscillations of conduction-band electrons in noble-metal (Au, Ag) nanostructures greatly induces enhanced electric ([italic E]) fields in confined nanoscale locations, such as on the tips of nanorods or in the junctions of nanodimers. These [italic E]-field enhanced locations are called hot spots. In the vicinity of hot spots, Raman scattering spectra of biochemicals can be substantially amplified with an [italic E]⁴ dependence due to the [italic E]-field enhancement of both the incident light and Raman spectra. This is called surface enhanced Raman scattering (SERS). SERS is known for its high sensitivity in providing fingerprint vibrational information of molecules. It has triggered intense interest because of its potential applications for label-free and multiplex biochemical detection relevant to medical, environmental and defense purposes. However, the tremendous potential of SERS for ultrasensitive detection has still not materialized because of four major obstacles: (1) it is extremely difficult to obtain a large number of hotspots for sensitive and reproducible detection due to the stringent requirement of hot spots of only a few nanometers; (2) it is arduous to achieve ultrasensitivity for the detection of a single/few molecules; (3) it is challenging to assemble the hot-spots at designated positions for location predicable sensing; and (4) it is even more difficult to change the state-of-the-art static/passive sensing schemes into dynamic/robotized schemes and also to incorporate multi-functionality into a single SERS nanostructure. In this research, we addressed the aforementioned problems by rational design, fabrication and robotization of ultrasensitive SERS nanomotor sensors. A nanomotor sensor consists of a tri-layer structure with a three-segment Ag/Ni/Ag nanorod as the core, a thin layer of silica in the center, and uniformly distributed Ag nanoparticles as the outer layer. The inner metallic nanorod core is the key structure in realizing the concept of the robotization of nanosensors, which can be electrically polarized and thus efficiently manipulated by electric tweezers. The presence of the Ni segment in the metallic nanowire core also allows manipulation and assembling by magnetic interactions. The central silica layer provides a supporting substrate for the synthesis of the Ag nanoparticles and separates the Ag nanoparticles from the metallic nanorod core to eliminate the effect of plasmonic quenching. Finally, the outermost layer made of Ag nanoparticles with optimized sizes and junctions provides a large number of hot spots (~1200/μm²) for ultrasensitive SERS detection with single molecule sensitivity and an enhancement factor (EF) of 1.1×10¹⁰. Moreover, two additional SERS enhancement mechanisms were investigated, i.e., the optical management with nanophotonic devices and the near field effect, which can readily increase the EF by 10 and 2 times, respectively, to at least 10¹¹. Finally, three applications of the SERS nanomotor sensors have been demonstrated: (1) the ultrasensitive SERS nanomotors were transported and assembled into a 3×3 array for location predicable sensing of multiplex molecules; (2) ultrasensitive SERS nanomotors were transported to individual living cells amidst many cells for single-cell bioanalysis; and (3) the SERS nanomotor sensors can be controlled to rotate by the electric tweezers for tunable biochemical release and detection. This research, exploring robotized nanosensors by integrating SERS and NEMS, is innovative in both material design and device concept, which could inspire a new device scheme for various bio-relevant applications.