Nanogap plasmonic structures, which can strongly enhance electromagnetic fields, enable widespread applications in surface-enhanced Raman spectroscopy (SERS) sensing. Although the directed self-assembly strategy has been adopted for the fabrication of micro/nanostructures on open surfaces, fabrication of nanogap plasmonic structures on complex substrates or at designated locations still remains a grand challenge. Here, a switchable self-assembly method is developed to manufacture 3D nanogap plasmonic structures by combining supercritical drying and capillary-force driven selfassembly (CFSA) of micropillars fabricated by laser printing. The polymer pillars can stay upright during solvent development via supercritical drying, and then can form the nanogap after metal coating and subsequent CFSA. Due to the excellent flexibility of this method, diverse patterned plasmonic nanogap structures can be fabricated on planar or nonplanar substrates for SERS. The measured SERS signals of different patterned nanogaps in fluidic environment show a maximum enhancement factor ≈8 × 10 7 . Such nanostructures in microchannels also allow localized sensing for anticancer drugs (doxorubicin). Resulting from the marriage of top-down and self-assembly techniques, this method provides a facile, effective, and controllable approach for creating nanogap enabled SERS devices in fluidic channels, and hence can advance applications in precision medicine.

Biological nanoparticles are important targets of study, yet their small size and tendency to aggregate makes their heterogeneity difficult to profile on a truly single-particle basis. Here we present a label-free system called ‘Raman-enabled nanoparticle trapping analysis’ (R-NTA) that optically traps individual nanoparticles, records Raman spectra and tracks particle motion to identify chemical composition, size, and refractive index. R-NTA has the unique capacity to characterize aggregation status and absolute chemical concentration at the single-particle level. We validate the method on NIST standards and liposomes, demonstrating that R-NTA can accurately characterize size and chemical heterogeneity, including determining combined morpho-chemical properties such as the number of lamellae in individual liposomes. Applied to extracellular vesicles (EVs), we find distinct differences between EVs from cancerous and noncancerous cells, and that knockdown of the TRPP2 ion channel, which is pathologically highly expressed in laryngeal cancer cells, leads the EVs to more closely resemble EVs from normal epithelial cells. Intriguingly, the differences in EV content are found in small subpopulations of EVs, highlighting the importance of single-particle measurements. These experiments demonstrate the power of the R-NTA system to measure and characterize the morpho-chemical heterogeneity of bionanoparticles.

Maskless etching approaches such as microdischarges and atmospheric pressure plasma jets (APPJs) have been studied recently. Nonetheless, a simple, long lifetime, and efficient maskless etching method is still a challenge. In this work, a separated type maskless etching system based on atmospheric pressure He/O2 plasma jet and microfabricated Micro Electro Mechanical Systems (MEMS) nozzle have been developed with advantages of simple-structure, flexibility, and parallel processing capacity. The plasma was generated in the glass tube, forming the micron level plasma jet between the nozzle and the surface of polymer. The plasma microjet was capable of removing photoresist without masks since it contains oxygen reactive species verified by spectra measurement. The experimental results illustrated that different features of microholes etched by plasma microjet could be achieved by controlling the distance between the nozzle and the substrate, additive oxygen ratio, and etch time, the result of which is consistent with the analysis result of plasma spectra. In addition, a parallel etching process was also realized by plasma microjets array.

Raman spectroscopy is a label-free method of obtaining detailed chemical information about samples. Its compatibility with living tissue makes it an attractive choice for biomedical analysis, yet its translation from a research tool to a clinical tool has been slow, hampered by fundamental Raman scattering issues such as long integration times and limited penetration depth. In this review we detail the how combining Raman spectroscopy with other techniques yields multimodal instruments that can help to surmount the translational barriers faced by Raman alone. We review Raman combined with several optical and non-optical methods, including fluorescence, elastic scattering, OCT, phase imaging, and mass spectrometry. In each section we highlight the power of each combination along with a brief history and presentation of representative results. Finally, we conclude with a perspective detailing both benefits and challenges for multimodal Raman measurements, and give thoughts on future directions in the field.

A localized maskless modification method of polyurethane (PU) films through an atmospheric pressure He/O2 plasma microjet (APPμJ) was proposed. The APPμJ system combines an atmospheric pressure plasma jet (APPJ) with a microfabricated silicon micronozzle with dimension of 30 μm, which has advantages of simple structure and low cost. The possibility of APPμJ in functionalizing PU films with hydroxyl (–OH) groups and covalent grafting of gelatin for improving its biocompatibility was demonstrated. The morphologies and chemical compositions of the modified surface were analyzed by scanning electronic microscopy (SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The fluorescent images show the modified surface can be divided into four areas with different fluorescence intensity from the center to the outside domain. The distribution of the rings could be controlled by plasma process parameters, such as the treatment time and the flow rate of O2. When the treatment time is 4 to 5 min with the oxygen percentage of 0.6%, the PU film can be effectively local functionalized with the diameter of 170 μm. In addition, the modification mechanism of PU films by the APPμJ is investigated. The localized polymer modified by APPμJ has potential applications in the field of tissue engineering.