While surface enhanced Raman spectroscopy (SERS) based biosensing has demonstrated great potential for point-of-care diagnostics in the laboratory, its application in the field is limited by the short life time of commonly used silver based SERS active substrates. In this work, we report our attempt towards SERS based field biosensing, involving the development of a novel sustained and cost-effective substrate composed of silver nanoparticles protected by small nitrogen-doped Graphene Quantum Dots, i.e. Ag NP@N-GQD, and its systematic evaluation for glucose sensing. The new substrate demonstrated significantly stronger Raman enhancement compared to pure silver nanoparticles. More importantly, the new substrate preserved SERS performance in a normal indoor environment for at least 30 days in both the wet and dry states, in contrast to only 10 days for pure silver nanoparticles. The Ag NP@N-GQD thin film in the dry state was then successfully applied as a SERS substrate for glucose detection in mouse blood samples. The new substrate was synthesized under mild experimental conditions, and the cost increase due to N-GQD was negligible. These results suggest that the Ag NP@N-GQD is a cost-effective and sustained SERS substrate, the development of which represents an important step towards SERS based field biosensing.

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Raman spectroscopic imaging is a powerful label-free tool for studying cells and tissues in biology and medicine, but it suffers from extremely slow data acquisition. In this Letter, a novel multi-channel Raman imaging technique is proposed to speed up Raman acquisition. Wide-field Raman images are taken in multiple narrow-band channels, each through a different bandpass filter, simultaneously in one camera frame. Then Wiener estimation is used to quickly reconstruct the full Raman spectrum at each pixel from narrow-band measurements. The proposed system with four channels was evaluated in the mixtures of two and three chemicals exhibiting strong Raman scattering because of convenience in the verification of reconstructed spectra. This new technique is expected to overcome the limitation of traditional Raman spectroscopic imaging in speed, and expand its applications in the label-free analysis of both biological and non-biological samples, where potential species are known and fast imaging is required to investigate temporally varying events.

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Depth sensitive Raman spectroscopy has been shown effective in the detection of depth dependent Raman spectra in layered tissues. However, the current techniques for depth sensitive Raman measurements based on fiber-optic probes suffer from poor depth resolution and significant variation in probe-sample contact. In contrast, those lens based techniques either require the change in objective-sample distance or suffer from slow spectral acquisition. We report a snapshot depth-sensitive Raman technique based on an axicon lens and a ring-to-line fiber assembly to simultaneously acquire Raman signals emitted from five different depths in the non-contact manner without moving any component. A numerical tool was developed to simulate ray tracing and optimize the snapshot depth sensitive setup to achieve the tradeoff between signal collection efficiency and depth resolution for Raman measurements in the skin. Moreover, the snapshot system was demonstrated to be able to acquire depth sensitive Raman spectra from not only transparent and turbid skin phantoms but also from ex vivo pork tissues and in vivo human thumbnails when the excitation laser power was limited to the maximum permissible exposure for human skin. The results suggest the great potential of snapshot depth sensitive Raman spectroscopy in the characterization of the skin and other layered tissues in the clinical setting or other similar applications such as quality monitoring of tablets and capsules in pharmaceutical industry requiring the rapid measurement of depth dependent Raman spectra.