Significance: Raman spectroscopy has been developed for surgical guidance applications interrogating live tissue during tumor resection procedures to detect molecular contrast consistent with cancer pathophysiological changes. To date, the vibrational spectroscopy systems developed for medical applications include single-point measurement probes and intraoperative microscopes. There is a need to develop systems with larger fields of view (FOVs) for rapid intraoperative cancer margin detection during surgery. Aim: We design a handheld macroscopic Raman imaging system for in vivo tissue margin characterization and test its performance in a model system. Approach: The system is made of a sterilizable line scanner employing a coherent fiber bundle for relaying excitation light from a 785-nm laser to the tissue. A second coherent fiber bundle is used for hyperspectral detection of the fingerprint Raman signal over an area of 1 cm 2. Machine learning classifiers were trained and validated on porcine adipose and muscle tissue. Results: Porcine adipose versus muscle margin detection was validated ex vivo with an accuracy of 99% over the FOV of 95 mm 2 in ∼3 min using a support vector machine. Conclusions: This system is the first large FOV Raman imaging system designed to be integrated in the workflow of surgical cancer resection. It will be further improved with the aim of discriminating brain cancer in a clinically acceptable timeframe during glioma surgery.

The performance of optical coatings may be negatively affected by the deleterious effects of mechanical stress. In this work, we propose an optimization tool for the design of optical filters taking into account both the optical and mechanical properties of the substrate and of the individual deposited layers. The proposed method has been implemented as a supplemental module in the OpenFilters open source design software. It has been experimentally validated by fabricating multilayer stacks using e-beam evaporation, in combination with their mechanical stress assessment performed as a function of temperature. Two different stress-compensation strategies were evaluated: (a) design of two complementary coatings on either side of the substrate and (b) implementing the mechanical properties of the individual materials in the design of the optical coating on one side only. This approach has been tested by the manufacture of a Fabry-Perot etalon used in astronomy while using evaporated SiO2 and TiO2 films. We found that the substrate curvature can be decreased by 85% and 49% for the first and second strategies, respectively.

Attainable levels of signal-to-background ratio (SBR) in Raman spectroscopy of biological samples is limited by the presence of endogenous fluorophores. It is customary to remove the ubiquitous fluorescence background using postacquisition data processing. However, new approaches are needed to reduce background contributions and maximize the fraction of the sensor dynamical range occupied by Raman photons. Time-resolved detection using pulsed lasers and time-gated

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