In this work, we utilize a short-wavelength, 532-nm picosecond pulsed laser coupled with a time-gated complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector to acquire Raman spectra of several drugs of interest. With this approach, we are able to reveal previously unseen Raman features and suppress the fluorescence background of these drugs. Compared to traditional Raman setups, the present time-resolved technique has two major improvements. First, it is possible to overcome the strong fluorescence background that usually interferes with the much weaker Raman spectra. Second, using the high photon energy excitation light source, we are able to generate a stronger Raman signal compared to traditional instruments. In addition, observations in the time domain can be performed, thus enabling new capabilities in the field of Raman and fluorescence spectroscopy. With this system, we demonstrate for the first time the possibility of recording fluorescence-suppressed Raman spectra of solid, amorphous and crystalline, and non-photoluminescent and photoluminescent drugs such as caffeine, ranitidine hydrochloride, and indomethacin (amorphous and crystalline forms). The raw data acquired by utilizing only the picosecond pulsed laser and a CMOS SPAD detector could be used for identifying the compounds directly without any data processing. Moreover, to validate the accuracy of this time-resolved technique, we present density functional theory (DFT) calculations for a widely used gastric acid inhibitor, ranitidine hydrochloride. The obtained time-resolved Raman peaks were identified based on the calculations and existing literature. Raman spectra using non-time-resolved setups with continuous-wave 785- and 532-nm excitation lasers were used as reference data. Overall, this demonstration of time-resolved Raman and fluorescence measurements with a CMOS SPAD detector shows promise in diverse areas, including fundamental chemical research, the pharmaceutical setting, process analytical technology (PAT), and the life sciences.Graphical abstractTime-resolved Raman measurement of a pharmaceutical sample using the complementary metal-oxide semiconductor (CMOS) single photon avalanche diode (SPAD) detector technologyElectronic supplementary materialThe online version of this article (doi:10.1007/s00216-015-9156-6) contains supplementary material, which is available to authorized users.

A refractive index sensor based on slot waveguide Young interferometer was developed in this work. The interferometer was fabricated on a polymer platform and operates at a visible wavelength of 633 nm. The phase shift of the interference pattern was measured with various concentrations of glucose-water solutions, utilizing both TE and TM polarization states. The sensor was experimentally observed to detect a refractive index difference of 6.4 × 10(-6) RIU. Furthermore, the slot Young interferometer was found to compensate for temperature variations. The results of this work demonstrate that high performance sensing capability can be obtained with a polymeric slot Young interferometer, which can be fabricated by a simple molding process.

We examine the conditions for appearance of symmetry breaking bifurcation in damped and periodically driven pendulum in the case of strong damping. We show that symmetry breaking, unlike other nonlinear phenomena, can exist at high dissipation. We prove that symmetry breaking phases exist between phases of symmetric normal and symmetric inverted oscillations. We find that symmetry broken solutions occupy a sufficiently smaller region of pendulum's parameter space in comparison to the statements made in earlier considerations [McDonald and Plischke, Phys. Rev. B 27 (1983) 201]. Our research on symmetry breaking in a strongly damped pendulum is relevant to an understanding of phenomena of dynamic symmetry breaking and rectification in a pure ac driven semiconductor superlattices.

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Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 × (2) × 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.