Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy.

Hydrogels, natural and synthetic origin, are actively studied for their use for implants and payload carriers. These biomaterials for delivery systems have enormous potential in basic biomedical research, drug development, and long-term delivery of biologics. Nanofibrillated cellulose (NFC) hydrogels, both natural and anionic (ANFC) ones, allow drug loading for immediate and controlled release via the slow drug dissolution of solid drug crystals into hydrogel and its subsequent release. This property makes NFC originated hydrogels an interesting non-toxic and non-human origin material as drug reservoir for long-term controlled release formulation or implant for patient care. A compelling tool for studying NFC hydrogels is Raman spectroscopy, which enables to resolve the chemical structures of different molecules in a high-water content like hydrogels, since Raman spectroscopy is insensitive to water molecules. That offers real time investigation of label-free drugs and their release in high-water-content media. Despite the huge potential of Raman spectroscopy in bio-pharmaceutical applications, the strong fluorescence background of many drug samples masking the faint Raman signal has restricted the widespread use of it. In this study we used a Raman spectrometer capable of suppressing the unpleasant fluorescence background by combining a pulsed laser and time-resolved complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode (SPAD) line sensor for the label-free investigation of Metronidazole and Vitamin C diffusivities in ANFC. The results show the possibility to modulate the ANFC-based implants and drug delivery systems, when the release rate needs to be set to a desired value. More importantly, the now developed label free real-time method is universal and can be adapted to any hydrogel/drug combination for producing reliable drug diffusion coefficient data in complex and heterogeneous systems, where traditional sampling-based methods are cumbersome to use. The wide temporal range of the time-resolved CMOS SPAD sensors makes it possible to capture also the fluorescence decay of samples, giving rise to a combined time-resolved Raman and fluorescence spectroscopy, which provides additional information on the chemical, functional and structural changes in samples.

Temporal and Spatial Focusing in SPAD-Based Solid-State Pulsed Time-of-Flight Laser Range Imaging.

The relation between signal and background noise strengths in single-photon avalanche diode (SPAD)-based pulsed time-of-flight 3-D range imaging is analyzed on the assumption that the SPAD detector is operating in the single photon detection mode. Several practical measurement cases using a 256-pixel solid-state pulsed time-of-flight (TOF) line profiler are presented and analyzed in the light of the resulting analysis. It is shown that in this case it is advantageous to concentrate the available optical average power in short, intensive pulses and to focus the optical energy in spatial terms. In 3-D range imaging, this could be achieved by using block-based illumination instead of the regularly used flood illumination. One modification of this approach could be a source that would illuminate the system FOV only in narrow laser stripes. It is shown that a 256-pixel SPAD-based pulsed TOF line profiler following these design principles can achieve a measurement range of 5-10 m to non-cooperative targets at a rate of ~10 lines/s under bright sunlight conditions using an average optical power of only 260 µW.

Fluorescence suppression in Raman spectroscopy using a time-gated CMOS SPAD.

A Raman spectrometer technique is described that aims at suppressing the fluorescence background typical of Raman spectra. The sample is excited with a high power (65W), short (300ps) laser pulse and the time position of each of the Raman scattered photons with respect to the excitation is measured with a CMOS SPAD detector and an accurate time-to-digital converter at each spectral point. It is shown by means of measurements performed on an olive oil sample that the fluorescence background can be greatly suppressed if the sample response is recorded only for photons coinciding with the laser pulse. A further correction in the residual fluorescence baseline can be achieved using the measured fluorescence tails at each of the spectral points.