Near-infrared analysis of nanofibrillated cellulose aerogel manufacturing.

Biomaterial aerogel fabrication by freeze-drying must be further improved to reduce the costs of lengthy freeze-drying cycles and to avoid the formation of spongy cryogels and collapse of the aerogel structures. Residual water content is a critical quality attribute of the freeze-dried product, which can be monitored in-line with near-infrared (NIR) spectroscopy. Predictive models of NIR have not been previously applied for biomaterials and the models were mostly focused on the prediction of only one formulation at a time. We recorded NIR spectra of different nanofibrillated cellulose (NFC) hydrogel formulations during the secondary drying and set up a partial least square regression model to predict their residual water contents. The model can be generalized to measure residual water of formulations with different NFC concentrations and the excipients, and the NFC fiber concentrations and excipients can be separated with the principal component analysis. Our results provide valuable information about the freeze-drying of biomaterials and aerogel fabrication, and how NIR spectroscopy can be utilized in the optimization of residual water content.

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.

Chemical imaging of human teeth by a time-resolved Raman spectrometer based on a CMOS single-photon avalanche diode line sensor.

Raman spectroscopy is a powerful analytical tool to be used in many biomedical applications and could be potentially translated into clinical work. The challenge of Raman spectroscopy in biomedical applications is the high inherent fluorescence of biological samples. One promising method to suppress the fluorescence background is to use pulsed lasers and time-gated detectors but the complexity of time-gated systems has hindered their widespread usage. We present here chemical imaging of human teeth by means of a new kind of compact and practical fluorescence-suppressed Raman spectrometer based on a time-resolved 16 × 256 CMOS single-photon avalanche diode (SPAD) line sensor with an integrated 256-channel 3-bit on-chip time-to-digital converter. The chemical images were constructed by utilizing a simple unsupervised machine learning algorithm (k-means clustering). The high quality of Raman spectra measured with the time-resolved CMOS SPAD-based Raman spectrometer was verified by comparing the spectra to those collected with a commercial conventional continuous wave (CW) Raman spectrometer. The spectra measured by using the time-resolved CMOS SPAD-based Raman spectrometer had 4.4-8.8 times higher signal to peak-to-peak noise ratio values than the spectra from the CW Raman spectrometer when the same radiant exposure (∼300 J mm-2) was used with both spectrometers. This paper shows in practice the potential of time-resolved CMOS SPAD-based Raman spectroscopy in the field of biomedicine and we expect that the presented technology could pave the way for the development of new kind of compact and practical fluorescence-suppressed Raman spectrometers to be used both in biomedical research and clinical settings.

Distance-Resolving Raman Radar Based on a Time-Correlated CMOS Single-Photon Avalanche Diode Line Sensor.

Remote Raman spectroscopy is widely used to detect minerals, explosives and air pollution, for example. One of its main problems, however, is background radiation that is caused by ambient light and sample fluorescence. We present here, to the best of our knowledge, the first time a distance-resolving Raman radar device that is based on an adjustable, time-correlated complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode line sensor which can measure the location of the target sample simultaneously with the normal stand-off spectrometer operation and suppress the background radiation dramatically by means of sub-nanosecond time gating. A distance resolution of 3.75 cm could be verified simultaneously during normal spectrometer operation and Raman spectra of titanium dioxide were distinguished by this system at distances of 250 cm and 100 cm with illumination intensities of the background of 250 lux and 7600 lux, respectively. In addition, the major Raman peaks of olive oil, which has a fluorescence-to-Raman signal ratio of 33 and a fluorescence lifetime of 2.5 ns, were distinguished at a distance of 30 cm with a 250 lux background illumination intensity. We believe that this kind of time-correlated CMOS single-photon avalanche diode sensor could pave the way for new compact distance-resolving Raman radars for application where distance information within a range of several metres is needed at the same time as a Raman spectrum.