The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization.

Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (Tg) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (Mw) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different Mw of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer Mw on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes-Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest Mw (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.

Influence of pump beam shaping and noise on performance of a direct diode-pumped ultrafast Ti:sapphire laser.

One of the major factors that limits the widespread use of ultrafast titanium sapphire (Ti:S) lasers in life science is its expensive and complex pump source. Broad area diode laser (BA-DL) based pump sources have high potential to solve this problem, since they are compact, inexpensive and very efficient. However, their non-diffraction limited beam profile makes it challenging to achieve high powers in Kerr-lens mode-locked (KLM) operation of Ti:S lasers. In this work, we show that the ideal way to beam shape two spectrally combined BA-DLs with different beam qualities is to aim for a compromise between matching to the cavity mode diameter and the cavity mode Rayleigh range. We furthermore conclude that the relative intensity noise (RIN) of the BA-DL pumped Ti:S laser, another important parameter for imaging applications, is sufficiently low for a wide range of life science applications. However, for applications that are highly sensitive to noise, new laser diode designs are likely necessary to reduce inherent noise originating within the laser diode.

Phosphor material dependent spot size limitations in laser lighting.

In laser lighting, a major benefit over other lighting techniques is the possibility to achieve very high luminous exitance. Focusing the exciting laser to a very small spot size on the phosphor, however, does not necessarily provide a very small emitting area for the white light. In this study we investigate experimentally and numerically the relationship between the white light spot size and the incident blue laser spot size. We show that the specific phosphor material properties have significant impact on this relationship and on the achievable minimum spot size. This constitutes a limitation on the minimum spot size achievable in laser lighting and has important implications in applications.

Practical, open source, GPU-accelerated, high-fidelity phase retrieval by simultaneous propagations.

Phase retrieval is a highly useful technique that allows the calculation of the complex electric field of a beam of spatially coherent radiation based only on recordings of intensity profiles with a camera. In this work, we demonstrate what we believe, to the best of our knowledge, is a new technique for single-beam multiple-intensity phase retrieval based on simultaneous propagations that provides improved fidelity results compared to standard methods (0.9931 compared to 0.9646) and a 34 dB reduction in background noise level. The implementation is fast, open source, user friendly, and can be run on either CPUs or GPUs. It is available for download at https://gitlab.gbar.dtu.dk/biophotonics/PhaseRetrieval.

Multi-photon attenuation-compensated light-sheet fluorescence microscopy.

Attenuation of optical fields owing to scattering and absorption limits the penetration depth for imaging. Whilst aberration correction may be used, this is difficult to implement over a large field-of-view in heterogeneous tissue. Attenuation-compensation allows tailoring of the maximum lobe of a propagation-invariant light field and promises an increase in depth penetration for imaging. Here we show this promising approach may be implemented in multi-photon (two-photon) light-sheet fluorescence microscopy and, furthermore, can be achieved in a facile manner utilizing a graded neutral density filter, circumventing the need for complex beam shaping apparatus. A "gold standard" system utilizing a spatial light modulator for beam shaping is used to benchmark our implementation. The approach will open up enhanced depth penetration in light-sheet imaging to a wide range of end users.