Abstract: A method and apparatus for photon, ion or particle counting described that provides seven orders of magnitude of linear dynamic range (LDR) for a single detector. By explicitly considering the log-normal probability distribution in voltage transients as a function of the number of photons, ions or particles present, the binomial distribution of observed counts for a given threshold, the mean number of photons, ions or particles can be determined well beyond the conventional limit.

Abstract: The present disclosure provides a system and method for efficiently mining multi-threshold measurements acquired using photon counting pixel-array detectors for spectral imaging and diffraction analyses. Images of X-ray intensity as a function of X-ray energy were recorded on a 6 megapixel X-ray photon counting array detector through linear fitting of the measured counts recorded as a function of counting threshold. An analytical model is disclosed for describing the probability density of detected voltage, utilizing fractional photon counting to account for edge/corner effects from voltage plumes that spread across multiple pixels. Three-parameter fits to the model were independently performed for each pixel in the array for X-ray scattering images acquired for 13.5 keV and 15.0 keV X-ray energies. From the established pixel responses, multi-threshold composite images produced from the sum of 13.5 keV and 15.

Abstract: An impact-driven apparatus and method to achieve triboluminescence of homochiral API crystals as a measurement tool for rapidly assessing the presence of trace crystallinity within nominally amorphous pharmaceutical powders. The apparatus may include a kinetic energy director and two plates which hold a sample for testing. The triboluminescence may also be achieve by an acoustic transducer.

Abstract: Methods for determining the 3-D structures of proteins. Such a method includes incorporating a compound into a protein crystal such that the compound enhances the activity of the protein crystal to second harmonic generation, illuminating the protein crystal with a sufficiently intense light to cause second harmonic generation by the protein crystal, and detecting a second harmonic generation response produced by the protein crystal that is suitable for protein structure determination by diffraction analysis.

Abstract: A method and apparatus for photon, ion or particle counting described that provides seven orders of magnitude of linear dynamic range (LDR) for a single detector. By explicitly considering the log-normal probability distribution in voltage transients as a function of the number of photons, ions or particles present, the binomial distribution of observed counts for a given threshold, the mean number of photons, ions or particles can be determined well beyond the conventional limit.

Abstract: Methods for determining the 3-D structures of proteins. Such a method includes incorporating a compound into a protein crystal such that the compound enhances the activity of the protein crystal to second harmonic generation, illuminating the protein crystal with a sufficiently intense light to cause second harmonic generation by the protein crystal, and detecting a second harmonic generation response produced by the protein crystal that is suitable for protein structure determination by diffraction analysis.

Abstract: A beam-scanning optical design is described for achieving up to kHz frame-rate optical imaging on multiple simultaneous data acquisition channels. In one embodiment, two fast-scan resonant mirrors direct the optical beam on a circuitous trajectory through the field of view, with the trajectory repeat-time given by the least common multiplier of the mirror periods. Dicing the raw time-domain data into sub-trajectories combined with model-based image reconstruction (MBIR) 3D in-painting algorithms allows for effective frame-rates much higher than the repeat time of the Lissajous trajectory. Because sub-trajectory and full-trajectory imaging are different methods of analyzing the same data, both high-frame rate images with relatively low resolution and low frame rate images with high resolution are simultaneously acquired.

Abstract: A beam-scanning optical design is described for achieving up to kHz frame-rate optical imaging on multiple simultaneous data acquisition channels. In one embodiment, two fast-scan resonant mirrors direct the optical beam on a circuitous trajectory through the field of view, with the trajectory repeat-time given by the least common multiplier of the mirror periods. Dicing the raw time-domain data into sub-trajectories combined with model-based image reconstruction (MBIR) 3D in-painting algorithms allows for effective frame-rates much higher than the repeat time of the Lissajous trajectory. Because sub-trajectory and full-trajectory imaging are different methods of analyzing the same data, both high-frame rate images with relatively low resolution and low frame rate images with high resolution are simultaneously acquired.

Abstract: A method for quantifying crystallinity within a sample using second harmonic generation microscopy is described herein. In one aspect, a method for reducing the timeframe for accelerated stability testing of amorphous solid dispersions of active pharmaceutical ingredients though identifying regions of interest to quantify crystallinity and composition is presented herein.

Abstract: A quantitative optical microscopy arrangement is described. Specifically, a digital filter derived from linear discriminant analysis is described for recovering impulse responses in applications that may include photon counting from a high speed photodetector and applied to remove ringing distortions from impedance mismatch in multiphoton fluorescence microscopy. Training of the digital filter is achieved by defining temporally coincident and non-coincident transients and identifying the projection within filter-space that best separates the two classes. The training allows rapid data analysis by digital filtering. The LDA filter is also capable of recovering deconvolved impulses for single photon counting from highly distorted ringing waveforms from an impedance mismatched photomultiplier tube.

Abstract: A beam-scanning optical design is described for achieving up to kHz frame-rate optical imaging on multiple simultaneous data acquisition channels. In one embodiment, two fast-scan resonant mirrors direct the optical beam on a circuitous trajectory through the field of view, with the trajectory repeat-time given by the least common multiplier of the mirror periods. Dicing the raw time-domain data into sub-trajectories combined with model-based image reconstruction (MBIR) 3D in-painting algorithms allows for effective frame-rates much higher than the repeat time of the Lissajous trajectory. Because sub-trajectory and full-trajectory imaging are different methods of analyzing the same data, both high-frame rate images with relatively low resolution and low frame rate images with high resolution are simultaneously acquired.

Abstract: The present disclosure provides a system and method for efficiently mining multi-threshold measurements acquired using photon counting pixel-array detectors for spectral imaging and diffraction analyses. Images of X-ray intensity as a function of X-ray energy were recorded on a 6 megapixel X-ray photon counting array detector through linear fitting of the measured counts recorded as a function of counting threshold. An analytical model is disclosed for describing the probability density of detected voltage, utilizing fractional photon counting to account for edge/corner effects from voltage plumes that spread across multiple pixels. Three-parameter fits to the model were independently performed for each pixel in the array for X-ray scattering images acquired for 13.5 keV and 15.0 keV X-ray energies. From the established pixel responses, multi-threshold composite images produced from the sum of 13.5 keV and 15.