Abstract: Raman systems and methods use advantages offered by increased laser mobility/path length and photon migration to analyze diffusively scattering solids, including pharmaceuticals. A collimated laser excitation beam having a first diameter induces from a sample a backscattered collimated Raman collection beam with a second diameter. The collimated laser excitation beam and the collimated Raman collection beam form a counter-propagating collimated optical path, and the collimated laser excitation beam is preferably smaller in diameter than the diameter of the backscattered collimated Raman beam. The collection beam to a spectrograph for Raman analysis of the sample. A Raman calibration standard may be placed in the collimated optical path, and/or the sample may be supported in a reflective holder that may be at least partially spherical and/or may form part of a multi-well plate. The counter-propagating collimated optical path may be contained within a Raman microscope.

Abstract: A Raman calibration standard incorporated within an optical Raman sampling accessory facilitates wavelength calibration in real time. The accessory may be a microscope objective, immersion probe, non-contact probe optic or flow cell utilizing laser light from the UV to the NIR, and the calibration standard material may comprise calcium fluoride, sapphire, diamond, magnesium fluoride or silicon. The calibration standard material may be disposed in a collimated light space within the accessory, and/or may function as a lens, sealed window, reflector or a combination thereof. A plurality of calibration standard materials may be incorporated into the accessory and used for independent calibration verification. The accessory may include a single lens or an achromatic focusing lens. The system may further include features to improve curve fitting and generate a more precise wavenumber value for the position of a reference Raman band generated by the calibration standard material.

Abstract: Raman systems and methods use advantages offered by increased laser mobility/path length and photon migration to analyze diffusively scattering solids, including pharmaceuticals. A collimated laser excitation beam having a first diameter induces from a sample a backscattered collimated Raman collection beam with a second diameter. The collimated laser excitation beam and the collimated Raman collection beam form a counter-propagating collimated optical path, and the collimated laser excitation beam is preferably smaller in diameter than the diameter of the backscattered collimated Raman beam. The collection beam to a spectrograph for Raman analysis of the sample. A Raman calibration standard may be placed in the collimated optical path, and/or the sample may be supported in a reflective holder that may be at least partially spherical and/or may form part of a multi-well plate. The counter-propagating collimated optical path may be contained within a Raman microscope.

Abstract: Achromatically corrected Raman immersion probes minimize chromatic and/or spherical aberration through the use of an achromat, apochromat, refractive/diffractive optics as opposed to a single lens geometry. The improved end optics are adapted for use with a probe body carrying a laser excitation and/or collection beam associated with Raman analysis. The achromatically corrected optic to focus the beam onto or within a sample. The sample may be a gas, a liquid, or a partial liquid such as a slurry. The achromatically corrected optic may be an achromat comprising a lens doublet or an achromat comprising a lens triplet or more optical elements. In one preferred embodiment, the achromatically corrected optic may be an apochromatic optic. A disclosed system includes the achromatically corrected end optic and Raman probehead operative to send and receive counter-propagating laser excitation and collection beams.

Abstract: Immersion Raman probes use collimated light as opposed to a diverging fiber bundle or lens-based focusing geometry to deliver and collect light to and from a sample, thereby eliminating problems associated with chromatic aberration. The probes convey counter-propagating excitation and collection beams to and from a distally sealed, signal-transmissive optical component such as a window immersed, in contact with, or otherwise exposed to a sample volume. The counter-propagating excitation and collection beams pass directly through the sealed optical component and into the sample volume in collimated form for Raman analysis thereof. The probe may further include a baffled sample chamber coupled to the distal end of the probe optic body, with one or more optical elements to reflect the counter-propagating beams. The sample chamber may be fixed or axially movable to facilitate path length adjustment. The invention finds utility in process Raman, microscopy and other applications.

Abstract: Spectroscopic probe light shields coupled to the end of an optical probe improve user safety, reduce unwanted stray light and enhance signal collection from a liquid or gaseous sample. Apertured inner and outer baffles with offset perforations allow a sample to flow through the baffles and past a counter-propagating focused or collimated excitation/collection beam. The spectroscopic probe may be a Raman or fluorescence probe, operating in the UV-visible or mid-IR region of the spectrum. The inner shield may include a retro-reflector to amplify light collection from the sample, or the inner shield may include a light absorber to reduce the intensity of a scattered excitation beam. One or both of the inner and outer shields may be cylindrical, and the apertures in the baffles may be slots, circles or other shapes. The baffle(s) may be adapted for temporary, permanent, or semi-permanent attachment to the distal end of the probe optic.

Abstract: Achromatically corrected Raman immersion probes minimize chromatic and/or spherical aberration through the use of an achromat, apochromat, refractive/diffractive optics as opposed to a single lens geometry. The improved end optics are adapted for use with a probe body carrying a laser excitation and/or collection beam associated with Raman analysis. The achromatically corrected optic to focus the beam onto or within a sample. The sample may be a gas, a liquid, or a partial liquid such as a slurry. The achromatically corrected optic may be an achromat comprising a lens doublet or an achromat comprising a lens triplet or more optical elements. In one preferred embodiment, the achromatically corrected optic may be an apochromatic optic. A disclosed system includes the achromatically corrected end optic and Raman probehead operative to send and receive counter-propagating laser excitation and collection beams.

Abstract: Immersion Raman probes use collimated light as opposed to a diverging fiber bundle or lens-based focusing geometry to deliver and collect light to and from a sample, thereby eliminating problems associated with chromatic aberration. The probes convey counter-propagating excitation and collection beams to and from a distally sealed, signal-transmissive optical component such as a window immersed, in contact with, or otherwise exposed to a sample volume. The counter-propagating excitation and collection beams pass directly through the sealed optical component and into the sample volume in collimated form for Raman analysis thereof. The probe may further include a baffled sample chamber coupled to the distal end of the probe optic body, with one or more optical elements to reflect the counter-propagating beams. The sample chamber may be fixed or axially movable to facilitate path length adjustment. The invention finds utility in process Raman, microscopy and other applications.

Abstract: Spectroscopic probe light shields coupled to the end of an optical probe improve user safety, reduce unwanted stray light and enhance signal collection from a liquid or gaseous sample. Apertured inner and outer baffles with offset perforations allow a sample to flow through the baffles and past a counter-propagating focused or collimated excitation/collection beam. The spectroscopic probe may be a Raman or fluorescence probe, operating in the UV-visible or mid-IR region of the spectrum. The inner shield may include a retro-reflector to amplify light collection from the sample, or the inner shield may include a light absorber to reduce the intensity of a scattered excitation beam. One or both of the inner and outer shields may be cylindrical, and the apertures in the baffles may be slots, circles or other shapes. The baffle(s) may be adapted for temporary, permanent, or semi-permanent attachment to the distal end of the probe optic.

Abstract: The present disclosure is directed to a method of particle size determination for particles suspended within a light-transmissive medium. The method includes directing a monochromatic light source into the medium and collecting from the medium a Raman-scattered light spectrum. The method includes analyzing the Raman spectrum to determine an amount of Tyndall scattering of the Raman spectrum caused by particles within the medium, and thus determine the size and the number of particles mediating the Tyndall scattering.

Abstract: The present disclosure is directed to a method of particle size determination for particles suspended within a light-transmissive medium. The method includes directing a monochromatic light source into the medium and collecting from the medium a Raman-scattered light spectrum. The method includes analyzing the Raman spectrum to determine an amount of Tyndall scattering of the Raman spectrum caused by particles within the medium, and thus determine the size and the number of particles mediating the Tyndall scattering.

Abstract: A compact Raman analysis system combines a near-infrared (NIR) laser source, a 2D array collecting anti-Stokes Raman spectra, and a probe configured to measure complex solid samples, including pharmaceutical tablets and other large-area targets with reduced background fluorescence at relatively low cost. The system collects spectra from an area of 1-mm or greater, preferably 3-12 mm or more, facilitating the collection of statistically useful data from inhomogeneous and laser-sensitive samples, among other applications. Potential pharmaceutical applications include tablet dosage level measurements, as well as online and at-line quality-control (QC) monitoring opportunities. Other applications include tablet identification as a forensic tool to identify counterfeit pharmaceutical products; granulation and blend uniformity for improved formulation via better process understanding.

Abstract: A compact Raman analysis system combines a near-infrared (NIR) laser source, a 2D array collecting anti-Stokes Raman spectra, and a probe configured to measure complex solid samples, including pharmaceutical tablets and other large-area targets with reduced background fluorescence at relatively low cost. The system collects spectra from an area of 1-mm or greater, preferably 3-12 mm or more, facilitating the collection of statistically useful data from inhomogeneous and laser-sensitive samples, among other applications. Potential pharmaceutical applications include tablet dosage level measurements, as well as online and at-line quality-control (QC) monitoring opportunities.

Abstract: A compact Raman/fluorescence probe is capable of collecting spectra from a relatively large spot size as compared to traditional confocal Raman probes. The inventive probe collects spectra from an area or 1 mm or greater, preferably 3–12 mm or more, compared to current instruments which utilize spot sizes on the order of 2–60 microns. The larger spot size facilitates the collection of statistically useful data from inhomogeneous and laser-sensitive samples, among other applications. Potential pharmaceutical applications include tablet dosage level measurements, as well as online and at-line quality-control (QC) monitoring opportunities. Other applications include tablet identification as a forensic tool to identify counterfeit pharmaceutical products; granulation and blend uniformity for improved formulation via better process understanding, and reactor cleanliness validation.

Abstract: A compact Raman/fluorescence probe is capable of collecting spectra from a relatively large spot size as compared to tradition confocal Raman probes. The inventive probe collects spectra from an area of 1 mmm or greater, preferably 3-12 mm or more, compared to current instruments which utilize spot sizes on the order of 2-60 microns. The larger spot size facilitates the collection of statistically useful data from inhomogeneous and laser-sensitive samples, among other applications. Potential pharmaceutical applications include tablet dosage level measurements, as well as online and at-line quality-control (QC) monitoring opportunities. Other applications include tablet identification as a forensic tool to identify counterfeit pharmaceutical products; granulation and blend uniformity for improved formulation via better process understanding, and reactor cleanliness validation.

Abstract: A method of monitoring sample crystallization from a solution. The method includes the collection of multiple Raman spectra from a sample dissolved in a solvent as a function of time and under conditions promoting crystallization. Within each of the multiple Raman spectra, a first signal is identified corresponding to the sample associated with the solvent. A second signal corresponding to the sample in a microcrystallite state is also identified. Thereafter, the intensity of the multiple Raman spectra are measured for an increase relating to formation of the sample in a microcrystallite state. A method of monitoring sample crystallization from a solution as a function of turbidity is also disclosed. The method includes the collection of multiple Raman spectra from a sample dissolved in a solvent as a function of time under conditions promoting crystallization.

Abstract: A method of monitoring sample crystallization from a solution. The method includes the collection of multiple Raman spectra from a sample dissolved in a solvent as a function of time and under conditions promoting crystallization. Within each of the multiple Raman spectra, a first signal is identified corresponding to the sample associated with the solvent. A second signal corresponding to the sample in a microcrystallite state is also identified. Thereafter, the intensity of the multiple Raman spectra are measured for an increase relating to formation of the sample in a microcrystallite state. A method of monitoring sample crystallization from a solution as a function of turbidity is also disclosed. The method includes the collection of multiple Raman spectra from a sample dissolved in a solvent as a function of time under conditions promoting crystallization.

Abstract: An optical spectrograph utilizes a plurality of holographic transmission optical gratings operative to receive an incoming source of light to be analyzed and diffract the light such that different spectral components impinge upon spatially separated regions of an opto-electronic detector. Various grating configurations are disclosed, including a physical stack of gratings conducive to extreme compactness, as well as a spaced-apart configuration used to preclude spectral cross talk in certain configurations. Diverging light emerging from a fiber-optic bundle is collimated by a first lens assembly prior to passing through the gratings, and a second lens assembly is used to focus the diffracted light onto the detectors, preferably in the form of a two-dimensional CCD array.

Abstract: A narrow bandwidth bandpass filter having high transmission efficiency for the passband and excellent out-of-band attenuation employs a transmission holographic grating sandwiched between the oblique faces of a pair of right angle glass prisms. An incoming laser beam to be filtered is incident normal to one of the prism faces so as to intersect the holographic grating at about 45.degree.. The grating frequency is such as to diffract light of the transmission wavelength through substantially 90.degree. so that it exits the cube formed by the two prisms from the right angle face of the second prism. The out-of-band wavelengths of the incident beam are either transmitted unaffected through the grating or diffracted at a different angle than the light of the transmission wavelength.

Abstract: An optical spectrograph utilizes a plurality of holographic transmission optical gratings operative to receive an incoming source of light to be analyzed and diffract the light such that different spectral components impinge upon spatially separated regions of an opto-electronic detector. Various grating configurations are disclosed, including a physical stack of gratings conducive to extreme compactness, as well as a spaced-apart configuration used to preclude spectral cross talk in certain configurations. Diverging light emerging from a fiber-optic bundle is collimated by a first lens assembly prior to passing through the gratings, and a second lens assembly is used to focus the diffracted light onto the detectors, preferably in the form of a two-dimensional CCD array.