Abstract: The present disclosure describes a differential refractometer for gradient chromatography. In an exemplary embodiment, the differential refractometer includes a solvent delay volume, an eluent flow meter coupled to an eluent inlet of a sample cell, a solvent flow regulator coupled to an outlet of the solvent delay volume and coupled to a solvent inlet of a reference cell, an instrument controller configured to receive the eluent flow rate from the eluent flow meter, configured to receive the solvent flow rate from the solvent flow regulator, configured to receive a flow rate ratio from a flow rate ratio data source, wherein the flow rate ratio indicates a ratio of the eluent flow rate to the solvent flow rate, and an optical bench configured to measure a difference between a refractive index of the eluent present in the sample cell and a refractive index of the solvent present in the reference cell.

Abstract: The present disclosure describes a differential refractometer for gradient chromatography. In an exemplary embodiment, the differential refractometer includes a solvent delay volume, an eluent flow meter coupled to an eluent inlet of a sample cell, a solvent flow regulator coupled to an outlet of the solvent delay volume and coupled to a solvent inlet of a reference cell, an instrument controller configured to receive the eluent flow rate from the eluent flow meter, configured to receive the solvent flow rate from the solvent flow regulator, configured to receive a flow rate ratio from a flow rate ratio data source, wherein the flow rate ratio indicates a ratio of the eluent flow rate to the solvent flow rate, and an optical bench configured to measure a difference between a refractive index of the eluent present in the sample cell and a refractive index of the solvent present in the reference cell.

Abstract: The present disclosure describes a computer implemented method, a system, and a computer program product of controlling the purification of a macromolecule solution via real-time multi-angle light scattering.

Abstract: The present disclosure describes a computer implemented method, a system, and a computer program product of purifying a sample solution via real-time multi-angle light scattering. In an embodiment, the method, system, and computer program product include receiving from a MALS instrument baseline scattering intensity values of a pure buffer, receiving from the MALS instrument scattering intensity values of a sample solution, and characterizing at least one component of the sample solution, resulting in a time series of values of a dimension, D, of the at least one component and a time series of values of excess Rayleigh ratio, R0, of the at least one component, and determining that the values of the dimension, D, fall within a dimension, D, value range and that the values of excess Rayleigh ratio, R0, fall within an excess Rayleigh ratio value range, and transmitting a collect sample solution command to collect the sample solution.

Abstract: The present disclosure describes a differential refractometer for gradient chromatography. In an exemplary embodiment, the differential refractometer includes a solvent delay volume, an eluent flow meter coupled to an eluent inlet of a sample cell, a solvent flow regulator coupled to an outlet of the solvent delay volume and coupled to a solvent inlet of a reference cell, an instrument controller configured to receive the eluent flow rate from the eluent flow meter, configured to receive the solvent flow rate from the solvent flow regulator, configured to receive a flow rate ratio from a flow rate ratio data source, wherein the flow rate ratio indicates a ratio of the eluent flow rate to the solvent flow rate, and an optical bench configured to measure a difference between a refractive index of the eluent present in the sample cell and a refractive index of the solvent present in the reference cell.

Abstract: The present disclosure describes a computer implemented method, a system, and a computer program product of calculating molar mass values of components of and molar concentration values of conjugate molecules/particles.

Abstract: A lid for a multiwell plates which allows improved light scattering measurement of liquid samples within the wells of a multiwell plate, and which at the same time mitigates evaporation from said samples is disclosed. A surface element protrudes from the bottom of the lid into the fluid in a well. The protruding element may be hollow or solid, and the beam of light, directed into the element may act to capture or direct the beam while preventing backscatter from reaching the light scattering detector or detectors. The protruding element may thus direct the beam from the well without the beam having to pass through a fluid/air interface. The angle and shape of the lid surfaces may be optimized to minimize or eliminate back-reflection. Light absorbing and/or light blocking colorization may also be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract: Various embodiments of integrated measurement cell systems for the simultaneous or near simultaneous measurement of light scattering and UV absorption measurements, and methods of their use, are disclosed. In the flow cell implementations, the height of the measurement cell is traversed by the UV beam multiple times by beam directing optics, allowing thereby, the accurate determination of concentration present in the integrated flow cell and allowing the user to select the desired sensitivity which is proportional to the number of passes the beam makes through the cell. Batch implementations also allow for near simultaneous measurement of light scattering and UV absorption within the cuvette. These embodiments aid in the reduction or elimination of errors due to interdetector band broadening while also decreasing the amount of sample required and improving design flexibility of integrated measurement systems.

Abstract: A lid for a multiwell plates which allows improved light scattering measurement of liquid samples within the wells of a multiwell plate, and which at the same time mitigates evaporation from said samples is disclosed. A surface element protrudes from the bottom of the lid into the fluid in a well. The protruding element may be hollow or solid, and the beam of light, directed into the element may act to capture or direct the beam while preventing backscatter from reaching the light scattering detector or detectors. The protruding element may thus direct the beam from the well without the beam having to pass through a fluid/air interface. The angle and shape of the lid surfaces may be optimized to minimize or eliminate back-reflection. Light absorbing and/or light blocking colorization may also be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract: A lid for multiwell plates, allowing improved optical measurement of liquid samples within its wells, while mitigating evaporation from said samples, is disclosed. A surface element protrudes from the bottom of the lid into the fluid within a well. The protruding element may be hollow or solid such that light directed into the element may act to capture or direct the beam while preventing backscatter from reaching one or more detectors. The protruding element may direct the beam from the well without requiring the beam to pass through a fluid/air interface. The angle and shape of the lid surfaces and/or light absorbing/blocking colorization may be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract: A method and apparatus for the illumination of a sample are disclosed. An imaging illumination light source is directed to pass through an absorbing/transmitting structure in order to illuminate the sample and any containing vessel. A diffuser may aid in properly dispersing the light from the imaging illumination source. A light sensitive detector such as a camera records an image therefrom. The beam from a light scattering source is directed through the sample and any containing vessel, and upon exiting the sample/vessel, impinges upon the absorbing/transmitting structure selected to absorb at the wavelength of the light scattering source. Scattered light from the sample is collected by a photo detector. Methods of use for the novel lighting system are also disclosed.

Abstract: Various embodiments of integrated measurement cell systems for the simultaneous or near simultaneous measurement of light scattering and UV absorption measurements, and methods of their use, are disclosed. In the flow cell implementations, the height of the measurement cell is traversed by the UV beam multiple times by beam directing optics, allowing thereby, the accurate determination of concentration present in the integrated flow cell and allowing the user to select the desired sensitivity which is proportional to the number of passes the beam makes through the cell. Batch implementations also allow for near simultaneous measurement of light scattering and UV absorption within the cuvette. These embodiments aid in the reduction or elimination of errors due to interdetector band broadening while also decreasing the amount of sample required and improving design flexibility of integrated measurement systems.

Abstract: A method and apparatus for the illumination of a sample are disclosed. An imaging illumination light source is directed to pass through an absorbing/transmitting structure in order to illuminate the sample and any containing vessel. A diffuser may aid in properly dispersing the light from the imaging illumination source. A light sensitive detector such as a camera records an image therefrom. The beam from a light scattering source is directed through the sample and any containing vessel, and upon exiting the sample/vessel, impinges upon the absorbing/transmitting structure selected to absorb at the wavelength of the light scattering source. Scattered light from the sample is collected by a photo detector. Methods of use for the novel lighting system are also disclosed.

Abstract: A lid for multiwell plates, allowing improved optical measurement of liquid samples within its wells, while mitigating evaporation from said samples, is disclosed. A surface element protrudes from the bottom of the lid into the fluid within a well. The protruding element may be hollow or solid such that light directed into the element may act to capture or direct the beam while preventing backscatter from reaching one or more detectors. The protruding element may direct the beam from the well without requiring the beam to pass through a fluid/air interface. The angle and shape of the lid surfaces and/or light absorbing/blocking colorization may be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract: A new method is presented for characterizing the associative properties of a solution of macromolecules at high concentration. Sample aliquots spanning a range of concentrations are injected sequentially into a light scattering photometer. Equilibrium association constants and association stoichiometry are derived from an analysis of the angular and concentration dependence of the scattering signals. Thermodynamic nonideality, which becomes important at high concentrations, is dealt with in the analysis in a simplified manner which is applicable to multiple associated species.

Abstract: Systems and methods for high-throughput screening can be used to determine whether binding occurs between different molecular species. Some systems compare measurements obtained from a static light scattering detector relative to a first solution that includes a target molecular species, a second solution that includes a test molecular species, and a third solution that includes a mixture of the target and test molecular species.

Abstract: A new method is presented for characterizing the associative properties of a solution of macromolecules at high concentration. Sample aliquots spanning a range of concentrations are injected sequentially into a light scattering photometer. Equilibrium association constants and association stoichiometry are derived from an analysis of the angular and concentration dependence of the scattering signals. Thermodynamic nonideality, which becomes important at high concentrations, is dealt with in the analysis in a simplified manner which is applicable to multiple associated species.

Abstract: A new method is presented for measuring the molecular properties of an unfractionated solution of macromolecules. Sample aliquots spanning a range of concentrations are injected sequentially into a stream of solution and flow towards the detectors. Each aliquot produces, thereby, an effective “peak” whose elements correspond to different concentrations of the diluted aliquot. The weight averaged molar mass, the mean square radius, and the second virial coefficient of the macromolecules in solution are derived from an analysis of the angular and concentration dependence of the scattering signals throughout the corresponding peaks. In contrast to earlier on-line methods, better accuracy is achieved, while using a smaller quantity of sample. A similar method for determining cross virial coefficients between two distinct species of macromolecules is also presented.

Abstract: A new method is presented for measuring the molecular properties of an unfractionated solution of macromolecules. Sample aliquots spanning a range of concentrations are injected sequentially into a stream of solution and flow towards the detectors. Each aliquot produces, thereby, an effective “peak” whose elements correspond to different concentrations of the diluted aliquot. The weight averaged molar mass, the mean square radius, and the second virial coefficient of the macromolecules in solution are derived from an analysis of the angular and concentration dependence of the scattering signals throughout the corresponding peaks. In contrast to earlier on-line methods, better accuracy is achieved, while using a smaller quantity of sample. A similar method for determining cross virial coefficients between two distinct species of macromolecules is also presented.

Abstract: An area of a substrate is imaged with and without heating, to obtain a hot image and a cold image respectively. The hot and cold images are compared with one another to identify one or more locations as being defective, e.g. if the result of comparison at one location differs significantly relative to other locations. The comparison results in all locations form a differential image, and in several embodiments a number of differential images are obtained by repeatedly heating, imaging and comparing. In such embodiments, multiple differential images are averaged at each location, to improve the signal to noise ratio. Pump and probe lasers may be used for heating and for illumination respectively, or alternatively a single laser may be employed to generate both pump and probe beams.