Abstract: A method for measuring the physical properties of a drug formulation suspended in a pressurized liquid propellant and a system to enable such measurements is disclosed. Drug formulations suspended in pressurized liquid propellant used in Pressurized Metered Dose Inhalers (pMDIs) are propelled in their native liquid state into an analytical instrument with a measurement cell capable of withstanding the pressure required to retain the sample in liquid form by employing a device to rapidly release the contents of the pMDI canister into the measurement instrument wherein the sample's electrophoretic mobility and size may be determined by MP-PALS or other techniques. A series of valves permits the maintenance of the high pressure in the system. Once the measurements are made, the pressurized liquid is allowed to pass to waste or another analytical instrument by opening an exit valve.

Abstract: An improved version of the capillary bridge viscometer that compensates for the effect of solvent compressibility is disclosed. A novel, yet simple and inexpensive modification to a conventional capillary bridge viscometer design can improve its ability to reject pump pulses by more than order of magnitude. This improves the data quality and allows for the use of less expensive pumps. A pulse compensation volume is added such that it transmits pressure to the differential pressure transducer without sample flowing there through. The pressure compensation volume enables the cancelation of the confounding effects of pump pulses in a capillary bridge viscometer.

Abstract: A method to filter out pump pulses from data collected with a chromatography system is disclosed. Baseline data is collected as a pump delivers solvent to an analytical instrument, which may be the IP signal of a capillary bridge viscometer. A Fourier transform is applied to the data to generate the power spectrum of the baseline signal. Fundamental and harmonic frequencies are determined and a comb filter is constructed therefrom and applied to sample collected from all of the affected instruments. The comb filter may be correlated to the pump and flow rate and stored in data analysis software or database. Other systems using other pumps may also generate associated comb filters, and the resulting filters and the flow rates at which they were generated may be stored in a database accessible to the data analysis software.

Abstract: This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, as a function of concentration. The series of average hydrodynamic radii as a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the average hydrodynamic radii value analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating. This method may also be used to characterize and quantify the association between a modulator and the associating species.

Abstract: Methods and apparatus for controlling interdetector band broadening during the analysis of a sample injected into a chromatography system. A column flow is diluted with a dilution flow after the sample exits the chromatography system, and the diluted sample is analyzed by one or a combination of analysis instruments such as a light scattering detector, refractive index detector, an ultraviolet absorption detector.

Abstract: A pressure transducer is disclosed wherein no wetted areas have been welded. A cavity is milled into the back of each of the blocks of a material which will make up the body of the transducer. Pickup coils are placed into these cavities and are held in place generally with epoxy cement. With the coils mounted within the sensor body, the surface which will be exposed to the sample or reference fluids is comprised of a single, solid material with no welding joints. Further, as the sensor block half is made of a single, solid material, fluid fitting connections may be machined directly into the body. The pickup coil placed within the improved sensor body may be wound on an open frame of nickel superalloy (NiSA). Another embodiment involves coating or encapsulating the sensing membrane within a soft, non-magnetic material protecting it from corrosion.

Abstract: This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. “Particle” refers to any discrete particle, such as a protein, nucleic acid, carbohydrate, liposome, virus, synthesized polymer, nanoparticle, colloid, latex sphere, etc. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, ravg, as a function of concentration. The series of ravg as a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the ravg value analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating.

Abstract: A method is presented by which means small particles in solution, of various structures and of sizes up to several hundred nanometers, may be measured by light scattering means. An inventive technique is described, permitting the traditional Rayleigh-Gans approximation to be extended, allowing thereby measurement of the mean square radii of particles over a greater size range. Such determinations obviate the need to fit the collected data to a particular closed form model of which, in any event, only a few exist. The new method is particularly important for determining structural features of irregular particles whose scattering depends on their orientation with respect to the direction of the incident illumination.

Abstract: An electrode for use in instruments capable of measuring the electrophoretic mobility of particles in solution is disclosed. The electrode is comprised of an inexpensive support member, generally made of titanium, onto a flat surface of which has been connected, generally by microwelding, a flat electrically conductive but chemically inert foil member, preferably platinum. A uniform texture can be generated on the exposed surfaces of the electrode by various means including tumbling the electrode with an abrasive. An oxide layer can be generated on the support member by soaking the composite electrode in an appropriate medium, protecting the exposed surface of the support member from fluid contact with the sample solution, while the foil member, unaffected by the oxidation process, is able to contact the sample solution.

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 method and apparatus are disclosed which enable the reduction of sample carryover in the measurement cell of an analytical instrument. A sample cell is defined as a region sealed within a first o-ring. Located outside of said sample region is another o-ring which seals and defines a seal wash region as the region between the first and second o-ring. After the fluid sample is injected into the measurement cell a pressure is applied to the seal wash region, forcing the first o-ring to the innermost extent of the groove in which it sits, expelling any trapped solvent and removing from the measurement cell a significant dead volume while the cell is flushed and prepared for a new sample and corresponding measurement.

Abstract: A method and apparatus is disclosed for suppression of bubbles in an optical measurement cell. A measurement cell is filled with a fluid sample. Valves connected through plumbing connections to the cell are operated such that any flow in and out of the cell is stopped. A pressure source is then applied through a valve and flow impedance mechanism to the liquid contained within the cell, causing any bubbles contained or generated within the cell to be dissolved back into solution or reduced in size such that optical measurements taken of the sample are more accurate and free of interference with the measurement beam and of measured stray light. Possible pressure sources include compressed gas, a piston, and a constant flow-rate pump.

Abstract: A cuvette for use with light scattering detectors is disclosed. A trough or moat within the cuvette can be filled with solvent which is not in fluid contact with the sample to be measured. This solvent moat creates saturated vapor pressure in the chamber preventing evaporation from the sample when the cuvette is capped. The cuvette itself may be made of an inexpensive polymer which can be polished to high optical quality while still being moldable in complex forms capable of enabling further utility, such as extra griping surfaces, identification tabs allowing the detection instrument to determine the cuvette model, and various sample chamber forms. The novel cuvette may have extremely small sample volumes, while allowing significant overfill of the measurement chamber, improving ease of sample loading. The polymers used may be relatively inexpensive, and therefore the cuvette can generally be discarded after a single use.

Abstract: This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. “Particle” refers to any discrete particle, such as a protein, nucleic acid, carbohydrate, liposome, virus, synthesized polymer, nanoparticle, colloid, latex sphere, etc. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, ravg, as a function of concentration. The series of ravg as a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the ravg value analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating.

Abstract: A pressure transducer is disclosed wherein no wetted areas have been welded. A cavity is milled into the back of each of the blocks of a material which will make up the body of the transducer. Pickup coils are placed into these cavities and are held in place generally with epoxy cement. With the coils mounted within the sensor body, the surface which will be exposed to the sample or reference fluids is comprised of a single, solid material with no welding joints. Further, as the sensor block half is made of a single, solid material, fluid fitting connections may be machined directly into the body. The pickup coil placed within the improved sensor body may be wound on an open frame of nickel superalloy (NiSA). Another embodiment involves coating or encapsulating the sensing membrane within a soft, non-magnetic material protecting it from corrosion.

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: Methods and apparatus for controlling interdetector band broadening during the analysis of a sample injected into a chromatography system. A column flow is diluted with a dilution flow after the sample exits the chromatography system, and the diluted sample is analyzed by one or a combination of analysis instruments such as a light scattering detector, refractive index detector, an ultraviolet absorption detector.