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 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: A novel filter housing assembly for use in liquid chromatography and similar fluid flow based systems capable of use at high pressure, well above 1000 psi, is disclosed. The filter housing assembly has a very low dead volume of approximately 11 ?L and is capable of holding brittle ceramic filter membranes as well as flexible membranes without the support of a fit. The filter housing is capable of being assembled and disassembled by hand without the need of any tools and makes use of an inexpensive, disposable filter retaining screen.

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 method is disclosed for measurement of the electrophoretic mobility of particles in solution. A sample is placed in a cell containing two electrodes that apply an alternating electric field. A monochromatic light beam passes through the sample. Light scattered by the particles, along with the unscattered beam, is collected and collimated as it exits the cell. This beam is combined in free space with a phase modulated reference beam. The interference forms a frequency modulated speckle pattern, which is detected by a photodetector array. Each array element collects a narrow range of well-defined scattering angles. The signal from each is demodulated to provide a first-principle measurement of the electrophoretic mobility of the scattering particles.

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: A method is disclosed for measurement of the electrophoretic mobility of particles in solution. A sample is placed in a cell containing two electrodes that apply an alternating electric field. A monochromatic light beam passes through the sample. Light scattered by the particles, along with the unscattered beam, is collected and collimated as it exits the cell. This beam is combined in free space with a phase modulated reference beam. The interference forms a frequency modulated speckle pattern, which is detected by a photodetector array. Each array element collects a narrow range of well-defined scattering angles. The signal from each is demodulated to provide a first-principle measurement of the electrophoretic mobility of the scattering particles.

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 are disclosed for measurement of the electrophoretic mobility of particles in solution. A sample is placed in a cell containing two electrodes that apply an alternating electric field. A monochromatic light beam passes through the sample. Light scattered by the particles, along with the unscattered beam, is collected and collimated as it exits the cell. This beam is combined in free space with a phase modulated reference beam. The interference forms a frequency modulated speckle pattern, which is detected by a photodetector array. Each array element collects a narrow range of well-defined scattering angles. The signal from each is demodulated to provide a measurement of the electrophoretic mobility of the scattering particles.

Abstract: A new type of asymmetric flow field flow fractionator, A4F, is described permitting improved sample fractionation means by providing a range of available channel lengths within the same A4F unit. With such an apparatus, samples may be optimally separated by performing such fractionations as a function of channel length. The ability to vary channel length within the same A4F unit has heretofore been unavailable.

Abstract: A field flow fractionator to separate particles contained within an injected sample aliquot is described. As required, said fractionator may be used to capture, for subsequent removal, specific predefined classes of such particles. Based upon the cross flow or asymmetric flow field flow fractionators, the fractionator disclosed contains means to vary the applied transverse flows at a plurality of locations along the length of its separating channel. One embodiment utilizes a plurality of separated compartments, each lying below a distinct and corresponding membrane supporting permeable frit segment, are provided individual means to control the localized flow through the membrane section thereabove. A corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when integrated with a hollow fiber fractionator.

Abstract: A method is described for separating and processing liquid-borne particles within an aliquot thereof following injection into a field flow fractionator. Said fractionation method may be employed also to capture, for subsequent segregation, specific predefined classes of such particles. The unique fractionation method disclosed contains means to control the applied transverse flow at each designated location along the length of said channel. In one embodiment of the method a separate compartment lies below each distinct location and corresponding membrane supporting permeable frit segment of the fractionator, providing the individual means to control the localized flow through the membrane section thereabove. Employment of a corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when applied to a hollow fiber fractionation means.

Abstract: A field flow fractionator to separate particles contained within an injected sample aliquot is described. As required, said fractionator may be used to capture, for subsequent removal, specific predefined classes of such particles. Based upon the cross flow or asymmetric flow field flow fractionators, the fractionator disclosed contains means to vary the applied transverse flows at a plurality of locations along the length of its separating channel. One embodiment utilizes a plurality of separated compartments, each lying below a distinct and corresponding membrane supporting permeable frit segment, are provided individual means to control the localized flow through the membrane section thereabove. A corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when integrated with a hollow fiber fractionator.

Abstract: A method is described for separating and processing liquid-borne particles within an aliquot thereof following injection into a field flow fractionator. Said fractionation method may be employed also to capture, for subsequent segregation, specific predefined classes of such particles. The unique fractionation method disclosed contains means to control the applied transverse flow at each designated location along the length of said channel. In one embodiment of the method a separate compartment lies below each distinct location and corresponding membrane supporting permeable frit segment of the fractionator, providing the individual means to control the localized flow through the membrane section thereabove. Employment of a corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when applied to a hollow fiber fractionation means.

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 field flow fractionator to separate particles contained within an injected sample aliquot is described. As required, said fractionator may be used to capture, for subsequent removal, specific predefined classes of such particles. Based upon the cross flow or asymmetric flow field flow fractionators, the fractionator disclosed contains means to vary the applied transverse flows at a plurality of locations along the length of its separating channel. A plurality of separated compartments, each lying below a distinct and corresponding membrane supporting permeable frit segment, are provided individual means to control the localized flow through the membrane section thereabove. A corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when integrated with a hollow fiber fractionator.

Abstract: A field flow fractionator to separate particles contained within an injected sample aliquot is described. As required, said fractionator may be used to capture, for subsequent removal, specific predefined classes of such particles. Based upon the cross flow or asymmetric flow field flow fractionators, the fractionator disclosed contains means to vary the applied transverse flows at a plurality of locations along the length of its separating channel. A plurality of separated compartments, each lying below a distinct and corresponding membrane supporting permeable frit segment, are provided individual means to control the localized flow through the membrane section thereabove. A corresponding concentric compartment implementation achieves the same type of compartmentalized cross flow when integrated with a hollow fiber fractionator.

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.