Abstract: A key problem associated with most types of separators based upon use of centrifugal forces is the difficulty such devices have with making absolute measurements of particle size and/or molar mass. By integrating means to produce and detect light scattered from samples undergoing centrifugal separation, particle sizes in the sub-micrometer range may be extracted from such measurements even in the presence of diffusion. The integration of light scattering detectors into an environment of high speed machinery is achieved by modifying the transparent surfaces of the sample holding region of the centrifuge. Such optical modifications allow the placement of stationary detector arrays able to collect light scattered by the samples during the brief collection times available. Three specific structures are addressed: A conventional disk centrifuge with a sample cavity integrated into the rotating structure; a disk centrifuge containing removable sample holding cuvettes, and an analytical ultracentrifuge.

Abstract: A new method is presented for measuring the molecular properties of an unfractionated solution of macromolecules. Sharing some similarities with the standard Zimm plot technique, the method begins with the preparation of several sample aliquots spanning a range of concentrations. The aliquots are then injected sequentially into a stream such as provided by a liquid chromatograph. Each aliquot produces, thereby, an effective “peak” whose elements correspond to different concentrations of the diluted aliquot. By analyzing the angular and concentration dependence of the scattering signals throughout the corresponding peaks, the weight averaged molar mass, the mean square radius, and the second virial coefficient may be derived. In contrast to earlier on-line methods, better accuracy is achieved, while using a smaller quantity of sample.

Abstract: An aerosol hazard classification and early warning network is composed of a large number of detector and analysis units, called “detector stations,” which are deployed throughout a region to be warned of a potentially hazardous aerosol intrusion. Such aerosol threats may originate from fires, volcanic eruptions, or overt releases of biological and chemical agents dispersed in aerosol form. Among the former are the characteristic toxic aerosols released during refinery fires or explosions. The latter biological agents include bacterial spores, lyophilized bacterial cells, and virus preparations, whereas chemical agents might include various forms of nerve gasses and other anti-personnel gasses such as mustard, all commonly deployed in aerosol form.

Abstract: A method is described to determine the 2nd virial coefficient of an ensemble of molecules dissolved in a selected solvent. Two distinct classes are described: monodisperse and polydisperse molecules. If the molecules are monodisperse, they must be prepared for a chromatographic separation and suitable columns selected. Following standard chromatographic separation procedures such as exemplified by the method of size exclusion chromatography, the sample passes through the separation columns, a multiangle light scattering detector, and a concentration detector. The effect of the columns is to produce a concentration profile of said sample that appears as a peak as it passes through the light scattering and concentration detectors. For each elution interval, &ngr;i, a corresponding concentration value ci and set of excess Rayleigh ratios Ri(&thgr;j) is measured for each scattering angle &thgr;j.

Abstract: A modified light scattering cell, and associated method, whereby an eluant of very small dimension transverse to its direction of flow is entrained successively by two sheath flows and presented to a fine light beam that illuminates the entrained eluant as it flows through the light beam. The light scattered by the entrained eluant is collected by detectors outside of a transparent flow cell enveloping the sheath flow entrained eluant. The windows of the transparent flow cell through which the light beam enters and leaves are far removed from the scattering eluant and kept clear of eluant-contained particles by means of flow components that will form subsequently one of the eluant sheath flows employed. The eluant source is typically from a fine capillary such as found in capillary electrophoresis, capillary hydrodynamic fractionation, and flow cytometry applications.

Abstract: This invention measures the change of a fluid's refractive index with changes in the concentration of a solute dissolved therein. A determination of this quantity is required for many types of chemical analyses especially for the determination of molecular weights. The fluid is restricted to a thin capillary channel (11) within a transparent material (10) such as glass. A fine light beam (18) is incident upon the capillary at an angle close to the critical angle. The axes of the light beam and capillary intersect at a point within the capillary defining thereby a plane within which the refraction occurs. A position sensing (27) device is placed to measure the displacement of the beam twice refracted during its passage through the capillary channel, said measure being used to generate a numerical value of the ratio dn/dc, where dc is the change of solute concentration resulting in a change dn of the solution's refractive index.

Abstract: A method is disclosed based on a single injection into a modified HPLC line by which means the light scattering data required to characterize the injected molecular suspension in terms of its weight-average molecular weight, z-average square radius, and second virial coefficient may be measured and collected. The method requires that a molecular suspension at a fixed concentration be prepared and injected into a flowing stream of pure solvent following standard liquid chromatographic procedures. The sample is then passed directly to a mixing chamber whose volume is preferably several times that of the injected volume. After this mixing, the sample enters a light scattering detector where its absolute scattering intensity as a function of angle is measured for each eluting fraction. From the data so-recorded, the concentration of each fraction may be calculated and a Zimm plot may be made to yield the required molecular parameters.

Abstract: A differential refractometer is described capable of measuring the refractive index charge, dn, of a transparent fluid corresponding to a change dc of the concentration of a solute in said fluid. The fluid is restricted to a fine capillary within a transparent material such as glass. Incident upon the capillary at an angle close to the critical angle is a fine light beam incident from said transparent material. The axes of the light beam and capillary intersect at a point within the capillary defining thereby a plane within which the refraction occurs. A position sensing device is placed to measure the displacement of the beam twice refracted during its passage through the capillary, said measure being used to generate a numerical value of the ratio dn/dc.

Abstract: The light intensity incident on a scattering sample contained in a scattering cell is monitored by simultaneous measurements of the light incident on the cell before entering it and the light transmitted through the cell after leaving it. Means to monitor the product of these signals is disclosed and how this product is related to the actual incident intensity at the sample is explained. The invention is presented in the context of the scattering cell of the parent application.

Abstract: A highly collimated light beam, such as produced by a laser, is coupled by optical means directly onto a semi-opaque object such as a human breast. The light transmitted and scattered therein is collected at a fixed surface element and direction relative to the incident light, and coupled optically into an image intensifier, preserving the spatial intensity variations passing through said fixed surface element. The intensified image is then collected on an array of detector elements which digitizes and then transfers said preserved image into memory means where it is processed to characterize the interior of said object. This invention has particular application to the early detection of breast cancer.

Abstract: An apparatus and process are described for the characterization and/or identification of suspensions of microparticles based upon the measurement of certain optical observables produced as the suspension is illuminated by a beam of light, or other electromagnetic radiation. Selected observables calculated from the scattered radiation detected by a plurality of detectors surrounding the thus-illuminated suspension are then used to recall specific maps, from a computer memory means, one for each observable. The common overlap region of said map yields characterizing or identifying particle suspension physical parameters.

Abstract: The measurement of the scattering properties of very small particles by electro-optical means generally requires the use of an intense, though highly spatially inhomogeneous, light source such as a laser. Many instruments require, therefore, that the intersection of the particle stream with the illumination source be precisely regulated so that the flux incident on the particle be known accurately. A method and apparatus are described by which means the absolute intensity of the light incident on the particle need not be known. A special structure and measurement process are described by which means small particles are differentiated from larger particles grazing the illumination beam.

Abstract: The invention provides improved methods and unique instrumentation for the detection and for the quantitation of chemical substances and has particular application for the detection and for the quantitation of immunological substances.

Abstract: A sample cell is described that permits the measurement of the light scattering properties of very small liquid-borne samples with negligible background interference form the illumination source. A technique is described whereby the cell construction permits the measurement of the illumination intensity at the scattering sample itself, permitting, thereby, the normalization of each detected scattered signal. The cell structure and detection method incorporated therein also permit measurement of extremely small angle scattered intensities without interference of the incident light beam itself.

Abstract: An apparatus and process are described for the characterization and/or identification of individual microparticles based upon the measurement of certain optical observables produced as each particle passes through a beam of light, or other electromagnetic radiation. A fine beam of, preferably, monochromatic linearly polarized light passes through a spherical array of detectors, or fiber optics means to transmit incident light to a set of detector means, and a stream of particles intersects the beam at the center of the spherical array. Selected observables calculated from the detected scattered radiation are then used to recall specific maps, from a computer memory means, one for each observable. The common overlap region of said maps yields characterizing or identifying particle physical parameters such as size, mean refractive index, and shape. A method for rapidly discriminating non-spherically symmetric particles is also disclosed.

Abstract: A process and apparatus is disclosed for characterizing an ensemble of microparticles and monitoring their response to environmental factors such as chemically and biologically active agents. The apparatus permits the very accurate measurement of light or radiation intensity scattered by the microparticles at two well-defined scattering angles with respect to the direction of the incident beam. This is achieved by measuring the scattered radiation at two sets of scattering angles each subtending the two defined angles, processing the detected intensities with a computer means to remove spurious data arising from artifacts in the scattering ensemble, and then functionally averaging the so-processed intensities of each set to yield a mean value for the scattered intensity at each of the two defined angles. Monitoring these two values before and after the addition of an environmental factor permits the calculation of a quantitative ensemble response to said environment.

Abstract: A method for deriving a quantitative measure of a beverage which will correlate to the subjective sensory stimuli response of beverage consumers. The method comprises illuminating an aliquot or a dilution thereof with a beam of monochromatic light, measuring the light scattering pattern produced, comparing this pattern to that of a reference pattern, and using the difference between the two patterns as the quantitative measure. A variation of the method is disclosed wherein a number of measurements at a selected set of angles over a period of time are measured and, at each selected angle, the intensity is measured several times. In this method, the average of the intensities so detected at each selected angle is determined, and the numerical set of the fluctuation of each detected value from the average is used to characterize the beverage.

Abstract: To characterize and differentiate large organic cells rapidly, individual particles are illuminated with monochromatic radiation of a wave length comparable to the size of the cell, producing a differential light scattering pattern about the illuminated cell. The pattern is sensed, preferably in the disclosed apparatus, by an array of detectors, and the sensed pattern employed as an identification and characterization of the cell. The pattern may be analyzed, or selected portions of the pattern employed, to differentiate cells embodying different features. The apparatus and process is especially useful for rapid identification and differentiation of leucocytes and other types of mammalian cells, the radiation for such analyses preferably being infrared radiation. A preferred structure for individually illuminating such cells with radiation and for sensing their differential light scattering pattern is disclosed.

Abstract: A programmable action sampler system (PASS) is described which holds a large number of discrete samples in a matrix of separate sample cups. The system is capable of dispensing a sample from a sample line into any one of the sample cups. At a pre-determined later time, using a cannula, the system addresses the sample from the cup for further measurement or analysis. In the preferred system, the samples flow sequentially through a tube, the liquid intermediate the samples being dispensed into a liquid waste line. The cannula between samples is bathed constantly in a wash tube, even while moving from one sample location to another. Further, in the preferred application, bacterial samples are employed, the sample cups being immersed in a constant temperature liquid bath to hold the bacterial samples at a constant incubation temperature. Among the various novel features employed in the system is a blade brake structure that accurately locates the sample head and cannula over any selected sample cup.