Particle Sizing Systems, Inc.

Other

University of California

Stable Solutions LLC

Agilent Technologies, Inc.

Nicoli, David F.

Bistrian, Bruce R.

Driscoll, David F.

David F Nicoli

Virgil B Elings

Paul Toumbas

David F Driscoll

Bruce R Bistrian

David Wells

Yu-Jain Chang

Jau-Sien Wu

A method for identifying an improved particle size distribution profile of a dispersion, the method including: (a) providing a dispersion comprising a liquid and particles dispersed in the liquid; (b) measuring a particle size distribution of the dispersion, resulting in a first particle size distribution profile; (c) adjusting at least one parameter associated with the dispersion; (d) measuring a dispersion characteristic, after adjustment of the at least one parameter; and (e) measuring the particle size distribution of the dispersion after adjustment of the at least one parameter, resulting in a second particle size distribution profile; wherein each of the first and second particle size distribution profiles comprises a plurality of data points of particle concentration values as a function of particle size.

Particle size distribution profiles and use thereof to adjust a dispersion characteristic

A single-particle optical sensor, which has high sensitivity and responds to relatively concentrated suspensions, uses a relatively narrow light beam to illuminate an optical sensing zone nonuniformly. The zone is smaller than the flow channel so that the sensor responds to only a fraction of the total number of particles flowing through the channel, detecting a statistically significant number of particles of any relevant diameter. Because different particle trajectories flow through different parts of the zone illuminated at different intensities, it is necessary to deconvolute the result. Two methods of deconvolution are used: modified matrix inversion or successive subtraction. Both methods use a few basis vectors measured empirically or computed from a theoretical model, and the remaining basis vectors are derived from these few. The sensor is compensated for turbidity. Several embodiments are disclosed employing light-extinction or light-scattering detection, or both.

Sensors and methods for high-sensitivity optical particle counting and sizing

An apparatus and method are disclosed for determining electrophoretic mobility using scattering light phase analysis comprising emitting a laser light along a path and transmitting a first portion of the laser light and reflecting a second portion of the laser light. The apparatus and method can also comprise deflecting one of the first and second portions of the laser in response to a drive signal, holding a sample to receive at least one of the first and second portions of the laser light under an electric field and output a composite light wave, outputting a photopulse signal based on the composite light wave, and measuring the electrophoretic mobility of the sample based on a phase shift analysis using cross-correlation of the photopulse signal with the drive signal.

Methods and apparatus for electrophoretic mobility determination using phase light scattering analysis

A method and apparatus for determining the stability of dispersions and emulsions accelerates the onset of significant particle agglomeration in a sample by stressing the sample by reducing the height of the interparticle potential energy barrier between the particles. This is achieved by adding one or more of three stress factors: changing the pH of the sample to reduce the surface charge on the particles; adding an adsorbing electrolyte so that ions of the appropriate charge are adsorbed onto the surfaces of the particles to reduce the net charge on the particles; and applying a monovalent, divalent, or trivalent salt to partially screen electrostatic repulsions between the charged particles. In a preferred embodiment, the increase in agglomeration is detected with single particle detection, such as SPOS, to generate a PSD from which a figure of merit is derived. Another embodiment detects turbidity or light scattering to generate a value X indicative of the extent of agglomeration.

Stability assessment of dispersions and emulsions

An automatic dilution system and method provides optimal dilution factor DF for a sample suspension containing particles mixed with a diluent. A diluent flows into a mixing chamber, and the sample is injected into the chamber. A sensor, such as a single particle optical sensor (SPOS), measures the value of a particular characteristic, which characteristic R,(0) is the initial rate of increase of a quantity related to particle concentration. A CPU/Controller calculates from R,(0) the optimal value of DF, and develops a control signal which adjusts the flow of the sample to provide the optimal value of DF. In a first embodiment, all of the diluted sample passes through the sensor. In a second embodiment, only a portion of the sample is directed through the sensor to shorten the time to reach equilibrium. The time to reach equilibrium is further reduced in a third embodiment in which the mixing means is a static mixer, having relatively small volume, inserted in series with a diluent flow tube. The sample is injected into the flow tube upstream of the mixer. Larger dilution factors are obtainable in a fourth embodiment in which the sample is first prediluted in a mixing chamber and then further diluted in a second mixing chamber. A fifth embodiment also predilutes the sample, but to shorten the time to reach equilibrium, uses a static mixer for the second dilution stage. In all embodiments, the diluted fluid may be fed to one of two branches, one having an SPOS and the other having a sensor using the light scattering principle.

Automatic dilution system for high-resolution particle size analysis

An optical sensor for counting and sizing particles, including a light extinction (LE) signal representative of the particles, and a light scattering (LS) signal representative of the particles. The light scattering signal and the light extinction signal are combined to form a single composite signal. The single composite signal has a substantially similar output to the light extinction (LE) signal for particle sizes in an upper range of particle sizes typically measured by the light extinction sensor. The single composite signal has a substantially similar output to the light scattering (LS) signal for particle sizes in a lower range of particle sizes typically measured by the light scattering sensor. The single composite signal has an output representing the combined light extinction (LE) signal and light scattering (LS) signal for particle sizes in a middle range of particle sizes.

Single-particle optical sensor with improved sensitivity and dynamic

A method of and apparatus for an automatic dilution system for providing a variable dilution of an unknown sample material, including a mixing chamber having at least one input and output, sample material and diluent. Injecting a quantity of the sample material into the input of the mixing chamber. Providing a flow of the diluent into the input of the mixing chamber to mix with the sample material and to continuously dilute the concentration of the sample material within the mixing chamber and flowing out of the mixing chamber to provide a variable dilution. Providing a measurement of a particular characteristic of the continuously variable diluted sample material, and controlling the flow of diluent in accordance with an optimal measurement of the particular characteristic.

Automatic dilution system

Apparatus and method for providing an optical detection of a binding reaction between a ligand and an antiligand, including, a pattern formed by a spatial array of microscopic dimensions of antiligand material, ligand material interacting with the antiligand material to produce a binding reaction between the ligand and the antiligand in the pattern, a source of optical radiation including energy at at least one wavelength directed to the pattern at a particular incidence angle to produce scattering of the energy from the pattern in accordance with the binding reaction and with a strong scattering intensity at one or more Bragg scattering angles, and at least one optical detector located relative to the pattern and aligned with a Bragg scattering angle to detect the strong scattering intensity at the Bragg scattering angle to produce a signal representative of the binding reaction.

Immunoassay using optical interference detection

Apparatus and method for an immunoassay of a binding reaction between a ligand and an antiligand which are typically an antigen and an antibody, including a spatial pattern formed by a spatial array of separate regions of antiligand material, and ligand material dispersed to interact with the spatial array of separate regions of antiligand material for producing a binding reaction between the ligand and the antiligand in the spatial patterns and with the bound complexes labeled with a particular physical characteristic. A source of input energy and with the input energy at a particular spectrum for interacting with particular physical characteristic of the labeled binding reaction. Scanning the spatial pattern with the input energy at the particular spectrum for producing output energy having amplitude levels formed by a substantially random background component and a non-random component representing the labeled bound complexes, and the non-random component representing the labeled bound complexes detected to produce an output signal in accordance with the labeled binding reaction.

Apparatus and method for homogeneous immunoassay

In the course of a reaction in which one of the reactants is on the surface of carrier particles in a solution and another of the reactants is tagged with a fluorescent substance, some of the fluorescently tagged reactant attaches to, or is displaced from the carrier particle. The present invention relates to a method and device for determining the amount of fluorescently-tagged reactant which is attached to the carrier particle or which is free in solution, without physically separating the carrier particles from the solution. In a particular application of the invention (immunoassay) the reaction is between antibodies and antigens, and from the amount of fluorescently-tagged reactant which is attached to the carrier particle one can determine the unknown amount of antigen in a sample. The number of fluorescent particles which are bound to the large carrier particles and which are in solution are determined by optical and electronic sensing and analyzing techniques, including (1) shadowing techniques in which large opaque carrier particles block the pick-up of fluorescent radiation from bound tagged reactants, and/or (2) autocorrelation techniques which selectively discriminate between radiation from the bound fluorescently tagged reactants on the large particles and the free fluorescently-tagged reactants which have a more rapid diffusion movement than the carrier particles.

Homogeneous fluoroimmunoassay involving autocorrelation processing of

Homogeneous fluoroimmunoassay involving sensing radiation for forward

A correlator for producing a correlation function by processing input data over a large number of coefficients of the correlation function by time sharing a smaller number of correlation channels, including a temporary storage device for receiving input data and for providing the input data as output data at particular successive time delay intervals relative to the input data, a group channel correlator responsive to the output data from the temporary storage device and to additional data for correlating the group of channels of data and for providing output sums representing coefficients of the correlation function, and means coupled to the temporary storage device and the group channel correlator for controlling the coupling of the output data from the temporary storage device to the group channel correlator to have the output data at the successive time delay intervals coupled to the group channel correlator to have the group channel correlator repetitively correlate successive groups of channels for providing the large number of coefficients in the correlation functions built up from the repetitive correlation of the successive groups of channels.

Growing community of inventors

Goleta, CA, United States of America

David F Nicoli