A method of investigating time varying sample characteristics is disclosed. The method comprises illuminating a sample comprising particles with a light beam, so as to produce scattered light by the interaction of the light beam with the sample, obtaining a measurement of the scattered light over a measurement period that is divided into a plurality of shorter sub-runs, classifying each sub-run, and determining the sample particle characteristic for the sub-runs. The method may further comprise transforming each sub-run prior to classifying each sub-run. Determining the sample particle characteristic for the sub-runs may occur prior to classifying each sub-run. The method may also comprise determining a variation in the sample particle characteristic over time for the sub-runs.
The present invention provides an apparatus ( 10) for characterising particles using nanoparticle tracking analysis (NTA). The apparatus ( 10) comprises: a flow cell (101) for containing a sample comprising a plurality of particles suspended in a fluid; a pump ( 102) configured to provide a flow of the sample through the flow cell ( 101); a light source (103) configured to illuminate the sample; an imaging system (104) configured to collect light scattered or fluoresced by particles moving within the flow cell (101) and within a detection region of the imaging system ( 104), and capture a video of the particles moving within the detection region; and a computer ( 105) configured to process the video. The computer (105) is configured to determine an estimated flow velocity of the sample through the flow cell ( 101). Determining the estimated flow velocity comprises performing 1 -dimensional particle tracking in a direction perpendicular to an expected flow direction of the sample.
G01N 15/1433 - Signal processing using image recognition
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
G01N 15/0227 - Investigating particle size or size distribution by optical means using imagingInvestigating particle size or size distribution by optical means using holography
G01N 15/075 - Investigating concentration of particle suspensions by optical means
G01N 15/00 - Investigating characteristics of particlesInvestigating permeability, pore-volume or surface-area of porous materials
G01N 15/0205 - Investigating particle size or size distribution by optical means
An apparatus (100) is provided for characterising particles using nanoparticle tracking analysis. The apparatus comprises: a cell (101) for containing a sample comprising a plurality of particles suspended in a fluid; a light source (102) configured to illuminate the sample; an imaging system (103) configured to collect light (112) scattered or fluoresced by particles moving within the cell (101) and within a detection region (111) of the imaging system (103) and capture a video of the particles moving within the detection region (111); and a computer (104). The computer is configured to process the video to automatically determine a depth of the detection region (111). Determining the depth of the detection region (111) comprises: tracking the particles moving within the detection region (111), thereby producing a track for each of the particles; and analysing how a measured property of the tracks within a subsection of the video changes as the size of the subsection is varied.
A temperature verification device for checking accuracy of a dynamic light scattering instrument temperature sensor, the temperature verification device comprising: a body configured to be received in the sample cell holder; a calibrated temperature sensor within the body at a position corresponding with a scattering volume of the dynamic light scattering instrument.
A method of automatically identifying data quality issues in background data for laser diffraction-particle characterisation is provided. The method comprises receiving background data corresponding to light intensity measured by each of a plurality of detectors in a laser-diffraction-based particle size analysis system. A processor is used to automatically determine if the background data contains at least one artefact that is indicative of a source of error in the particle size analysis system. If the background data is found to contain at least one artefact an indication is provided that the background data contains at least one artefact. Furthermore, the at least one artefact is classified, and the classification is reported.
A method of automatically selecting an optimal value or range for at least one measurement parameter for particle characterisation by laser diffraction is disclosed. The method comprises receiving a plurality of measurements and associated measurement parameters, wherein the measurements are performed on at least one particulate sample by using laser diffraction to determine at least one particle characteristic, and wherein the plurality of measurements were obtained using a plurality of values for the at least one measurement parameter. The method further comprises using a processor to automatically select, based on the at least one particle characteristic and the associated measurement parameters, an optimal value or range of at least one measurement parameter for performing particle characterisation by laser diffraction.
A particle characterisation instrument (100, 200) is disclosed, comprising: a sample cell(106, 206), for holding a sample (104, 204) comprising particles suspended in diluent fluid; a light source (101, 201) configured to illuminate the sample (104, 204) with alight beam (108, 208), thereby producing scattered light from the interaction of the light beam (108, 208) with the particles; a light detector (103, 203), configured to detect the scattered light and to output scattering data indicative of the diffusion coefficient of the particles in the diluent; a processor (105, 205), configured to determine a property of the particles from the scattering data; and a temperature sensor (107, 207), in conductive thermal contact with a wall (116, 216) of the sample cell (106, 206) and at a distance of less than 5mm from the sample (104, 204). The processor (105, 205) is configured to use the output of the temperature sensor (107, 207) in determining the property of the particles such that the property of the particles determined by the processor (105, 205) is responsive to an output from the temperature sensor (107, 207).
A method of preparing a representative particle size and refractive index database, for use in determining the size and refractive index of one or more particles within a sample (8) is disclosed. A method of determining the size and refractive index of one or more particles contained within a sample (8) is also disclosed. The size and refractive index determination method comprises: obtaining a measured scattering pattern for said particles, the measured scattering pattern comprising a number of data dimensions; reducing, using a processor (14), the number of data dimensions associated with the measured scattering pattern to obtain dimensionally reduced measured data; comparing, using the processor, the dimensionally reduced measured data with a representation of reference scattering patterns, said reference scattering patterns corresponding to particles having a range of known sizes and refractive indices; and selecting, as the size and refractive index of the one or more particles contained within the sample, the known size and refractive index corresponding to the representation of the reference scattering patterns which most closely corresponds to the dimensionally reduced measured data.
A particle-sizing instrument is provided, comprising: a sample cell (10) for receiving a sample (12) comprising a plurality of particles; a light source (4) configured to illuminate the sample (12) with a light beam (8) to produce scattered light by the interaction of the light beam (8) with the particles; a first optical system (30) comprising a first and second optical element (31, 32) respectively configured to split a portion of the scattered light into a first and second portion of scattered light: a second optical system (40) configured to receive the first and second portion of scattered light from the first optical system (30), and to recombine the first and second portion of scattered light to produce an interference signal (25) at a detection location, and a detector (14) configured to detect the interference signal (25) at the detection location.
iiii2n12nn using a non-linear solver; c) solving for x using a linear solver; d) calculate residual; e) repeat steps b) to d) while the residual is greater than a predefined exit tolerance.
A method and an apparatus (100, 200, 300) for characterising a sample comprising particles is disclosed. The method comprises performing a first measurement on the sample using a first particle characterisation technique; flowing the sample from the first particle characterisation technique to a particle separating device; separating the sample with the particle separating device; and performing a second measurement on the separated sample. The apparatus (100, 200, 300) is configured to perform the method, and comprises a measurement system for performing measurements according to a first particle characterisation technique (104, 105, 106) and a particle separating device (102) for separating samples comprising particles.
A method of using a computer (304) to classify measurement data (241) obtained by Taylor Dispersion Analysis, the measurement data (241) comprising a time series of measurements obtained as a sample flows past a detector, the method comprising: obtaining the measurement data (241) from a Taylor Dispersion Analysis; applying a neural network (130) to the measurement data (241) to classify the measurement data (241), wherein the neural network (130) has been trained to identify at least one class of TDA measurement.
G01N 13/00 - Investigating surface or boundary effects, e.g. wetting powerInvestigating diffusion effectsAnalysing materials by determining surface, boundary, or diffusion effects
G06F 17/18 - Complex mathematical operations for evaluating statistical data
G01N 15/00 - Investigating characteristics of particlesInvestigating permeability, pore-volume or surface-area of porous materials
G01N 15/02 - Investigating particle size or size distribution
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
G01N 21/31 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
A method of characterising particles in a sample, comprising: obtaining a scattering measurement (601) comprising a time series of measurements of scattered light from a detector, the scattered light produced by the interaction of an illuminating light beam with the sample; producing a corrected scattering measurement, comprising compensating for scattering contributions from contaminants (602) by reducing a scattering intensity in at least some time periods of the scattering measurement; determining a particle characteristic from the corrected scattering measurement.
A particle characterisation apparatus comprising: a light source (302) for illuminating a sample with a light beam; a detector (306) arranged to detect scattered light from the interaction of the light beam (108) with the sample; a focus tuneable lens (125, 145) arranged to collect the scattered light for the detector (306) from a scattering volume and/or to direct the light beam (108) into the sample, a sample holder (110) with an opposed pair of electrodes and configured to hold a sample in position in a measurement volume between the pair of electrodes such that a planar surface of the sample is aligned orthogonally to the electrode surfaces, the planar surface (150) adjacent to the scattering volume, wherein adjustment of the focus tuneable lens (125, 45) results in adjustment of the relative position of the planar surface (150) and the scattering volume by moving the scattering volume.
A particle characterisation instrument (200), comprising a light source (201), a sample cell (202), an optical element (204) between the light source (201) and sample cell (202) and a detector (203). The optical element (204) is configured to modify light from the light source (201) to create a modified beam (207), the modified beam (207): a) interfering with itself to create an effective beam (208) in the sample cell (202) along an illumination axis (206) and b) diverging in the far field to produce a dark region (209) along the illumination axis (206) that is substantially not illuminated at a distance from the sample cell (202). The detector (203) is at the distance from the sample cell (202), and is configured to detect light scattered from the effective beam (208) by a sample in the sample cell (202), the detector (203) positioned to detect forward or back scattered light along a scattering axis (306) that is at an angle of 0° to 10° from the illumination axis (206).
A method of characterising particles (140) by using a processor (301) to identify a particle boundary (165) of at least one particle (140) in an image (135, 171). The method comprises processing the image (135, 171) using a thresholding method to determine a first boundary (160a) corresponding with the at least one particle (140) and processing the image (135, 171) using an edge detection method to determine a second boundary (160b) corresponding with at the least one particle (140). The first boundary (160a) and second boundary (160b) are combined to create a combined boundary (160). A particle boundary (165) of the at least one particle (140) is determined using the combined boundary. A parameter used by the edge detection method is adaptive, and determined with reference to the image (135, 171).
An apparatus (200) for particle characterisation, comprising: a sample cell (210) for holding a sample (215); a light source (220) configured to illuminate the sample (215) with an illuminating beam (230) and a plurality of light detectors (240, 241, 242), each light detector (240, 241, 242) configured to receive scattered light resulting from the interaction between the illuminating beam (230) and the sample (215) along a respective detector path (250, 251, 252), wherein each respective detector path (250, 251, 252) is at substantially the same angle (260) to the illuminating beam (230).
A method (101) of using an apparatus comprising a processor to determine a diffusion coefficient (D) of a solute in a solution flowing in a capillary, comprising: obtaining a first signal (501) comprising a plurality of measurements of solute concentration measured at a first measurement location corresponding with a first mean measurement time that is before a full dispersion condition is met;obtaining a second signal (502) comprising a plurality of measurements of solute concentration measured at a second measurement location corresponding with a second mean measurement time that is after the first mean measurement time and before a full dispersion condition is met; determining a first front amplitude A1 of a solute front from the first signal (501); determining a second front amplitude A2 of a solute front from the second signal (502), the second front amplitude corresponding to the arrival of fast moving molecules travelling at or near a central streamline at the second measurement location; calculating: an actual front height ratio A2 /A1 of the second front amplitude A2 to the first front amplitude A1; a convection front height ratio h expected for a pure convection regime; and a proportion f of the solute that dispersed between the first mean measurement time and the second mean measurement time, the proportion f calculated using the actual front height ratio A2 /A1 and the convection front height ratio h;deriving a value of the diffusion coefficient (D) of the solute from a relationship between the proportion f and the diffusion coefficient, the relationship corresponding with the measurement conditions of the first and second signal.
A method of characterising particles in a sample (106). The method comprises: illuminating the sample (106) in a sample cell (104) with a light beam (103), so as to produce scattered light by the interaction of the light beam (103) with the sample (106); obtaining a time series of measurements of the scattered light from a single detector (110); determining, from the time series of measurements from the single detector (110), which measurements were taken at times when a large particle was contributing to the scattered light; determining a particle size distribution, including correcting for light scattered by the large particle.
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