36results about "Imaging particle spectrometry" patented technology

A method and system for calculating the arrival time window of a plume at an analyzer is presented. The plume is generated from a tissue or geological sample by laser ablation. In some embodiments, external sensors measure ambient parameters such as temperature and pressure to more accurately calculate the arrival time window. In other embodiments, direct measurements of the plume's arrival time or non-contact measurements of the plume's flow velocity in a pipe are used to determine the arrival time window of the plume at the analyzer.

The invention relates to an imaging elemental analyzer for imaging one or more analyte elements in an organic sample, wherein the analyzer comprises: a chamber for receiving an organic sample containing one or more analyte elements to be imaged, wherein the internal chamber pressure surrounding the sample is in the range of 10 -5 up to 10 -2mbar; at least one irradiant selected from: (i) an ion gun for irradiating the sample with a high-intensity primary ion beam, wherein the primary ions are generated in the ion gun at a pressure below 1 mbar, the ion gun serving to focus the primary ion beam onto a localized spot on the sample surface and to move the spot over time to a plurality of locations on the sample surface; (ii) a laser for irradiating a localized spot on the sample surface and to move the spot over time to a plurality of locations on the sample surface; a gas-filled RF ion guide for receiving the generated ions, comprising the elements released from the sample in response to irradiation by the primary ions or the laser, wherein the RF ion guide prevents the propagation of any ions whose m / z values ​​are less than the mass or mass range of the analyte elements;and a time-of-flight (TOF) mass analyzer for recording the ions or reaction products of the secondary ions formed from the RF ion guidance, wherein the TOF mass analyzer is configured for a repetition rate of at least 5 kHz. The invention also relates to a corresponding method and a corresponding device for imaging one or more inorganic, non-volatile elements.

Systems and methods for image and / or video processing of mass spectrometry data comprise a processor in communication with a storage device, and computer system code executed by the processor that causes the processor to perform an image or video analysis comparison between a second data plot image or video to a first data plot image or video, and generate a delta dataset based on the comparison. The delta dataset is representative of the differences between the first and second data plots. In additional systems and methods the computer system code can perform an image or video analysis comparison between the first and second data plots and a reference data plot, generate first and second delta datasets based on the comparisons, which are representative of the differences between the first and second data plots and the reference data plot, and perform a statistical analysis on the first and second delta datasets.

The invention generally relates to mass spectral analysis. In certain embodiments, methods of the invention involve analyzing a lipid containing sample using a mass spectrometry technique, in which the technique utilizes a liquid phase that does not destroy native tissue morphology during analysis.

The invention relates to an apparatus for multimodal analysis of sample material, for example from a tissue, which detects molecular image information from the sample material in a spatially resolved manner, for example using a MALDI time-of-flight mass analyser, records light microscopy image information from the sample material in a spatially resolved manner, and associates the two with improved accuracy to give spatially resolved co-registered overall image information.

Immunohistochemistry (INC) and in situ hybridization (ISH) methods are used for the targeted detection and localization of biomolecules (e.g., proteins and miRNAs) in tissues or cells, for research applications and clinical applications such as those of pathologists (e.g., biomarker analysis of resected tumors or tumor biopsies). These methods include mass spectrometry imaging (MSI) as a mode for detecting and localizing biomolecules in tissues or cells. The methods employ optically cleavable mass-tagged reagents linked to probes such as antibodies and nucleic acids and used to enable multiplexed immunohistochemistry and in situ hybridization, with MSI as the detection / readout mode. The methods also include multi-omics MSI procedures in which MSI of optically cleavable mass-tagged probes is combined with other MSI modes, such as direct label-free MSI of endogenous biomolecules from biological samples (e.g., tissues).

An MS2 analysis for one precursor ion is performed to collect data on each micro area within a measurement target area (S1). A plurality of product ions are extracted based on those data (S2), and a mass spectrometric (MS) imaging graphic is created for each m / z of the product ion (S3). Hierarchical cluster analysis is performed on the created MS imaging graphics to group the product ions based on the similarity of the graphics (S4). Product ions having similar distributions are sorted into the same group. Such a group of ions can be considered to have originated from the same compound. Accordingly, the intensity information of a plurality of product ions is totaled in each group and for each micro area (S5), and an MS imaging graphic is created based on the totaled intensity information (S6). Even if there are a plurality of compounds overlapping the precursor ion, the influence of the overlapping can be eliminated through those steps. Thus, a graphic having a higher level of SN ratio, sensitivity and dynamic range than an MS imaging graphic obtained at a single product ion can be created and displayed.

A multiplex method for co-detecting a plurality of different types of biomarkers in a tissue sample on a single slide comprises: (a) providing a tissue sample on a single slide; (b) performing antigen

Disclosed herein is a method of analysing a tissue sample. The method comprises identifying one or more regions of interest within the tissue sample based on a tissue stain that has been applied to the tissue sample. Analyte material is then generated from the one or more regions of interest identified based on the tissue stain using a direct surface sampling probe (10), which analyte material is then received at a sampling inlet (30) and passed towards a mass and / or ion mobility spectrometer (50) for analysis.

The invention relates to a method and an apparatus for analyzing a sample material on a sample carrier, comprising the following modes of operation: providing a time-of-flight mass analyzer having an ion generating unit, an ion generation unit having a mount for the sample carrier, an ion receiver, a flight path defining a longest flight time therebetween, an ion selector disposed along the path, and a clock generator for repeatedly triggering an ion generation pulse at the sample carrier and a subsequent pulse for accelerating ion species into the flight path; defining one or more mass-to-charge ratio (m / z) ranges, each range upper limit corresponding to a flight time shorter than the longest flight time; selecting the cycle period of the ion generation pulse so that the continuous pulse interval is shorter than the longest flight time but longer than the acceleration time; and using the mass analyzer, selecting a pulse cycle mode and an ion selector to analyze the sample material.

The invention relates to a method for analysing a sample material arranged on a sample carrier, comprising:-providing the sample material to the sample carrier,-exciting a fluorescence light emission of the sample material,-detecting the emitted fluorescence light,-analyzing the sample material by means of the detected fluorescence light. Position data of the sample material is determined along a z-axis substantially perpendicular to the sample carrier plane, using the determined position data such that a focal plane, an object plane and / or an image plane of the imaging optics used in scanning the sample material substantially coincide with the sample material, and an ion spectroscopy of the sample material is performed. The invention also relates to a device for carrying out such a method.

In one embodiment, a method for imaging a biological specimen is disclosed, which includes defining a plurality of reference points across the surface of the biological specimen; directing ablation radiation to the biological specimen at a first plurality of specimen locations corresponding to a first subset of the defined reference points, thereby ablating at least a portion of the specimen at each of the locations, thereby generating a gas-phase sample from each of the specimen locations; ionizing each of the gas-phase samples to generate ions corresponding to the gas-phase sample; acquiring one or more mass signals corresponding to the ions associated with each of the ablated portions; and identifying at least one region of interest based on the analysis of the mass signals. An image of the identified region of interest can be acquired using image mass cytometry.

An aspect of the present invention is an analysis method using MALDI-MS and LA-ICP-MS, both capable of imaging mass spectrometry, the method comprising: a step of setting a region A on a sample to which a matrix has been applied (S2); a step of executing mass spectrometry for each of a plurality of micro-regions within the region A using MALDI-MS (S3); a step of setting, on the sample, a region B that includes all of the region A and a range where the matrix exists that is different from the region A (S4); a step of executing mass spectrometry for each of a plurality of micro-regions within the region B using LA-ICP-MS (S5); a step of determining the presence or absence of an influence of a matrix-related component based on the data within the region A and the data in the range outside the region A obtained by LA-ICP-MS (S6); and a step of correcting the signal intensity in the data obtained in S5 as necessary based on the determination result (S7).

Provided are an analysis device and an analysis method by which more minute defects on the surface of a semiconductor substrate can be analyzed. The analysis device comprises: a surface defect measurement unit that measures the presence or absence of defects on the surface of a semiconductor substrate and obtains position information regarding the position on the surface of the semiconductor substrate of a defect on the surface of the semiconductor substrate; and an analysis unit which, on the basis of the position information regarding the position of the defect on the surface of the semiconductor substrate, irradiates laser light onto the defect on the surface of the semiconductor substrate, collects, with a carrier gas, an analysis sample obtained through the irradiation, and subjects the result to inductively-coupled plasma mass spectrometry.

A method for mass spectrometry which includes the following steps: Providing a library of matrix data wherein the matrix data exhibit one or more physicochemical properties of one or more matrix components as a function of the chromatographic retention time, wherein the matrix components are endogenous compounds of a matrix, chromatographic separation of a sample, wherein the sample contains at least some of the matrix components and one or more analyte components, Using a mass spectrometer to analyze the sample at several chromatographic retention times to obtain sample data, wherein the sample data exhibit one or more physicochemical properties of a plurality of sample components as a function of the chromatographic retention time, Calculating one or more error values ​​as a function of the chromatographic retention time based on a comparison between the sample data and the matrix data, wherein the step of calculating one or more error values ​​comprises: determining the difference between a physicochemical property of the matrix components in the sample data and a corresponding physicochemical property of the matrix components in the matrix data at a given chromatographic retention time or in a given chromatographic retention time range, wherein the one or more error values ​​correspond to the determined difference, and wherein the one or more physicochemical properties include one or more of the following: mass / charge ratio, drift time, collision cross section (“CCS”), interaction cross section, ion mobility, and differential ion mobility.

An (air / load) lock 10 for moving a sample carrier (16, Figure 2D) into a mass spectrometer, the (air / load) lock 10 having two openings (11, Figure 1B), 12, one for bringing the sample carrier (16, Fig

A pre-processor applies a pre-process to an original mass image produced through mass spectrometry of a sample, to produce a model input image. An image quality converter has an image quality conversion model produced through machine learning based on a group of images produced by a scanning electron microscope, and produces a model output image through image quality conversion of the model input image. A post-processor applies a post-process to the model output image, to produce a mass image after image quality conversion.

A method for adaptive secondary ion mass spectroscopy, the method may include (a) adaptively setting a detection parameter that impacts an instantaneous count rate of a detector; (b) scanning an evaluated sample with a focused primary ion beam; (c) sensing, by the detector, secondary ions ejected due to the scanning, to provide detection signals; and (d) analyzing a composition of the evaluated sample based on (i) the detection signals, and (ii) a mapping between values of the detection parameter and the instantaneous count rate of the detector.

The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection / readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).

A method for the spectrometric analysis of sample material located in at least one ablation area 4 on a sample support 2 comprises: determining an ablation area dimension between opposing boundaries o

The invention relates to methods and devices for analyzing sample material on a sample carrier, comprising an operating mode as follows: - providing a time-of-flight mass analyzer comprising an ion generation unit with a holder for the sample carrier, an ion receiver, a flight path between the ion generation unit and the ion receiver which determines a maximum flight time, an ion selector along the flight path, and a clock for repeatedly triggering an ion generation pulse locally at the sample carrier and a subsequent pulse for accelerating ion species directly from the ion generation unit onto the flight path, - defining one or more ranges of mass-to-charge ratios m / z, each with an upper m / z limit corresponding to a flight time that is shorter than the maximum flight time, - selecting a timing of ion generation pulses such thatthat the time interval between two successive ion generation pulses is shorter than the longest flight time and longer than the acceleration time of ion species from the ion generation unit, - Analyzing the sample material using the time-of-flight mass analyzer, the selected timing of ion generation pulses, and the ion selector.

Systems and devices are disclosed to generate a multidimensional mass fingerprint that allows for identification on a low-resolution mass spectrometer equipped with post-ionization fragmentation. For this approach, rather than interrogating a sample that is processed into peptides using a single high resolution MS scan as in traditional fingerprinting, a raw unprocessed sample (containing all biochemical species: lipids, proteins, peptides, and metabolites) is analyzed by combining Matrix-Assisted Laser Dissociation / Ionization (MALDI) ionization with low resolution tandem mass spectrometry. The proposed system combines improvements in MS hardware and software with state-of-the-art machine learning (ML) approaches to usher in rapid biological detection. This technique does not require any prior separation (liquid or gas chromatography) and is therefore rapid (e.g. less than 5 sec) and amenable to high throughput (e.g. greater than 384 samples / hr).

A method of analysing a sample comprises analysing a sample in a first mode of operation so as to produce a spatially resolved data set representative of the sample, and analysing the data set so as to identify one or more regions of the sample. For each of one or more identified regions of the sample, a tandem mass spectrometry (MS / MS) data set is produced for that region by determining a path through the region, and analysing the sample along the path using Desorption Electrospray Ionisation (“DESI”) in a tandem mass spectrometry (MS / MS) mode of operation.

An (air / load) lock (10, Figure 1A) for moving a sample carrier (16, Figure 2D) into a mass spectrometer, the (air / load) lock (10, Figure 1A) having two openings (11, Figure 1B; 12, Figure 1A), one for

To process data determined from image charge / current signals representing multiple ions of a given charge state (Q), each undergoing vibrational motion at respective oscillation frequencies (f) within an ion analysis apparatus.SOLUTION: A data set includes a measured signal frequency (f0) common to a plurality of measured image charge / current signals, and a plurality of estimated ion charge values corresponding to the respective amplitudes of the measured image charge / current signals. Using an integer charge value ([Qi]) corresponding to one of the estimated ion charge values rounded to the nearest integer, a plurality of different image charge / current signal frequency candidate values (fiCand) is calculated. The plurality of calculated image charge / current signal frequency candidate values (fiCand) is compared with the plurality of different signal frequencies (f) of the measured image charge / current signals to measure a score value representing the similarity between them on the basis of the comparison.SELECTED DRAWING: Figure 2b

An imaging mass spectrometer according to the present invention includes: a measurement unit to acquire data by performing mass spectrometry on each of a plurality of micro regions in a measurement region on a sample; a narrowing unit to perform a process of narrowing a peak width with respect to each peak detected in each of a plurality of profile spectra based on the data individually obtained in the plurality of micro regions to be averaged or summed; a spectrum calculation unit to obtain an overall mass spectrum by averaging or summing the plurality of mass spectra processed by the narrowing unit; a peak selection reception unit to display the overall mass spectrum and receive an instruction from a user to select a peak on the mass spectrum; and an image creation unit to create a mass spectrometry image corresponding to the peak received by the peak selection reception unit.

The invention relates to methods and devices for analysing sample material on a sample carrier, comprising an operating mode as follows: providing a time-of-flight mass analyser with an ion generating unit having a mount for the sample carrier, an ion receiver, a flight route between them determining the longest time-of-flight, an ion selector along the route, and a clock generator for repeatedly triggering an ion generating pulse at the sample carrier and a subsequent pulse for accelerating ion species onto the flight route; defining one or more ranges of mass-to-charge ratios (m / z), each with an upper limit corresponding to a time-of-flight shorter than the longest time-of-flight; selecting a cycling of ion generating pulses such that the duration between successive pulses is shorter than the longest time-of-flight but longer than the acceleration time; and analysing the sample material using the mass analyser, the selected pulse cycling, and the ion selector.

In one aspect, a method of imaging a biological specimen is disclosed, which includes defining a plurality of reference location points across a surface of the biological specimen, directing ablating radiation to the biological specimen at a first plurality of sample locations corresponding to a first subset of the defined reference location points to ablate at least a portion of the specimen at each of said locations, thereby generating a gas phase sample from each of said sample locations, ionizing each of the gas phase samples to generate ions corresponding to that gas phase sample, acquiring one or more mass signals corresponding to ions associated with each of the ablated portions, and identifying at least one region of interest based on analysis of the mass signals. An image of the identified region of interest can be acquiring using image mass cytometry.

A method and apparatus for monitoring and / or controlling the extent of denaturation and / or bond cleavages of proteins on any surface (e.g., biological tissues, biofilms, etc.). In one embodiment, a low power laser (e.g., a 5 mW, 362 nm diode laser) is directed through a biological sample to a photodetector. The sample is heated by a set of radiant heaters to between about 220° C. and about 250° C. in a time period of between 10 seconds to 60 seconds. The baseline transmissivity of the sample is monitored continuously throughout treatment of the biological sample via continuous monitoring of the signal voltage detected at the photodetector. Upon detection of increase in relative transmissivity in the biological sample, the heating treatment is concluded and the biological sample is removed for in situ protein identification as part of an imaging MALDI-MS measurement.

In one aspect, a method of imaging a biological specimen is disclosed, comprising: defining a plurality of reference location points on a surface of the biological specimen; directing ablation radiation to the biological specimen at a first complex of sample locations corresponding to a first subset of the defined reference location points to ablate at least a portion of the specimen at each of the locations to produce a gas phase sample from each of the sample locations; ionizing each of the gas phase samples to produce ions corresponding to the gas phase samples; obtaining one or more mass signals corresponding to ions associated with each ablated moiety; and identifying at least one region of interest based on the analysis of the quality signal. An image of the identified region of interest may be acquired using imaging mass spectrometry flow cytometry.