106results about "Imaging particle spectrometry" patented technology

A method and corresponding devices to reduce the presence of unwanted ions within the pseudo-potential well of the RF fields for inductively coupled plasma mass spectrometry is disclosed. This method reduces space-charge effects and leaves more room available for the ions of interest and, hence, leads to increased transmission of the desired ions into the mass analyzer. In the present invention, the space charge is reduced by adding a low-band resolving DC potential, or a fast sweeping resolving DC potential with a notch, or a fast constant resolving DC potential with a notch, or by adding auxiliary quadrupolar or dipolar RF potential to the quadrupole ion guide, such that all the unwanted ions will be outside the stable region and therefore ejected. This reduces the charge density in the ion beam and ameliorate space charge effects.

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.

A needle for mass spectrometry having a solid shaft and a first end with a tip having a radius of curvature of less than 1500 nm, wherein the tip is distal from a second end of the needle, wherein the second end is configured to accept an electrical potential, and wherein the tip provides an ionization region when the electrical potential is applied. Methods of manufacturing a needle having a radius of curvature of less than 1500 nm. Methods and systems including at least one needle of the present disclosure for qualitative and / or quantitative analysis.

The present invention relates to a method for analyzing and measuring sample materials deposited on the surface of a sample holder, comprising: (a) defining a plurality of regions on the surface, some of which are in contact with the sample material, (b1) using a desorption beam to sample a sample segment on one region to generate desorbed molecules, which are ionized and transferred to an analyzer, (b2) scanning the region along a non-linear trajectory selected from a plurality of predefined non-linear trajectories on the region by changing the orientation of the beam relative to the surface, while keeping the holder in one position, (c) using a spatial adjustment device of the sample holder to transition from the scanned region to the next region to be scanned, and (d) repeating steps (b1), (b2) and (c) until a predetermined termination condition is met. The present invention also relates to a system for analyzing ions, which has an ion generating device and a control unit.

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.

Methods and systems to calculate 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, an external sensor measures the ambient parameters such as temperature and pressure to calculate the arrival time window more accurately. In other embodiments, direct measurement of plume arrival times or non-contact measurement of the flow speed of the plume in a tube are used to determine the arrival time window of the plume at an analyzer.

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 methods for analyzing a tissue sample. In certain aspects, the invention provides methods that involve obtaining a tissue sample including an unsaturated compound, conducting a radical reaction on the tissue sample that targets a carbon- carbon double bond within the unsaturated compound to thereby produce a plurality of compound isomers, subjecting the plurality of compound isomers to mass spectrometry analysis to identify a location of the carbon-carbon double bond within the unsaturated compound, and quantifying the plurality of compound isomers in order to distinguish normal tissue from diseased tissue.

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 present invention relates to an apparatus and method for performing a desorption scan on an analyte material placed on a sample carrier, which may include the following operating modes: (a) setting the position of the carrier to be close to the impact area at which the beam is aligned for local desorption of the analyte material; (b) determining the actual position of the carrier after setting the position; (c) comparing the determined actual position with the target position of the carrier to determine any deviation; (d) if a deviation is detected, adjusting the beam orientation so that the beam is aligned to the impact area that would have been produced on the carrier in the absence of a deviation; (e) applying the beam to the impact area to locally desorb the analyte material and convey it to an analyzer; and (f) checking whether a predetermined end condition is satisfied, and if not, repeating steps (a)-(e) for subsequent non-conforming impact areas.

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).

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.

One mode of an imaging analysis apparatus according to the present invention includes: a measurement unit configured to acquire analysis result data by performing ion mobility mass spectrometry for each of a plurality of micro regions in a predetermined measurement region in a sample; a correlation investigation unit (22, 23) configured to investigate a correlation between an m / z and an ion mobility in the analysis result data based on the analysis result data acquired by the measurement unit; and a data reduction unit (24, 25) configured to reduce an amount of the analysis result data by limiting an ion mobility range according to the m / z or limiting an m / z range according to the ion mobility based on the correlation obtained by the correlation investigation unit.

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.

According to one aspect of the present invention, an analysis method using MALD I-MS and LA-ICP-MS both capable of performing imaging mass analysis comprises: a step (S2) for setting a region (A) on a sample coated with a substrate; a step (S3) for performing mass analysis on each of the plurality of minute regions in the region A using MALD I-MS; a step (S4) for setting, on the sample, a region (B) including the entire region (A) and a region in which the matrix is present, the region (B) being different from the region (A); a step (S5) for performing mass analysis on each of the plurality of minute regions in the region B using LA-ICP-MS; a step (S6) for determining the presence or absence of an influence of the matrix-related component on the basis of data within the region A and data of a range outside the region A generated by LA-ICP-MS; and a step (S7) of correcting, as necessary, the signal strength in the data obtained in (S5) on the basis of the determination result.

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

The present invention relates to a method for single-cell imaging mass spectrometry (MS) by correlating an optical image of a cell sample with an MS image. The method of the invention is in particular useful in research to test concomitantly optical and molecular phenotypes at a single-cell resolution.

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.

A method for ion mapping of a sample, which has the following features: Application of a liquid sample to a metallic target surface, Separation of components of the liquid sample on the metallic target surface according to one or more physicochemical properties in a first spatial dimension and in a second spatial dimension and Ionizing and mass-analyzing multiple separated areas of the separated sample to generate an ion map of at least a portion of the sample separated on the target surface, wherein the components of the sample are applied to the target surface and separated by mechanical, hydrodynamic and / or aerodynamic means, and wherein the one or more physicochemical properties include one or more from the group comprising surface binding, surface affinity, solubility, binding affinity and polarity.

A SIMS-based analysis system, that includes (a) a memory circuit that is configured to store (i) an estimated model of a non-planar three dimensional (3D) structural element, and (ii) a measured SIMS spectrum of the 3D structural element; (b) a calibration information circuit that is configured to obtain calibration information, (c) a SIMS simulating circuit that is configured to provide a (i) an updated model of the 3D structural element, the updated model is indicative of changes undergone by the 3D structural element during the sputtering process, and (ii) a simulated SIMS spectrum of the 3D structural element; and (d) a fitting circuit that is configured to determine at least one of geometry and material concentration parameters based on the simulated SIMS spectrum and the measured SIMS spectrum.

A computer-implemented method for detecting at least one analyte in a sample with a laser desorption mass spectrometer (220) is disclosed. The method comprises:a) at least one imaging step comprising imaging at least one reflective target (128) by using at least one imaging device (235), wherein the sample comprising the at least one analyte is applied to the reflective target (128);b) at least one sample recognition step comprising localizing at least one sample region on the reflective target (128); andc) at least one analyte detection step comprising detecting the at least one analyte in the sample using surface assisted laser desorption ionization mass spectrometry (SALDI-MS) with the laser desorption mass spectrometer (220), wherein laser irradiation is applied to the reflective target (128) by using at least one laser source (222) of the laser desorption mass spectrometer (220) such that at least one ion of the at least one analyte is generated which is detected by using at least one of a mass analyzing unit (224) or an ion-mobility spectrometry device of the laser desorption mass spectrometer (220), wherein the laser irradiation is steered on the localized sample region by using at least one control device (237).

A system and device are disclosed that generate multidimensional mass fingerprints that allow identification on low-resolution mass spectrometers with post-ionization fragmentation. In this approach, rather than interrogating samples processed into peptides using a single high-resolution MS scan as in traditional fingerprinting, the raw raw sample (containing all biochemical species such as 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 pioneer rapid biological detection. The technique does not require prior separation (liquid or gas chromatography) and is therefore rapid (e.g., less than 5 seconds) and amenable to high throughput (e.g., more than 384 samples / hour).

A mass spectrometry method including: focusing an excitation beam by an excitation beam optical system at a predetermined position of the sample stage, and recording a position of a beam irradiation system including the excitation beam optical system and a movable sample stage at that time as a reference position and a temperature of the beam irradiation system at that time as a reference temperature (Steps 1 and 2); acquiring temperature dependency information which is information representing a change in position of the excitation beam optical system and the sample stage with respect to a change in temperature of the beam irradiation system and recording the temperature dependency information (Step 3); and correcting a focusing position of an excitation beam using the moving mechanism based on a difference between a temperature of the beam irradiation system during use and the reference temperature and the temperature dependency information (Step 7).

Disclosed herein are systems for imaging and ablating a sample. An imaging / ablating device (110) includes an optical assembly (112), a sample stage (114), and a receiver (116). The optical assembly (112) is disposed in an inverted position below the sample stage (114) and the receiver (116) is positioned above the sample stage (112). The optical assembly enables imaging of a sample disposed on the sample stage (114). The optical assembly (112) also enables ablation of a region of interest within the sample. The laser light propagated from the optical assembly during ablation propagates substantially in the same direction as the direction of travel of the ablation plume (20) toward the receiver (116).

Described herein are systems and methods for imaging mass spectrometry, including imaging mass cytometry. Aspects of interest include devices and methods for imaging mass spectrometry (IMS) that improve sample capture speed, signal sensitivity, and / or signal stability. The systems and methods described herein may minimize the transport time and / or minimize the diffusion of a plume of removed sample material from a delivered sample to components of an imaging mass spectrometer or mass cytometer that ionize and analyze the sample material.

Immunohistochemistry (INC) and in situ hybridization (ISH) methods for targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells, for example, for research applications and clinical use by pathologists (e.g., biomarker analysis of resected tumors or tumor biopsies), include mass spectrometry imaging (MSI) as a mode for detecting and mapping biomolecules within tissues or cells. The methods utilize photocleavable mass tag reagents coupled to probes such as antibodies and nucleic acids and used to achieve multiplexed immunohistochemistry and in situ hybridization, with MSI as the detection / readout modality. The methods also encompass multi-omic MSI procedures, in which MSI of photocleavable mass tag probes is combined with other modes of MSI, such as direct, label-free MSI of endogenous biomolecules from biological samples (e.g., tissues).

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.

In a data-analyzing method in which an analysis based on a plurality of data groups each obtained by an instrumental analysis on each of a plurality of samples, with each data group including signal values having an n-dimensional array structure (where n≥2), is performed by using a computer, to obtain desired information concerning a difference between the samples, the method includes: a computational processing step for performing, in each data group, a persistent-homology processing on data including signal values having an m-dimensional array structure (where 2≤m≤n) obtained from one data group, to create a persistence diagram (PD); and an analytical processing step for comparing PDs respectively obtained from the data groups, to obtain the desired information based on a difference in the dispersion state of plots across the entire PDs being compared and / or based on information concerning a plot having no positional correspondence determined on the PDs being compared.

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.