A method for mass spectrometry comprises ionizing an analyte in an ionizer to generate a plurality of precursor ions; applying temporally modulated energy to the plurality of precursor ions within the ionizer to generate a plurality of fragments of the plurality of precursor ions; and introducing a subset of ions generated in the ionizer into a downstream chamber of a mass spectrometer. In some embodiments, applying the energy may include flowing a gas toward the precursor ions. In various embodiments, the gas may include a heating gas or a cooling gas.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
2.
ANALYSIS OF CRISPR/CAS9 SYSTEM ASSOCIATED MOLECULES USING CAPILLARY ZONE ELECTROPHORESIS
The disclosed technology provides capillary electrophoresis methods and kits for the separation of multiple components in one or two runs with high resolution.
Disclosed and claims are a method for analyzing at least one analyte, the method including introducing a composition into a separation channel, wherein the composition includes at least one pH gradient compound, an amine buffer, and at least one analyte of interest; applying an electric field across the separation channel to create a pH gradient using the at least one pH gradient compound and separate the composition via isoelectric focusing, generating at least one focused analyte peak; mobilizing the at least one focused analyte peak; and wherein the amine buffer is configured to modify the pH gradient.
Described and claimed herein are systems and methods that provide streamlined coupling of CE (e.g., CE-SDS) separation with MS analysis (e.g., such as CE(SDS)-AEX-MS).
G01N 30/96 - Recherche ou analyse de matériaux par séparation en constituants utilisant l'adsorption, l'absorption ou des phénomènes similaires ou utilisant l'échange d'ions, p.ex. la chromatographie en utilisant l'échange d'ions
The n spectra of a DIA method are compared to a library of product ion spectra to identify an initial i compounds corresponding to l spectra. A reinforcement learning algorithm (RLA) is performed. (a) An agent of the RLA performs an action At that includes searching one or more compound databases for compounds related to the i compounds, producing j related compounds, and applying one or more deep learning prediction algorithms to predict k spectra for the i+j compounds. (b) An environment of the RLA compares the k spectra to the n spectra, producing a state, St, in which i+j compounds produce m matching compounds and a reward, Rt, for the agent if m>i. (c) If the Rt is produced, the i compounds are set to the m compounds and the l spectra are set to the k spectra, and steps (a)-(c) are repeated.
Methods and systems for assessing a quality of mass analysis data generated by a mass analysis device, including collecting mass spectrometry data for a given compound, deriving a measured isotope profile based on the collected mass spectrometry data, determining a predicted isotope profile, determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks, determining a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data, determining an overall quality score as a combination of the first quality score and the second quality score, and assessing a quality of a compound library based on the determined overall quality score.
The presently claimed and described technology provides a sample processing system comprising at least one sample introduction device, wherein the at least one sample introduction device is configured to receive a sample; a mass analyzer coupled to the sample introduction device; a control system configured to at least control the at least one sample introduction device and/or the mass analyzer, wherein the mass analyzer is configured to perform a first mass analysis on the sample, wherein the first mass analysis is mass screening for an analyte of interest in the sample, and wherein if the analyte of interest is detected in the sample, the mass analyzer is configured to perform a second mass analysis, wherein the second mass analysis is a quantitative analysis, comprising: ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte; determining intensity and/or abundance of the at least one product ion transition and/or the at least one isotopic ion transition; and quantifying the at least one analyte present in the sample using the intensity and/or abundance of the at least one product ion transition and/or isotopic ion transition.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
A method for annotating product ions of a spectrum is disclosed. A product ion mass spectrum is received. A parameter that indicates the mass spectrum was produced using a radical-induced dissociation method is received. At least one charge state mass-to-charge ratio (m/z) adjustment based on the parameter is performed for at least one product ion peak of the mass spectrum and the adjustment is compared to one or more other product ion peaks of the mass spectrum. The at least one product ion peak is annotated based on the comparison. The charge state adjustment includes the loss of an electron or the loss or gain of a hydrogen atom. The radical-induced dissociation method includes electron-based dissociation (ExD), ultraviolet photodissociation (UVPD), or infrared photodissociation (IRMPD).
The presently described and claimed disclosure relates to method for characterizing nucleic acid purity comprising denaturing a nucleic acid sample, loading the nucleic acid sample onto a capillary electrophoresis (CE) capillary, wherein the CE capillary is filled with a buffer comprising a polymer matrix, applying a separation voltage to the CE capillary, wherein during the separation of the nucleic acids, the temperature of the CE capillary is increased, and detecting nucleic acids separated from the nucleic acid sample with a detector. Kits and instructions for use are also described.
Calibrant compositions comprising a plurality of synthetic peptides for calibration of a mass spectrometer in either positive or negative mode are provided. The synthetic peptide calibrants exhibit desirable ionization characteristics, solubility, and solution stability, and are easily washed out of the system such that no interfering signals are left behind. Methods for calibration of mass spectrometer in positive or negative ion mode using a single calibrant composition are also provided.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
11.
METHODS AND SYSTEMS FOR DETERMINING MOLECULAR MASS
Methods and systems for adjusting instrument setting, improving fidelity of isotope pattern for mass spectra, and/or determining molecular mass with improved accuracy are disclosed. In one example, a method for determining Mmono of a compound of interest in a sample using a mass spectrometer is provided. The method comprises: (1) tuning or adjusting instrument setting of the mass spectrometer using at least one known compound, wherein the instrument setting comprises at least one parameter for improving accuracy; (2) analyzing the compound of interest using the adjusted instrument setting to obtain a mass spectrum thereof, wherein the mass spectrum comprises an isotope pattern thereof; and determining the Mmono of the compound of interest from the mass spectrum thereof.
Systems and methods are disclosed for performing a DDA mass spectrometry experiment. A precursor ion survey scan of a mass range is performed to generate a precursor ion peak list. A series of steps are performed for each precursor ion peak of the peak list. A peak mass range including the precursor ion peak is selected. A precursor ion mass selection window with a width smaller than the peak mass range is canned across the peak mass range in overlapping steps, producing a series of overlapping windows across the peak mass range. Each overlapping precursor ion mass selection window of the series is fragmented. Product ions produced from each overlapping precursor ion mass selection window of the series are mass analyzed, producing a product ion spectrum for each overlapping precursor ion mass selection window of the series and a plurality of product ion spectra for the peak.
A method for determining a convolved peak intensity in a sample trace includes ejecting a plurality of sample ejections from a sample well plate. An ejection time log is generated which includes an ejection time of each of the plurality of sample ejections from the sample well plate. The plurality of sample ejections is analyzed with a mass analyzer. The sample trace of intensity versus time values is produced for the plurality of sample ejections based on the analysis. A known peak shape is obtained. A convolved peak intensity is determined for a convolved peak of the sample trace based at least in part on the known peak shape and the ejection time log.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
Methods and system that determines disulfide and trisulfide linkages within analytes (e.g., polypeptides) is described. In certain aspects. a sample comprising polypeptides (such as an antibody) may be subjected to dissociation using an electron activated dissociation (which can include electron capture dissociation and electron transfer dissociation) and the fragmentated portions are analyzed using a mass spectrometer to produce a spectrum. The spectrum is analyzed by a processor to identify peaks from the spectrum that are related to one another in the spectra by a separation of 32 mass units. In identifying an antibody comprising peptide segments linked via a trisulfide bond. for example, four different peaks representing two different peptides are searched for and identified representing a first peptide portion having mass/charge of A and A+32 and a second peptide having mass/charge of B and B+32.
G16C 20/20 - Identification d’entités moléculaires, de leurs parties ou de compositions chimiques
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
G16B 40/10 - Traitement du signal, p.ex. de spectrométrie de masse ou de réaction en chaîne par polymérase
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
H01J 49/42 - Spectromètres à stabilité de trajectoire, p.ex. monopôles, quadripôles, multipôles, farvitrons
15.
METHODS AND SYSTEMS FOR PROCESSING IN REAL-TIME AND USING GAUSSIAN
Systems and methods are provided for processing in real-time and using Gaussian fitting digitized signals from ions detection in time-of-flight (TOP) mass spectrometry. Acquisition/analog-to-digital conversion may be applied in the course of Ion detection during time-of-flight (TOP) mass spectrometry, with the acquisition/analog-to-digital conversion including generating, in response to detection of ions, one or more time-of-flight (TOP) based signals, and digitizing, using analog-to-digital conversion, the one or more TOP based signals, to generate corresponding digitized data. The digitized data may then be processed, in real-time and based on use of Gaussian fitting, to generate result data corresponding to the time-of-flight (TOP) mass spectrometry. The Gaussian fitting may comprise applying second (2nd) degree polynomial fit, such as by least squares via QR factorization.
Methods and systems for background processing include ionizing a first sample and a second sample, the first sample including the target molecule, and the second sample including a target molecule-ligand combination, capturing a raw mass spectrum for the ionized first sample and second sample, generating a deconvoluted mass spectrum for the first sample and the second sample, determining an intensity ratio of a background intensity at a mass window corresponding to a sum of a mass of the target molecule and a mass of the ligand in the first sample to a signal intensity at a mass window corresponding to the target molecule in the first sample, and determining, based on the determined intensity ratio, a background intensity of the target molecule- ligand combination in the deconvoluted mass spectrum of the second sample at a mass window corresponding to the mass of the target molecule-ligand combination.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
C12Q 1/6872 - Méthodes de séquençage faisant intervenir la spectrométrie de masse
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
G16C 20/20 - Identification d’entités moléculaires, de leurs parties ou de compositions chimiques
17.
SYSTEMS AND METHODS FOR FLASH BOILING OF A LIQUID SAMPLE
A method of ejecting a sample from a nebulizer nozzle fluidically coupled to a port via a transfer conduit includes receiving at the port a transport liquid and the sample. The transport liquid and the sample in the transfer conduit is transported from the port to a transfer conduit exit comprising an electrode tip. The transport liquid is ejected from the transfer conduit exit. The sample is ejected from the transfer conduit exit substantially simultaneously with ejecting the transport liquid. During ejection of the transport liquid and the sample from the transfer conduit exit, a pressure is generated at the transfer conduit exit substantially similar to a vapor pressure of the transport liquid.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/16 - Sources d'ions; Canons à ions utilisant une ionisation de surface, p.ex. émission thermo-ionique ou photo-électrique
H01J 49/24 - Systèmes à vide, p.ex. maintenant des pressions voulues
18.
Systems and Methods for Background Ion Detection in Mass Spectrometry
A method for performing mass spectrometry (MS) comprises receiving MS data corresponding to a plurality of MS runs, wherein MS data corresponding to an MS run of the plurality of MS runs comprises detected intensities for a plurality of mass over charge ratios (MZ values) during the MS run; finding a recurrent MZ value of the plurality of MZ values, wherein a detected intensity for the recurrent MZ value appears as a recurrent peak in MS data corresponding to a subset of the plurality of MS runs; and the subset of the plurality of MS runs includes at least two MS runs of the plurality of MS runs; and identifying the recurrent MZ value as corresponding to a background ion.
In one aspect, a mass spectrometer is disclosed, which includes an ion path along which an ion beam can propagate, and an ion beam deflector positioned in the ion path and configured to modulate transfer of an ion beam received from an upstream section of the ion path to a downstream section thereof, said ion beam deflector comprising at least one electrically conductive electrode positioned relative to one another to provide an opening through which the ion beam can pass, where the two electrodes are electrically insulated relative to one another so as to allow maintaining each electrode at a DC potential independent of a DC potential at which the other electrode is maintained.
A method of sampling with an open port interface (OPI) comprises operating the OPI. A liquid sample is contacted with the OPI. An aliquot from the liquid sample is pinned to the OPI. The aliquot includes a predetermined volume which terminates contact between the OPI and the liquid sample. The aliquot is aspirated from the OPI via a removal conduit within the OPI.
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p.ex. dispositifs d'aspiration, dispositifs d'injection
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
21.
OPTIMIZATION OF DMS SEPARATIONS USING ACOUSTIC EJECTION MASS SPECTROMETRY (AEMS)
Disclosed are methods and systems that provide for the analysis of one or more analytes of interest in an acoustic ejection mass spectrometer (AEMS) system that incorporates an open port interface (OPI) and differentiation mass spectrometry (DMS) that allows for operation of the system in a pseudo-continuous mode to scan and determine optimal DMS settings for the one or more analytes of interest, and for operation of the system in a discontinuous mode to analyze for the presence of the one or more analytes of interest in a sample.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
G01N 27/624 - Spectrométrie de mobilité ionique différentielle [DMS]; Spectrométrie de mobilité ionique à haut champ asymétrique [FAIMS]
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
Methods and systems for spectral comparison and quality assessment are disclosed. In one example, a method for assessing quality of a mass spectrum (MS) of a sample is provided. The method comprises: predefining one or more features or attributes indicative of the sample quality with reference to a target compound; and calculating a quality score for the MS with respect to the selected features or attributes.
Methods and systems for identifying analytes in a sample using mass spectrometry are provided. A method for identifying analytes in mass spectrometry data comprises: introducing a sample to a mass spectrometer; analyzing the sample with the mass spectrometer in a plurality of cycles; generating, for each cycle, a mass spectrum comprising at least one peak; annotating peaks in the mass spectrum based on their relationships; assigning best ion types to each peak; processing each cycle of the mass spectrum to assign a score to each of the at least one peak thereof with respect to the likely neutral mass related to the peak; grouping peaks that share a common neutral mass; and outputting the analyte neutral mass.
Methods and systems for building and using an analyte library are provided. One aspect is a method for building an analyte library, the method comprising receiving mass spectrum data from analysis of a sample using mass spectrometry, mass spectrum data including a mass spectrum and a sample matrix, and the sample including an analyte, identifying peaks in the mass spectrum, assigning at least one ion type to the peaks, annotating the peaks for the analyte based on the sample matrix, extracting an ion fingerprint for the analyte based on the annotated peaks and storing an analyte identification entry including the ion fingerprint for the analyte.
In one aspect, a mass spectrometer is disclosed, which includes an ion trapping device, at least one pressurized ion guide configured to allow establishment of an adjustable axial field therein such that the axial field can be adjusted to operate the pressurized ion guide in any of a fast and a slow operational setting, a mass analyzer for receiving ions passing through the pressurized ion guide and configured to provide mass analysis of the received ions, and a controller in communication with said at least one pressurized ion guide for causing the adjustment of the axial field so as to switch the operational setting of the pressurized ion guide between the fast and the slow operational settings based on an operational mode of the mass spectrometer.
A method of calibrating a signal measurement system includes performing a first number of calibration measurements for a first number of samples of a compound, the samples having known concentrations, by measuring a signal for each sample, receiving a signal for a sample having an unknown concentration of the compound; selecting a second number of calibration measurements from the first number of calibration measurements, the second number being smaller than the first number; performing a regression on the selected second number of calibration measurements; and determining the unknown concentration based on the performed regression.
An ion mass filter for use in a mass spectrometer is disclosed, which includes a plurality of rods arranged in a multipole configuration to provide a passageway through which ions can travel, said plurality of rods being configured for application of RF voltages thereto to generate an electromagnetic field within the passageway for providing radial confinement of the ions and further configured for application of a DC voltage thereto, and at least two pairs of auxiliary electrodes interspersed between the plurality of multipole rods, where one pair forms a first pole of the auxiliary electrodes and the other pair forms a second pole of the auxiliary electrodes. A controller can provide one or more control signals to the DC voltage source so as to switch the polarity of the DC voltage differential between the two poles according to a predefined criterion.
A method for improved mass spectrometry by determining charge state of precursor ions from an analysis of product ions, includes receiving sample ions. A group of precursor ions is selected from the received sample ions based on mobility. A fragmentation device fragments the group of precursor ions to produce a group of product ions. A tandem mass spectrometry analysis is performed on the group of product ions to generate an intensity and mass-to-charge ratio (m/z) of the group of product ions. An ionogram is generated, based on the generated intensities and mass, to charge ratios for the groups of product ions generated for each of the mobility selection. The ionogram includes a first axis representing compensation voltage value and another axis representing intensity. A product ion peak is identified in the ionogram. At least one peak characteristic is identified of the product ion peak. A charge state of a precursor ion that was fragmented to form the product ions represented in the product ion peak is determined based on the at least one peak characteristic of the produce ion peak.
In one aspect, a method of operating a mass spectrometer is disclosed, which comprises ionizing a sample to generate a plurality of ions, and introducing at least a portion of the ions into an inlet orifice of the mass spectrometer. At least a portion of the ions and/or fragments thereof is detected by a downstream detector to generate a plurality of ion detection events, and the ion detection events are monitored to determine an ion count. The ion count is compared with a reference level to determine whether the detected level exceeds the reference level.
Systems and methods are disclosed for analyzing a sample using overlapping precursor isolation windows. A mass analyzer of a tandem mass spectrometer is instructed to select and fragment at least two overlapping precursor isolation windows across a precursor ion mass range of a sample using a processor. The tandem mass spectrometer includes a mass analyzer that allows overlapping precursor isolation windows across the mass range of the sample.
In one aspect, an ion filter for use in a mass spectrometer is disclosed, which includes a plurality of rods arranged in a multipole configuration to provide a passageway through which ions can travel, said plurality of rods being configured for application of RF voltages thereto to provide an electromagnetic field within the passageway for providing radial confinement of the ions and further configured for application of a DC voltage thereto. At least two pairs of auxiliary electrodes are interspersed between the plurality of rods and are configured for application of a DC bias voltage with one polarity to one of said pairs and a DC bias voltage with an opposite polarity to the other one of said pairs to provide a DC potential difference between the auxiliary electrodes and the plurality of rods.
One or more known compounds are separated from a mixture using a separation device that allows processor-controlled adjustment of a separation parameter. The separated compounds are ionized and, for each cycle of a plurality of cycles, a mass spectrometer executes on the ion beam a series of MRM transitions read from a list. Two or more contiguous groups of MRM transitions to be monitored separately are received. Each group includes at least one sentinel transition that identifies a next group that is to be monitored and identifies a value for the separation parameter for the next group. A first group is placed on the list. When a sentinel transition of the first group is detected, a next group identified by the sentinel transition is placed on the list and the separation parameter is adjusted to a value identified by the sentinel transition for the next group.
Methods and systems for identifying one or more analytes in a sample are provided. One aspect is a method of predicting an identity of analytes in an unknown sample, the method comprising accessing a database comprising a plurality of results from analyzing samples using mass spectrometry to identify analytes, the plurality of results including annotated ion fingerprints, training a machine learning model with the plurality of results, and applying the machine learning model to the unknown sample to predict an identity of one or more analytes in the unknown sample.
Disclosed are methods for separating target and non-target analytes in a sample. The methods can utilize an acoustic droplet ejector (ADE) and an open port interface (OPI) to achieve liquid chromatography (LC)-like separation for an analytical instrument such as, for example, a mass spectrometer.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
35.
Methods and Systems for Increasing Sensitivity of Direct Sampling Interfaces for Mass Spectrometric Analysis
Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of desorption solvent within a sampling probe fluidly coupled to an ion source can be selectively controlled such that one or more analyte species can be desorbed from a sample substrate inserted within the sampling probe within a decreased volume of desorption solvent for subsequently delivery to the ion source. In various aspects, sensitivity can be increased due to higher desorption efficiency (e.g., due to increased desorption time) and/or decreased dilution of the desorbed analytes. The methods and systems described herein can additionally or alternatively provide for the selective control of the flow rate of the desorption solvent within the sampling interface so as to enable additional processing steps to occur within the sampling probe (e.g., multiple samplings, reactions).
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
G01N 30/00 - Recherche ou analyse de matériaux par séparation en constituants utilisant l'adsorption, l'absorption ou des phénomènes similaires ou utilisant l'échange d'ions, p.ex. la chromatographie
H01J 49/16 - Sources d'ions; Canons à ions utilisant une ionisation de surface, p.ex. émission thermo-ionique ou photo-électrique
36.
INTENSITY-INDEPENDENT PRECURSOR INFERENCE IN MASS SPECTROSCOPY
Methods for correlating a product ion in a mass spectrum to a precursor ion are disclosed herein, comprising determining a precursor ion ml z corresponding to the product ion as an m/z at which the product ion appears in a maximum amount of the series of mass spectra. Methods also can comprise obtaining a series of mass spectra for a sample across a mass range, each of the series of mass spectra having a precursor ion transmission window defined by a width (W) that overlaps with that of at least two of the series of mass spectra by a step size (S).
Improved systems, apparatus, methods, and programming useful for the automated analysis of complex compounds using mass spectrometers. Systems, apparatus, methods, and programming according to the invention provide for the automatic determination by a controller 54 of a mass spectrometer 14, 214 of an analysis operation to be implemented using the mass spectrometer, the analysis operation adapted specifically for analysis of one or more substances based contained within a compound based on identification of the compound and/or substances provided by a user of the spectrometer, and a database 66 or other library of information concerning suitable processes or process steps for analyzing substances.
A method for measuring a concentration of an analyte in a sample includes: sampling, from a first sample, a first one or more droplets for mass analysis, wherein the first sample includes the sample; performing mass analysis on the first one or more droplets to determine a first intensity of an analyte in the first one or more droplets; sampling, from a second sample, a second one or more droplets for mass analysis, wherein the sec-ond sample includes the sample and a first spike of the analyte; performing mass analysis on the second one or more droplets to determine a second intensity of the analyte in the second one or more droplets; fitting a curve to the first intensity and the second intensity; and based on the fitted curve, calculating an analyte concentration for the sample.
Systems and methods are provided for correcting a measured retention time or expected retention time of an ion intensity measurement. A measured sentinel retention time is received for each of a plurality of sentinel ion intensity measurements. During acquisition, sentinel analysis is performed. In sentinel analysis, a plurality of ion intensity measurements is divided into two or more groups so that different groups of the two or more groups are measured separately. At least one sentinel ion intensity measurement in each group of the two or more groups is selected to identify a next group of the two or more groups to be measured. A measured retention time or an expected retention time of at least one non-sentinel ion intensity measurement of the two or more groups is corrected using the plurality of measured sentinel retention times.
A method for identifying peaks in a mass spectrum is provided. The method includes: accessing a mass spectrum (300), having an intensity signal, generated for analysis of a sample; performing a wavelet transformation on the intensity signal to generate a wavelet space representation (310) of the intensity signal; generating a scale-space-processing (SSP) response signal (412, 414, 416) from the wavelet space representation of the intensity signal, wherein the SSP response signal (412, 414, 416) represents the SSP response from the wavelet scale representation (310) at different wavelet scales for a particular m/z starting position (312, 314, 316); identifying a first wavelet scale for a first local maximum in the SSP response signal; based on the first wavelet scale, detect a first baseline intensity signal; subtracting the first baseline intensity signal from the intensity signal to generate a first adjusted intensity signal; and detecting one or more peaks in the first adjusted intensity signal.
A liquid handling system for a mass spectrometer (MS), the liquid handling system including an open port interface (OPI) including a body defining a port and an internal volume. At least one removal conduit is disposed in the body and fluidically coupled to the internal volume. A plurality of transfer conduits is fluidically coupled to the at least one removal conduit. A single one of a plurality of nebulizer nozzles are fluidically coupled to each of the plurality of transfer conduits.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/16 - Sources d'ions; Canons à ions utilisant une ionisation de surface, p.ex. émission thermo-ionique ou photo-électrique
42.
SYSTEMS AND METHODS FOR HANDLING AND ANALYZING SAMPLES
Methods and systems for handling and/or analyzing samples are provided. In one example, a method comprises: introducing (406), with a liquid handler (322), at least one assisting agent into a sample well (310) of a well plate (312), wherein the sample comprises a sample volume; and ejecting (408), with an acoustic droplet ejector, ADE, (306), a mixture comprising the sample mixed with the at least one assisting agent from the sample well, wherein the at least one assisting agent interacts (406) with an analyte of the sample to limit gel formation at a top surface of the sample volume, prior to the mixture ejection.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
43.
IDENTIFICATION OF AMINO ACID ISOMERS USING DIAGNOSTIC FRAGMENT IONS IN MS/MS DATA
Computer-implemented methods and non-transitory computer readable storage media for isobaric amino acid differentiation, where an MS/MS data set may be processed, wherein the processing includes determining whether a protein sample comprises at least one isobaric amino acid, analyzing whether any diagnostic fragment ions of the at least one isobaric amino acid are present in the protein sample, assigning a score to the at least one isobaric amino acid based on the diagnostic fragment ions present in the MS/MS data set, evaluating the identity of the at least one isobaric amino acid present in the protein sample based on the assigned score, and reporting the evidence of the identity of the at least one isobaric amino acid present in the protein sample.
A precursor ion transmission window is moved in overlapping steps across a precursor ion mass range. The precursor ions transmitted at each overlapping step by the mass filter are fragmented or transmitted. Intensities or counts are detected for each of the one or more resulting product ions or precursor ions for each overlapping window that form mass spectrum data for each overlapping window. Each unique product ion detected is encoded in real-time during data acquisition. This encoding includes sums of counts or intensities of each unique ion detected the overlapping windows and positions of the windows associated with each sum. The encoding for each unique ion is stored in a memory device rather than the mass spectral data. A deblurring algorithm or numerical method is used to determine a precursor ion of each unique ion from the encoded data.
G06F 17/17 - Opérations mathématiques complexes Évaluation de fonctions par des procédés d'approximation, p.ex. par interpolation ou extrapolation, par lissage ou par le procédé des moindres carrés
45.
SYSTEMS AND METHODS FOR PURITY CALCULATION FOR THE COMPOUND QC WORKFLOW
A method for quantifying a purity of a target analyte in a sample includes introducing into a mass spectrometer, via a sample introduction, a plurality of sample ions generated by ionizing at least a portion of analytes in the sample; obtaining, via the mass spectrometer, a plurality of mass spectra including a sample mass spectrum associated with the sample introduction; analyzing the sample mass spectrum to identify a target signal corresponding to the target analyte; deriving, from the target signal, a target signal intensity corresponding to the target analyte; deriving, from at least a portion of the sample mass spectrum, a sample signal intensity; and quantifying the purity of the target analyte based on the target signal intensity and the sample signal intensity.
In one aspect, a method of acquiring mass data in a mass spectrometric system is disclosed, which includes introducing a plurality of ions into a mass filter providing a mass selection window to allow passage of precursor ions having m/z ratios within the mass selection window through the mass filter and scanning the mass selection window and adjusting a width thereof across a mass range during acquisition of mass data.
A method for determining a composition of a sample utilizing mass spectrometry includes introducing a plurality of sample ions, obtaining a plurality of mass spectra including a sample introduction mass spectrum associated with the sample introduction event, identifying a set of background signals, identifying a set of sample ion signals by removing background ions, and deriving, from the set of sample ion signals, an ion list corresponding to the composition of the sample.
In one aspect, a mass spectrometer system includes an ion mobility spectrometer (IMS), a gas supply for providing a curtain gas, a modifier supply for providing a liquid modifier, and a nebulizer for receiving the liquid modifier from the modifier supply and generating liquid droplets for delivery to a curtain chamber of the IMS. The spectrometer includes a fluid manifold for receiving the liquid modifier and delivering the liquid modifier to the nebulizer and to receive the curtain gas from the gas supply and provide a first portion of the curtain gas to the nebulizer as a nebulizing gas and provide a second portion of the curtain gas as a sheath flow to a region in vicinity of a nozzle of the nebulizer such that a combination of the sheath flow and gas exiting the nebulizer flows as a curtain gas entraining the liquid droplets to the curtain chamber.
G01N 27/623 - Spectrométrie de mobilité ionique combinée à la spectrométrie de masse
B05B 5/00 - Pulvérisation électrostatique; Dispositifs de pulvérisation comportant des moyens pour charger électriquement le pulvérisat; Pulvérisation de liquides ou d'autres matériaux fluides par voies électriques
49.
METHOD AND SYSTEM FOR TIMED INTRODUCTION OF SAMPLE INTO A MASS SPECTROMETER
Systems and methods are disclosed for timed introduction of samples into a mass spectrometer may include receiving a plurality of sample ion pulses in a mass spectrometer from a sampling interface, where the sample ion pulses are received at a pre-determined time pattern; detecting the received sample ion pulses to generate a signal; isolating an analyte signal by signal conditioning the generated signal based on the pre-determined time pattern; and identifying a presence of an analyte based on the isolated analyte signal. The signal conditioning may include pulse-based averaging based on the pre-determined time pattern or may include converting the generated signal to a frequency-domain signal and calculating a modulus to isolate the analyte signal. The pre-determined time pattern may be periodic where the signal conditioning comprises performing a Fourier Transform on the signal to convert it to a frequency-domain signal.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
A mass spectrometer that includes a mass filter and a TOF mass analyzer receives the ion beam from an ion source device that ionizes a compound of a sample. The mass filter selects a precursor ion mass range and the mass analyzer mass analyzes the mass range. A continuous flow of selected precursor ions is maintained between the mass filter and the mass analyzer. A first set of parameters is applied to the mass spectrometer to produce a resolution above a first resolution threshold. A space charge effect is detected by determining if the measured TIC exceeds a TIC threshold or the measured resolution is less than the first resolution threshold. If a space charge effect is detected, at least one precursor ion transmission window with a width smaller than the mass range is applied to the ion beam by the mass filter and mass analyzed to reduce the space charge.
In one aspect, a circuit for generating an asymmetric waveform for application to electrodes of a differential mobility mass (DMS) spectrometer is disclosed, which includes two digital waveform synthesizers for generating digital waveforms, which are converted to analog waveforms for application to electrodes of the DMS spectrometer. Analog feedback signals associated with the applied waveforms are digitized into digital amplitude calibration feedback signals and digital phase correction feedback signals. An amplitude calibration circuit is employed apply an RF calibration factor to at least one of the digital waveform synthesizers based on digital the amplitude calibration feedback signals. A digital passband filter is employed to filter the digital phase correction feedback signals, which are then employed to determine a phase correction signal for application to at least one of the digital waveform synthesizers for maintaining a substantially constant phase difference between the waveforms generated by the digital waveform synthesizers.
In one aspect, a circuit for generating an asymmetric waveform for application to electrodes of a differential mobility mass (DMS) spectrometer is disclosed, which includes two digital waveform synthesizers for generating digital waveforms, which are converted to analog waveforms for application to electrodes of the DMS spectrometer. Analog feedback signals associated with the applied waveforms are digitized and a digital passband filter is employed to filter the digital feedback signals, which are then employed to determine a phase correction signal for application to at least one of the digital waveform synthesizers for maintaining a substantially constant phase difference between the waveforms generated by the digital waveform synthesizers.
Examples of the disclosure relate to a modular radiant light generation apparatus, including a modular receiver including a recessed portion, a radiant light source on a bottom surface of the recessed portion of the modular receiver, a first fitting on the radiant light source, a fiber optic jacket including a fiber optic core therein, a first portion of the fiber optic jacket coupled to the second fitting being inserted in the first fitting, and a third fitting including a threaded projection and a biasing element the second fitting being coupled to the first fitting being configured to align the fiber optic core with the radiant light source, and the biasing element being configured to keep the fiber optic core in contact with the radiant light source.
A method for calibrating a mass spectrometry (MS) system includes: receiving at least one input through a corresponding to a calibrator in a sample, wherein the sample includes an analyte, and wherein the sample is analyzed by the MS system; automatically determining a plurality of transitions in the sample corresponding to the calibrator according to natural abundances of isotopes; automatically determining concentrations of the plurality of transitions according to a concentration of the calibrator in the sample; identifying a plurality of transitions as calibrator transitions and for identifying a different one of the plurality of transitions as an internal standard; detecting a concentration of each of the plurality of transitions and the calibrator in the sample; automatically calibrating the MS system based in part on the detected concentrations of the plurality of calibrator transitions and the internal standard; and detecting the concentration of the analyte in response to execution of the calibration instructions.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
G06F 3/0484 - Techniques d’interaction fondées sur les interfaces utilisateur graphiques [GUI] pour la commande de fonctions ou d’opérations spécifiques, p.ex. sélection ou transformation d’un objet, d’une image ou d’un élément de texte affiché, détermination d’une valeur de paramètre ou sélection d’une plage de valeurs
56.
Bent PCB Ion Guide for Reduction of Contamination and Noise
In one aspect, an ion guide for use in a mass spectrometer is disclosed, which comprises a first plurality of conductive electrodes disposed on a first surface, a second plurality of conductive electrodes disposed on a second surface, wherein the two surfaces are positioned relative to one another and shaped so as to provide a passageway having an inlet for receiving an ion beam and an outlet through which target ions of interest exit the passageway. The ion guide further includes an orifice formed in at least one of those surfaces through which neutral species and/or large ion clusters, when present in the ion beam, exit the ion guide.
In one aspect, a calibration system for use in a mass spectrometer having an open port interface (OPI) for receiving a sample for mass analysis is disclosed, which includes a fluidic junction having a first inlet in fluid communication with a first reservoir, which is configured for storing a calibration liquid, and a second inlet in fluid communication with a second reservoir, which is configured for storing a transport liquid. The fluidic junction can further include an outlet in fluid communication with the first and second inlets such that any of the calibration liquid and the transport liquid can exit the fluidic junction via said outlet.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
58.
RF AMPLITUDE AUTO-CALIBRATION FOR MASS SPECTROMETRY
Systems and methods are disclosed for RF amplitude auto-calibration for mass spectrometry. As non-limiting examples, various aspects of this disclosure provide in a mass spectrometer comprising an RF gain block, a peak detector, and a controller: applying a DC voltage to the coil using the controller; measuring a DC calibration voltage using the peak detector; applying an RF voltage to the RF gain block using the controller; measuring an RF calibration voltage; calculating an RF calibration factor based on the measured calibration voltages using the controller; and during operation, and applying a combined RF and DC signal to the RF gain block based on the RF calibration factor. The DC voltage may be generated utilizing a first signal sent from the controller to the RF gain block via a DC amplifier.
Computer-implemented methods and non-transitory computer readable storage media for determining compound structures from two or more MS/MS data sets obtained using orthogonal fragmentation, where the two or more MS/MS data sets may be processed, aligned, and consolidated to determine a lead candidate structure.
Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings. MS-based systems and methods are provided in which the flow of solvent into an open port sampling probe fluidly coupled to an ion source can be selectively stopped during the addition of one or more reagents into the drained open end of the sampling probe. Upon re-initiating the flow of solvent, the reagents and/or the reaction products can be delivered to the ion source. In one aspect, a method for chemical analysis is provided, the method comprising directing a flow of a first solvent from a solvent conduit to an ion source via a sampling space of a sampling probe, wherein the sampling space is at least partially defined by an open end of the sampling probe. The flow of the first solvent into the sampling space from the solvent conduit may be terminated for a first duration, and the sampling space drained. A second solvent and one or more reactants may then be added to the drained sampling space through the open end during the first duration. Thereafter, the flow of the first solvent may again be directed from the solvent conduit to the ion source via the sampling space such that the second solvent is delivered to the ion source, and such that one or more reaction products contained within the second solvent and generated by said one or more reactants may be ionized for mass spectrometric analysis.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
61.
AUTOMATED SYSTEMS AND METHODS FOR SEPARATING COMPOUNDS
A gas introduction system for a differential mobility spectrometer (DMS) includes a manifold including a gas inlet and a gas outlet. A mixing channel fluidically couples the gas inlet to the gas outlet. A plurality of modifier liquid supply inlets is coupled to the mixing channel and a plurality of selectively operable valves. One of the plurality of selectively operable valves is coupled to one of the plurality of modifier liquid supply inlets. A control system is in communication with each of the plurality of the selectively operable valves. The control system is configured to actuate each of the plurality of selectively operable valves.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
G01N 27/623 - Spectrométrie de mobilité ionique combinée à la spectrométrie de masse
G01N 27/624 - Spectrométrie de mobilité ionique différentielle [DMS]; Spectrométrie de mobilité ionique à haut champ asymétrique [FAIMS]
The technology relates to systems and methods for performing mass spectrometry analysis of a sample. An example method may include receiving, as input via an input device, a target mass-to-charge (m/z) ratio for a fragment ion of interest; setting a target m/z range based on the target m/z ratio; ionizing the sample to generate precursor ions; fragmenting the precursor ions to generate fragment ions having a range of mass-to-charge ratios larger than the target m/z range; accelerating the fragment ions to a detector such that fragment ions inside and outside of the target m/z ratio are detected; summing a count of fragment ions within the target m/z range without storing ion counts for fragment ions outside of the target m/z range; and storing the summed ion count as corresponding with the target mass-to-charge ratio.
Systems and methods are disclosed for determining an isomer of a non¬ derivatized glycan. A first intensity of a first product ion and a second intensity of a second product ion for a non-derivatized glycan produced using electron-based dissociation (ExD) mass spectrometry are received. The isomer is determined by differentiating between a first isomer and a second isomer of the non-derivatized glycan. Differentiating between the first isomer and the second isomer includes comparing an intensity ratio of the first intensity and the second intensity to a ratio threshold value. The ratio threshold value differentiating the first isomer from the second isomer varies with the kinetic energy of the mass spectrometry The electron kinetic energy of the ExD is greater than or equal to 11 eV and less than or equal to 25 eV.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
64.
SYSTEMS AND METHODS FOR INTRODUCING SAMPLES TO OPEN PORT INTERFACE
United States of America, as represented by the Secretary, Department of Health and Human Services (USA)
Inventeur(s)
Verma, Meghav
Michael, Samuel
Janiszewski, John
Liu, Chang
Covey, Thomas R.
Abrégé
A method of processing a sample plate containing a plurality of samples includes aspirating simultaneously, from the sample plate, a first sample droplet from a first sample of the plurality of samples with a first pipette and a second sample droplet from a second sample of the plurality of samples with a second pipette. The sample plate also includes dispensing sequentially, from the first pipette and the second pipette, the first sample drop and the second sample drop into an open port interface (OPI).
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p.ex. dispositifs d'aspiration, dispositifs d'injection
An ion mirror for use in a time-of-flight mass spectrometer includes a mirror ring sub-assembly for creating an electric potential field to decelerate incoming ions and accelerate outgoing ions, and a grid sub-assembly comprising one or more grid plates, which define bounds of the electrical potential field of the ion mirror. The mirror ring sub-assembly and the grid sub-assembly are coaxially superposed, and the mirror ring sub-assembly is mechanically engaged with the grid sub-assembly only at one of the grid plates.
In one aspect, a method of introducing a sample into an open port interface (OPI) of a mass spectrometer is disclosed, which includes mixing the sample with a solvent in which a matrix of an aqueous phase of the sample is immiscible and in which at least a target analyte, when present in the sample, is miscible so as to extract at least a portion of the target analyte into said at least one solvent, thereby generating a multi-phase liquid having said aqueous phase and one or more organic phases, wherein at least one of those organic phases contains at least a portion of the target analyte. In some embodiments, the method further calls for ejecting a plurality of droplets from at least one of the phases of the multi-phase liquid for introduction into the OPI of the mass spectrometer.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
In one aspect, a method of assessing hydrophobicity of a target analyte is disclosed, which includes introducing a sin-gle-phase system containing a concentration of the target analyte into a mass spectrometer to acquire at least one mass signal associated with the target analyte, introducing a phase-separated system (e.g., a two-phase system) containing substantially the same concentration of the target analyte into the mass spectrometer to acquire at least one mass signal associated with said target analyte, and utilizing a ratio of the intensities of the mass signals to assess hydrophobicity of the target analyte.
G01N 23/2208 - Combinaison de plusieurs mesures, l'une au moins étant celle d’une émission secondaire, p.ex. combinaison d’une mesure d’électrons secondaires [ES] et d’électrons rétrodiffusés [ER] toutes les mesures portant sur l’émission secondaire, p.ex. combinaison de la mesure ES et des rayons X caractéristiques
G16C 20/30 - Prévision des propriétés des composés, des compositions ou des mélanges chimiques
68.
Methods and Systems for Injecting Ions into an Electrostatic Linear Ion Trap
Systems and methods described herein provide for the injection of ions into an ELIT at a variety of kinetic energies such that the ions turn around at various locations. In certain aspects, such systems and methods for operating an ELIT may reduce ion density at the turning points to reduce the impact of the space charge effect. Various aspects of the present teachings also provide for the design or optimization of the ELIT electrode spacing and/or injection potentials to reduce the impact of the space charge effect. In some related aspects, the ELIT may additionally provide time-focusing of the various ion groups at the detector as they oscillate along their respective path lengths.
Described and claimed herein are capillary electrophoresis methods and kits for characterizing encapsulation efficiency or characterizing a biomolecule on an encapsulation.
In one aspect, a method of performing mass spectrometry is disclosed, which includes acquiring mass detection signals generated by an ion detector during an ion extraction event in a time-of-flight (ToF) mass analyzer in response to incidence of ions thereon, and applying an adjustable gain to the mass detection signals, wherein the step of applying the adjustable gain to the mass detection signals is performed dynamically based on m/z regions associated with said mass detection signals.
An automated method of operating a mass spectrometer (MS) comprising a differential mobility spectrometer (DMS) includes: introducing a first compound to the DMS; calculating a first alpha function for the first compound; introducing a second compound to the DMS; calculating a second alpha function for the second compound; and determining operation parameters of the DMS to achieve sufficient separation of the first compound and the second compound, based on the first alpha function and the second alpha function.
A mass spectrometer includes at least one ion optic for influencing the trajectory of at least one ion in an ionized sample. A casing includes a plurality of walls. Power supply components are disposed in the casing for supplying power to the at least one ion optic. An expansion component is within the casing. An encapsulant is disposed in the casing and encapsulates the power supply components. The encapsulant is in contact with the expansion component.
A method and system for sample processing, the system including an open port interface (OPI 104) comprising a removal conduit (125), the removal conduit comprising a removal conduit inlet and a removal conduit outlet and being configured to transport liquid between the (OPI 104) and a downstream device (120) via the removal conduit outlet, a fluid delivery pump (126) configured to provide a liquid flow to the OPI, a transfer capillary (302) in fluid communication with the removal conduit inlet, the transfer capillary (302) comprising a transfer capillary tip (312) located at a distance from the removal conduit inlet, and a distance adjusting device configured to adjust the distance between the transfer capillary tip and the removal conduit inlet.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
74.
SYSTEMS AND METHODS FOR IMPROVED SEQUENCE COVERAGE IN ANALYSIS OF LARGE POLYPEPTIDES
In some embodiments, a method for improved sequence coverage of a polypeptide comprises removing interchain disulfide bonds and retaining essentially all intrachain disulfide bonds of a first sample and performing a first mass spectrometry (MS) analysis of the first sample to determine a first amino acid sequence, removing interchain disulfide bonds and intrachain disulfide bonds of a second sample and performing a second MS analysis to determine a second amino acid sequence, and combining the first and second sequence to determine a combined amino acid sequence of the polypeptide.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
75.
SYSTEMS AND METHODS FOR IMPROVED INTENSIT Y DETERMINATIONS IN MASS ANALYSIS INSTRUMENTS
Systems and methods for performing mass analysis. An example method may include ejecting, from a first well of a well plate, a first sample into a transport fluid; ionizing the first sample and the transport fluid to generate first ions; detecting the first ions over a first period of time; and when a count rate of the detected first ions is above a background count rate threshold, accumulating a count of the detected first ions. The method may also include ejecting, from a second well of the well plate, a second sample into the transport fluid; ionizing the second sample and the transport fluid to generate second ions; detecting the second ions over a second period of time; and when a count rate of the detected second ions is above the background count rate threshold, accumulating a count of the detected second ions.
A method of operating a system including a differential mobility spectrometer (DMS) and a mass spectrometer. A sample is introduced to the DMS. The sample is analyzed with the DMS. Data is generated based at least in part on an analyte ion generated from the sample and at least one transport gas composition. Library data of the analyte ion is accessed from a library. The generated data is compared to the library data. A signal is sent when the generated data deviates from the library data by more than a predetermined threshold.
In one aspect, a computer implemented method for determining expected cleavage products of a macromolecule includes defining at least one residue of the macromolecule as having a core and at least one linker, where said at least one linker is defined as a sequence of two or more structural units that are coupled to one another via one or more chemical bonds. A digital data processor can be utilized to determine one or more expected bond cleavages, if any, between the structural units of said at least one linker and between adjacent residues when the macromolecule undergoes cleavage, e.g., in response to application of energy thereto, so as to predict expected cleavage products of the macromolecule.
A system for analyzing a sample includes a sample preparation sub-system for preparing at least one sample in a sample vessel and a magnetic bead storage sub-system. A sample intake sub-system receives the at least one sample. A mass spectrometer (MS) is communicatively coupled to the sample intake sub-system. A transfer sub-system includes a tool for moving the sample vessel from the sample preparation sub-system to the sample intake sub-system.
During each time cycle, a precursor ion transmission window is stepped in k overlapping steps that are Δm m/z apart entirely across a mass range from a starting mlm/z. The window is stepped n−1 more times starting at n−1 different offsets from ml between ml and ml+Δm. A total of n scans of the mass range. A total of k×n product ion spectra are produced that are a function of precursor ion m/z for each time cycle. A product ion is selected from the spectra. For at least one time cycle, an intensity of the product ion as a function of precursor ion m/z is reconstructed with a resolving power greater than Δm by combining intensities of the product ion measured during each of the n scans using a linear reconstruction algorithm, such as Drizzle.
Ions fragmented from a known precursor ion of a known compound are received by an ion guide that ejects the ions into an extraction region of a TOF mass analyzer. The ion guide ejects the ions using Zeno pulsing mode and the TOF mass analyzer measures intensities of the ions over time, producing a Zeno group of mass spectra. The ion guide then switches to a normal pulsing mode, producing a normal group of mass spectra. A gain is calculated for Zeno mode in comparison to normal mode as a series of ratios of intensities of one or more ions obtained from the Zeno group to corresponding intensities of the one or more ions obtained from the normal group. The gain is used to calculate a percentage of the theoretical gain and is used along with the theoretical gain to quantitate a compound in an on-demand Zeno pulsing quantitation experiment.
A mass spectrometer that includes an MCP detector selects and analyzes a calibrant compound that has a first isotope and a second isotope with a known abundance ratio. The mass spectrometer measures the intensity of the first isotope that produces multiple-ion strikes at the MCP detector and the intensity of the second isotope that produces single-ion strikes at the MCP detector while the bias voltage of the MCP detector is stepped through a sequence of one or more different voltages. At each step, the ratio of the measured intensities is compared to the known abundance ratio for the two isotopes. When the measured ratio is within a predetermined threshold of the known abundance ratio, an optimum voltage for the MCP detector is calculated using one or more measured ratios calculated for voltages of the sequence of voltages.
In one aspect, a mass spectrometric method for sequencing a morpholino oligomer is disclosed, which includes ionizing the morpholino oligomer to generate a positively-charged precursor ion, dissociating the positively-charged precursor ion using electron-based dissociation to generate a plurality of product ions, and determining one or more nucleotides of the morpholino oligomer based on analysis of m/z ratios of one or more of the product ions. A mass spectrum of the product ions can be generated for determining their m/z ratios.
During an accumulation time period of each time cycle of an ion guide and before a ramped AC voltage is applied to at least one set of axial rods to eject ions according to m/z value, a number of steps are performed. Ions are received from outside of the ion guide through an entrance aperture and into a first cell. A low DC voltage is applied to a barrier electrode to receive ions from the first cell into a second cell. And, a high DC voltage is applied to an exit electrode to prevent ions from exiting the ion guide. During a cooling time period before the AC time period, a high DC voltage is applied to the barrier electrode to trap and cool ions in the second cell and to continue to receive ions into the first cell without being affected by the ramped AC voltage.
Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which an open port of a sampling probe for receiving a specimen may be exposed to washing solvent to wash the sampling probe while fluid within the sampling probe remains continuously flowing.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/24 - Systèmes à vide, p.ex. maintenant des pressions voulues
85.
IMPROVEMENTS TO PEAK INTEGRATION BY INTEGRATION PARAMETER ITERATION
Methods and systems for improving peak integration in mass spectrometry. A method may include accessing an ion data series; generating a set of prospective peak integrations for a target peak in the ion data series; providing, as input to a trained machine learning model, at least one peak characteristic for each prospective peak integration in the set of prospective peak integrations; processing the provided input, by the trained machine learning model, to generate an output from the trained machine learning model; based on the output, generating a ranking of one or more of the prospective peak integrations; and based on one of the prospective peak integrations, generating an ion amount represented by the target peak.
Methods and kits for preparing liquid samples are presently claimed and described. The method may include treating a liquid sample with enzyme-conjugated magnetic beads are suspended in a buffer solution that comprises at least one internal standard, hydrolyzing the liquid sample to prepare a hydrolysate, and purifying the hydrolysate with magnetic based purification. Kits for preparing a liquid sample can include the, a liquid chromatography column, one or more solvents to be used as mobile phases, one or more calibrant solutions, and instructions for use.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/94 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des narcotiques
87.
Method of Performing MS/MS of High Intensity Ion Beams Using a Bandpass Filtering Collision Cell to Enhance Mass Spectrometry Robustness
A mass spectrometer comprises a first mass filter for receiving a plurality of ions and having a transmission bandwidth configured to allow transmission of ions having m/z ratios within a desired range, and a second mass filter that is disposed downstream of the first mass filter for selecting ions having a target m/z value within a transmission window thereof for mass analysis. The transmission bandwidth of the first mass filter encompasses at least two m/z ratios of interest such that one of said m/z ratios corresponds to said target m/z value within the transmission window of said second mass filter.
In one aspect, an electron capture dissociation (ECD) device for use in a mass spectrometer is disclosed, which is configured to trap precursor ions and cause the trapped precursor ions (or a portion thereof) to exit the ion trap, via radial excitation thereof by a resonant AC voltage, such that the released precursor ions can enter an ion-electron interaction region in which at least a portion of the precursor ions undergo fragmentation via interaction with an electron beam. The fragment ions are trapped and prevented from undergoing multiple dissociations. Once the fragmentation of the precursor ions is completed and/or after a predefined period, the fragment ions are released from the ECD to be received by downstream components of the mass spectrometer in which the ECD device is incorporated.
A curtain chamber includes an orifice plate defining an orifice plate bore. A curtain plate is disposed adjacent to the orifice plate and defines a curtain plate bore. The orifice plate bore is disposed adjacent the curtain plate bore. A biasing element includes a first portion disposed in the orifice plate bore and a second portion disposed in the curtain plate bore. The biasing element biases the curtain plate towards the orifice plate. A race is defined by at least one of the orifice plate and the curtain plate. The race defines a race depth. A seal is disposed in the race. The seal includes an uncompressed seal depth greater than the race depth and a compressed seal depth less than the uncompressed seal depth.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
H01J 49/06 - Dispositifs électronoptiques ou ionoptiques
H01J 49/16 - Sources d'ions; Canons à ions utilisant une ionisation de surface, p.ex. émission thermo-ionique ou photo-électrique
90.
METHODS AND SYSTEMS FOR AUTOMATED CONTROL OF SAMPLING EVENTS
Methods and systems for automatically controlling a sampling event, the methods and systems including performing a sampling trigger A corresponding to a triggering time A (511), ejecting a sample A from a sample source, wherein the sample ejection A corresponds to a sampling time A (530), determining a delay time based on the sampling time A and a sampling time B of a previous sample B, and performing a sampling trigger C, wherein the sampling trigger C is performed based at least in part on the delay time. This allows to increase the rate of high throughput mass spectrometry while avoiding the problem of potential signal overlapping.
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
91.
Sampling From A Magnetic Induced Heterogenous System
In one aspect, a method of extracting a target analyte from a sample for introduction into a mass spectrometer is disclosed, which includes mixing the sample with a paramagnetic medium to form a mixture, subjecting the mixture to a magnetic field gradient to form a non-homogenous distribution of at least one of the analyte and at least one interfering component of the sample, if any, thereby enhancing a concentration of the target analyte within a spatial location of said mixture, extracting at least a portion of the target analyte from that spatial location, and introducing at least a portion of the extracted target analyte into said mass spectrometer.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
92.
Native Fluorescence Detection for Protein Analysis in Capillary Electrophoresis
Methods and systems for determining concentration of a target protein in a sample using a capillary electrophoresis (CE) system are disclosed. In certain aspects, the method can include flowing a sample through a capillary tube of the CE system and utilizing a light source to generate radiation containing at least one excitation wavelength suitable for exciting at least one native fluorophore of at least one target protein in the sample. An excitation beam containing the at least one excitation wavelength can be directed onto a transparent portion of the capillary tube so as to excite said at least one native fluorophore of the target protein passing through a lumen of the transparent portion in order to cause the at least one native fluorophore to generate fluorescent radiation, and at least a portion of fluorescent radiation emitted by the excited target protein can be detected.
A method and system for reducing data storage requirements in mass spectrometry data analysis, the method including ionizing a plurality of samples from a sample repository, and for at least one ionized sample of the plurality of samples, capturing a plurality of mass spectra over a period of time, generating an ion chromatogram based on the captured plurality of mass spectra, the ion chromatogram extending over the period of time, isolating an individual peak of the ion chromatogram, determining at least one of a starting point, an apex, and an ending point of the isolated individual peak, correlating the determined at least one of the starting point, the apex and the ending point to the ionized sample, and storing the correlated at least one of the starting point, the apex, the ending point and the ionized sample in a data repository.
Methods and systems for automatically analyzing a collection of samples, the method including ionizing a plurality of samples, capturing a plurality of raw mass spectra for the ionized plurality of samples, and for at least one sample of the plurality of samples: generating a deconvoluted mass spectrum of the sample based on the captured plurality of raw mass spectra, accessing a reference mass of the sample, comparing the generated deconvoluted mass spectrum to the reference mass, and determining a covalent bonding in the sample based on the comparison, wherein the generating, the accessing, the comparing and the determining is performed contemporaneously for more than one sample of the plurality of samples.
H01J 49/00 - Spectromètres pour particules ou tubes séparateurs de particules
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
In one aspect, an ion guide for use in a mass spectrometer is disclosed, which comprises a pair of printed circuit boards (PCBs) having an inlet for receiving a plurality of ions from an upstream ion source and outlet through which the ions exit the ion guide. The ion guide includes at least two ion paths provided in the space between the two PCBs for transmission of ions from the inlet to the outlet. The ion guide can further include at least one ion-routing device that can be coupled to the ions paths for selecting a propagation path of the ions between those ion paths. In some embodiments, the two ion paths can have at least one segment in common.
Methods and systems for operating an ELIT are provided herein. In accordance with various aspects of the present teachings, and ELIT is provided that can enable simultaneous trapping of two different groups of ions as each group oscillates along a different path length within the ELIT.
In some disclosed example embodiments, an apparatus, such as an ion detector or ion optics in a mass spectrometer, includes a power supply having two terminals and configured to provide a voltage of a first value between the two terminals, and a voltage regulator connected between the two terminals of the power supply. The voltage regulator includes a varistor, such as a metal-oxide varistor (MOV), and a current limiting circuit, such as a resistance device, connected in series with the varistor. The current limiting circuit is configured to bias the varistor to operate continuously in a breakdown mode. The apparatus can further include electrodes, such as those configured to influence flight of charged particles, with at least one of the electrodes connected to one end of the varistor, and at least another one of the electrodes connected to the other end of the varistor.
G05F 3/16 - Régulation de la tension ou du courant là où la tension ou le courant sont continus utilisant des dispositifs non commandés à caractéristiques non linéaires consistant en des dispositifs à semi-conducteurs
H01J 49/02 - Spectromètres pour particules ou tubes séparateurs de particules - Détails
In one aspect, a method for transmitting ions in a mass spectrometer includes using rods arranged in a multipole configuration and extending from proximity of an inlet of an ion guide to proximity of an outlet of the ion guide to generate an electromagnetic field for radially confining ions received via the inlet into a space between said rods, using auxiliary electrodes positioned between the rods to generate an electric field in a first region of the ion guide for reducing radial confinement of a first subset of the received ions in said first region to inhibit passage thereof to a downstream second region of the ion guide while allowing a second subset of the ions to reach the downstream second region, and axially accelerating said second subset of the ions in said downstream second region to expedite exit of said second subset of the ions from the ion guide.
A cartridge assembly for a mass spectrometer includes two detector plates. Each of the two detector plates includes (a) an active area defining a plurality of channels from a first side of each of the two detector plates to a second side of each of the two detector plates, and (b) a plurality of clamping areas. A spacer is disposed between the two detector plates and includes a plurality of clamping tabs aligned with each of the plurality of clamping areas. A washer is disposed proximate a second detector plate and includes a plurality of clamping blocks aligned with each of the plural-ity of clamping tabs. A cartridge housing includes a first portion disposed adjacent a first detector plate, and a second portion disposed adjacent the second detector plate, and fasteners span the first and second portions. A biasing element is disposed between the washer and the first portion.
H01J 49/04 - Dispositions pour introduire ou extraire les échantillons devant être analysés, p.ex. fermetures étanches au vide; Dispositions pour le réglage externe des composants électronoptiques ou ionoptiques
A first product ion mass spectrum of a nucleic acid analyzed using a CID method is received. Also, a second product ion mass spectrum of the nucleic acid analyzed using a radical-induced dissociation method is received. Peak m/z values of the first spectrum, peak m/z values of the second spectrum, and an m/z value of a precursor ion of the nucleic acid are converted to a single charge. A peak m/z value of the first spectrum is determined that differs from a peak m/z value of the second spectrum by a mass value of a structure within the nucleic acid the radical-induced dissociation method is known to not be able to dissociate and the CID method is known to be able to dissociate. The structure includes a phosphorus atom and an optionally substituted 5 -membered ring containing an oxygen.
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