In a method for determining if internal product ions are used to provide evidence for a bond of a polymeric compound, two or more theoretical product ions resulting from the cleavage of at least one bond of the sequence of the compound are calculated. A product ion spectrum is searched for the theoretical product ions. The theoretical internal product ions are calculated and the spectrum is searched for the theoretical internal product ions if one or more theoretical product ions of the theoretical product ions match a product ion of the spectrum. In another embodiment, a mass tolerance is automatically determined for comparing theoretical mass peaks to mass peaks of an experimental mass spectrum using the subset of product ions most likely to be found for the fragmentation method used. In another embodiment, charge filtering is used to find an experimental product ion of a compound.
A mass spectrometry system comprises an ion mobility separation device (IMSD) configured to receive a plurality of ions, and to perform an ejection of a set of ions of the plurality of ions by adjusting a set of mobility control parameters to a set of mobility parameter values; a mass analyzer configured to receive the set of ions, to perform a detection of the set of ions, and to generate a set of detection signals corresponding to the detection of the set of ions; and a controller configured to receive data including the set of mobility control parameter values and the set of detection signals, and to perform a mapping of the set of mobility control parameter values and the set of detection signals.
Systems and methods described herein can provide for “top down” mass spectrometric analysis of proteins or peptides in a sample using ExD, in some aspects via direct infusion of the sample to the ion source without on-line LC separation, while deconvoluting the ambiguity in the ExD spectra generated by impure samples. For example, methods and systems in accordance with various aspects of the present teachings can utilize patterns in charge-reduced species following ExD to correlate the ExD fragments with their precursor ions in order to more confidently identify the precursor ion from which the detected product ions originated.
Pole electrodes are disclosed for use in an ion reaction apparatus, e.g., an electron induced dissociation cell, to reduce fouling due to polymer build-up and increase the useful lifetime of such electrodes. To reduce fouling, the novel pole electrode designs include a Xshaped aperture in lieu of the conventional central circular aperture. The pole electrodes are particularly useful in systems having a plurality of branched electrodes defining a first axis for controlled passage of charged ions and a transverse axis for passage of an electron beam. The pole electrodes are adapted for disposition between an electron source and the branched electrodes to provide an aperture for passage of an electron beam while also impeding escape of ions and reaction products from the apparatus. The X-shaped aperture eliminates or reduces the portion of the pole electrode surface that is most prone to fouling by polymeric build-up.
A user interface is provided for displaying in the same panel and at the same time a sequence of a polymeric compound and multiple pieces of spectral evidence from an experimental product ion spectrum that are linked to a bond of the sequence. The sequence and the spectrum of the polymeric compound are received, where one or more product ions of the spectrum are assigned to at least one bond of the sequence. The sequence is displayed in a panel of a display device with at least one interactive icon between at least two elements of the sequence representing the bond. When the interactive icon is selected, at least two different spectral plots of the spectrum showing two different product ions of the spectrum that support a cleavage of the bond are displayed in the same panel of the sequence and at the same time as the sequence.
Known mass spectral data of a library of spectra corresponding to known compounds or known mass spectral data determined from a database of known compounds are compressed using a neural network encoder, producing a group of corresponding compressed known representations of known mass spectral data. Experimental mass spectral data of an experimental mass spectrum is compressed using the neural network encoder, producing a compressed experimental representation of the experimental mass spectral data. The experimental representation is compared to the group of known representations and each comparison is scored. At least one comparison with a score above a predetermined score threshold is selected. A known compound is determined from the selected at least one comparison. The known compound is identified as a compound of the experimental spectrum.
In one aspect, a method of operating a high-throughput mass analysis device is disclosed, which includes sampling an unseparated sample from at least one sample holding element during a sampling interval for introduction of the sample into an ion source for ionizing the sample to generate a plurality of ions associated with at least one target analyte (herein also referred to as a target compound), if any, in said sample for delivery to an ion mobility separation device, and activating at least one control parameter of said ion mobility separation device for detection of said ions based on timing of the sampling of the sample and at least one identifier associated with the sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
8.
System and Methods for High Throughput Mass Spectrometry
System and method for high-throughput mass spectrometry are disclosed. In some embodiments the system comprises a sample introduction device, an ion source, an ion mobility separation device, a mass analyzer and a controller adapted to receive certain parameters from the IMSD and determine a mass range for more efficient operation of the mass analyzer. In some embodiments, the controller is adapted to provide data to, and receive data from other components to make the operation of the IMSD and the mass analyzer more efficient.
Systems and methods of quantifying a target analyte including two or more chromatographic peaks in an output from a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The method includes obtaining a set of output data from the LC-MS/MS for a sample including the target analyte, integrating each of the two or more chromatographic peaks associated with the target analyte to yield an area for each of the two or more chromatographic peaks, and summing the area of each of the two or more chromatographic peaks associated with the target analyte based on the integrating. The method further includes generating a calibration curve for the target analyte as a regression curve using the summed area of the two or more chromatographic peaks associated with the target analyte and determining a concentration of the target analyte in the sample using the calibration curve.
In various aspects, provided are methods of stabilizing the gain of an optical ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ultraviolet photons thereon are received by the scintillator to generate photons, which include configuring the MCP for generating a plurality of electrons in response to incidence of ultraviolet photons on the MCP, exposing the MCP to a beam of ultraviolet photons to generate a plurality of electrons for irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of one or more molecules adsorbed on the scintillator's input surface, and maintaining such irradiation over a temporal period until the optical ion detector exhibits a substantially stable gain profile.
In one aspect, a method of stabilizing the gain of an ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ions thereon are received by the scintillator to generate photons is disclosed, which includes configuring the MCP for generating a plurality of electrons in response to incidence of ions on the MCP, exposing the MCP to an ion beam so as to generate a plurality of electrons irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of one or more gases adsorbed on the scintillator's input surface, and monitoring a gain of the ion detector during exposure of the MCP to the ion beam over a temporal period until the ion detector exhibits a substantially stable gain profile.
Disclosed are systems, methods, and other implementations, including a method of operating a time-of-flight (TOF) mass analyzer, that includes introducing a plurality of ions into the mass analyzer, applying a plurality of voltage pulses to a pusher electrode of the mass analyzer to direct at least a portion of the plurality of ions into an acceleration region of the mass analyzer to generate accelerated ions, using an ion detector to detect the accelerated ions after passage thereof through a field-free region so as to generate ion detection data during a data acquisition period, and adjusting a pulse duration of the voltage pulses during the data acquisition period such that ion detection data is acquired during the data acquisition period at two or more different voltage pulse durations.
Disclosed are assemblies, systems, methods, and other implementations, including an ion lens assembly that includes one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer. The lens assembly includes a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.
Systems and methods for determining a molecular structure include obtaining mass spectrum data for an unknown parent ion. The mass spectrum data is recorded at each collision energy of a series of collision energies and includes an abundance of one or more substructures of the unknown parent ion. The molecular structure of the unknown parent ion is determined by composing the mass spectrum data into a fragmentation profile and embedding the fragmentation profile into a reduced dimension profile. The reduced dimension profile is mapped into a fragmentation space. One or more proximate molecules in the fragmentation space are identified using the mapping and a candidate for the parent ion is identified using the one or more proximate molecules.
In one aspect, a method of performing mass spectrometry is disclosed, which includes introducing a plurality of samples of a specimen into an ion source of a mass spectrometer at a sample introduction rate as fast as about 0.16 seconds per sample up to 60 seconds per sample to ionize at least a molecule (herein also referred to as an analyte) and an internal standard associated with the molecule in each sample so as to generate precursor ions corresponding to the molecule and its associated internal standard. For each sample, the following steps are performed: using a mass filter of the mass spectrometer to isolate at least the precursor ions, dissociating the isolated precursor ions to generate product ions, and generating a mass spectrum of the plurality of the product ions. The mass spectrum of the product ions can be utilized to quantify the target analyte, e.g., to determine the concentration of the target analyte in the specimen under study.
Methods and systems for performing differential mobility spectrometry-MS/MS are provided herein. In various aspects, methods and systems described herein can determine corresponding MS data from differential mobility spectrometry-MS/MS data obtained at each of a plurality of SV-COV combinations applied to the differential mobility spectrometry device, without requiring a separate differential mobility spectrometry-MS run, for example, each time the COV-combination is adjusted. Furthermore, the population of analyte ions, which are present in each of the plurality of product ion scans obtained at different SV-COV combinations, can be identified.
A mount assembly for holding a microchannel plate in an ion detector includes an input side clamping plate including a plurality of input side pads; and an output side clamping plate including a plurality of output side pads, wherein, when assembled, the input side clamping plate and the output side clamping plate are configured to allow positioning between the input side clamping plate and the output side clamping plate the microchannel plate having a plurality of microchannels each having an input side opening and an opposed output side opening; hold the microchannel plate; and position the subset of the input side pads and the subset of the output side pads in a staggered configuration such that when a microchannel of a plurality of microchannels is obstructed in a first opening, a second opening of the microchannel opposing the first opening is unobstructed.
In one aspect, a time-of-flight (TOF) mass analyzer is disclosed, which includes an input for receiving a plurality of ions (herein also referred to as "primary ions"), an ion acceleration region through which the received ions are accelerated, a push electrode for directing the received ions into the ion acceleration region, and a field-free ion drift region for receiving said accelerated ions, said field-free ion drift region having an ion detector positioned at a distal end thereof. At least one magnet is positioned relative to the electric field-free region so as to establish a magnetic field in at least a portion of the electric field-free region for deflecting electrons entering the electric field-free region so as to inhibit the electrons from reaching the ion detector.
A method for correcting detection bias includes detecting spectral data of a standard sample, the standard sample comprising two or more analytes. Each analyte has a known quantity, and the spectral data of the standard sample includes a peak for each of the two or more analytes. The method further includes determining a bias parameter for each of the two or more analytes based on the peak for each of the two or more analytes of the standard sample.
A method for scoring a bond of a polymeric compound of a sample from evidence determined from an experimental a product ion spectrum measured from the sample. At least one experimental product ion spectrum is received for the polymeric compound. One or more product ions of the at least one spectrum are assigned to at least one bond of the polymeric compound. At least two different types bond level scores are calculated for the at least one bond from the assigned matching one or more product ions. The at least two different bond level scores are combined, producing a combined bond score for the at least one bond. Additionally, a combined bond score is found for each bond of the polymeric compound and the combined bond scores are calculated as a function of the position of the bonds in the polymeric compound, producing a score profile for the polymeric compound.
A method for dissociating an oligonucleotide is disclosed. A plurality of precursor ions of one or more oligonucleotides is loaded into an ion trap. Negative radical-induced dissociation is applied to the plurality of precursor ions in the ion trap during a first time period, producing charge-reduced ions. Resonant CID is applied in the ion trap during a second time period to dissociate the charge-reduced ions. A pause without any dissociation in the ion trap is performed during a third time period to cool ions produced from the previous resonant CID or again negative radical-induced dissociation is applied in the ion trap during the third time period to again produce charge-reduced ions from the plurality of precursor ions while at a same time allowing ions produced from the previous resonant CID to be cooled. The last two steps are repeated one or more times.
A method of sampling a sample liquid disposed in a receptacle includes forming a meniscus of a transport liquid at a port of an open port interface (OPI). The sample liquid is contacted with the transport liquid, thereby transferring at least some of the contents of the sample liquid to the transport liquid.
G01N 1/38 - Diluting, dispersing or mixing samples
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
24.
Ultra Low Noise Floated High Voltage Supply For Mass Spectrometer Ion Detector
A high-voltage power supply system for a mass spectrometer comprises a ground-referenced power supply with a first transformer having a primary winding and a secondary winding, the primary winding is electrically coupled to a first source of AC power, and a floated bias voltage power supply with a second transformer having a primary winding and a secondary winding, the primary winding of the second transformer is electrically coupled to a second source of AC power. A return electrical path of the floated bias voltage power supply is electrically coupled to the ground-referenced power supply to bias an output voltage of the ground-referenced power supply. A floating shield is around the floating bias voltage power supply, and at least one resistive element is in the return electrical path of the floated bias voltage power supply to reduce noise coupled from the floated bias voltage power supply to the ground-referenced power supply.
Disclosed herein are methods for analyzing biological samples using capillary electrophoresis, including the characterization of genome integrity, assessment of genomic integrity and the sequencing of a nucleic acid genome, such as an RNA genome. Kits for characterizing genome integrity are also disclosed.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Mass analysis systems, computing systems, non-transitory computer-readable media, and methods analyze peaks of interest in a mass spec data signal while accounting for acquisition parameters of a mass spectrometer that affect noise present in the mass spec data signal.
Systems and methods for evaluating the operational state of a mass measuring system, including its tuning include a first mass separator in series with a second mass separator, with the second mass separator being faster than the first mass separator. Unprocessed mass data of detection of a set of ions is received from the second mass separator. A known ion is identified in the unprocessed mass data, and an actual appearance and an actual disappearance of the known ion is mapped to determine an appearance period of the known ion. The appearance period is compared with an intended appearance period for the known ion, and, based on the comparing, a match status between the appearance period and the intended appearance period is determined for the unfragmented mass.
Systems and methods of constructing mass spectrometry data structures for increased high-dimensional extraction. Mass spectrometry data, including intensities for one or more product ions and an offset for each of the intensities, is obtained and the intensities for the one or more product ions are recorded in a first m x n matrix with an n-dimension corresponding to a time dimension and an m-dimension corresponding to a mass-to-charge dimension. The first m x n matrix is transposed into a second m x n matrix with an n-dimension corresponding to a mass-to-charge dimension and an m- dimension corresponding to a time dimension and each of the first and second m x n matrices is stored as an index of the mass spectrometry data.
In one aspect, a calibration mass standard for use in mass spectrometry is disclosed, which includes a plurality of natural isotopologues of a compound, where the natural isotopologues are present in the mass standard at relative concentrations corresponding to their natural atomic abundances.
A measured mass spectrum and intensity data provided as a function of m/z and at least one additional dimension are received. Peaks of the measured spectrum are compared to peaks of each of a plurality of library mass spectra. A set of library mass spectra is identified using a fit score. For each spectrum of the set, a group of related peaks of the measured spectrum calculated using a deconvolution algorithm is recalculated. The recalculation lowers a threshold for selection in the group if a matching peak of the library spectrum contributed to the fit score. A group of related peaks of the measured spectrum is produced for each library spectrum. For each spectrum of the set, peaks of the group are compared to peaks of the library spectrum and a purity score is calculated. At least one library spectrum of the set with the highest purity score is identified.
Integrated system for delivering sample to a mass spectrometer, which includes a chamber extending from a top to bottom end, an open port probe disposed in the chamber such that an open end of the probe, which is configured for receiving a sample, is positioned in proximity to top end of the chamber. The system can further include a solvent inlet port coupled to said chamber for receiving a solvent and directing said solvent to said probe, and a solvent outlet port for receiving a flow of the solvent from the open port probe and directing the received solvent out of the chamber. The system can also include an adapter for receiving a sample holder having an outlet port, the adapter is releasable and replaceable and couple with chamber to align the outlet port of sample holder with open end of probe for delivering sample to the probe.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
32.
SYSTEMS AND METHODS FOR IMPROVING ANALYSIS OF CHARGE SERIES SPECTRA
A method and system include receiving a charge series spectrum having charge series peaks, determining reconstructed mass values based on the received charge series spectrum, displaying the reconstructed mass values, receiving a selection of a displayed reconstructed mass value, and displaying a plurality of icons including a marker and a corresponding charge series peak, the marker identifying a charge of the spectrum. Another method and system include receiving a charge series spectrum having charge series peaks, determining reconstructed mass values based on the received charge series spectrum, and for each reconstructed mass value, determining a plurality of markers corresponding to charges of the charge series and having a corresponding charge series peak, and determining that the reconstructed mass value is a probable artifact when a difference between one of the markers and a local maximum of the corresponding charge series peak is greater than a threshold.
Examples of this disclosure include methods and systems of enzyme engineering, including preparing a plurality of DNA samples, combining at least one of the plurality of DNA samples with a host cell, incubating the combined at least one of the plurality of DNA samples and the host cell at one of a desired first temperature and for a desired first period of time to generate a plurality of first enzymes, adding a first cell lysis reagent to the combined at least one of the plurality of DNA samples and the host cell to release the plurality of first enzymes, adding a first catalyzing substrate to the plurality of first enzymes to generate a first product and a first by-product for each first enzyme via catalysis, evaluating a first reaction yield for each first enzyme, and selecting a first enzyme from the plurality of first enzymes based on the evaluation.
The disclosure provides compositions, methods, and kits that find use in calibrating a mass spectrometer, and can include one or more predetermined concentration(s) of one or more calibrant molecule(s) that comprise a polyethylene glycol (PEG) compounds that have a single functional group that can be ionized by an ion source, and a solvent for dissolving the calibrant molecule(s). The calibrant molecule(s) and compositions including them can be used in either positive or negative ionization mode, and can be used for calibrating a variety of mass spectrometers (e.g., APCI, ESI) operating in a variety of acquisition modes (e.g., MRM, MS/MS, etc.).
Disclosed are systems and methods for facilitating compound identification based on analytical data obtained from an analytical instrument such as, for example, a mass spectrometer.
In various aspects, integrated specimen collection and analyte extraction devices are provided herein. For example, in accordance with various aspects of the present teachings. a device for extracting analytes from a specimen is provided, the device comprising a housing (12) defining an extraction chamber (14) for containing a known volume of a liquid specimen and having an inlet (16) for receiving the liquid specimen. A stationary phase (20) is configured to be disposed within the extraction chamber (14) in contact with the liquid sample so as to adsorb one or more analyte species thereto, wherein at least one of the stationary phase (20) and the one or more analytes adsorbed thereto within the extraction chamber (14) is removable from the extraction chamber (14) for analysis by a chemical analyzer.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
Methods and systems for mass analysis are disclosed herein. An example system includes: a sample ejector configured to eject a plurality of samples from a plurality of wells of a well plate; a capture probe configured to capture the ejected samples and dilute and transport the captured samples; a nebulizer nozzle configured to receive and ionize the transported diluted samples to produce sample ions; a mass analysis instrument configured to filter and detect ions of interest from the sample ions; a controller configured to coordinate operations of the sample ejector, the capture probe, the nebulizer nozzle, and the mass analysis instrument; and a data processing system configured to acquire data from the mass analysis instrument and conduct an automatic data processing process.
G01N 30/88 - Integrated analysis systems specially adapted therefor, not covered by a single one of groups
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
38.
Method and Systems for Analyzing Ions Using Differential Mobility Spectrometry and Ion Guide Comprising Additional Auxiliary Electrodes
Methods and systems for performing differential mobility spectrometry-mass spectrometry (DMS-MIS) are provided herein. In various aspects, methods and systems described may be effective to improve the performance of a differential mobility spectrometry device and a MS device operating in tandem relative to conventional systems for DMS-MS. In certain aspects, methods and systems in accordance with the present teachings utilize an ion guide which comprises a multipole rod set and a plurality of auxiliary electrodes to which a DC voltage is applied during transmission of ions through the ion guide so as to generate an axial electric field along a longitudinal axis of the ion guide to accelerate the ions toward the outlet end of the ion guide. This may significantly reduce a pause duration between the application of different compensation voltage values without substantially increasing the likelihood of contamination or cross-talk between groups of ions transmitted by the differential mobility spectrometry device at each compensation voltage value.
In one aspect, a time-of-flight (TOF) mass analyzer is disclosed, which includes an inlet for receiving ions, a first ion acceleration region in which at least a portion of the received ions is accelerated to a first energy, a first field-free ion drift region positioned downstream of the first ion acceleration region for receiving the accelerated ions, a second ion acceleration region positioned downstream of the first field-free ion drift region for receiving ions exiting the first field-free ion drift region and accelerating the ions to a second energy, a second field-free ion drift region positioned downstream of the second ion acceleration region for receiving the ions exiting the second ion acceleration region, and an ion detector for receiving ions passing through the second field-free ion drift region and generating ion detection data. The ion detection data can be analyzed to generate a mass spectrum of the detected ions.
A system for applying RF voltages to a multipole ion processing device, configured for use in a mass spectrometer, includes a first RF generator configured to generate a first RF voltage and apply to a first pole electrode set, a second RF generator configured to generate a second RF voltage and apply to a second pole electrode set, a first amplitude adjustor configured to adjust an amplitude of the first RF voltage, a second amplitude adjustor configure to adjust an amplitude of the second RF voltage, and a phase adjustor in communication with the first RF generator and the second RF generator to adjust phase output of at least one of the first RF generator and the second RF generator so as to adjust a phase differential between the first RF voltage and the second RF voltage to be within a desired range.
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, correlating captured respective subsets of the raw mass spectra to each sample of the plurality of samples, and for each sample of the plurality of samples, generating a reconstructed mass spectrum based on the respective subset of the raw mass spectra of the sample. Methods and systems also include correlating the captured respective subsets of the raw mass spectra to each sample by generating a chronogram, and correlating a timeline of a sampling of the sample with the chronogram to correlate the captured respective subsets of the raw mass spectra to each sample. Methods and systems also include analyzing the generated reconstructed mass spectrum for each sample of the plurality of samples.
In one aspect, a method for fragmenting ions in a mass spectrometer is disclosed, which includes introducing a plurality of precursor ions into a collision cell of a mass spectrometer, generating a potential barrier in the collision cell to cause at least a portion of ions in the collision cell to be trapped within a region in proximity of said potential barrier, and applying ultraviolet (UV) radiation to said trapped ions so as to cause fragmentation of at least a portion of any of said precursor ions and fragment ions thereof to generate a plurality of product ions such that a space charge generated in said region in proximity of said potential barrier due to accumulation of ions will impart sufficient kinetic energy to at least a portion of the product ions so as to overcome said potential barrier, thereby exiting said region.
An analytical instrument produces intensity versus time measurements or intensity versus m/z measurements for each acquisition of n acquisitions using m instrument parameter values for each acquisition of n acquisitions, wherein n is a number greater than or equal to two and m is a number equal to or greater than one. For each acquisition of the n acquisitions, the instrument stores a data file that includes m one or more instrument parameter values applied to the instrument, producing n data files. A first data file of the n data files for a first acquisition is retrieved. A next data file of the n data files of a next acquisition is retrieved. The m corresponding parameter values of the first data file and the next data file are compared. If any corresponding parameter values differ between the first data file and the next data file, a notification of an instrument parameter difference corresponding to a name of the next data file is displayed.
In one aspect, a method of operating an analytical device for measuring at least one analyte within a sample is disclosed, which includes utilizing a digital data processor to receive a sample acquisition rate for introduction of the sample into the analytical device, and to compute one or more optimal operating parameters of the analytical device based on the sample acquisition rate by optimizing a figure-of-merit associated with measurement of the analyte, where the operating parameters include a temporal duration of a measurement cycle and/or selectivity associated with the measurement. The analytical device can be operated at the optimal operating parameters while receiving the sample at the sample acquisition rate to generate sample measurement data corresponding to the analyte. The sample measurement data can be processed to derive information about the analyte.
Methods and systems for controlling a filament of an electron emitter associated with an ion reaction cell in accordance with various aspects of the present teachings may account for inter-filament and inter-instrument variability and can provide improved reproducibility in EAD experiments and ease of use. In some aspects, a method of operating an ion reaction device of a mass spectrometer system is provided. The method comprises applying a calibration drive voltage to a filament of an electron emitter associated with an ion reaction cell and determining a value representative of the calibration electron emission current generated by the filament while having the calibration drive voltage applied thereto. A calibration saturation voltage can be determined by iteratively increasing the calibration drive voltage applied to the filament and determining the value of the calibration electron emission current at each corresponding calibration drive voltage until the filament reaches a saturation condition.
Methods and systems for analyzing a sample that includes a protein and a binding ligand, the method including receiving the sample at an ionization device via non-contact sampling, the first sample being in a non-denaturing carrier solvent, ionizing the first sample, generating a deconvoluted mass spectrum for the ionized first sample, and detecting binding between the protein and the binding ligand in the first sample based at least in part on the deconvoluted mass spectrum. The non-contact sampling is performed via a non-contact sample ejector. Methods and systems for analyzing a sample that includes a protein includes receiving the sample via non-contact sampling, the sample being in one of a plurality of non-denaturing carrier solvents, and for non-denaturing carrier solvent, ionizing the sample, generating a deconvoluted mass spectrum for the ionized sample, and detecting protein binding in the first sample based at least in part on the deconvoluted mass spectrum.
H01J 49/00 - Particle spectrometers or separator tubes
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
In one aspect, a heat transfer structure for use in a mass spectrometer can include a collar for surrounding a plurality of rods arranged in a multipole configuration, at least one ceramic pad positioned to be in thermal contact with at least one of the rods, and at least one thermally conductive plate positioned to provide a heat transfer path between the at least one ceramic pad and the collar. The heat transfer structure can further include a bracket mounted on a bracket mounting portion of the collar for transferring heat from the collar to a rail.
Systems, apparatus, and computer-readable storage media are disclosed for analyzing samples of a well plate. Systems may include a well plate, a mass spectrometer, and a computing device. The well plate may include rows of wells. The mass spectrometer may sequentially capture a sample from each well of the rows of wells and generate spectral data that includes mass spectrum data for each captured sample. The computing device may receive the spectral data generated by the mass spectrometer, detect rows of spectral data in the spectral data, wherein each row of spectral data corresponds to a row of wells in the well plate; and generate a spectral data matrix from the detected rows of spectral data such that each row of wells comprises a corresponding row of spectral data in the spectral data matrix.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
49.
SYSTEMS AND METHODS FOR INTRODUCING SOLVENTS TO A SAMPLING INTERFACE
A solvent delivery system for an open port interface (OPI) includes a first diverter which includes a wash solvent inlet, a carrier solvent inlet, and a first diverter outlet. A wash solvent pump is fluidically coupled to the wash solvent inlet. A carrier solvent pump is fluidically coupled to the carrier solvent inlet. A second diverter includes a second diverter inlet fluidically coupled to the first diverter outlet. An OPI port is configured to be coupled to an OPI. A waste outlet is configured to be coupled to a waste container.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
50.
METHODS AND SYSTEMS FOR GENERATING A CONTROLLABLE AXIAL PSEUDOPOTENTIAL BARRIER IN MULTIPOLE ROD SETS OF MASS SPECTROMETERS
The present teachings are generally related to generating a pseudo potential barrier via an axial RF field. As discussed herein in more detail, such a pseudo potential barrier can be employed in a variety of different applications. By way of example, such a pseudo potential barrier can be employed for trapping ions within a rod set comprising a plurality of rods arranged in a multipole configuration. In other applications, an adjustment of the height of the pseudo potential barrier established in a rod set together with application of a DC potential between the rod set and an external electrode can be utilized to cause mass selective extraction of ions trapped within the rod set. In yet other applications, such a pseudo potential barrier can be employed in multiplexing approaches for performing mass spectrometry.
The present teachings are generally related to a method of performing mass spectrometry, which includes dissociating a plurality of precursor ions to generate a first set of product ions, wherein ions with approximately same m/z are associated in a group, and wherein said first set of product ions contains at least two groups of ions with distinct m/z's. The method further includes introducing the first set of product ions into an ion trap; transferring different groups of the first set of product ions during different time intervals from the ion trap to an ion dissociation device so as to cause dissociation of at least a portion of the first set of product ions to generate a second set of product ions, and acquiring a mass spectrum of the second set of product ions.
A method of performing mass spectrometry is disclosed. which comprises introducing a plurality of ions into an ion guide of a mass spectrometer via an inlet orifice thereof. where the ion guide includes a plurality of rods arranged in a multipole configuration and spaced from one another to provide a passageway for transit of the ions therethrough. applying RF voltages to the rods so as to generate an electromagnetic field within the passageway for providing radial confinement of the ions passing through the passageway, identifying a space charge effect, which can adversely affect operation of the mass spectrometer, based on detection of a variation of an intensity of an ion detection signal associated with at least one ion population transmitted through said ion guide and having an m/z ratio greater than a threshold, and in response to said identification of the adverse space charge effect. adjusting at least one of frequency and amplitude of the RF voltages to counteract said space charge effect.
Leak detection systems and methods in accordance with various aspects of the present teachings can, in various embodiments, sequester fluid leaking from the interface between a sample source and the inlet of the ion source, alert an operator as to a leak condition, and/or automatically terminate the experiment. In various aspects, a liquid leak detection system is accordance with the present teachings comprises a collection basin configured to couple to a proximal end of a conduit in fluid communication with a discharge end of an ion source of a mass spectrometer such that the proximal end of the conduit extends through the internal volume of the basin. The system may also comprise a drainage tube having an inlet end opening into an internal volume of the collection basin and configured to drain liquid therefrom, a sensor disposed within the basin or the drainage tube and configured to generate a signal indicative of liquid therewithin, and a processor that is configured to cause a user to be alerted and/or cause an experiment to be terminated upon receiving from the sensor a signal indicative of a leak.
G01M 3/20 - Investigating fluid tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material
54.
SYSTEMS AND METHODS FOR ERROR CORRECTION IN FAST SAMPLE READERS
A method and system for detecting a signal measurement error, the method including providing a well plate including error correction wells and sample wells, each sample well including a single sample, and each error correction well including a mixture of samples from two or more sample wells. The method includes receiving an aliquot from the wells at a sample receiver, measuring a signal for the received aliquot, calculating an expected signal for each of the error correction wells, comparing the measured signal to the calculated expected signal for each error correction well, and determining whether an error exists in the signal of at least one sample well. When the error exists, the method correlates the error to one or more sample wells.
Mass spectrometry systems and methods are disclosed. In some embodiments, the mass spectrometry system comprises an ion trap configured to receive a plurality of precursor ions and to load the plurality of precursor ions in a trap region; an electron gun configure to perform an irradiation operation by applying an electron beam to the trap region to produce fragmented ions; an RF gate configured to perform an extraction operation by extracting, from the trap region, a high m/z subset of the fragmented ions with m/z ratios greater than a specific value; and a mass spectrometer configured to perform mass spectrometry analysis on a subset of the fragmented ions remaining in the trap region, wherein an irradiation-extraction operation, including performing the irradiation operation and the extraction operation, is repeated at least twice before performing the mass spectrometry analysis on the subset of the fragmented ions remaining in the trap region.
The present teachings are generally related to generating a pseudo potential barrier via an axial RF field. A first RF voltage is applied to a first pair of rods arranged in a multipole configuration, a second RF voltage is applied to a second pair of rods, and a difference between amplitudes and/or phases of said first RF voltage and said second RF voltage is adjusted. As discussed herein in more detail, such a pseudo potential barrier can be employed in a variety of different applications. By way of example, such a pseudo potential barrier can be employed for trapping ions within a rod set comprising a plurality of rods arranged in a multipole configuration. In other applications, an adjustment of the height of the pseudo potential barrier established in a rod set together with application of a DC potential between the rod set and an external electrode can be utilized to cause mass selective extraction of ions trapped within the rod set. In yet other applications, such a pseudo potential barrier can be employed in multiplexing approaches for performing mass spectrometry.
The presently claimed and described technology provides methods for analyzing an encapsulated biomolecule by loading the encapsulated biomolecule on a capillary electrophoresis (CE) capillary, wherein the CE capillary is filled with a buffer comprising a polymer matrix; applying a voltage to the CE capillary to release the biomolecule from the encapsulating material; and detecting the biomolecule released from the encapsulating material. Kits for analyzing an encapsulated biomolecule are also disclosed.
The presently claimed and described technology is directed to electrophoretic methods for conditioning a capillary using a conditioning buffer including a surface active polymer and a separation reagent including a separation polymer.
Methods and systems for operating an OPI of a sample analysis system, the OPI having a transport liquid conduit and a sample removal conduit and being configured to flow a transport liquid therethrough to a capture region, the method including introducing the OPI at a liquid sample in a sample reservoir while supplying the transport liquid at a first flow rate to the capture region, aspirating a first amount of the liquid sample through the removal conduit via the transport liquid flowing at the first flow rate, switching a flow rate of the transport liquid flowing through the OPI to a second flow rate when a first condition is met, the second flow rate being different from the first flow rate, and aspirating a second amount of the liquid sample through the removal conduit via the transport liquid flowing at the second flow rate. Fast flow rate switching is enabled by a transport liquid flow control apparatus comprising a selectable valve having a pair of valve outlets coupled to different flow paths having different flow resistances.
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
60.
REDUCTION OF UNUSED PRECURSORS IN ELECTRON ACTIVATED DISSOCIATION (EAD)
In one aspect, a method of performing mass spectrometry is disclosed, which comprises introducing a plurality of precursor ions into an ion dissociation device, dissociating at least a portion of the precursor ions into a first plurality of product ions having m/z ratios less than an m/z ratio of the precursor ions, discarding at least a portion of any precursor ions remaining subsequent to said dissociation step within said ion dissociation device, and subsequently, allowing at least a portion of said first plurality of product ions to exit from the ion dissociation device through an outlet of the ion dissociation device.
Methods and non-transitory computer readable storage media for loading a reactive agent onto a fluidic device, loading a sample comprising the at least one analyte onto the fluidic device; applying a voltage to the fluidic device, wherein when the voltage is applied the reactive agent remains confined to a region in the separation channel and the at least one analyte is separated from the sample and migrates towards the fluid outlet; generating a first data set and a second data set; converting the second data set by removing a baseline; and correlating the first data set and the converted second data set.
In one aspect, a voltage regulator is disclosed, which comprises a first voltage regulator unit configured for regulating a voltage generated by a positive high voltage source, a second voltage regulator unit configured for regulating a voltage generated by a negative high voltage source, a polarity switch for connecting said first and second voltage regulator units to said positive and negative high voltage sources, respectively, and an output voltage port for receiving a regulated positive and negative high voltage from said first and said second voltage regulator units, respectively.
G05F 1/595 - Regulating voltage or current wherein the variable actually regulated by the final control device is DC using semiconductor devices in series with the load as final control devices including plural semiconductor devices as final control devices for a single load semiconductor devices connected in series
G05F 1/575 - Regulating voltage or current wherein the variable actually regulated by the final control device is DC using semiconductor devices in series with the load as final control devices characterised by the feedback circuit
63.
ELECTROSPRAY EMITTER MODULE FOR CAPILLARY ELECTROPHORESIS DEVICE
A capillary emitter includes a coupling sleeve, a separation capillary inside the coupling sleeve, the separation capillary extending along a longitudinal axis of the coupling sleeve, a tip at an end of the coupling sleeve, the tip comprising an orifice and having an internal base, a first hollow internal cavity defined on one side thereof by the internal base in the coupling sleeve, the first hollow internal cavity comprising the separation capillary, and a fluid pathway within the first hollow internal cavity, the fluid pathway surrounding the separation capillary, wherein, at the internal base of the tip, the separation capillary and the fluid pathway are fluidly connected within the first hollow internal cavity.
An integrated sample processing system including an analyzer and a mass spectrometer is disclosed. The integrated sample processing system can perform multiple different types of detection, thereby providing improved flexibility and better accuracy in processing samples. The detection systems in the sample processing system may include an optical detection system and a mass spectrometer.
The present disclosure provides methods and systems for performing mass spectrometry in which at least two batches of precursor ions generated via ionization of at least two different portions of a sample are exposed to electron beams at different energies to cause fragmentation of at least a portion of the precursor ions. In some embodiments, the electron energies can be selected such at one of the electron energies, EIEIO fragmentation can occur while at the other electron energy, EIEO fragmentation channel is not available. The mass spectra corresponding to the two energies can then be utilized to generate a resultant mass spectrum in which mass peaks corresponding to ion fragments generated by EIEIO dissociation are more readily identifiable.
Methods and systems for mass spectrometry are disclosed. In one example, a method comprises: receiving, by a mass spectrometer via a sampling system operably connected thereto, at least one sample containing at least one known compound; modulat-ing at least one instrument parameter of the mass spectrometer through a plurality of instrument parameter values; analyzing the at least one sample while applying each of the plurality of instrument parameter values; acquiring a plurality of mass spectral (MS) datasets each corresponding to one of the applied plurality of instrument parameter values; encoding each of the plurality of MS datasets to generate a corresponding plurality of MS results each corresponding to one of the applied instrument parameter values; and compiling and storing the MS datasets and MS results in a spectral library in association with the applied instrument parameter values.
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
Improvements in acoustically dispensed samples that are injected into an open port probe (OPP) are described. Apparatus and method are described that calibrate the volume dispensing determination and mechanisms in the acoustic dispenser to produce accurate and precise volumetric delivery.
B05B 12/00 - Arrangements for controlling deliveryArrangements for controlling the spray area
B05B 12/08 - Arrangements for controlling deliveryArrangements for controlling the spray area responsive to condition of liquid or other fluent material discharged, of ambient medium or of target
B05B 17/06 - Apparatus for spraying or atomising liquids or other fluent materials, not covered by any other group of this subclass operating with special methods using ultrasonic vibrations
G01F 22/00 - Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/16 - Ion sourcesIon guns using surface ionisation, e.g. field-, thermionic- or photo-emission
68.
Method for Noise Reduction and Ion Rate Estimation Using an Analog Detection System
Ion intensities measured by an ADC detector subsystem are filtered using equivalent TDC event realizations. In one embodiment, an intensity measurement is received for at least one ion made by an ADC detector subsystem for each of m extractions of an ion beam, producing m intensities for the ion. Equivalent TDC event realizations are received for the ion for each intensity of the m intensities, producing m equivalent TDC event realizations. A filtered intensity for the ion is calculated that is a combination of the m intensities and the m event realizations. In another embodiment, for the ion, an equivalent TDC event realization is accumulated for ion events up to a threshold count of event realizations, N, and the ADC intensities are accumulated for all remaining ion events. A filtered intensity for the ion is calculated that is a combination of the equivalent TDC event realization and the ADC intensities.
Various embodiments relate to the reduction of chemical noise at or near the mass of an analyte of interest prior to selection by a mass filter. The use of a narrow bandpass in the ion optics removes chemical noise that can repopulate ions at or near the mass of an analyte of interest by removing other chemical noise ions that can fragment into the same or similar mass as the mass of an analyte of interest through collision induced dissociation.
The disclosed technology provides capillary electrophoresis methods and kits for the separation of multiple components in one or two runs with high resolution.
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 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
72.
METHODS AND COMPOSITIONS FOR ELECTOPHORETIC SEPARATIONS
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 - Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography using ion-exchange
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
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.
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 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
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.
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.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sourcesIon guns using surface ionisation, e.g. field-, thermionic- or photo-emission
H01J 49/24 - Vacuum systems, e.g. maintaining desired pressures
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 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.
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 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
90.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
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.
patents
