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.
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 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.
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
12.
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.
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
17.
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.
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.
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 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.
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.
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
24.
Method to Operate a Mass Spectrometer to Counteract Space Charge Effects
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
26.
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.
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.
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
29.
Integrated Sample Processing System with Multiple Detection Capability
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
33.
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.
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.
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
38.
CAPILLARY ELECTROPHORESIS PURITY ANALYSIS OF COMPLEMENTARY STRAND NUCLEIC ACID MOLECULES
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.
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.
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
45.
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.
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.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
59.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
G01N 30/00 - Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography
H01J 49/16 - Ion sourcesIon guns using surface ionisation, e.g. field-, thermionic- or photo-emission
60.
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.
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 - 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
65.
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 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
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
66.
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.
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 - 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 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.
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 - Particle spectrometers or separator tubes
G06F 3/0484 - Interaction techniques based on graphical user interfaces [GUI] for the control of specific functions or operations, e.g. selecting or manipulating an object, an image or a displayed text element, setting a parameter value or selecting a range
71.
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 - 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
73.
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.
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 - 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
75.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
G01N 27/623 - Ion mobility spectrometry combined with mass spectrometry
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.
United States of America, as represented by the Secretary, Department of Health and Human Services (USA)
Inventor
Verma, Meghav
Michael, Samuel
Janiszewski, John
Liu, Chang
Covey, Thomas R.
Abstract
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).
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.
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 - Combination of two or more measurements, at least one measurement being that of secondary emission, e.g. combination of secondary electron [SE] measurement and back-scattered electron [BSE] measurement all measurements being of secondary emission, e.g. combination of SE measurement and characteristic X-ray measurement
G16C 20/30 - Prediction of properties of chemical compounds, compositions or mixtures
81.
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.
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.
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.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/24 - Vacuum systems, e.g. maintaining desired pressures
92.
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.
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.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/06 - Electron- or ion-optical arrangements
H01J 49/16 - Ion sourcesIon guns using surface ionisation, e.g. field-, thermionic- or photo-emission
97.
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 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
98.
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.
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.
patents
