In one aspect, a method of performing mass spectrometry is disclosed, which comprises introducing a plurality of ions into a mass spectrometer, selecting a portion of the precursor ions having m/z ratios within a first desired range to provide a plurality of precursor ions, causing fragmentation of at least a portion of the precursor ions to generate a plurality of product ions, selecting a portion of the product ions having m/z ratios within a second desired range, and performing mass analysis of the selected productions.
A method of adjusting a position of an electrode within a nebulizer probe of a mass spectrometry device having an open port interface for receiving a sample includes performing a first analysis of the sample at a first analysis condition including a first position of the electrode and a first flow rate. After performing the first analysis, a second analysis of the sample is performed at a second analysis condition including the first position of the electrode and a second flow rate higher than the first flow rate. Thereafter, a third analysis of the sample is performed at a third analysis condition including a second position of the electrode and the second flow rate.
In one aspect, a mass spectrometer is disclosed, which comprises an ion trap having a plurality of electrodes arranged in a multipole configuration so as to provide an inlet for receiving ions along a longitudinal axis into a space between the electrodes, where at least one of the plurality of electrodes comprises a passageway through which ions can be extracted radially from the ion trap. The electrodes are configured for application of one or more RF voltages thereto for providing radial confinement of the ions, and a DC voltage source configured to apply a dipolar DC voltage pulse across said at least one electrode and an opposed electrode for causing radial extraction of at least a portion of said ions from said ion trap through said passageway.
In one aspect, systems and method are provided for calibrating a hybrid mass spectrometer. The calibration may include, for instance, an accurate mass calibration and a nominal mass calibration performed across a plurality of transmission widths and scanning speeds applied for each reference standard, ideally each reference standard representing a different m/z, to produce a matrix of correction factors corresponding to each of the transmission width and scanning speed pairs at the m/z values for the reference standards evaluated. A multi-parameter interpolation may be applied to identify a correction factor to be used for a subsequent analysis transmission width and scanning speed pair that differs from the plurality of transmission widths and scanning speeds used to produce the correction factors.
A method of adjusting a position of a tip of an electrode relative to an end of a nebulizer nozzle of a mass spectrometry device includes providing a conduit and the electrode connected to the conduit at a first end of the conduit. The electrode tip is disposed at a first position relative to the nebulizer nozzle end. The pressure gauge is connected to a second end of the conduit. A gas ejection is initiated from the nozzle with the electrode tip at the first position. During the gas ejection, the position of the electrode tip is adjusted from the first position towards a second position relative to the nozzle end. Adjusting the position from the first position towards the second position is terminated when the pressure gauge displays a pressure condition. Once adjusting is terminated, the electrode tip is at the second position.
Disclosed are methods and systems that can detect, monitor, adjust, and optimize fluid dynamic conditions within a sampling system comprising a transport capillary (e.g., an open port interface). The methods and systems detect an acoustic signal within the sampling system and, based on characteristics of the detected acoustic signal, adjust flow rate conditions of the liquid and/or airflow in the sampling system. Also provided are automated control and feedback systems (e.g., automated feedback adjustments made to an inlet pump flow rate, nebulizer gas flow rate, or both) that adjust, tune, and maintain flow conditions within a transport line based on a detected acoustic signal.
G01F 1/66 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters
G01F 15/00 - MEASURING VOLUME, VOLUME FLOW, MASS FLOW, OR LIQUID LEVEL; METERING BY VOLUME - Details of, or accessories for, apparatus of groups insofar as such details or appliances are not adapted to particular types of such apparatus
A method of sampling an ejection of a sample from a liquid container includes disposing the liquid container adjacent an open port in-terface. The container includes a sampling port. The open port interface en-gages with the sampling port. The sample from the liquid container is eject-ed, through the sampling port, and into the open port interface. The sample is analyzed with a mass spectrometry device.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
8.
DYNAMIC HEATING OF A DIFFERENTIAL MOBILITY SPECTROMETER CELL
A method of operating a differential mobility spectrometer (DMS) includes providing a heater disposed proximate a ceramic body of a DMS cell. A first control voltage is applied to the heater. A first threshold is detected by a first sensor disposed within a curtain plate that substantially surrounds the DMS cell. A second control voltage is applied to the heater based at least in part on the detected first threshold. During application of the second control voltage, a mass spectrometry analysis of a gas within the DMS cell is performed.
The disclosure provides systems and methods for segmented flow analysis. More particularly, the disclosure relates to introducing a liquid sample and a segmenting liquid into a transport capillary for segmented flow analysis, wherein the liquid sample and/or the segmenting liquid are dispensed into the transport capillary as discrete droplets.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
10.
Pressure Control in Vacuum Chamber of Mass Spectrometer
In one aspect, an ion guide for use in a mass spectrometry system is disclosed, which comprises an inlet for receiving a plurality of ions entrained in a gas flow, and a plurality of rods arranged in a multipole configuration so as to provide a passageway through which the received ions can traverse. At least one of the rods is configured for application of a DC and/or an RF voltage thereto for generating an electromagnetic field within the passageway suitable for focusing the ions, and a controller configured to maintain an operational pressure of the ion guide within a predefined range.
A method of delivering transport fluid from an open port interface to an outlet via a transfer conduit includes delivering, to the open port interface, a transport liquid at a first flow rate. The open port interface is disposed in a pressure environment having a first pressure. A second pres-sure is applied at the outlet, wherein the second pressure is less than the first pressure. The pressure applied at the outlet generates a motive flow on the transport liquid, thereby drawing into the transfer conduit (a) the transport fluid, wherein the transport fluid is in contact with a wall of the transport conduit, and (b) a gas present in the pressure environment. The gas forms an air core within the drawn transport fluid. The air core extends substantially an entire length of the transfer conduit.
G01N 1/10 - Devices for withdrawing samples in the liquid or fluent state
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 locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
12.
Method and System for Mass Spectrometry Signal Quality Assessment
The disclosed signal quality assessment is particularly useful for mass spectrometry. In an embodiment of the disclosed system, a processor utilizes a wavelet-based feature extraction for the signal quality assessment of a chromatogram signal. The signal quality assessment may be used to control operational parameters, such as a flowrate of a pump that moves liquid droplets toward an ionization device of a mass spectrometer.
The disclosure provides a series of polyol solutions that are useful in capillary gel electrophoresis methods and compositions of matter (e.g., capillaries, capillary cartridges, and kits). The polyol solutions can maintain, protect, and improve capillary integrity and useful lifespan, polymer coating rehydration characteristics, avoid damage to polymer coatings, and increase the consistency in capillary performance between multiple separations.
An external calibration curve relies on external calibrators containing known concentrations of a target analyte that can deteriorate over time, leading to inaccurate results. Generating new calibration curves often requires preparing several calibrators to obtain calibration points needed for generating the calibration curves. Preparing the calibrators necessary for multi-point calibration curves requires operator preparation time and can introduce handling errors. The presently claimed and described technology provides a clinical laboratory automation system, including a fluid handling system, an analyzer component, and a mass spectrometer. The clinical laboratory automation system can provide automated calibration using one calibrator to prepare one or more calibrator dilutions used to generate a calibration curve for the quantitative measurement of a target analyte in a sample. The clinical laboratory automation analyzer may also provide an automated evaluation of pipettor dispensing volume and adjustment of the pipettor actuator to deliver an accurate dispensing volume.
Methods and systems for conducting affinity selection by mass spectrometry in high throughput assays are disclosed herein. The methods can comprise identifying a set of hit com-pounds having a selected affinity to a binding target immobilized onto a magnetic particle. Methods can comprise forming an assay mixture within an assay vessel comprising a plurality of drug candidates and a binding target immobilized onto a magnetic particle. Methods also can comprise preparing at least a portion of the assay mixture for mass analysis transferring a sample containing the set of hit compounds to an open port sampling interface of a mass spectrometer.
A method of ejecting a plurality of samples from a well plate includes receiving a first sample intensity prediction associated with a first sample in a first well of the well plate. A second sample intensity prediction associated with a second sample in a second well is also received. The second sample intensity prediction is less than the first sample intensity prediction. An ejection time delay value for a subsequent analysis of the first sample and the second sample is determined, based at least in part on the second sample intensity prediction. Thereafter, the first sample is acoustically ejected from the first well, and the second sample is acoustically ejected from the second well.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
The disclosure provides systems and methods for introducing a sample into an open port interface of an analytical device. More particularly, the disclosure relates to a sampling system that includes a dispenser, a hollow tip that releasably couples to the dispenser, and a gantry for receiving the tip. The gantry can be mounted to the open port interface of an analytical device.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
18.
SYSTEMS AND METHODS FOR IMPROVED MASS ANALYSIS INSTRUMENT OPERATIONS
The technology relates to a system for improved mass analysis operation by proactively identifying contamination. The system includes a mass analysis instrument comprising mass analysis hardware components, a processor, and memory storing instructions that, when executed by the processor, cause the system to perform a set of operations. The set of operations include performing, by the mass analysis instrument at a first time, a predefined series of operational tests to produce first mass analysis results for a calibrant; performing, by the mass analysis instrument at a second time, the predefined series of operational tests to produce second mass analysis results for the calibrant; determining an analysis difference between the first mass analysis results and the second mass analysis results; and based on a magnitude of the analysis difference, generating at least one of a contamination indicator or a degradation indicator.
Method for separating, detecting, and/or quantifying steroid isomers using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the method can provide for the separation of racemic or non-racemic mixtures of steroid isomers that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), including both steroid stereoisomers and constitutional steroid isomers. The method may further comprise detecting the ionized derivatized steroids transported from the differential mobility spectrometer at a first combination of compensation voltage and separation voltage and at a second combination of compensation voltage and separation voltage applied to the differential mobility spectrometer, wherein the first combination is configured to optimize transmission of a first ionized derivatized steroid corresponding to a first steroid of an isomeric steroid pair and the second combination is configured to optimize transmission of a second ionized derivatized steroid corresponding to a second steroid of the isomeric steroid pair.
One embodiment of the invention is directed to a sample processing system for analyzing a biological sample from a patient. The sample processing system comprises: a plurality of analyzers comprising at least one mass spectrometer, wherein each analyzer in the plurality of analyzers is configured to acquire at least one measurement value corresponding to at least one characteristic of the biological sample; at least one data storage component which stores (i) a list of parameters for the plurality of analyzers, and (ii) at least two condition sets, which contain data associated with completing one or more test orders. The condition sets contain data which differ by at least one variable; and a control system operatively coupled to the plurality of analyzers, and the at least one data storage component. The control system is configured to (i) determine which condition set of the at least two condition sets to use based on the determined condition set, (ii) determine which analyzer or analyzers of the plurality of analyzers to use to process each test order based on the determined condition set and one or more parameters from the list of parameters, and (iii) cause the determined analyzer or analyzers to acquire one or more measurement values for the biological sample.
Methods and systems for generating verified mass analysis results for a sample. An example method may include acquiring process data for performing a mass analysis test on the sample; performing, by a mass analysis instrument, the mass analysis test based on the acquired process data to generate mass analysis results for the sample; recording machine-level characteristics for the mass analysis instrument during the mass analysis test; generating verification data that includes at least a portion of the recorded machine-level characteristics; generating a secure analytical data file that includes the verification data and at least a portion of the mass analysis results; and transmitting the secure analytical data file.
A method for processing a fluid sample containing a first target analyte includes introducing a first batch of magnetic particles into a fluid conduit, the fluid conduit having a first open end, a second open end, and a first electromagnetic trap between the first open end and the second open end. The magnetic particles include a first receptor to bind the first target analyte in the fluid sample. The method further includes activating the first electromagnetic trap to trap and mix the magnetic particles within the first electromagnetic trap. A flow of the fluid sample is introduced through the fluid conduit from the first open end to the second open end. Deactivating first electromagnetic trap releases the magnetic particles from the first electromagnetic trap.
Systems and methods are disclosed for ion injection into an electrostatic trap. As non-limiting examples, various aspects of this disclosure provide a quadrupole comprising first, second, and third quadrupole segments. The second quadrupole segment may be arranged between the first and third quadrupole segments and the first quadrupole segment and the third quadrupole segment may each comprise four poles with auxiliary electrodes arranged between each pair of the four poles. The second quadrupole segment may comprise four poles and the first and third quadrupoles each may comprise four individual auxiliary electrodes, two pairs of auxiliary electrodes, two electrodes, or one pair of auxiliary electrodes. The auxiliary electrodes of the first quadrupole segment and the entrance lens may be biased at a same direct current (DC) voltage. The auxiliary electrodes of the third quadrupole segment and the exit lens may be biased at a same DC voltage.
Systems and methods are disclosed for ion injection into an electrostatic trap. Various aspects of this disclosure provide a mass spectrometer system including a primary ion path including a plurality of quadrupoles; and a secondary ion path coupled to the primary ion path utilizing turning elements. The secondary ion path may include an electrostatic linear ion trap (ELIT), the ELIT being operable to analyze ions diverted from the primary ion path and return them to the primary ion path. The primary ion path may include a time-of-flight mass analyzer. The secondary ion path may be bi-directional. Ions may travel in a first direction when coupled into the secondary ion path using a first turning element in the primary ion path and may travel in a second direction when coupled into the secondary ion path utilizing a second turning element in the primary ion path. The secondary ion path may include a collision quadrupole.
A well tray includes a base including an upper surface, a lower surface and at least one edge surface connecting the upper surface to the lower surface. The at least one edge surface defines a slot. The slot is in communication with a magnet receiver at least partially defined between the upper surface and the lower surface. The magnet receiver is configured to slidably receive a removable magnet. The tray includes a plurality of wells disposed on an upper surface of the base.
Mass spectra are received over time for a compound of interest. A primary XIC is calculated for a primary product ion of the compound and a secondary XIC is calculated for a secondary product ion from the mass spectra. A primary value is calculated from a combination of intensities of one or more points corresponding to one or more times of a primary peak of the primary XIC and a secondary value is calculated from a combination of intensities of one or more points corresponding to the one or more times of a secondary peak of the secondary XIC. Or, the primary value is calculated as an area of a time window within the primary peak and the secondary value is calculated as an area of the time window within the secondary peak. A ratio is calculated from the primary value and the secondary value.
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 a specimen may be received within an open port of a sampling probe and continuously delivered via a jet pump assembly to an ion source for subsequent mass spectrometric analysis.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
28.
SYSTEMS AND METHODS FOR FOURIER TRANSFORM ELECTROSTATIC ION TRAP WITH MICROCHANNEL PLATE DETECTOR
A Fourier Transform electrostatic linear ion trap (ELIT) is disclosed with an electron multiplier detector comprising one of a microchannel plate and a channel electron multiplier. An (ELIT) is provided comprising a central axis along which ions travel; an image current detector disposed at least partially around the central axis of the ELIT; and an electron multiplier detector arranged in an opening of the image current detector, the electron multiplier detector being operable to receive ions deflected from the central axis. The electron multiplier detector may have a front surface that is perpendicular to the central axis of the ELIT. The electron multiplier detector may comprise two separate elements at non-normal angles to the central axis of the ELIT. The image current detector may comprise a cylinder with the opening on one side in which the electron multiplier detector is arranged, a U-shape, or a half-tube detector.
A tandem mass spectrometer may be operative to receive sample ions and to monitor a MS scan for a sentinel ion. Upon detection of the sentinel ion in MS1, the mass spectrometer switches to a group of at least one MS/MS scan associated with the sentinel ion to fragment incoming sample ions and to mass analyze resulting product ions of the fragmentation.
A compound is separated or introduced from a sample at a plurality of different times. The compound is ionized, producing an ion beam. The compound is selected and mass analyzed or the compound is selected, fragmented, and fragments of the compound are analyzed from the ion beam at the plurality of different times, producing a plurality of mass spectra. An XIC is calculated for the compound using the plurality of mass spectra. A chemical structure of the compound received in notation form is converted to a numerical vector using a processing algorithm operable to convert the notation form to the numerical vector. A plurality of peak shape parameters is calculated for the compound using the numerical vector and a machine trained model. A peak of the XIC is identified as a peak of the compound using the plurality of peak shape parameters and optionally a peak integration algorithm.
An ion sequestering apparatus and methods or systems using one or more auxiliary electrodes in an ion reaction instrument having RF electrodes adapted to guide positively-charged precursor ions along a first axis, and an electron source for introduction of an electron beam along a second axis transverse to the first axis such that electron activated dissociation of the precursor ions into reaction products can occur, the auxiliary electrode configured to apply a supplemental AC signal to permit selective extraction of reaction products while sequestering precursor ions along the second central axis. For example, the supplemental AC signal can comprises an notched white noise signal with a notch that suppresses frequencies at which the precursor ions (and/or charge reduced species that have the same molecular mass but have a different charge state) would otherwise be excited.
MS-based methods and systems are provided herein in which a desorption solvent desorbs one or more analyte species from an SPME device within a sampling interface that is fluidly coupled to an ion source for subsequent mass spectrometric analysis. In accordance with various aspects of the applicants teachings, the sampling interface includes an internal sampling conduit that provides increased interaction between the desorption solvent and the sampling substrate, thereby improving mass transfer (e.g., increased extraction or desorption speed).
G01N 27/623 - Ion mobility spectrometry combined with mass spectrometry
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
G01N 27/624 - Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
33.
Charge Reduced Mass Spectrometry for Sequencing of Oligonucleotide Therapeutics
In one aspect, a method of performing mass spectrometry is disclosed, which comprises ionizing a plurality of oligonucleotides to generate a plurality of negatively charged oligonucleotide ions, and interacting a plurality of charged reagent ions with the negatively charged oligonucleotide ions to reduce the negative charge state of the negatively charged oligonucleotide ions.
Methods and systems for identifying or classifying charge states of detected ions. An example method for classifying a charge state of detected ions may include generating a pulse for each ion in a plurality of ions detected by a detector, wherein each pulse has a pulse characteristic; generating a pulse-characteristic distribution of the generated pulses; and based on the pulse-characteristic distribution, generating an identification of the charge state of one or more ions in the plurality of ions.
Dynamic skimmer pulsing and dynamic equilibration times are used for MS and MS/MS scans. A target percentage transmission of the ion beam is calculated based on a previous percentage transmission and a previous TIC or a previous highest intensity of a previous cycle time. An equilibration time is calculated based on the current percentage transmission and the target percentage transmission. A skimmer of a tandem mass spectrometer is controlled to attenuate the ion beam to the target percentage transmission to prevent saturation of a detector of the tandem mass spectrometer and to increase the dynamic range of the tandem mass spectrometer. The tandem mass spectrometer is controlled to perform an MS scan or an MS/MS scan after the calculated equilibration time to reduce the cycle time.
An analyzer and sample handling system suitable for retrieving and processing a sample housed within a suitably configured reaction vessel, and then discarding the used reaction vessel by vertically or axially pushing downward on the vessel supported in a suitably configured tray with a pressing member that forms part of an autosampler assembly are disclosed herein.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
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 locks; Arrangements for external adjustment of electron- or ion-optical components
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
37.
FAST AND EFFECTIVE CONDITIONING SOLUTION FOR NEUTRAL CAPILLARY USED IN CAPILLARY ISOELECTRIC FOCUSING
The presently claimed and described technology is directed to an acidic high polymer composition comprising about 1.0% (w/v) polymer and about 4% (v/v) carboxylic acid. The acid high polymer composition may be used as a neutral capillary storage or conditioning solution or in a method of improving capillary isoelectric focusing (cIEF) robustness or performance. The technology is also directed to a kit comprising an acidic high polymer composition, at least one stabilizer, an anolyte, and a catholyte.
A 3-D array of intensity measurements measured as a function of m/z and time is received from a separation device coupled mass spectrometer. The 3-D array is converted to an intensity matrix D. The rows correspond to measured m/z or m/z related values. The columns correspond to time or time-related values. NMF is applied to the D matrix to solve for matrix M and matrix A of the equation D=MA. The NMF is applied to produce in a row (i) of the A matrix time or time-related intensity values for a peak (i) that separates the peak (i) from the 3-D array. The NMF is also applied to produce in column (i) of the M matrix m/z or m/z related intensity values corresponding to the peak (i). A profile of peak (i) is displayed from row (i) or a sum of two or more rows.
In one aspect, a method of performing Fourier Transform (FT) mass spectrometry is disclosed, which comprises passing a plurality of ions through an FT mass analyzer comprising a plurality of rods arranged in a multipole configuration, where the plurality of rods include an input port for receiving ions and an output port through which ions can exit the mass analyzer. The method can further include applying at least one RF voltage to at least one of the rods so as to generate an RF field for radial confinement of the ions as they pass through the mass analyzer, and applying a resonant burst of an AC signal to at least one of said rods so as to remove ions having selected m/z ratios, e.g., m/z ratios within a desired range, from the ions introduced into the FT mass analyzer.
In one aspect, a method for performing mass spectrometry is disclosed, which comprises using a Fourier transform mass analyzer, which extends from an inlet port to an outlet port, to acquire a first mass spectrum of a first plurality of ions generated by ionizing a sample, where the first plurality of ions are radially confined within the mass analyzer under a first radial confinement condition. The method further includes using the Fourier transform mass analyzer to acquire a second mass spectrum of a second plurality of ions generated by ionizing the sample, where the second plurality of ions are radially confined within said mass analyzer using a second radial confinement condition, and comparing said first and second mass spectra to identify spurious mass signals.
A method and apparatus are provided for separating and distinguishing between isotopic or isobaric opioid and/or benzodiazepine species within a sample. The method comprises introducing ions of the sample to an inlet of a differential mobility spectrometer (DMS), introducing a transport gas to carry the ions through the DMS, supplying an acetate modifier to the transport gas to modify the differential mobility of the ions, transporting the ions through the DMS in the presences of the acetate modifier and selectively transporting each of the species by selectively applying a corresponding compensation voltage for that species to allow that species to transport through and exit from the DMS.
A system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (“ADE”) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte. When the analytical instrument is a mass spectrometer or other type of device requiring the analyte to be in ionized form, the exiting droplets pass through an ionization region, e.g., an electrospray ion source, prior to entering the mass spectrometer or other analytical instrument. The method employs active flow control and enables real-time kinetic measurements.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
H01J 49/00 - Particle spectrometers or separator tubes
G01N 29/22 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object - Details
A method for assigning charge state in mass spectrometry includes receiving a detector response signal corresponding to a plurality of ion arrival events. The detector response signal includes information related to individual ion responses generated by a detector for each ion arrival event. Detector response profiles are generated for mass-to-charge (m/z) bins of a mass spectrum generated from the ion arrival events based on the detector response signal. The m/z bins are grouped into a plurality of groups based on a similarity of the detector response profiles of the m/z bins. A charge state is assigned to one or more features based on the groups of m/z bins.
At least one molecule is ionized and a mass spectrometer mass analyzes an m/z range, producing an m/z mass spectrum. A range of N sequential charge states is received. A copy of the m/z mass spectrum is created for each of the N charge states, producing N m/z spectra. Each spectrum of the N spectra is converted to a neutral mass mass spectrum using a different charge state of the N charge states, producing N neutral mass mass spectra. The N neutral mass mass spectra are aligned by neutral mass. When two or more spectra of the N neutral mass mass spectra corresponding to two or more different and sequential charge states include a neutral mass peak above a predetermined intensity threshold at a neutral mass value within a predetermined neutral mass tolerance, the neutral mass value is identified as a neutral mass of the at least one molecule.
A derivatizing reagent, set of derivatizing reagents, and derivatizing techniques are provided herein for the relative quantitation, absolute quantitation, or both, of analytes containing carboxyl and/or phenolic functional groups including those analytes that may be difficult to analyze via mass spectrometry using traditional techniques of ionization. By way of non-limiting examples, such analytes can include fatty acids, carnitines, eicosanoids, and estrogens. Methods for producing the derivatizing reagent are also disclosed.
In one aspect, a method of performing mass spectrometry is disclosed, which comprises ionizing a sample to generate a plurality of precursor ions, passing the precursor ions through a mass filter to select at least one subset of the ions, introducing the selected ions into a branched radiofrequency (RF) ion trap and subjecting at least a portion of said selected precursor ions to fragmentation within the ion trap so as to generate a first plurality of fragment ions. The method can further include isolating at least a portion of the first plurality of fragment ions in at least one branch of the branched RF ion trap, removing unwanted fragment ions, releasing the remaining ions from said at least one branch and subjecting at least a portion thereof to fragmentation so as to generate a second plurality of fragment ions. Any combination of collision induced dissociation (CID) and electron activation dissociation (EAD) can be employed for fragmenting the ions.
A separation time of an isomer of one or more isomers of a sialylated glycopeptide of a sample is calculated from a peak of a precursor XIC. Product ion intensities of the first group are summed at the separation time producing a first sum and product ion intensities of the second group are summed at the separation time producing a second sum using XICs of the first and second groups. A ratio of the first sum to the second sum is calculated. The ratio at the separation time is compared to predetermined ratio ranges that each corresponds to a combination of a selection from a set of the first linkage and the second linkage taken one or more times. One or more linkages of the sialic acid to the glycan of the isomer are identified from a combination found to match the ratio in the comparison.
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
G01N 30/88 - Integrated analysis systems specially adapted therefor, not covered by a single one of groups
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
In one aspect, an ion source for use in a mass spectrometry system is disclosed, which comprises a housing, a first and a second ion probe coupled to said housing, and a first and a second emitter configured for coupling, respectively, to said first and second ion probes. The first ion probe is configured for receiving a sample at a flow rate in nanoflow regime and the second ion probe is configured for receiving a sample at a flow rate above the nanoflow regime. Each of the ion probes includes a discharge end (herein also referred to as the discharge tip) for ionizing at least one constituent of the received sample. In some embodiment, each ion probe receives the sample from a liquid chromatography (LC) column. Further, the ion probes can be interchangeably disposed within the housing.
Systems and methods are provided for microbial identification using cleavable tags. Control information is sent to a mass spectrometer to fragment one or more nucleic acid primers labeled with a first tag and monitor for an intensity of the first tag in a mass spectrometry (MS) method. An ion source provides a beam of ions from a polymerase chain reaction amplified sample that includes one or more nucleic acid primers labeled with the first tag. The first tag binds to one or more nucleic acid primers of a known microbe and is cleaved from the nucleic acid primers during the MS method. The mass spectrometer receives the beam of ions and is adapted to perform the MS method on the beam of ions. If the intensity of the first tag received from the mass spectrometer exceeds a threshold value, the known microbe is identified in the sample.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
In a system for affinity selection by mass spectrometry, wherein a plurality of drug candidates in solution are separated based on affinity, a method is provided comprising introducing a solid-phase device having binding affinity for a selected protein into the solution, binding at least one of the plurality of drug candidates to the solid-phase device as a selected drug candidate, washing the solid-phase device and selected drug candidate to separate unbound material, sampling the selected drug candidate in capture fluid flowing through a sampling region of an open port sampling interface and directing the sampled selected drug candidate and capture fluid to an ionization source.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
G01N 27/624 - Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
G01N 27/74 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids
51.
Identification of a First Sample in a Series of Sequential Samples
An ADE device identifies an identifiable sequence of one or more ejections from at least one sample using a different value or pattern of values for one or more ADE parameters. The identifiable one or more ejections are performed to produce one or more mass peaks that have a different feature value or pattern of feature values for one or more peak features than other mass peaks produced. Ejection times are stored. One or more detected peaks with the different feature values or pattern of feature values are identified as produced by the identifiable one or more ejections. A delay time is calculated from the time of the identifiable ejections and the time of the identified detected peaks and the peaks are aligned with samples using delay time, stored times, and order of the samples.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
Technology for analyzing collections of substance samples. Systems in accordance with the disclosure can include one or more sample handlers, sample capture devices, mass analysis instruments, and controllers; the controllers being operative, in accordance with instructions received from at least one of an operator input device and machine-interpretable instructions stored in memory accessible by the controller, to generate signals configured to cause the sample handler to collectively retrieve from a sample source a plurality of samples of one or more substances, and deliver the plurality of collected samples to the at least one sample capture device; cause the sample capture device to independently capture at least one of the collectively retrieved samples delivered by the sample handler, and transfer the at least one captured sample to a mass analysis instrument; and cause the mass analysis instrument to ionize and detect one or more particles of the transferred treated sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
Each sample of a series of samples is ejected at an ejection time and according to a sample order. Each ejected sample of the series is ionized, producing ion beam. A list of different sets of MRM transitions is received. Each set of the list corresponds to a different sample. A group of one or more different sets is selected from the list. Initially, each set selected for the group corresponds to a different sample of one or more first samples of the series. A mass spectrometer is instructed to execute each transition of each set of the group on the ion beam until a transition of a set of the group is detected, upon which, one or more next sets are selected from the list to be monitored using the set of the detected transition and the sample order.
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
In a sampling interface for mass spectrometry, a method and apparatus are set forth for preventing liquid overflow from a sampling probe into a sample. The apparatus comprises a substrate adapted to retain a droplet of liquid as it forms at an open end of the sampling probe, and a sensor on a surface of the substrate opposite the sample adapted to detect the droplet of liquid and generate a signal for controlling the droplet of liquid before it overflows into the sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
H01J 49/02 - Particle spectrometers or separator tubes - Details
An optimal value is calculated for at least one parameter of an ADE device, an OPI, or an ion source device. For each value of a plurality of parameter values for at least one parameter of the ADE device, the OPI, or the ion source device, three steps are performed using a processor. First, the at least one parameter is set to the value. Second, the ADE device, the OPI, the ion source device, and a mass spectrometer are instructed to produce one or more intensity versus time mass peaks for a sample. Third, a feature value is calculated for at least one feature of the one or more intensity versus time mass peaks. A plurality of feature values corresponding to the plurality of parameter values is produced. An optimal value is calculated for the at least one parameter from the plurality of feature values.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
A trace of intensity versus time values is received for a series of samples produced by a mass spectrometer. Also, a series of ejections times corresponding to the series of samples produced by a sample introduction system is received. A series of expected peak times corresponding to the series of ejection times are calculated using a known delay time from ejection to mass analysis. At least one isolated peak of the trace is identified using the series of expected peak times. A peak profile is calculated by fitting a mixture of at least two different distribution functions to the at least one isolated peak. For at least one time of the series of expected peak times, an area of a peak at the one time is calculated by fitting the peak profile to the trace at the one time and calculating an area of the fitted peak profile.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
57.
HIGH FLOWRATE FLUSHING FOR OPEN PORT SAMPLING PROBE
In a sampling system for mass spectrometry, a method and apparatus are set forth for high flow-rate flushing and sample delivery via a sampling probe (10). The sampling system includes a sampling probe (10) having a first fluid conduit (40) with an inlet, a second fluid conduit (42) with an outlet, and a sampling port fluidly connecting the first fluid conduit (40) and second fluid conduit (42). A fluid source (50) is attached to the inlet and a vacuum source (60) is attached to the outlet for causing fluid to flow through the first fluid conduit (40) past the sampling port and exit through the second fluid conduit (42). A cap (90) is provided for selectively closing and opening the sampling port. When the cap is removed, thus when the sampling port is open, sample may be introduced into, and captured by fluid flowing through the sampling port. When the cap is in place, thus when the sampling port is closed, a flushing fluid is supplied for flushing the sampling probe (10).
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/24 - Vacuum systems, e.g. maintaining desired pressures
58.
INTEGRATED QJET AND Q0 RODSETS SHARING THE SAME ROD DIAMETERS AND RF POTENTIAL
In one aspect, an ion guide assembly for use in a mass spectrometry system is disclosed, which comprises a first plurality of multipole rods that are arranged to allow passage of ions therebetween, a second plurality of multipole rods that are arranged to allow passage of ions therebetween, and a board disposed between the first and second plurality of rods, the board comprising an ion lens. The first and second plurality of rods are coupled to the board, and the rods of the first plurality of rods are pairwise aligned with, and coupled to, rods of the second plurality of rods.
A system and method are provided for controlling the temperature gradient along a differential mobility spectrometer having a differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas. The differential mobility spectrometer has an internal operating pressure, electrodes, and at least one voltage source for providing DC and RF voltages to the electrodes for separating ions that are transported from the inlet to the outlet. A gas port is provided near the outlet for introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer and thereby adjust the ion residence time. A heater is provided for controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer. A method of calibrating a DMS is also disclosed.
Systems and methods disclosed herein utilize an interface positioned between an ion source and an ion guide of a mass spectrometry system that can be useful to control transmission ions from an ion source to a downstream mass analyzer. In various aspects, the present disclosure provides methods of modulating an introduction of ions into an ion guide. In some embodiments, the present disclosure provides methods of making and using disclosed interface elements and mass spectrometry systems. In some embodiments, implementations of the present disclosure are useful in mass spectrometry systems, including, for example, improving signal-to-noise and reducing contamination.
A CE based method and kit for the determination of the size and purity of an AAV genome which relies on Capillary Electrophoresis-Laser Induced Fluorescence (CE-LIF) analysis. These methods and kits are capable of detecting intact and partial genomes in a virus vectors such as adeno-associated viruses as well as remove small size impurities. In one example, the method can include creating a nucleic acid ladder using CE-LIF, releasing the genome from within an adeno-associated virus, purifying said genome and analyzing said genome using CE-LIF and comparing the results of the analysis of the genome to the nucleic acid ladder to determine a size of nucleic acids in the genome.
A mass spectrometer comprises an orifice plate having an orifice, a first multipole ion guide in a first chamber downstream of said orifice plate, said first multipole ion guide comprising a plurality of rods, and a second multipole ion guide in a second chamber downstream of said first chamber, said second multipole ion guide comprising a plurality of rods. A first ion lens is between the first and the second multipole ion guides. A third multipole ion guide is in a third chamber downstream of the second chamber, the third multipole ion guide comprises a plurality of rods. A second ion lens is between the second and third chambers. A tunable DC voltage source applies a tunable DC offset voltage to at least one of the above ion guide and ion lenses to increase an axial kinetic energy of the ions to cause at least one of declustering and/or fragmentation.
An ion source assembly for use in a mass spectrometry system comprises a housing defining an ionization chamber disposed in fluid communication with a sampling orifice of a mass spectrometer system. The housing defines a first opening for coupling to a first electrospray probe to discharge a liquid sample at flow rates greater than a nanoflow range along a longitudinal axis that is substantially orthogonal to a central axis of the sampling orifice. An elongate auxiliary electrode assembly extends from the housing to an electrically conductive distal end disposed in the ionization chamber such that the electrically conductive distal end is disposed substantially on the central axis of the sampling orifice. The electrically conductive distal end may be coupled to a power supply to generate an electric field to improve the desolvation of the sample plume and the transport of ions ejected from the sample plume into the sampling orifice.
An electromagnetic sampling device is disclosed, which comprises a needle having a hollow housing that extends from a proximal end to a distal end, and an electromagnet comprising an electromagnetic coil and a metal core, at least a portion of said metal core extending through said hollow housing of the needle and be configured to transition between an extended position in which the distal end of the metal core extends beyond the distal end of the needle's hollow housing and a retracted position in which the distal end of the metal core is positioned within the needle's housing, wherein an activation of said electromagnetic coil magnetizes the metal core.
A DMS device receives a curtain gas that includes a chemical modifier into its curtain plate. Before or while receiving ions of an analyte, the DMS device steps the CoV through a series of values in order to apply different CoV values to at least one precursor ion derived from the chemical modifier. For each CoV value of the series of values, a mass spectrometer selects and mass analyzes the at least one precursor ion. An intensity is produced for each CoV value of the series of values. An intensity versus CoV value peak is calculated from the intensities measured. A representative CoV value is calculated for the peak. The difference between the representative CoV value and known CoV values that represent an uncontaminated curtain plate is calculated. If the difference is greater than or equal to a predetermined threshold value, the curtain plate is determined to be contaminated.
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 locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
G01N 30/00 - Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography
67.
CAPILLARY ELECTROPHORESIS METHODS FOR VIRAL VECTOR SEPARATION, ANALYSIS, CHARACTERIZATION AND QUANTIFICATION
The disclosure provides methods for analyzing Adeno-Associated Vims (AAV) vectors. More particularly, the disclosure relates to capillary electrophoresis methods for separating, characterizing, and quantifying AAV vectors as having a full length exogenous polynucleotide, having an exogenous polynucleotide fragment, or lacking any exogenous polynucleotide. In one method, the analysis uses capillary isoelectric focusing (cIEF) on a sample comprising viral vectors containing exogenous polynucleotide under conditions and for a duration sufficient to separate the viral vectors based on the isoelectric point (pI) of each viral vector.
Systems and methods are disclosed for utilizing an ion mobility cell to improve desolvation prior to interaction with a hydrogen-deuterium exchange reagent, thereby improving the accuracy of the HDX data generated by MS and reducing the effects of conformational changes that can occur with increased temperatures.
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
H01J 49/24 - Vacuum systems, e.g. maintaining desired pressures
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/42 - Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
69.
Method of Mass Analysis - Controlling Viscosity of Solvent for OPP Operation
A droplet (415) is ejected from a surface (411) of a fluid sample containing an analyte using an ejector (420). A solvent is pumped into a solvent inlet (432) of an open port probe (OPP) (430) spaced apart from the surface using a pump (438). The solvent is pumped to send it from the solvent inlet (432) to a tip (431) of the OPP (430) through a solvent capillary (434) of the OPP (430), receive the droplet (415) at the tip (431) where the droplet is combined with the solvent to form an analyte-solvent dilution, and transport the dilution from the tip (431) to an output (435) of the OPP (430) through a sample capillary (436) of the OPP (430). The solvent is heated to a temperature above a threshold temperature using a heating element (437). The solvent is heated to reduce the viscosity of the solvent below a threshold viscosity and maintain the viscosity below the threshold viscosity as the dilution is transported from the tip (431) to the outlet (435).
In one aspect, a mass spectrometer is disclosed, which comprises a Fourier Transform (FT) mass analyzer having an input port for receiving ions and an exit port through which the ions exit the FT mass analyzer, a detector disposed downstream of said FT analyzer for detecting ions exiting the FT analyzer, and a multi-segment ion guide having a plurality of segments, said multi-segment ion guide being disposed upstream of said FT mass analyzer and having an input port for receiving ions and an output port through which ions exit the FT mass analyzer. The segments of the ion guide are configured to be independently activated via application of a DC offset voltage thereto so as to adjust a length through which ions passing through the ion guide experience collisional cooling.
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.
In one aspect, a method of calibrating a Fourier Transform (FT) multipole mass spectrometer is disclosed, which comprises measuring a plurality of secular frequencies of a calibrant ion in a multipole FT mass analyzer for a plurality of RF voltages (VRF) applied to at least one rod of the multipole mass analyzer adjusted q analyzer, calculating Mathieu β and q parameters for each of 5 the measured secular frequencies, and determining RF voltage amplitude (VRF) for each calculated q parameter. For each calculated q parameter, an offset RF voltage amplitude (ΔVRF) corresponding to a deviation of the applied VRF and the calculated VRF is determined so as to generate a ΔVRFv.s. q calibration curve.
In a DIA method, a specified precursor ion m/z range of interest is divided into a set of two or more precursor ion mass selection windows. A tandem mass spectrometer is instructed to select, dissociate using a first dissociation technique, and mass analyze each precursor ion mass selection window of the set within a specified cycle time. Product ion intensity and m/z measurements are produced for each window of the set using the first dissociation technique. The tandem mass spectrometer is also instructed to select, dissociate using a second dissociation technique, and mass analyze each precursor ion mass selection window of the set within the same cycle time. Product ion intensity and m/z measurements are produced for each window of the set using the second dissociation technique. Product ion measurements from both the first and second dissociation techniques are used to identify or quantitate compounds of a sample.
A dual-mode capillary electrophoresis system (100) is disclosed, which comprises a plurality of capillaries for receiving a plurality of samples, a UV radiation source (120) for generating UV radiation along a first path (PB), a laser light source (110) for generating laser radiation along a second path (PA), and a galvanometric mirror (116) configured to receive radiation from said UV radiation source along said first path and to receive light from said laser light source along said second path, and to direct said received UV radiation and said laser light onto a common optical path, said galvanometric minor further being configured to scan said UV radiation and said laser light sequentially over said plurality of capillaries. The system can further include a detector (190) for detecting the UV radiation as well as a detector (180) for detecting fluorescent radiation via optical fibers (185) emitted by the samples in response to laser excitation.
Pole electrodes (150) 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 X-shaped aperture (160) in lieu of the conventional central circular aperture. The pole electrodes are particularly useful in systems having a plurality of branched electrodes (152) 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.
First, an MS scan of a mass range of a control sample that does not include a metabolite is performed (601) producing background peak m/z and intensity values for background precursor ions (602). Background peaks are selected for an exclusion list and in the exclusion list an m/z value and an intensity value are included for each background peak (604). Next, an MS scan of the mass range of an experimental sample that does include a metabolite is performed (610) producing peak m/z and intensity values for precursor ions (612). Peaks are selected for a peak list and in the peak list an m/z value and an intensity value are included for each peak (614). Finally, each peak of the peak list that has both an m/z value and an intensity value that correspond to an m/z value and an intensity value of a background peak of the exclusion list is excluded from the peak list (616).
In various aspects, methods and systems disclosed herein are capable of operating a Fourier Transform Mass Spectrometry (FTMS) quadrupole mass analyzer in two operational modes: transmitting mode and trapping mode. In the trapping mode, ions are first trapped and cooled within the FTMS quadrupole mass analyzer prior to being subjected to an excitation pulse and ejected from the FTMS quadrupole mass analyzer for detection. However, in transmitting mode, the FTMS quadrupole mass analyzer may provide more rapid analysis because the excitation pulse is applied to the ions of an ion beam that is being continuously transmitted through the FTMS quadrupole mass analyzer.
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
79.
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.
A dissociation device fragments a precursor ion, producing at least two different product ions with overlapping m/z values in the dissociation device. The dissociation device applies an AC voltage and a DC voltage creating a pseudopotential that traps ions below a threshold m/z including the at least two product ions. The dissociation device receives a charge reducing reagent that causes the trapped at least two product ions to be charge reduced until their m/z values increase above the threshold m/z set by the AC voltage. The increase in the m/z values of the at least two product ions decreases their overlap. The at least two product ions with increased m/z values are transmitted to another device for subsequent mass analysis by applying the DC voltage to the dissociation device relative to a DC voltage applied to the other device.
A known compound and at least one adduct, modified form, or peptide of the known compound are separated from a sample mixture and analyzed. An XIC is calculated for each of M product ions of the known compound and L product ions of the at least one adduct, modified form, or peptide. A first XIC peak group is calculated from the M XICs and a second XIC peak group is calculated from the L XICs using curve subtraction. Representative first and second XIC peaks are selected for the two XIC peak groups. The retention time of the second XIC peak is shifted by an expected retention time difference found from a database. The retention time of the first XIC peak is verified as the retention time of the known compound if the difference of the retention times of the first and second XIC peaks is within a threshold.
Before a sample is introduced into a liquid sample delivery device, an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes compounds of the aqueous mobile phase solution, producing an ion beam. A tandem mass spectrometer performs a first neutral loss scan of the ion beam with a first neutral loss value set to a molecular weight of a first known solvent, producing a first intensity, and performs a second neutral loss scan of the ion beam with a second neutral loss value set to a molecular weight of a second known solvent, producing a second intensity. A ratio of the first intensity to the second intensity is calculated. It is determined if the aqueous mobile phase solution is properly being delivered by the liquid sample delivery device based on the ratio.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
Before each sample of a series of batch samples is introduced into a liquid sample delivery device, an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes its compounds, producing an ion beam. A tandem mass spectrometer performs a neutral loss or precursor ion scan on the ion beam to measure intensities of two or more precursor ions corresponding to a known aqueous mobile phase solution compound. Intensity measurements for each of the two or more different precursor ions are compared to previously stored intensities to determine the threshold times at which these measurements indicate orifice contamination. A threshold time is then predicted for a known compound of interest of the batch samples based on the m/z value of the known compound of interest and the m/z value and the threshold time of each of the two or more different precursor ions.
A plurality of known compounds with known CCS values is analyzed using a DMS device. The DMS device determines how the intensities of their transmitted ions vary with different separation voltages (SVs) and compensation voltages (CVs). A machine learning algorithm builds a data model from the known m/z value, known CCS value, and measured pairs of CV and SV values that provide optimal transmission through the DMS device for each of the known compounds. An unknown compound with an unknown CCS value is then analyzed. The DMS device determines how the intensity of its ions varies with the same different SVs and CVs. Finally, the machine learning algorithm predicts the CCS value of the unknown compound from the data model, the known m/z of the unknown compound, and the measured pairs of CV and SV values that provide optimal transmission through the DMS device for the unknown compound.
G01N 27/623 - Ion mobility spectrometry combined with mass spectrometry
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
In DM-SWATH a plurality of CoVs and a precursor ion mass range are received. A processor performs an iterative series of steps for each CoV of the plurality of CoVs. For each CoV of the plurality of CoVs, the CoV is applied to the DMS device to select a group of precursor ions. A mass filter is instructed to select precursor ions of the group that are within the precursor ion mass range, producing a subgroup of precursor ions. A fragmentation device is instructed to fragment the subgroup of precursor ions, producing a group of product ions. A mass analyzer is instructed to measure the intensity and m/z of the group of product ions, producing a product ion spectrum for each CoV of the plurality of CoVs. DM-SWATH is further used to validate if a known compound is in a sample.
H01J 49/42 - Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
86.
SAMPLE PREPARATION BY TEMPERATURE GRADIENT DENATURATION AND SCALE-UP FOR DEEP N-GLY-COMIC ANALYSIS OF SERUM FOR CAPILLARY ELECTROPHORESIS AND CE-ESI-MS
A sample preparation workflow to facilitate deep N-glycomics analysis of human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection accommodates the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS). A temperature gradient denaturing protocol is applied on amine functionalized magnetic bead partitioned glycoproteins to avoid precipitation. This also results in the free sugar content of the serum being significantly decreased which allows PNGase F mediated release of the N-linked carbohydrates. The liberated oligosaccharides were tagged with aminopyrene-trisulfonate, utilizing a modified evaporative labeling protocol. This workflow provides appropriate amounts of material for example for use in CE-ESI-MS analysis in negative ionization mode.
An operational condition of a liquid chromatography (LC) system (2110) is detected and displayed without user intervention. A plurality of pressure measurements over time are received from a pressure sensor (2119) of the LC system. A processor (2140) calculates values from the measurements for six parameters including a beginning pressure (PB), an ending pressure (PE), an average pressure (T1) for a first half of the separation, an average pressure (T2) for a second half of the separation, a ratio T1/PB, and a ratio T2/PB. The values of the six parameters are classified as one of one or more operational conditions of the LC system using a machine learning model. The machine learning model is created from values of the six parameters calculated from known separations for each of the one or more operational conditions. The operational condition found from the classification is displayed on a display device (2141).
Apparatus, systems, and methods disclosed herein utilize a lid for closing, substantially sealing, and providing an electrical interface for mass spectrometry systems. In various aspects, the present disclosure provides a lid having a plurality of layers with electrical connections therethrough. In some embodiments, lids for use in a mass spectrometry system as are disclosed herein can include a plurality of layers having electrical connections such that their inputs and outputs are laterally staggered across these layers. In some embodiments, the present disclosure provides methods of making and using disclosed lids and mass spectrometry systems. In some embodiments, implementations of the present disclosure are useful in mass spectrometry systems, including, for example, improving and simplifying assembly.
Methods, compositions, kits, and apparatuses for MS-based quantification of a target analyte (e.g., a peptide, a hormone) in a sample are provided for increasing the productivity and/or throughput of samples by reducing the time and/or cost associated with conventional techniques for external instrument calibration that typically utilize a series of calibrators that are sequentially run through the same analytical process as a batch of samples. In various aspects, calibration mixtures are provided containing a known quantity of a plurality of calibrants for a target analyte of interest, with each calibrant being distinguishable in the calibration mixture by mass spectrometry such that a complete calibration curve can be generated from a single external calibration run.
Apparatus, systems and methods disclosed herein utilize an ion source region generally disposed between a sample introduction port and an ion guide of a mass spectrometry system to thermally fragment ions for transmission to and analysis by a downstream mass analyzer. In various aspects, the present disclosure provides methods of thermally fragmenting ions in an ion source region of a mass spectrometry system. Thermally fragmenting a plurality of ions can include increasing a temperature of the ions present in an ion source region. Thermally fragmenting a plurality of ions can include increasing the temperature of the ions in an ionization/fragmentation region associated with an ion source region defined by a substantially collision-free path. Implementations of the present disclosure are useful in mass spectrometry systems, including, for example, generating an enhanced fragmentation pattern.
Apparatus is provided and an IDA method is modified to detect and separately dissociate alkali-metal adducts of a compound. An ion source device ionizes one or more compounds of a sample, producing an ion beam. A mass filter selects a mass range of precursor ions from the ion beam, a mass analyzer measures intensities and m/z values of the precursor ions, and one or more of the precursor ions are selected for a peak list. For each pair of precursor ions of the peak list, if an m/z difference between the pair corresponds to an m/z difference between an alkali metal ion and another alkali metal ion or a proton, an ExD device is used to dissociate one precursor ion or both precursor ions of the pair using the processor. A CID device is used to dissociate all other precursor ions of the peak list.
In one aspect, a method of modulating transmission of ions in a mass spectrometer is disclosed, which comprises generating an ion beam comprising a plurality of ions, directing the ion beam to an ion optic positioned in the path of the ion beam, wherein the ion optic includes at least one opening through which the ions can pass, and applying one or more voltage pulses at a selected duty cycle to said ion optic so as to obtain a desired attenuation of brightness of the ion beam passing through the ion optic, where a pulse width of said voltage pulses at said selected duty cycle is determined by identifying a pulse width on a calibration normalized ion intensity versus pulse width relation for said ions that corresponds to said desired attenuation on an ideal normalized ion intensity versus pulse width relation for said ions.
In one aspect, a method of processing ions in a mass spectrometer is disclosed, which comprises trapping a plurality of ions having different mass-to-charge (m/z) ratios in a collision cell, releasing said ions from the collision cell in a descending order in m/z ratio, and receiving the ions in a mass analyzer having a plurality of rods to at least one of which an RF voltage is applied, where the RF voltage is varied from a first value to a lower second value as the released ions are received by the mass analyzer.
The resolution of a TOF mass analyzer is maintained despite a loss of resolution in one or more channels of a multichannel ion detection system by selecting the highest resolution channels for qualitative analysis. Ion packets that impact a multichannel detector are converted into multiplied electrons and emitted from two or more segmented electrodes that correspond to impacts in different regions across a length of the detector. The electrons received by each electrode of the two or more segmented electrodes for each ion packet are converted into digital values in a channel of a multichannel digitizer, producing digital values for at least two or more channels. Qualitative information about the ion packets is calculated using digital values of a predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution.
A separation device is instructed to separate a compound from a sample over a time period. A mass spectrometer is instructed to measure a plurality of intensities of at least one ion of the separated compound over the time period, producing a chromatogram. At least one peak of the at least one ion is identified from the chromatogram using a peak-finding algorithm. Two or more different peak integration areas are calculated for the at least one peak by applying the peak-finding algorithm with two or more different values for at least one peak-finding parameter. Two or more plots of the at least one peak that each shows graphically a different peak integration area are displayed on a display device at the same time. In response, data is received from a user selection device that indicates user selection of one of the two or more plots.
Each of one or more unknown compounds are separated from a sample over a separation time period. Separated compounds are ionized, producing one or more compound precursor ions for each of the unknown compounds and a plurality of background precursor ions. A precursor ion mass spectrum is measured for the combined compound and background precursor ions at each time step of a plurality of time steps spread across the separation time period, producing a plurality of precursor ion mass spectra. One or more background precursor ions are selected from the plurality of precursor ion mass spectra that have a resolving power in a range below a threshold expected resolving power. A separation time is detected for an unknown compound when a decrease in an intensity measurement of the selected background precursor ions over a time period exceeds a threshold decrease in intensity with respect to time.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
H01J 49/42 - Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
H01J 49/44 - Energy spectrometers, e.g. alpha-, beta-spectrometers
97.
Method for Real Time Encoding of Scanning SWATH Data and Probabilistic Framework for Precursor Inference
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 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.
Method and devices for performing top down analysis of an antibody are described which involve utilizing an ion source to generate a plurality of ions from a sample containing at least one intact antibody. Further, transmitting said plurality of ions through a quadrupole rod set while applying an RF signal thereto and in the absence of a resolving DC voltage so as to preferentially transmit precursor ions having an m/z value greater than a low mass cutoff of about 1500 m/z from the quadrupole rod set to an ECD cell. The method and device can also performing an ECD reaction in the ECD cell on said precursor ions and also detect reaction products from the ECD reaction.
An electrospray probe for use in an electrospray ion source is disclosed, which comprises a cannula extending from a proximal end having an inlet aperture for receiving a liquid sample containing at least one analyte to a discharge emitter end having an outlet aperture through which charged liquid droplets containing ions of said analyte are discharged, and an electrically conductive coating covering at least a portion of an external surface and at least a portion of an internal surface of said emitter end.
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