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 first analysis of a mass range of a first sample is performed using a separation coupled mass spectrometer, producing a first set of multivariate data that includes both retention time and mass spectral data. A second analysis of a mass range of a second sample is performed using a separation coupled mass spectrometer, producing a second set of multivariate data that includes both retention time and mass spectral data. Each of the first set and the second set is divided into two or more subsets corresponding to two or m/z sub-ranges of the mass range. One or more chromatographic peaks in each of the two or more subsets of the first set are independently aligned with one or more chromatographic peaks in each corresponding subset of the two or more subsets of the second set using an alignment method.
Systems and methods are provided for predicting the mass spectrum of an unknown compound. An experimental mass spectrum of a known compound is obtained. One or more mass peaks of the experimental mass spectrum corresponding to a substructure of the known compound are annotated with at least one modification an unknown compound is predicted to include. An in- silico mass spectrum is created for the unknown compound from the experimental mass spectrum and the annotated one or more mass peaks. The unknown compound is then identified from a sample by mass analyzing the sample, producing an unknown experimental mass spectrum, and comparing the unknown experimental mass spectrum to the in-silico mass spectrum.
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.
A method and system of DMS analysis using a DMS device, the method including introducing a sample at an opening of the DMS device, sequentially applying a plurality of separation voltages between opposing electrodes, wherein for each applied separation voltage: applying a plurality of incrementally increasing compensation voltages between the opposing electrodes, following each applied compensation voltage: interrupting application of the separation voltage and of the compensation voltage, collecting MS data for the sample exiting the DMS device while the separation voltage and the compensation voltage are interrupted, and determining an optimum compensation voltage out of the plurality of compensation voltages based on the collected MS data, repeating the sequentially applying the plurality of separation voltages to the introduced sample a plurality of times, and determining a CCS value for the sample based on the applied separation voltages and their corresponding determined optimum compensation voltages.
A method of processing a liquid sample includes providing the sample. A first set of beads is introduced to the sample. The first set of beads includes a bead characteristic and a first bead performance value. A second set of beads is introduced to the sample. The second set of beads includes the bead characteristic and a second bead performance value different than the first bead performance value. The sample is mixed with the first set of beads and the second set of beads. The first set of beads is captured in a first location within the sample.
B01D 15/20 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01J 20/28 - Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
B03C 1/01 - Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
7.
Mass and Kinetic Energy Ordering of Ions Prior to Orthogonal Extraction Using Dipolar DC
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
12.
SINGLE TUBE SAMPLE PREPARATION AND CALIBRATION FOR BOTH SCREENING AND QUANTIFICATION OF ANALYTES
The presently claims and described technology provides methods and kits for quantifying at least one analyte in a sample by mass analysis using a labeled isotopologues as an internal standards and to generate internal calibration curves.
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
15.
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
17.
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
22.
ADENO-ASSOCIATED VIRUS VECTORS EMPTY/FULL RATIO ANALYSIS USING CE- BASED GENOME AND CAPSID QUANTIFICATION
The presently described and claimed disclosure relates to capillary electrophoresis methods for quantifying an intact AAV genome and protein components in an AAV using the same capillary electrophoresis system. The claimed and described approach offers an automated analysis of AAV samples and provides information to determine the AAV empty/full ratio.
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
24.
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.
A method for mass spectrometric analysis of a peptide having at least one fragile moiety includes using electrospray ionization to generate a negatively charged ion of said peptide, trapping and cooling the negatively charged peptide ion in a radiofrequency (RF) ion trap containing a cooling buffer gas, and exposing said cooled, trapped peptide ion to an electron beam so as to cause negative electron activated dissociation (negative EAD) of the negatively charged peptide ion to generate a plurality of fragment ions.
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
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
26.
Methods For Detection Of Isomeric Steroids Using Differential Mobility Spectrometry
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.
An open port interface includes an outer housing which defines an interior volume. A transport liquid port is communicatively coupled to the interior volume and configured to be fluidically coupled to a transport liquid pump. A removal conduit is disposed within the outer housing and fluidically coupled to the interior volume for removing a transport liquid from the interior volume. A sample inlet tip is removably coupled to the outer housing. The sample inlet tip defines a sample inlet port configured to receive a sample and communicatively coupled to the interior volume. At least a portion of the sample inlet tip proximate the sample inlet port includes a tip surface having a hydrophobicity different than a hydrophobicity of the outer housing.
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
29.
DEVICE, SYSTEM, AND METHOD FOR VERIFICATION OF ANALYSIS DATA
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.
A radio frequency (RF) choke for use in a mass spectrometer, comprising a bobbin having a hollow channel, a plurality of wire windings wrapped around said bobbin, each of said wire windings exhibiting a lattice winding pattern having about 1 to about 4 crossover per turn, and magnetic core disposed in said hollow channel of the bobbin.
A cartridge 300 for capillary electrophoresis includes a housing which includes a base 202 at least partially defining a cavity 250 defining a cavity volume. A cover plate 304 that is secured to the base 202 defines a window. A volume displacement structure 360 projects from at least one of the base 202 and the cover plate 304 and into the cavity 250 when the cover plate is secured to the base. The volume displacement structure 360 and cavity 250 together at least partially define a coolant liquid flow path 366 having a coolant liquid flow path volume less than the cavity volume. A plurality of capillaries 326 is disposed in the coolant liquid flow path. Each of the plurality of capillaries includes a capillary inlet 222 and a capillary outlet 224 projecting from 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.
A method of performing negative electron activation dissociation (negative EAD) in mass spectrometry includes introducing a plurality of negatively charged analyte ions into an ion trap positioned in a chamber and trapping said negatively charged analyte ions in a reaction region of said ion trap, introducing a buffer gas into the chamber, using an electron source positioned in the chamber and external to the ion trap to generate electrons, and accelerating the electrons to form an electron beam and introducing the electron beam into the ion trap such that the accelerated electrons are capable of ionizing at least a portion of molecules of the buffer gas to generate a plurality of positively charged ions. The accelerated electrons interact with at least a portion of the analyte ions trapped in said reaction region to cause negative EAD thereof, thereby generating a plurality of fragment product ions.
A system for analyzing mass spectra of a deprotonated oligonucleotide comprises a mass spectrometer configured to collect mass spectrometry data and an analyzer module configured to receive and analyze the mass spectrometry data by identifying experimental isotopic peaks corresponding to a precursor ion generated from the deprotonated oligonucleotide; determining characteristics of the precursor ion; identifying experimental isotopic peaks corresponding to a fragment ion generated from the precursor ion; determining characteristics of the fragment ion; selecting a candidate fragment for the fragment ion; determining mass shifted isotopic peaks of the candidate fragment based on data that include the characteristics of the precursor ion and the characteristics of the fragment ion; comparing the experimental isotopic peaks corresponding to the fragment ion and the mass shifted isotopic peaks of the candidate fragment; and identifying the fragment ion as the candidate fragment based on the comparing.
A method of dissociating an analyte in a mass spectrometer includes ionizing the analyte to generate a plurality of ions of the analyte, introducing and trapping the analyte ions into an ion trap, using an electron source to generate electrons, introducing a gas comprising a reagent molecule into a region between the electron source and a gate electrode, and using the gate electrode to cause ionization of the reagent molecules thereby generating a plurality of ions of the reagent molecule. The electron source inhibits entry of the accelerated electrons into the ion trap, the gate electrode is maintained at an electric potential to accelerate the reagent ions for entry into the ion trap as a positively charged ion beam, and the ion beam causes negative electron transfer dissociation of at least a portion of the analyte ions.
A method of dissociation of an oligonucleotide in a mass spectrometer includes introducing the oligonucleotides into an electrospray ionization source operated in a negative mode to cause deprotonation of said oligonucleotide for generating a negatively charged ion of said oligonucleotides, trapping said negatively charged oligonucleotide ions in linear radiofrequency (RF) ion traps with T bar electrodes, filling the linear ion trap with a buffer gas, and using a resonant dipole AC excitation signal applied to the T bar electrodes to resonantly excite the negatively charged oligonucleotide ions at secular frequencies thereof to cause selective fragmentation of said negatively charged oligonucleotide ions via collision with molecules of said buffer gas.
A method and system of data acquisition in an acoustic ejection mass spectrometer including a plurality of reservoirs, each reservoir containing a sample, the method including scheduling a plurality of ejection events for the plurality of reservoirs, setting an analysis method for each ejection event, ejecting a first sample at a first ejection time, starting a first analysis method of the ejected first sample at a first start time, ejecting a second sample at a second ejection time, and starting a second analysis method of the ejected second sample at a second start time, the second start time being or equal to or earlier than the first end time. For example, before starting the first analysis method, it is determined whether an ejection of the first sample has occurred, and if the ejection of the first sample is determined not to have occurred, the second sample is ejected.
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
43.
Exhaust Flow Boosting for Sampling Probe for Use in Mass Spectrometry Systems and Methods
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
44.
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.
Calibration of a droplet dispenser includes providing a liquid sample including a calibrant and, for each liquid level of a range of different liquid levels providing the liquid sample to a set of wells at the liquid level. Further, over a range of different droplet dispenser parameters, the droplet dispenser is used to dispense droplets from the set of wells into a flowing transport fluid. A mass of calibrant ions generated from the flowing transport fluid is measured using a mass spectrometer. Volumes of the droplets from are determined from the calibrant mass.
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
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.
A method and system for correcting a measurement in a sample analyzing system, the method including receiving a first sample at an interface of the sample analyzing system, the first sample being a portion of a sample source; measuring a first signal for the received first sample to generate a measured first signal; comparing the measured first signal to an expected characteristic of the sample analyzing system to determine whether the measured first signal is valid; and when the measured first signal is determined not to be valid: taking one or more corrective actions on one of the sample analyzer and the sample source; receiving a second sample at the sampling interface, the second sample being another portion of the sample source; and measuring a second signal for the received other sample to generate a measured second signal.
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
A temperature regulation system for samples in a microplate includes a housing defining an interior volume and first and second airflow ports defined by a first and second exterior surfaces of the housing. The system includes an electromagnetic mixing system that has a base plate defining a plurality of openings, and a plurality of electromagnets. Each electromagnet defines an axis that extends substantially vertically from the base plate. The base plate is disposed in the interior volume and each of the plurality of electromagnets extend toward the first airflow port. A fan is disposed in the interior volume substantially below the base plate. Activation of the fan draws air into the first or second airflow port, substantially parallel to each axis of the plurality of electromagnets, through the plurality of openings, and out of the other of the second and first airflow port.
A method for processing a sample in a container includes introducing the sample to the container. A cap is applied to the container. The cap contains a plurality of beads. The plurality of beads is mixed with the sample. The plurality of beads is separated from the sample. Subsequent to removing the plurality of beads, a further process is initiated.
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]
53.
DETECTION SATURATION CORRECTION AND DE-COALESCENCE BY ION BEAM MODULATION
In one aspect, a mass spectrometer is disclosed, which comprises an ion source configured to receive a sample and ionize at least one analyte in the sample to generate a plurality of analyte ions, and at least a first ion routing device having a first inlet for receiving at least a portion of the plurality of the analyte ions and at least a first and a second outlet through which a first and a second portion of the received analyte ions can exit the ion-routing device, respectively. The mass spectrometer can further include at least two charge reduction devices one of which is coupled via a first inlet thereof to the first outlet and the other is coupled via an inlet thereof to the second outlet of the ion routing device to receive said first and second portions of the ions exiting the ion routing device.
In one aspect, a mass spectrometer is disclosed, which includes an ion source configured to receive a sample and ionize at least one analyte in the sample to generate a plurality of ions of that analyte, at least a first ion routing device having a first inlet for receiving at least a portion of the plurality of the analyte ions and at least a first and a second outlet through which a first and a second portion of the received analyte ions can exit the ion-routing device, respectively, andat least two charge reduction devices one of which is coupled via a first inlet thereof to the first outlet and the other is coupled via an inlet thereof to the second outlet of the ion routing device to receive the first and second portions of the ions exiting the ion routing device.
A method for performing mass spectrometry comprises generating a plurality of ions from an analyte; directing the plurality of ions into an ion detector to generate a plurality of ion detection signals; generating a plurality of data points corresponding to the plurality of ion detection signals, each data point of the plurality of data points representing an intensity of detected ions as a function of an X-parameter, wherein the X-parameter is a function of a mass-to-charge ratio for the detected ions; identifying a cut off intensity corresponding to a set of cut off data points of the plurality of data points; identifying a set of selected data points of the plurality of data points based on the set of cut off data points; and deriving from the set of selected data points at least one characteristic corresponding to a maximum point associated with the plurality of data points.
In one aspect, a method for mass spectrometric analysis of analyte ions is disclosed, which includes filtering a plurality of ions to sequentially transmit a plurality of precursor ion subsets to a charge reduction device (e.g., a proton reaction device). For each precursor ion subset, a charge reduction reaction is performed within the proton reaction device to generate a set of charge-reduced precursor ions associated with one of the precursor ion subsets. One or more portions of the set of charged-reduced product ions associated with each respective precursor ion subset are selectively transmitted to a fragmentation device. The charge-reduced precursor ions are fragmented in the fragmentation device to generate a set of fragment ions associated with each respective precursor ion subset and mass spectra of each set of fragment ions associated with a respective precursor ion subset are generated.
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.
Various embodiments, systems, components, devices, and combinations thereof are provided that generate a data signal from a sample and correlate features in the data signal with features in a template by shifting features of the data signal along the time axis. Such temporal shifting may better align or correlate features in the data signal with features in the template. The features in shifted data may then be compared to the features in the template to determine whether the sample contains the respective features represented by the template.
In one aspect, a method of performing mass spectrometry is disclosed, which includes selecting a precursor ion having an m/z ratio in a range of interest from among a plurality of ions, identifying a charge state of the selected precursor ion, e.g., based on distribution of mass peaks associated with different isotopes in a mass spectrum. The charge state of the selected precursor ion can be reduced to generate a respective charge-reduced ion at a known m/z ratio. The charge-reduced ion can be subjected to fragmentation to generate a plurality of product ions (which are herein also referred to as fragment ions). A mass analysis of the product ions can then be performed.
In one aspect, a method for monitoring a bias voltage applied to an ion detector of a mass spectrometer is disclosed, which comprises applying an initial bias voltage to the ion detector, using the ion detector with the initial bias voltage applied thereto to acquire at least two viable ion detection signals corresponding to at least two different ion signal detection threshold values, and using said at least two viable ion detection signals to determine whether an adjustment of said bias voltage is required.
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.
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 mass spectrometry system comprises an ion mobility separation device (IMSD) configured to receive a plurality of ions, and to perform an ejection of a set of ions of the plurality of ions by adjusting a set of mobility control parameters to a set of mobility parameter values; a mass analyzer configured to receive the set of ions, to perform a detection of the set of ions, and to generate a set of detection signals corresponding to the detection of the set of ions; and a controller configured to receive data including the set of mobility control parameter values and the set of detection signals, and to perform a mapping of the set of mobility control parameter values and the set of detection signals.
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
66.
SINGLE PANEL REPRESENTATION OF MULTIPLE CHARGE EVIDENCE LINKED TO A BOND IN THE PROTEIN
A user interface is provided for displaying in the same panel and at the same time a sequence of a polymeric compound and multiple pieces of spectral evidence from an experimental product ion spectrum that are linked to a bond of the sequence. The sequence and the spectrum of the polymeric compound are received, where one or more product ions of the spectrum are assigned to at least one bond of the sequence. The sequence is displayed in a panel of a display device with at least one interactive icon between at least two elements of the sequence representing the bond. When the interactive icon is selected, at least two different spectral plots of the spectrum showing two different product ions of the spectrum that support a cleavage of the bond are displayed in the same panel of the sequence and at the same time as the sequence.
In a method for determining if internal product ions are used to provide evidence for a bond of a polymeric compound, two or more theoretical product ions resulting from the cleavage of at least one bond of the sequence of the compound are calculated. A product ion spectrum is searched for the theoretical product ions. The theoretical internal product ions are calculated and the spectrum is searched for the theoretical internal product ions if one or more theoretical product ions of the theoretical product ions match a product ion of the spectrum. In another embodiment, a mass tolerance is automatically determined for comparing theoretical mass peaks to mass peaks of an experimental mass spectrum using the subset of product ions most likely to be found for the fragmentation method used. In another embodiment, charge filtering is used to find an experimental product ion of a compound.
Known mass spectral data of a library of spectra corresponding to known compounds or known mass spectral data determined from a database of known compounds are compressed using a neural network encoder, producing a group of corresponding compressed known representations of known mass spectral data. Experimental mass spectral data of an experimental mass spectrum is compressed using the neural network encoder, producing a compressed experimental representation of the experimental mass spectral data. The experimental representation is compared to the group of known representations and each comparison is scored. At least one comparison with a score above a predetermined score threshold is selected. A known compound is determined from the selected at least one comparison. The known compound is identified as a compound of the experimental spectrum.
System and method for high-throughput mass spectrometry are disclosed. In some embodiments the system comprises a sample introduction device, an ion source, an ion mobility separation device, a mass analyzer and a controller adapted to receive certain parameters from the IMSD and determine a mass range for more efficient operation of the mass analyzer. In some embodiments, the controller is adapted to provide data to, and receive data from other components to make the operation of the IMSD and the mass analyzer more efficient.
H01J 49/00 - Particle spectrometers or separator tubes
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
H01J 49/42 - Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
70.
HIGH-THROUGHPUT ANALYSIS USING ION MOBILITY AND MASS SPECTROSCOPY
In one aspect, a method of operating a high-throughput mass analysis device is disclosed, which includes sampling an unseparated sample from at least one sample holding element during a sampling interval for introduction of the sample into an ion source for ionizing the sample to generate a plurality of ions associated with at least one target analyte (herein also referred to as a target compound), if any, in said sample for delivery to an ion mobility separation device, and activating at least one control parameter of said ion mobility separation device for detection of said ions based on timing of the sampling of the sample and at least one identifier associated with the sample.
H01J 49/00 - 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
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
71.
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.
Systems and methods for performing calibration of compound markers in mass spectrometry (MS) detection are presently claimed and described. The example systems and methods provide for automatic identification of all or substantially all pI markers in a sample, constructing a calibration curve of pI and time, and/or converting the time scale into pI scale. Given the correlation between the time and pI scales, pI can be correlated to intensity and presented to an operator for further analysis.
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.
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.
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.
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
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.
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.
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 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
90.
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
93.
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 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
98.
METHOD AND SYSTEMS FOR ANALYZING IONS USING DIFFERENTIAL MOBILITY SPECTROMETRY AND AN ION GUIDE COMPRISING ADDITIONAL AUXILIARY ELECTRODES
Methods and systems for performing differential mobility spectrometry-mass spectrometry (DMS-MS) 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 spectrometrydevi ce at each compensation voltage value.
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.
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.
patents
