In one aspect, a method of operating a mass spectrometer having an ion source, at least one ion optic positioned downstream of the ion source and at least one ion mass filter positioned downstream of the ion optic is disclosed, which includes transitioning an operational mode of the mass spectrometer from an active mass collection mode to a park mass mode, and configuring the ion optic to function as a bandpass ion filter for substantially inhibiting passage of ions generated by the ion source during the park mass mode to the downstream ion mass filter.
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 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
6.
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.
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.
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
9.
OPEN PORT INTERFACE HAVING HYDROPHOBIC OR HYDROPHILIC PROPERTIES
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
10.
RF CHOKE FOR USE IN A MASS SPECTROMETER AND RF CHOKE
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.
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
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
19.
SYSTEMS AND METHODS FOR AUTOMATIC SAMPLE RE-RUNS IN SAMPLE ANALYSYS
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.
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.
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.
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.
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
35.
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
36.
SYSTEMS AND METHODS FOR CAPILLARY ISOELECTRIC FOCUSING-MASS SPECTROMETRY (CIEF-MS) ISOELECTRIC POINT (pl) CALIBRATION
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 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.
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.
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.
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.
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.
A method of performing mass spectrometry is disclosed, which comprises introducing a plurality of ions into an ion guide of a mass spectrometer via an inlet orifice thereof, where the ion guide includes a plurality of rods arranged in a multipole configuration and spaced from one another to provide a passageway for transit of the ions therethrough, applying RF voltages to the rods so as to generate an electromagnetic field within the passageway for providing radial confinement of the ions passing through the passageway, identifying a space charge effect, which can adversely affect operation of the mass spectrometer, based on detection of a variation of an intensity of an ion detection signal associated with at least one ion population transmitted through said ion guide and having an m/z ratio greater than a threshold, and in response to said identification of the adverse space charge effect, adjusting at least one of frequency and amplitude of the RF voltages to counteract said space charge effect.
Leak detection systems and methods in accordance with various aspects of the present teachings can, in various embodiments, sequester fluid leaking from the interface between a sample source and the inlet of the ion source, alert an operator as to a leak condition, and/or automatically terminate the experiment. In various aspects, a liquid leak detection system is accordance with the present teachings comprises a collection basin configured to couple to a proximal end of a conduit in fluid communication with a discharge end of an ion source of a mass spectrometer such that the proximal end of the conduit extends through the internal volume of the basin. The system may also comprise a drainage tube having an inlet end opening into an internal volume of the collection basin and configured to drain liquid therefrom, a sensor disposed within the basin or the drainage tube and configured to generate a signal indicative of liquid therewithin, and a processor that is configured to cause a user to be alerted and/or cause an experiment to be terminated upon receiving from the sensor a signal indicative of a leak.
G01M 3/20 - Investigating fluid tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material
48.
CAPILLARY ELECTROPHORESIS PURITY ANALYSIS OF COMPLEMENTARY STRAND NUCLEIC ACID MOLECULES
The presently described and claimed disclosure relates to method for characterizing nucleic acid purity comprising denaturing a nucleic acid sample, loading the nucleic acid sample onto a capillary electrophoresis (CE) capillary, wherein the CE capillary is filled with a buffer comprising a polymer matrix, applying a separation voltage to the CE capillary, wherein during the separation of the nucleic acids, the temperature of the CE capillary is increased, and detecting nucleic acids separated from the nucleic acid sample with a detector. Kits and instructions for use are also described.
Disclosed herein are methods for analyzing biological samples using capillary electrophoresis, including the characterization of genome integrity, assessment of genomic integrity and the sequencing of a nucleic acid genome, such as an RNA genome. Kits for characterizing genome integrity are also disclosed.
Methods and systems for mass spectrometry are disclosed. In one example, a method comprises: receiving, by a mass spectrometer via a sampling system operably connected thereto, at least one sample containing at least one known compound; modulating at least one instrument parameter of the mass spectrometer through a plurality of instrument parameter values; analyzing the at least one sample while applying each of the plurality of instrument parameter values; acquiring a plurality of mass spectral (MS) datasets each corresponding to one of the applied plurality of instrument parameter values; encoding each of the plurality of MS datasets to generate a corresponding plurality of MS results each corresponding to one of the applied instrument parameter values; and compiling and storing the MS datasets and MS results in a spectral library in association with the applied instrument parameter values.
H01J 49/00 - Particle spectrometers or separator tubes
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
mmmmmm event realizations. In another embodiment, for the ion, an equivalent TDC event realization is accumulated for ion events up to a threshold count of event realizations, N, and the ADC intensities are accumulated for all remaining ion events. A filtered intensity for the ion is calculated that is a combination of the equivalent TDC event realization and the ADC intensities.
Ion optical elements in accordance with various aspects of the present teachings can, in various embodiments, be utilized to replace conventional stacked-ring ion optical elements (e.g., ion guides, ion tunnels, ion funnels, reflectrons), which typically contain a plurality of individual conductor rings and insulating spacers that must be manufactured with exacting tolerances and precisely aligned during assembly. In various aspects, methods of producing ion optical elements are also disclosed herein, which according to various aspects may reduce the cost and/or complexity associated with precisely manufacturing and assembling the many parts of conventional stacked-ring devices.
Disclosed are methods for detecting and quantifying target analytes in a sample by mass analysis that include detecting the presence of ions of the target analyte in the sample and quantifying the amount of the target analyte. The methods can include one or more standards (e.g., internal and/or external standards) that may be labelled (e.g., isotopically labelled).
The presently claimed and described technology provides a sample processing system comprising at least one sample introduction device, wherein the at least one sample introduction device is configured to receive a sample; a mass analyzer coupled to the sample introduction device; a control system configured to at least control the at least one sample introduction device and/or the mass analyzer, wherein the mass analyzer is configured to perform a first mass analysis on the sample, wherein the first mass analysis is mass screening for an analyte of interest in the sample, and wherein if the analyte of interest is detected in the sample, the mass analyzer is configured to perform a second mass analysis, wherein the second mass analysis is a quantitative analysis, comprising: ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte; determining intensity and/or abundance of the at least one product ion transition and/or the at least one isotopic ion transition; and quantifying the at least one analyte present in the sample using the intensity and/or abundance of the at least one product ion transition and/or isotopic ion transition.
H01J 49/00 - 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
55.
UTILIZING NATURAL ISOTOPIC ABUNDANCE OF COMPOUNDS TO EXTEND THE DYNAMIC RANGE OF AN INSTRUMENT
The presently claims and described technology provides methods for quantifying at least one analyte in a sample by mass analysis by ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte; wherein if the product ion transition meets a condition, the method further comprises determining the intensity and/or abundance of at least one isotopic ion transition; and quantifying the at least one analyte present in the sample using the intensity and/or abundance of the at least one isotopic ion transition. Computer-implemented methods for quantifying at least one analyte in a sample are also disclosed.
Methods and systems for performing differential mobility spectrometry-MS/MS are provided herein. In various aspects, methods and systems described herein can determine corresponding MS data from differential mobility spectrometry-MS/MS data obtained at each of a plurality of SV-COV combinations applied to the differential mobility spectrometry device, without requiring a separate differential mobility spectrometry-MS run, for example, each time the COV- combination is adjusted. Furthermore, the population of analyte ions, which are present in each of the plurality of product ion scans obtained at different SV-COV combinations, can be identified.
Systems and methods are provided for processing in real-time and using Gaussian fitting digitized signals from ions detection in time-of-flight (TOP) mass spectrometry. Acquisition/analog-to- digital conversion may be applied in the course of Ion detection during time-of-flight (TOP) mass spectrometry, with the acquisition/analog-to-digital conversion including generating, in response to detection of ions, one or more time-of-flight (TOP) based signals, and digitizing, using analog- to-digital conversion, the one or more TOP based signals, to generate corresponding digitized data. The digitized data may then be processed, in real-time and based on use of Gaussian fitting, to generate result data corresponding to the time-of-flight (TOP) mass spectrometry. The Gaussian fitting may comprise applying second (2nd) degree polynomial fit, such as by least squares via QR factorization.
A mount assembly for holding a microchannel plate in an ion detector includes an input side clamping plate including a plurality of input side pads; and an output side clamping plate including a plurality of output side pads, wherein, when assembled, the input side clamping plate and the output side clamping plate are configured to allow positioning between the input side clamping plate and the output side clamping plate the microchannel plate having a plurality of microchannels each having an input side opening and an opposed output side opening; hold the microchannel plate; and position the subset of the input side pads and the subset of the output side pads in a staggered configuration such that when a microchannel of a plurality of microchannels is obstructed in a first opening, a second opening of the microchannel opposing the first opening is unobstructed.
In one aspect, a method for fragmenting ions in a mass spectrometer is disclosed, which includes introducing a plurality of precursor ions into a collision cell of a mass spectrometer, generating a potential barrier in the collision cell to cause at least a portion of ions in the collision cell to be trapped within a region in proximity of said potential barrier, and applying ultraviolet (UV) radiation to said trapped ions so as to cause fragmentation of at least a portion of any of said precursor ions and fragment ions thereof to generate a plurality of product ions such that a space charge generated in said region in proximity of said potential barrier due to accumulation of ions will impart sufficient kinetic energy to at least a portion of the product ions so as to overcome said potential barrier, thereby exiting said region.
In one aspect, a mass spectrometer is disclosed, which includes an ion path along which an ion beam can propagate, and an ion beam deflector positioned in the ion path and configured to modulate transfer of an ion beam received from an upstream section of the ion path to a downstream section thereof, said ion beam deflector comprising at least one electrically conductive electrode positioned relative to one another to provide an opening through which the ion beam can pass, where the two electrodes are electrically insulated relative to one another so as to allow maintaining each electrode at a DC potential independent of a DC potential at which the other electrode is maintained.
A method for performing mass spectrometry (MS) comprises receiving MS data corresponding to a plurality of MS runs, wherein MS data corresponding to an MS run of the plurality of MS runs comprises detected intensities for a plurality of mass over charge ratios (MZ values) during the MS run; finding a recurrent MZ value of the plurality of MZ values, wherein a detected intensity for the recurrent MZ value appears as a recurrent peak in MS data corresponding to a subset of the plurality of MS runs; and the subset of the plurality of MS runs includes at least two MS runs of the plurality of MS runs; and identifying the recurrent MZ value as corresponding to a background ion.
In one aspect, a method of operating a mass spectrometer is disclosed, which comprises ionizing a sample to generate a plurality of ions, and introducing at least a portion of the ions into an inlet orifice of the mass spectrometer. At least a portion of the ions and/or fragments thereof is detected by a downstream detector to generate a plurality of ion detection events, and the ion detection events are monitored to determine an ion count. The ion count is compared with a reference level to determine whether the detected level exceeds the reference level.
Methods and system that determines disulfide and trisulfide linkages within analytes (e.g., polypeptides) is described. In certain aspects, a sample comprising polypeptides (such as an antibody) may be subjected to dissociation using an electron activated dissociation (which can include electron capture dissociation and electron transfer dissociation) and the fragmentated portions are analyzed using a mass spectrometer to produce a spectrum. The spectrum is analyzed by a processor to identify peaks from the spectrum that are related to one another in the spectra by a separation of 32 mass units. In identifying an antibody comprising peptide segments linked via a trisulfide bond, for example, four different peaks representing two different peptides are searched for and identified representing a first peptide portion having mass/charge of A and A+32 and a second peptide having mass/charge of B and B+32.
A method for determining a convolved peak intensity in a sample trace includes ejecting a plurality of sample ejections from a sample well plate. An ejection time log is generated which includes an ejection time of each of the plurality of sample ejections from the sample well plate. The plurality of sample ejections is analyzed with a mass analyzer. The sample trace of intensity versus time values is produced for the plurality of sample ejections based on the analysis. A known peak shape is obtained. A convolved peak intensity is determined for a convolved peak of the sample trace based at least in part on the known peak shape and the ejection time log.
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
Methods and systems for spectral comparison and quality assessment are disclosed. In one example, a method for assessing quality of a mass spectrum (MS) of a sample is provided. The method comprises: predefining one or more features or attributes indicative of the sample quality with reference to a target compound; and calculating a quality score for the MS with respect to the selected features or attributes.
Disclosed are systems and methods for facilitating compound identification based on analytical data obtained from an analytical instrument such as, for example, a mass spectrometer.
nnn dimensions. Two clustering algorithms are applied to the measurements, producing two sets of clusters, and compounds in the sets are identified. Two or more compounds found in a cluster of both sets are identified. The two or more compounds are compared to groups of compounds related to a biological process to identify a group that includes the two or more compounds. An additional compound is selected from the group. The two sets are reanalyzed to identify the compound in the sets. A co-occurrence matrix is calculated that quantifies the co-occurrence of the compound and each of the two or more compounds in the sets. If no co-occurrence quantity for the compound and each of the two or more compounds in the matrix is below a threshold, the two or more compounds are verified.
G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
69.
OPTIMIZATION OF DMS SEPARATIONS USING ACOUSTIC EJECTION MASS SPECTROMETRY (AEMS)
Disclosed are methods and systems that provide for the analysis of one or more analytes of interest in an acoustic ejection mass spectrometer (AEMS) system that incorporates an open port interface (OPI) and differentiation mass spectrometry (DMS) that allows for operation of the system in a pseudo-continuous mode to scan and determine optimal DMS settings for the one or more analytes of interest, and for operation of the system in a discontinuous mode to analyze for the presence of the one or more analytes of interest in a sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum 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]
70.
ION TYPE TAILORED LIBRARY SEARCH PRE-PROCESSING, CONSTRAINTS AND SPECTRAL DATABASE BUILDING
A method of ejecting a sample from a nebulizer nozzle fluidically coupled to a port via a transfer conduit includes receiving at the port a transport liquid and the sample. The transport liquid and the sample in the transfer conduit is transported from the port to a transfer conduit exit comprising an electrode tip. The transport liquid is ejected from the transfer conduit exit. The sample is ejected from the transfer conduit exit substantially simultaneously with ejecting the transport liquid. During ejection of the transport liquid and the sample from the transfer conduit exit, a pressure is generated at the transfer conduit exit substantially similar to a vapor pressure of the transport liquid.
H01J 49/16 - 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
74.
METHODS AND SYSTEMS FOR DETERMINING MOLECULAR MASS
Methods and systems for mass analysis are disclosed herein. An example system includes: a sample ejector configured to eject a plurality of samples from a plurality of wells of a well plate; a capture probe configured to capture the ejected samples and dilute and transport the captured samples; a nebulizer nozzle configured to receive and ionize the transported diluted samples to produce sample ions; a mass analysis instrument configured to filter and detect ions of interest from the sample ions; a controller configured to coordinate operations of the sample ejector, the capture probe, the nebulizer nozzle, and the mass analysis instrument; and a data processing system configured to acquire data from the mass analysis instrument and conduct an automatic data processing process.
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
76.
METHODS AND SYSTEMS FOR ASSESSING A QUALITY OF MASS ANALYSIS DATA GENERATED BY A MASS SPECTROMETER
Methods and systems for assessing a quality of mass analysis data generated by a mass analysis device, including collecting mass spectrometry data for a given compound, deriving a measured isotope profile based on the collected mass spectrometry data, determining a predicted isotope profile, determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks, determining a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data, determining an overall quality score as a combination of the first quality score and the second quality score, and assessing a quality of a compound library based on the determined overall quality score.
Methods and systems for automatically analyzing a collection of samples, the method including ionizing a plurality of samples, capturing a plurality of raw mass spectra for the ionized plurality of samples, correlating captured respective subsets of the raw mass spectra to each sample of the plurality of samples, and for each sample of the plurality of samples, generating a reconstructed mass spectrum based on the respective subset of the raw mass spectra of the sample. Methods and systems also include correlating the captured respective subsets of the raw mass spectra to each sample by generating a chronogram, and correlating a timeline of a sampling of the sample with the chronogram to correlate the captured respective subsets of the raw mass spectra to each sample. Methods and systems also include analyzing the generated reconstructed mass spectrum for each sample of the plurality of samples.
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
78.
PREDICTION OF PRECURSOR CHARGE STATE IN DM-SWATH ANALYSIS
A method for improved mass spectrometry by determining charge state of precursor ions from an analysis of product ions, includes receiving sample ions. A group of precursor ions is selected from the received sample ions based on mobility. A fragmentation device fragments the group of precursor ions to produce a group of product ions. A tandem mass spectrometry analysis is performed on the group of product ions to generate an intensity and mass-to-charge ratio (m/z) of the group of product ions. An ionogram is generated, based on the generated intensities and mass, to charge ratios for the groups of product ions generated for each of the mobility selection. The ionogram includes a first axis representing compensation voltage value and another axis representing intensity. A product ion peak is identified in the ionogram. At least one peak characteristic is identified of the product ion peak. A charge state of a precursor ion that was fragmented to form the product ions represented in the product ion peak is determined based on the at least one peak characteristic of the product ion peak.
An ion mass filter for use in a mass spectrometer is disclosed, which includes a plurality of rods arranged in a multipole configuration to provide a passageway through which ions can travel, said plurality of rods being configured for application of RF voltages thereto to generate an electromagnetic field within the passageway for providing radial confinement of the ions and further configured for application of a DC voltage thereto, and at least two pairs of auxiliary electrodes interspersed between the plurality of multipole rods, where one pair forms a first pole of the auxiliary electrodes and the other pair forms a second pole of the auxiliary electrodes. A controller can provide one or more control signals to the DC voltage source so as to switch the polarity of the DC voltage differential between the two poles according to a predefined criterion.
A system for applying RF voltages to a multipole ion processing device, configured for use in a mass spectrometer, includes a first RF generator configured to generate a first RF voltage and apply to a first pole electrode set, a second RF generator configured to generate a second RF voltage and apply to a second pole electrode set, a first amplitude adjustor configured to adjust an amplitude of the first RF voltage, a second amplitude adjustor configure to adjust an amplitude of the second RF voltage, and a phase adjustor in communication with the first RF generator and the second RF generator to adjust phase output of at least one of the first RF generator and the second RF generator so as to adjust a phase differential between the first RF voltage and the second RF voltage to be within a desired range.
Systems and methods are disclosed for performing a DDA mass spectrometry experiment. A precursor ion survey scan of a mass range is performed to generate a precursor ion peak list. A series of steps are performed for each precursor ion peak of the peak list. A peak mass range including the precursor ion peak is selected. A precursor ion mass selection window with a width smaller than the peak mass range is canned across the peak mass range in overlapping steps, producing a series of overlapping windows across the peak mass range. Each overlapping precursor ion mass selection window of the series is fragmented. Product ions produced from each overlapping precursor ion mass selection window of the series are mass analyzed, producing a product ion spectrum for each overlapping precursor ion mass selection window of the series and a plurality of product ion spectra for the peak.
In various aspects, integrated specimen collection and analyte extraction devices are provided herein. For example, in accordance with various aspects of the present teachings, a device for extracting analytes from a specimen is provided, the device comprising a housing (12) defining an extraction chamber (14) for containing a known volume of a liquid specimen and having an inlet (16) for receiving the liquid specimen. A stationary phase (20) is configured to be disposed within the extraction chamber (14) in contact with the liquid sample so as to adsorb one or more analyte species thereto, wherein at least one of the stationary phase (20) and the one or more analytes adsorbed thereto within the extraction chamber (14) is removable from the extraction chamber (14) for analysis by a chemical analyzer.
In one aspect, an ion filter for use in a mass spectrometer is disclosed, which includes a plurality of rods arranged in a multipole configuration to provide a passageway through which ions can travel, said plurality of rods being configured for application of RF voltages thereto to provide an electromagnetic field within the passageway for providing radial confinement of the ions and further configured for application of a DC voltage thereto. At least two pairs of auxiliary electrodes are interspersed between the plurality of rods and are configured for application of a DC bias voltage with one polarity to one of said pairs and a DC bias voltage with an opposite polarity to the other one of said pairs to provide a DC potential difference between the auxiliary electrodes and the plurality of rods.
The disclosure provides compositions, methods, and kits that find use in calibrating a mass spectrometer, and can include one or more predetermined concentration(s) of one or more calibrant molecule(s) that comprise a polyethylene glycol (PEG) compounds that have a single functional group that can be ionized by an ion source, and a solvent for dissolving the calibrant molecule(s). The calibrant molecule(s) and compositions including them can be used in either positive or negative ionization mode, and can be used for calibrating a variety of mass spectrometers (e.g., APCI, ESI) operating in a variety of acquisition modes (e.g., MRM, MS/MS, etc.).
H01J 49/00 - Particle spectrometers or separator tubes
C08G 65/331 - Polymers modified by chemical after-treatment with organic compounds containing oxygen
C08G 65/332 - Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides or esters thereof
C08G 65/333 - Polymers modified by chemical after-treatment with organic compounds containing nitrogen
C08G 65/334 - Polymers modified by chemical after-treatment with organic compounds containing sulfur
A curtain chamber includes an orifice plate defining an orifice plate bore. A curtain plate is disposed adjacent to the orifice plate and defines a curtain plate bore. The orifice plate bore is disposed adjacent the curtain plate bore. A biasing element includes a first portion disposed in the orifice plate bore and a second portion disposed in the curtain plate bore. The biasing element biases the curtain plate towards the orifice plate. A race is defined by at least one of the orifice plate and the curtain plate. The race defines a race depth. A seal is disposed in the race. The seal includes an uncompressed seal depth greater than the race depth and a compressed seal depth less than the uncompressed seal depth.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
H01J 49/06 - Electron- or ion-optical arrangements
86.
INTENSITY-INDEPENDENT PRECURSOR INFERENCE IN MASS SPECTROSCOPY
Methods for correlating a product ion in a mass spectrum to a precursor ion are disclosed herein, comprising determining a precursor ion m/z corresponding to the product ion as an m/z at which the product ion appears in a maximum amount of the series of mass spectra. Methods also can comprise obtaining a series of mass spectra for a sample across a mass range, each of the series of mass spectra having a precursor ion transmission window defined by a width (W) that overlaps with that of at least two of the series of mass spectra by a step size (S).
A mass spectrometer that includes a mass filter and a TOF mass analyzer receives the ion beam from an ion source device that ionizes a compound of a sample. The mass filter selects a precursor ion mass range and the mass analyzer mass analyzes the mass range. A continuous flow of selected precursor ions is maintained between the mass filter and the mass analyzer. A first set of parameters is applied to the mass spectrometer to produce a resolution above a first resolution threshold. A space charge effect is detected by determining if the measured TIC exceeds a TIC threshold or the measured resolution is less than the first resolution threshold. If a space charge effect is detected, at least one precursor ion transmission window with a width smaller than the mass range is applied to the ion beam by the mass filter and mass analyzed to reduce the space charge.
Disclosed are methods for separating target and non-target analytes in a sample. The methods can utilize an acoustic droplet ejector (ADE) and an open port interface (OPI) to achieve liquid chromatography (LC)-like separation for an analytical instrument such as, for example, a mass spectrometer.
A method for measuring a concentration of an analyte in a sample includes: sampling, from a first sample, a first one or more droplets for mass analysis, wherein the first sample includes the sample; performing mass analysis on the first one or more droplets to determine a first intensity of an analyte in the first one or more droplets; sampling, from a second sample, a second one or more droplets for mass analysis, wherein the second sample includes the sample and a first spike of the analyte; performing mass analysis on the second one or more droplets to determine a second intensity of the analyte in the second one or more droplets; fitting a curve to the first intensity and the second intensity; and based on the fitted curve, calculating an analyte concentration for the sample.
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
A method for identifying peaks in a mass spectrum is provided. The method includes: accessing a mass spectrum (300), having an intensity signal, generated for analysis of a sample; performing a wavelet transformation on the intensity signal to generate a wavelet space representation (310) of the intensity signal; generating a scale- space-processing (SSP) response signal (412, 414, 416) from the wavelet space representation of the intensity signal, wherein the SSP response signal (412, 414, 416) represents the SSP response from the wavelet scale representation (310) at different wavelet scales for a particular m/z starting position (312, 314, 316); identifying a first wavelet scale for a first local maximum in the SSP response signal; based on the first wavelet scale, detect a first baseline intensity signal; subtracting the first baseline intensity signal from the intensity signal to generate a first adjusted intensity signal; and detecting one or more peaks in the first adjusted intensity signal.
A liquid handling system for a mass spectrometer (MS), the liquid handling system including an open port interface (OPI) including a body defining a port and an internal volume. At least one removal conduit is disposed in the body and fluidically coupled to the internal volume. A plurality of transfer conduits is fluidically coupled to the at least one removal conduit. A single one of a plurality of nebulizer nozzles are fluidically coupled to each of the plurality of transfer conduits.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum 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
92.
PREVENTING ERRORS IN PROCESSING AND INTERPRETING MASS SPECTROMETRY RESULTS
nnnmmnnnn data files of a next acquisition is retrieved. The m corresponding parameter values of the first data file and the next data file are compared. If any corresponding parameter values differ between the first data file and the next data file, a notification of an instrument parameter difference corresponding to a name of the next data file is displayed.
Methods and systems for handling and/or analyzing samples are provided. In one example, a method comprises: introducing (406), with a liquid handler (322), at least one assisting agent into a sample well (310) of a well plate (312), wherein the sample comprises a sample volume; and ejecting (408), with an acoustic droplet ejector, ADE, (306), a mixture comprising the sample mixed with the at least one assisting agent from the sample well, wherein the at least one assisting agent interacts (406) with an analyte of the sample to limit gel formation at a top surface of the sample volume, prior to the mixture ejection.
G01N 1/14 - Suction devices, e.g. pumps; Ejector devices
B05B 17/06 - Apparatus for spraying or atomising liquids or other fluent materials, not covered by any other group of this subclass operating with special methods using ultrasonic vibrations
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
One or more known compounds are separated from a mixture using a separation device that allows processor-controlled adjustment of a separation parameter. The separated compounds are ionized and, for each cycle of a plurality of cycles, a mass spectrometer executes on the ion beam a series of MRM transitions read from a list. Two or more contiguous groups of MRM transitions to be monitored separately are received. Each group includes at least one sentinel transition that identifies a next group that is to be monitored and identifies a value for the separation parameter for the next group. A first group is placed on the list. When a sentinel transition of the first group is detected, a next group identified by the sentinel transition is placed on the list and the separation parameter is adjusted to a value identified by the sentinel transition for the next group.
The present disclosure provides methods and systems for performing mass spectrometry in which at least two batches of precursor ions generated via ionization of at least two different portions of a sample are exposed to electron beams at different energies to cause fragmentation of at least a portion of the precursor ions. In some embodiments, the electron energies can be selected such at one of the electron energies, EIEIO fragmentation can occur while at the other electron energy, EIEO fragmentation channel is not available. The mass spectra corresponding to the two energies can then be utilized to generate a resultant mass spectrum in which mass peaks corresponding to ion fragments generated by EIEIO dissociation are more readily identifiable.
Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of solvent into an open port sampling probe fluidly coupled to an ion source can be selectively stopped during the addition of one or more reagents into the drained open end of the sampling probe. Upon re-initiating the flow of solvent, the reagents and/or the reaction products can be delivered to the ion source. In one aspect, a method for chemical analysis is provided, the method comprising directing a flow of a first solvent from a solvent conduit to an ion source via a sampling space of a sampling probe, wherein the sampling space is at least partially defined by an open end of the sampling probe. The flow of the first solvent into the sampling space from the solvent conduit may be terminated for a first duration, and the sampling space drained. A second solvent and one or more reactants may then be added to the drained sampling space through the open end during the first duration. Thereafter, the flow of the first solvent may again be directed from the solvent conduit to the ion source via the sampling space such that the second solvent is delivered to the ion source, and such that one or more reaction products contained within the second solvent and generated by said one or more reactants may be ionized for mass spectrometric analysis.
H01J 49/00 - 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
97.
A TECHNIQUE TO NEUTRALIZE CHARGE ON A DIFFERENTIAL PUMPING APERTURE
In one aspect, a method for performing mass spectrometry is disclosed, which comprises passing a plurality of ions from an upstream ion guide to a downstream ion guide through an aperture of an ion lens disposed between the ion guides, and depositing a plurality of charged particles having an electric charge with opposite polarity relative to an electric charge of said plurality of ions on at least a portion of a surface of the ion lens, e.g., a surface facing the ions, so as to reduce an effect of a plurality of said ions, if any, deposited on said ion lens surface on a trajectory of the ions passing through the lens aperture, as ions pass from the upstream ion guide to the downstream ion guide.
Systems and methods are disclosed for RF amplitude auto-calibration for mass spectrometry. As non-limiting examples, various aspects of this disclosure provide in a mass spectrometer comprising an RF gain block, a peak detector, and a controller: applying a DC voltage to the coil using the controller; measuring a DC calibration voltage using the peak detector; applying an RF voltage to the RF gain block using the controller; measuring an RF calibration voltage; calculating an RF calibration factor based on the measured calibration voltages using the controller; and during operation, and applying a combined RF and DC signal to the RF gain block based on the RF calibration factor. The DC voltage may be generated utilizing a first signal sent from the controller to the RF gain block via a DC amplifier.
A gas introduction system for a differential mobility spectrometer (DMS) includes a manifold including a gas inlet and a gas outlet. A mixing channel fluidically couples the gas inlet to the gas outlet. A plurality of modifier liquid supply inlets is coupled to the mixing channel and a plurality of selectively operable valves. One of the plurality of selectively operable valves is coupled to one of the plurality of modifier liquid supply inlets. A control system is in communication with each of the plurality of the selectively operable valves. The control system is configured to actuate each of the plurality of selectively operable valves.
The technology relates to systems and methods for performing mass spectrometry analysis of a sample. An example method may include receiving, as input via an input device, a target mass-to-charge (m/z) ratio for a fragment ion of interest; setting a target m/z range based on the target m/z ratio; ionizing the sample to generate precursor ions; fragmenting the precursor ions to generate fragment ions having a range of mass-to-charge ratios larger than the target m/z range; accelerating the fragment ions to a detector such that fragment ions inside and outside of the target m/z ratio are detected; summing a count of fragment ions within the target m/z range without storing ion counts for fragment ions outside of the target m/z range; and storing the summed ion count as corresponding with the target mass-to-charge ratio.
patents
