In one aspect, a mass spectrometer system includes an ion mobility spectrometer (IMS), a gas supply for providing a curtain gas, a modifier supply for providing a liquid modifier, and a nebulizer for receiving the liquid modifier from the modifier supply and generating liquid droplets for delivery to a curtain chamber of the IMS. The spectrometer includes a fluid manifold for receiving the liquid modifier and delivering the liquid modifier to the nebulizer and to receive the curtain gas from the gas supply and provide a first portion of the curtain gas to the nebulizer as a nebulizing gas and provide a second portion of the curtain gas as a sheath flow to a region in vicinity of a nozzle of the nebulizer such that a combination of the sheath flow and gas exiting the nebulizer flows as a curtain gas entraining the liquid droplets to the curtain chamber.
An uncertainty weighted average of the equalized amounts of two or more quantifier ions is calculated from a quantitation experiment itself. n known i ions of a compound are mass analyzed over time in each of m different samples, producing n XIC peaks for each of the m samples. A reference ion j is selected that is a j ion of the n i ions or a hypothetical ion j. A ratio r(j,i) of a peak area of the j ion to a peak area of each ion of the n i ions is calculated for each of the m samples, producing m r(j,i) ratios for each of the n i ions. An expected ratio rq(j,i) is calculated for each ion of the n i ions from the m r(j,i) ratios for each of the n i ions. For each sample, the uncertainty weighted average is calculated using rq(j,i).
In one aspect, a method of acquiring mass data in a mass spectrometric system is disclosed, which includes introducing a plurality of ions into a mass filter providing a mass selection window to allow passage of precursor ions having m/z ratios within the mass selection window through the mass filter and scanning the mass selection window and adjusting a width thereof across a mass range during acquisition of mass data.
Systems, methods, and processes for processing mass spectrum data for quantification. The mass spectrum data is parsed into one or more data subsets having fragment ion intensities and precursor ion intensities. The mass spectrum data is determined to be convoluted, for each of the one or more data subsets. A target species is quantified using the determining of whether the mass spectrum data is convoluted. The quantifying is performed such that: for the case where the mass spectrum data is determined to be convoluted, the target species is quantified using the fragment ion intensities, and for the case where the mass spectrum data is determined to be unconvoluted, the target species is quantified using the precursor ion intensities.
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 locksArrangements for external adjustment of electron- or ion-optical components
6.
Modular Radiant Light Generation in Analysis System
Examples of the disclosure relate to a modular radiant light generation apparatus, including a modular receiver including a recessed portion, a radiant light source on a bottom surface of the recessed portion of the modular receiver, a first fitting on the radiant light source, a fiber optic jacket including a fiber optic core therein, a first portion of the fiber optic jacket coupled to the second fitting being inserted in the first fitting, and a third fitting including a threaded projection and a biasing element the second fitting being coupled to the first fitting being configured to align the fiber optic core with the radiant light source, and the biasing element being configured to keep the fiber optic core in contact with the radiant light source.
Disclosed herein are powerwash systems and methods of use therein including sampling probes with a transport channel including an inlet, an outlet, and a sampling inlet deposed between the inlet and the outlet and configured to receive at least a portion of a sample into the sampling inlet of the transport channel and configured to transport the sample via a transport fluid that flows from the inlet to the outlet of the transport channel; and a wash channel with a wash channel inlet and a wash channel outlet, where the wash channel is configured to transport one or more wash fluids from the wash channel inlet to the wash channel outlet, and where the one or more wash fluids are configured to exit the wash channel outlet and flow adjacent to the transport channel and toward the sampling inlet.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
8.
Power Supply Including Amplitude Calibration and Phase Correction for Mass Spectrometry
In one aspect, a circuit for generating an asymmetric waveform for application to electrodes of a differential mobility mass (DMS) spectrometer is disclosed, which includes two digital waveform synthesizers for generating digital waveforms, which are converted to analog waveforms for application to electrodes of the DMS spectrometer. Analog feedback signals associated with the applied waveforms are digitized into digital amplitude calibration feedback signals and digital phase correction feedback signals. An amplitude calibration circuit is employed apply an RF calibration factor to at least one of the digital waveform synthesizers based on digital the amplitude calibration feedback signals. A digital passband filter is employed to filter the digital phase correction feedback signals, which are then employed to determine a phase correction signal for application to at least one of the digital waveform synthesizers for maintaining a substantially constant phase difference between the waveforms generated by the digital waveform synthesizers.
Systems and methods are provided for correcting a measured retention time or expected retention time of an ion intensity measurement. A measured sentinel retention time is received for each of a plurality of sentinel ion intensity measurements. During acquisition, sentinel analysis is performed. In sentinel analysis, a plurality of ion intensity measurements is divided into two or more groups so that different groups of the two or more groups are measured separately. At least one sentinel ion intensity measurement in each group of the two or more groups is selected to identify a next group of the two or more groups to be measured. A measured retention time or an expected retention time of at least one non-sentinel ion intensity measurement of the two or more groups is corrected using the plurality of measured sentinel retention times.
Methods, systems, and computer program products for processing data from a mass spectrometer. A mass spectrum dataset with data in a first dimension, a second dimension, and a third dimension is obtained and divided into one or more slices across the first dimension. An intensity distribution is generated for each of the one or more slices across at least a second dimension and, for each intensity distribution generated, one or more features are located to produce a slice feature list. One or more slice feature lists are consolidated to produce a combined feature list across all slices.
In one aspect, a circuit for generating an asymmetric waveform for application to electrodes of a differential mobility mass (DMS) spectrometer is disclosed, which includes two digital waveform synthesizers for generating digital waveforms, which are converted to analog waveforms for application to electrodes of the DMS spectrometer. Analog feedback signals associated with the applied waveforms are digitized and a digital passband filter is employed to filter the digital feedback signals, which are then employed to determine a phase correction signal for application to at least one of the digital waveform synthesizers for maintaining a substantially constant phase difference between the waveforms generated by the digital waveform synthesizers.
In one aspect, a method of processing a mass spectrum is disclosed, which includes receiving a measured mass spectrum, determining an assessment score for the measured mass spectrum based on a comparison of a plurality of mass peaks in the measure mass spectrum with library mass peaks associated with a set of one or more library mass spectra of one or more known compounds, and analyzing the measured mass spectrum for identification of at least one compound associated with the measured mass spectrum only when the assessment score is greater than the threshold.
A method and system for sample processing, the system including an open port interface (OPI 104) comprising a removal conduit (125), the removal conduit comprising a removal conduit inlet and a removal conduit outlet and being configured to transport liquid between the (OPI 104) and a downstream device (120) via the removal conduit outlet, a fluid delivery pump (126) configured to provide a liquid flow to the OPI, a transfer capillary (302) in fluid communication with the removal conduit inlet, the transfer capillary (302) comprising a transfer capillary tip (312) located at a distance from the removal conduit inlet, and a distance adjusting device configured to adjust the distance between the transfer capillary tip and the removal conduit inlet.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
14.
QUANTIFICATION OF CHEMICAL SPECIES USING DATA INDEPENDENT ACQUISITION
A mass spectrum dataset including precursor ions and ion fragments is obtained, with each of the precursor ions associated with a location. An abundance of a target ion is quantified by identifying the location of the target ion and analyzing a range including the location to output a set of precursor ions associated with the range. The target ion is a subset of the set of precursor ions. A set of the ion fragments associated with the range is analyzed and a target relationship is determined. The target relationship is a precursor relationship between at least one of the ion fragments and the target ion. An intensity of the at least one of the ion fragments is determined and the target ion is quantified using the intensity of the at least one of the ion fragments and the target relationship.
A method and system for reducing data storage requirements in mass spectrometry data analysis, the method including ionizing a plurality of samples from a sample repository, and for at least one ionized sample of the plurality of samples, capturing a plurality of mass spectra over a period of time, generating an ion chromatogram based on the captured plurality of mass spectra, the ion chromatogram extending over the period of time, isolating an individual peak of the ion chromatogram, determining at least one of a starting point, an apex, and an ending point of the isolated individual peak, correlating the determined at least one of the starting point, the apex and the ending point to the ionized sample, and storing the correlated at least one of the starting point, the apex, the ending point and the ionized sample in a data repository.
In one aspect, a method for performing a plurality of MRM measurements is disclosed, which includes ionizing a sample to generate sample ions, selecting at least one precursor ion from among said sample ions. For the selected at least one precursor ion, performing at least two consecutive MRM measurements including a first and a subsequent, second consecutive MRM measurements associated with a plurality of fragment ions generated via dissociation of said at least one precursor ion, where one of the first and the second MRM measurement includes an ion emptying period and the other MRM measurement lacks an ion emptying period.
In one aspect, a method for transmitting ions in a mass spectrometer includes using rods arranged in a multipole configuration and extending from proximity of an inlet of an ion guide to proximity of an outlet of the ion guide to generate an electromagnetic field for radially confining ions received via the inlet into a space between said rods, using auxiliary electrodes positioned between the rods to generate an electric field in a first region of the ion guide for reducing radial confinement of a first subset of the received ions in said first region to inhibit passage thereof to a downstream second region of the ion guide while allowing a second subset of the ions to reach the downstream second region, and axially accelerating said second subset of the ions in said downstream second region to expedite exit of said second subset of the ions from the ion guide.
In one aspect, provided are methods for processing ions in mass spectrometry. The methods, in various embodiments, apply an RF field to the ion optical element upstream of a collision cell at a first amplitude to deliver a first population of transmitted sample ions into the collision cell and apply the RF field to the ion optical element at a second amplitude to deliver a second population of transmitted sample ions into the collision cell, and detect a first population of fragment ions associated with the first population of transmitted sample ions and detecting a second population of fragment ions associated with the second population of transmitted sample ions, to generate a mass spectrum based on the detected first and second populations of fragment ions.
In one aspect, a method of performing MRM mass spectrometry is disclosed, which includes identifying a plurality of precursor ions expected to arrive at an ion guide positioned upstream of a mass filter during a predefined time period subsequent to MRM analysis of a current precursor ion selected by the mass filter, determining a bandpass window for application to said ion guide based on a maximum m/z difference between an m/z of the current precursor ion and m/z ratios of said plurality of precursor ions to be analyzed in said subsequent time period, and configuring the ion guide to provide said bandpass window.
Disclosed herein are a source housing, systems, and methods of use thereof. The source housing of a mass spectrometer includes a liquid sample inlet and one or more heaters, where the one or more heaters include a substrate, where the substrate includes an inlet, an outlet, and one or more fluid channels extending from the inlet to the outlet, where the one or more fluid channels are configured to convey a fluid to desolvate a liquid sample, and where an inner surface of the one or more fluid channels is configured to transfer heat to the fluid.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
In one aspect, an ion guide is disclosed, which includes a plurality of rods arranged in a multipole configuration and configured for application of RF voltages thereto and a first set of auxiliary electrodes interposed between said plurality of rods and configured for application of at least one DC voltage thereto so as to generate a bandpass filter. The ion guide further includes a second set of auxiliary electrodes positioned upstream or downstream of said first set of auxiliary electrodes, where the second set of auxiliary electrodes is DC biased relative to the first set of auxiliary electrodes to generate an axial electric field for imparting energy to ions for overcoming a DC potential barrier caused by contamination of the first set of auxiliary electrodes by charged species.
An ion guide is provided for use in a mass spectrometer. The ion guide includes a plurality of electrodes arranged in a multipole configuration, and a plurality of auxiliary electrodes interposed between said plurality of electrodes, wherein a ratio of a field radius of the auxiliary electrodes relative to a field radius of the plurality of electrodes is greater than 1.1.
Methods and systems of determining sampling triggers for an analysis device, the methods and systems including obtaining a frequency of sampling triggers, a cycle time to acquire a single data point, a number of data points to be acquired for a single peak, and a baseline signal width of a single sampling trigger peak, determining a desired number of sampling triggers to be performed and a delay time between sampling events based on the frequency of sampling triggers, the cycle time, the number of data points to be acquired for the single peak, and the baseline signal width of the single sampling trigger peak, and performing a measurement of a sample by executing the determined desired number of sampling triggers from the sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/02 - Particle spectrometers or separator tubes Details
Disclosed are methods, systems, apparatus, devices, and other implementations, including a method of operating a mass spectrometry system that includes applying a first AC voltage pulse cycle, from a plurality of AC voltage pulses each having a varying amplitude defined by a waveform, to at least one electrode of a mass spectrometer, with the waveform including a ramp-down portion. The method further includes obtaining an amplitude value of a resultant voltage signal produced from the first voltage pulse during a stabilized portion of the waveform prior to a beginning of the ramp-down portion, comparing the amplitude value with a predefined amplitude setpoint, and adjusting the waveform for a second AC voltage pulse following the first AC voltage pulse based on a difference between said amplitude value and said predefined amplitude setpoint.
In one aspect, a method of processing mass spectrometric data is disclosed, which includes using a multi-channel ion detection system comprising n multiple independent channels to receive ions, wherein each of the channels generates an independent output signal associated with an ion detection period, identifying an ion detection event as corresponding to a single ion detection based on a predefined pattern of the output signals associated with the ion detection period, where the output signals are generated substantially concurrently.
In one aspect, a mass calibration method for use in mass spectrometry is disclosed, which includes generating a plurality of mass spectra corresponding to at least two calibrant ions having different m/z ratios for a plurality of different intensities of said at least two calibrant ions, using the mass spectra to determine an m/z ratio for each of said calibrant ions and for each of said ion intensities. For each of said calibrant ions and each of said ion intensities, a shift of said determined m/z ratio is determined relative to the m/z ratio of that calibrant ion and the m/z shifts are used to generate an intensity-dependent correction factor for correcting a measured m/z ratio of a target ion associated with an analyte in a sample.
A method of performing mass spectrometry can include: for each of a plurality of standard samples containing different concentrations of a target analyte, integrating at least one ion detection peak of the target analyte over a time window defined by an expected delivery time and an initial delivery time window width corresponding to delivery of the target analyte via a delivery device to an ion source of a mass spectrometer so as to obtain integrated peak areas for the standard samples. A calibration curve corresponding to the integrated peak areas as a function of the concentration of the target analyte can be used to identify at least a subset of the standard samples that exhibit an expected variation of their peak areas as a function of target analyte concentration. Sample delivery times of those standard samples can be used to obtain a calibrated sample delivery time and associated window width.
A source housing for a mass spectrometer includes a first opening configured to couple with an off-axis probe substantially orthogonal to a central axis of an inlet to the mass spectrometer and a second opening configured to couple with an on-axis probe substantially coincident with the central axis, where the off-axis probe and the on-axis probe are in fluid communication with the inlet to the mass spectrometer and where the on-axis probe is configured to direct a fluid at an angle to the central axis. A system includes the source housing and a mass spectrometer. A method includes using the source housing or the system; flowing a calibrant fluid through the on-axis probe; and generating a calibration mass scale.
A method and system for investigating and analyzing data from a mass spectrometer, the system including a spectral database, a count service for receiving scan data generated by the mass spectrometer and identifying a number of spectra in the data, a scaling service for receiving the scan data generated by the mass spectrometer, receiving the number of spectra from the count service, and initiating a plurality of query services, each query service of the plurality of query services corresponding to at least one spectra of the number of spectra and for querying the spectral database with the corresponding at least one spectra and returning a match between the corresponding at least one spectra and at least one known spectra from the spectral database, and a results service for retrieving each match, and formatting each match into an output data structure.
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.
Systems and methods for calibrating compound markers in mass spectrometry (MS) detection are disclosed. The systems and methods automatically identify a plurality of isoelectric point (pI) markers in a sample, generate a calibration curve correlating pI with time, and convert the time scale to a pI scale. Based on the established correlation between time and pI, the system further associates pI with intensity values, enabling presentation to an operator for analysis.
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 method of identifying mass spectrum peaks for quantitative analysis includes receiving a first mass spectrum for a first sample and identifying a plurality of peaks in the first mass spectrum. The first sample includes a compound of interest and a matrix, and each peak of the plurality of peaks corresponds to a different mass to charge ratio. The method further includes generating a plurality of first scores, a plurality of second scores, and a plurality of combined scores. The method yet further includes determining a first candidate quantification peak of the plurality of peaks by identifying a first peak of the plurality of peaks having a greatest combined score of the plurality of combined scores and outputting, via a user interface, an indication of a mass to charge ratio of the first candidate quantification peak.
In one aspect, a method for compound identification using mass spectrometry is disclosed, which includes passing a plurality of different precursor ions through an ion dissociation device to cause fragmentation thereof to generate a plurality of fragment ions, acquiring one or more fragment ion signals associated with said plurality of fragment ions, and assigning to at least one of the fragment ion signals an uncertainty corresponding to at least one ion attribute such that the assigned uncertainty is independent of a respective uncertainty assigned to any other one of said fragment ion signals.
In one aspect, an apparatus for use in a mass spectrometer is disclosed, which comprises an ion reaction device, which includes an ion dissociation unit (e.g., an ion-electron interaction unit) that can receive a plurality of precursor ions and cause their dissociation to generate a plurality of product ions, and a linear ion trap that can receive the product ions and isolate a target product ion of interest for mass analysis. The linear ion trap is positioned in a magnetic field and includes a set of quadrupole rods formed of a paramagnetic material to substantially shield the space between the quadrupole rods from the magnetic field, thereby reducing and preferably eliminating the interference of the magnetic field with the process of isolating the target product ion of interest.
Systems and methods described herein utilize a multipole ion guide that can receive ions from an ion source for transmission to downstream mass analyzers while preventing unwanted/interfering/contaminating ions from being transmitted into the high vacuum changes of mass spectrometry systems. In various aspects, RF and/or DC signals can be provided to auxiliary electrodes interposed within a quadrupole rod set so as to control or manipulate the transmission of ions from the multiple ion guide.
A mass spectrometry system comprises a detector configured to detect a plurality of signals corresponding to a plurality of compounds in a sample; and an analyzer module configured to receiving, from the detector, signal data corresponding to the plurality of signals; performing an analysis of a signal of the plurality of signals corresponding to a compound of the plurality of compounds to detect an onset of an increase in the signal, wherein the analysis is different from comparing an intensity of the signal with a threshold; and increasing a dwell time for the compound in response to detecting the onset. In some embodiments, the analyzer module is further configured to determine an onset probability as the probability of occurrence for the onset; and utilize the onset probability in detecting the onset.
In one aspect, a method of performing mass spectrometry is disclosed, which includes ionizing a sample received from an analyte-delivery device to generate one or more precursor ions, acquiring a precursor ion signal associated with said one or more precursor ions, passing the plurality of precursor ions through a mass filter as an m/z window of the mass filter is scanned so as to select different subsets of the precursor ions having m/z values within different m/z ranges of the scanning m/z window, generating one or more derivative ions of said subsets of the precursor ions exiting the mass filter, acquiring at least one derivative ion signal associated with said one or more derivative ions, and deconvolving the at least one precursor ion signal utilizing the at least one precursor ion signal and the at least one derivative ion signal, to produce a deconvolved precursor ion signal.
A method of determining a confidence measure of precursor inference in mass spectrum data. The method includes evaluating the response profile using response profile metrics and reporting the confidence measure of the precursor inference using the response profile and the evaluating of the response profile. Also a method of detecting conflicting relationships between precursors including filtering an intensity at at least one position across the scanning ion transmission window dimension. Another method a method of detecting conflicting relationships between precursors includes generating, based on an encoding, a trace of the scanning ion transmission window dimension wherein each sum is substituted with a binary metric for presence of the at least one unique product ion in each window. Further a method of identifying a precursor m/z including determining an intercept between the rising linear function and the falling linear function, and identifying the precursor m/z using the intercept.
A system and method are provided for controlling the temperature gradient along a differential mobility spectrometer having a differential mobility spectrometer having an inlet and an outlet, wherein the inlet is configured to receive ions transported from an ion source by a transport gas. The differential mobility spectrometer has an internal operating pressure, electrodes, and at least one voltage source for providing DC and RF voltages to the electrodes for separating ions that are transported from the inlet to the outlet. A gas port is provided near the outlet for introducing a throttle gas to control the flow rate of the transport gas through the differential mobility spectrometer and thereby adjust the ion residence time. A heater is provided for controlling the temperature of the throttle gas to minimize the temperature gradient between the inlet and outlet of the differential mobility spectrometer.
A 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.
A first product ion mass spectrum of a nucleic acid analyzed using a CID method is received. Also, a second product ion mass spectrum of the nucleic acid analyzed using a radical-induced dissociation method is received. Peak m/z values of the first spectrum, peak m/z values of the second spectrum, and an m/z value of a precursor ion of the nucleic acid are converted to a single charge. A peak m/z value of the first spectrum is determined that differs from a peak m/z value of the second spectrum by a mass value of a structure within the nucleic acid the radical-induced dissociation method is known to not be able to dissociate and the CID method is known to be able to dissociate. The structure includes a phosphorus atom and an optionally substituted 5-membered ring containing an oxygen.
A precursor ion transmission window is moved in overlapping steps across a precursor ion mass range. The precursor ions transmitted at each overlapping step by the mass filter are fragmented or transmitted. Intensities or counts are detected for each of the one or more resulting product ions or precursor ions for each overlapping window that form mass spectrum data for each overlapping window. Each unique product ion detected is encoded in real-time during data acquisition. This encoding includes sums of counts or intensities of each unique ion detected the overlapping windows and positions of the windows associated with each sum. The encoding for each unique ion is stored in a memory device rather than the mass spectral data. A deblurring algorithm or numerical method is used to determine a precursor ion of each unique ion from the encoded data.
In one aspect, a system is disclosed, which includes at least one capillary configured for receiving a sample, a first light source for generating a first light, a second light source for generating a second light, an optical element for receiving and directing the first and the second light into the at least one capillary, an absorbance detector, and a shutter positioned between the absorbance detector and the at least one capillary. The shutter is movable between an undeployed position and a deployed position. In the undeployed position, at least a portion of the first light passing through the at least one capillary can be received by the absorbance detector. In the deployed position, the shutter inhibits back reflection of the light exiting the at least one capillary to the at least one capillary.
In one aspect, a dual-mode capillary electrophoresis system is disclosed, which comprises a plurality of capillaries for receiving a plurality of samples, a UV radiation source for generating UV radiation along a first path, a laser light source for generating laser radiation along a second path, and a galvanometric mirror configured to receive radiation from said UV radiation source along said first path and to receive light from said laser light source along said second path, and to direct said received UV radiation and said laser light onto a common optical path, said galvanometric mirror further being configured to scan said UV radiation and said laser light sequentially over said plurality of capillaries. The system can further include detectors for detecting the UV radiation as well as fluorescent radiation emitted by the samples in response to laser excitation.
Devices and methods are described for assigning charge state to detected ions from a mass analysis instrument. In one of the methods, the charge state may be assigned, for instance, by evaluation a detector response signal including information related to individual ion responses generated by an ion detector for each ion arrival event captured by the detector. The detector response signal may then be evaluated in combination with one or more additional features corresponding to the ion arrival event to assign a charge state for that ion arrival event.
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.
In one aspect, a method of performing mass spectrometry is disclosed, which includes acquiring mass detection signals generated by an ion detector during an ion extraction event in a time-of-flight (ToF) mass analyzer in response to incidence of ions thereon, and applying an adjustable gain to the mass detection signals, wherein the step of applying the adjustable gain to the mass detection signals is performed dynamically based on m/z regions associated with said mass detection signals.
At least one molecule is ionized and a mass spectrometer mass analyzes an m/z range, producing an m/z mass spectrum. A range of N sequential charge states is received. A copy of the m/z mass spectrum is created for each of the N charge states, producing N m/z spectra. Each spectrum of the N spectra is converted to a neutral mass mass spectrum using a different charge state of the N charge states, producing N neutral mass mass spectra. The N neutral mass mass spectra are aligned by neutral mass. When two or more spectra of the N neutral mass mass spectra corresponding to two or more different and sequential charge states include a neutral mass peak above a predetermined intensity threshold at a neutral mass value within a predetermined neutral mass tolerance, the neutral mass value is identified as a neutral mass of the at least one molecule.
A 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.
H01J 49/02 - Particle spectrometers or separator tubes Details
H01F 1/03 - Magnets or magnetic bodies characterised by the magnetic materials thereforSelection of materials for their magnetic properties of inorganic materials characterised by their coercivity
51.
Dissociation Method and System of Deprotonated Peptides with Fragile Moieties
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.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
52.
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.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
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 locksArrangements for external adjustment of electron- or ion-optical components
H01J 49/00 - Particle spectrometers or separator tubes
H01J 49/42 - Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
54.
ASSEMBLIES COMPRISING MULTIPLE ION GUIDES, AND EXTRACTION TOOLS THEREFOR
Disclosed are methods, systems, apparatus, devices, and other implementations, that include a mass spectrometry (MS) system including a casing defining a cavity, a removable ion guide sub-assembly configured to be disposed within the cavity and including at least two mechanically coupled ion guides each defining a separate chamber at different pressures when engaged with the casing, with the removable ion guide sub-assembly including one or more insertion alignment elements to rotationally and/or angularly align the ion guide assembly for insertion into the cavity, and one or more receiving alignment elements disposed in the cavity and configured to receive a corresponding one of the one or more insertion alignment elements. The ion guide sub-assembly is configured to be axially removable from the casing with the at least two ion guides remaining mechanically coupled to each other and retaining the casing upon removal of the ion-guide sub-assembly from the casing.
Disclosed are methods, systems, apparatus, devices, and other implementations, that include a mass spectrometry (MS) system including a casing defining a cavity, a removable ion guide sub-assembly configured to be disposed within the cavity and including at least two mechanically coupled ion guides each defining a separate chamber at different pressures when engaged with the casing, with the removable ion guide sub-assembly including one or more insertion alignment elements to rotationally and/or angularly align the ion guide assembly for insertion into the cavity, and one or more receiving alignment elements disposed in the cavity and configured to receive a corresponding one of the one or more insertion alignment elements. The ion guide sub-assembly is configured to be axially removable from the casing with the at least two ion guides remaining mechanically coupled to each other and retaining the casing upon removal of the ion-guide sub-assembly from the casing.
Methods and apparatus for processing fluids are described in various aspects, a fluid processing system may include a magnetic assembly that includes a plurality of magnetic structures configured to generate a magnetic field gradient within a fluid container. The magnetic structures may be formed as a plurality of electromagnets configured to be individually actuated by a controller. Each of the electromagnets may generate a magnetic field within the fluid container. The electromagnets may be differentially actuated to create a magnetic field gradient within the fluid container to agitate, mix, or otherwise influence magnetic particles disposed within the fluid container. Activation of the electromagnets of an electromagnetic structure may generate a magnetic field gradient that influences magnetic particles in an x-y direction. In addition, activation of the electromagnets of a plurality of electromagnetic structures may generate magnetic field gradients that influences magnetic particles in an x-y direction and z-direction.
B01F 33/451 - Magnetic mixersMixers with magnetically driven stirrers wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
B03C 1/01 - Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
B03C 1/033 - Component partsAuxiliary operations characterised by the magnetic circuit
B03C 1/30 - Combinations with other devices, not otherwise provided for
G01N 1/38 - Diluting, dispersing or mixing samples
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
57.
Resonant CID for Sequencing of Oligonucleotides in Mass Spectrometry
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 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.
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.
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.
In one aspect, a method of positioning an open end of an open port interface (OPI) relative to a sample surface to be analyzed by mass spectrometry is disclosed. The OPI includes a liquid delivery conduit for delivering a liquid to the open end of the OPI and a liquid exhaust conduit for removing liquid from the open end of the OPI. The method includes establishing a fluid flow along a path extending from the liquid delivery conduit to the open end of the OPI, monitoring fluid pressure at one or more locations along the fluid flow path and adjusting a position of the open end of the OPI relative to the sample surface based on the monitored fluid pressure. The fluid can be a gas or a liquid. Further, the sample surface can be a liquid surface or a solid surface.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
62.
Reduction of Internal Fragmentation in Electron Activated Dissociation Devices and Methods
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.
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 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 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.
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 49/00 - Particle spectrometers or separator tubes
G01F 25/00 - Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
67.
BEAD CONSUMABLES AND LAB TECHNIQUES FOR SAMPLE PREPARATION
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.
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 49/00 - Particle spectrometers or separator tubes
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
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.
Systems and methods are disclosed for dynamically switching an ion guide and a TOF mass analyzer between concentrating or not concentrating ions in a targeted acquisition. Product ions are ejected from the ion guide into the TOF mass analyzer and the intensity of a known product ion is measured at two or more time steps. The ion guide initially ejects product ions using a sequential or Zeno pulsing mode that concentrates product ions with different m/z values within the TOF mass analyzer at the same time. If the intensity of the product ion is increasing and greater than a threshold intensity, the ion guide switches to a continuous or normal pulsing mode that does not concentrate ions with different m/z values in the TOF mass analyzer at the same time. Similarly, if the intensity decreases below a threshold in continuous mode, the ion guide switches back to sequential mode.
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.
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, and 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 the first and second portions of the ions exiting the ion routing device.
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.
Disclosed are methods, systems, apparatus, devices, and other implementations, that includes a method of operating a mass spectrometry (MS) system to analyze a sample, including that includes obtaining compound analysis data for multiple compounds of interest, obtaining compound detectability data for each of the multiple compounds of interest over a plurality of sets of operating parameters of the MS system, determining, based on the detectability data and evaluation conditions, at least one set of optimal operating parameter values for one or more operating parameters of the MS system to analyze the multiple compounds of interest, and storing the optimal operating parameter values corresponding to the sample. In some embodiments, the method can further include retrieving the stored optimal operating parameter values, controllably adjusting the one or more operating parameters of the MS system according to the optimal operating parameter values, and analyzing the sample using the determined optimal operating parameters.
In one aspect, a method for identifying an operating condition of a mass spectrometer is disclosed, which includes measuring at least one transit time associated with passage of at least one target ion through at least one ion optic positioned in an ion path extending from an orifice of the mass spectrometer to an ion detector of thereof, and evaluating an operating condition associated with said at least one optic based on said at least one transit time.
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.
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 a method for determining if internal product ions are used to provide evidence for a bond of a polymeric compound, two or more theoretical product ions resulting from the cleavage of at least one bond of the sequence of the compound are calculated. A product ion spectrum is searched for the theoretical product ions. The theoretical internal product ions are calculated and the spectrum is searched for the theoretical internal product ions if one or more theoretical product ions of the theoretical product ions match a product ion of the spectrum. In another embodiment, a mass tolerance is automatically determined for comparing theoretical mass peaks to mass peaks of an experimental mass spectrum using the subset of product ions most likely to be found for the fragmentation method used. In another embodiment, charge filtering is used to find an experimental product ion of a compound.
A mass spectrometry system comprises an ion mobility separation device (IMSD) configured to receive a plurality of ions, and to perform an ejection of a set of ions of the plurality of ions by adjusting a set of mobility control parameters to a set of mobility parameter values; a mass analyzer configured to receive the set of ions, to perform a detection of the set of ions, and to generate a set of detection signals corresponding to the detection of the set of ions; and a controller configured to receive data including the set of mobility control parameter values and the set of detection signals, and to perform a mapping of the set of mobility control parameter values and the set of detection signals.
Systems and methods described herein can provide for “top down” mass spectrometric analysis of proteins or peptides in a sample using ExD, in some aspects via direct infusion of the sample to the ion source without on-line LC separation, while deconvoluting the ambiguity in the ExD spectra generated by impure samples. For example, methods and systems in accordance with various aspects of the present teachings can utilize patterns in charge-reduced species following ExD to correlate the ExD fragments with their precursor ions in order to more confidently identify the precursor ion from which the detected product ions originated.
Pole electrodes are disclosed for use in an ion reaction apparatus, e.g., an electron induced dissociation cell, to reduce fouling due to polymer build-up and increase the useful lifetime of such electrodes. To reduce fouling, the novel pole electrode designs include a Xshaped aperture in lieu of the conventional central circular aperture. The pole electrodes are particularly useful in systems having a plurality of branched electrodes defining a first axis for controlled passage of charged ions and a transverse axis for passage of an electron beam. The pole electrodes are adapted for disposition between an electron source and the branched electrodes to provide an aperture for passage of an electron beam while also impeding escape of ions and reaction products from the apparatus. The X-shaped aperture eliminates or reduces the portion of the pole electrode surface that is most prone to fouling by polymeric build-up.
A user interface is provided for displaying in the same panel and at the same time a sequence of a polymeric compound and multiple pieces of spectral evidence from an experimental product ion spectrum that are linked to a bond of the sequence. The sequence and the spectrum of the polymeric compound are received, where one or more product ions of the spectrum are assigned to at least one bond of the sequence. The sequence is displayed in a panel of a display device with at least one interactive icon between at least two elements of the sequence representing the bond. When the interactive icon is selected, at least two different spectral plots of the spectrum showing two different product ions of the spectrum that support a cleavage of the bond are displayed in the same panel of the sequence and at the same time as the sequence.
Known mass spectral data of a library of spectra corresponding to known compounds or known mass spectral data determined from a database of known compounds are compressed using a neural network encoder, producing a group of corresponding compressed known representations of known mass spectral data. Experimental mass spectral data of an experimental mass spectrum is compressed using the neural network encoder, producing a compressed experimental representation of the experimental mass spectral data. The experimental representation is compared to the group of known representations and each comparison is scored. At least one comparison with a score above a predetermined score threshold is selected. A known compound is determined from the selected at least one comparison. The known compound is identified as a compound of the experimental spectrum.
In one aspect, a method of operating a high-throughput mass analysis device is disclosed, which includes sampling an unseparated sample from at least one sample holding element during a sampling interval for introduction of the sample into an ion source for ionizing the sample to generate a plurality of ions associated with at least one target analyte (herein also referred to as a target compound), if any, in said sample for delivery to an ion mobility separation device, and activating at least one control parameter of said ion mobility separation device for detection of said ions based on timing of the sampling of the sample and at least one identifier associated with the sample.
H01J 49/04 - Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locksArrangements for external adjustment of electron- or ion-optical components
86.
System and Methods for High Throughput Mass Spectrometry
System and method for high-throughput mass spectrometry are disclosed. In some embodiments the system comprises a sample introduction device, an ion source, an ion mobility separation device, a mass analyzer and a controller adapted to receive certain parameters from the IMSD and determine a mass range for more efficient operation of the mass analyzer. In some embodiments, the controller is adapted to provide data to, and receive data from other components to make the operation of the IMSD and the mass analyzer more efficient.
Systems and methods of quantifying a target analyte including two or more chromatographic peaks in an output from a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The method includes obtaining a set of output data from the LC-MS/MS for a sample including the target analyte, integrating each of the two or more chromatographic peaks associated with the target analyte to yield an area for each of the two or more chromatographic peaks, and summing the area of each of the two or more chromatographic peaks associated with the target analyte based on the integrating. The method further includes generating a calibration curve for the target analyte as a regression curve using the summed area of the two or more chromatographic peaks associated with the target analyte and determining a concentration of the target analyte in the sample using the calibration curve.
In various aspects, provided are methods of stabilizing the gain of an optical ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ultraviolet photons thereon are received by the scintillator to generate photons, which include configuring the MCP for generating a plurality of electrons in response to incidence of ultraviolet photons on the MCP, exposing the MCP to a beam of ultraviolet photons to generate a plurality of electrons for irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of one or more molecules adsorbed on the scintillator's input surface, and maintaining such irradiation over a temporal period until the optical ion detector exhibits a substantially stable gain profile.
In one aspect, a method of stabilizing the gain of an ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ions thereon are received by the scintillator to generate photons is disclosed, which includes configuring the MCP for generating a plurality of electrons in response to incidence of ions on the MCP, exposing the MCP to an ion beam so as to generate a plurality of electrons irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of one or more gases adsorbed on the scintillator's input surface, and monitoring a gain of the ion detector during exposure of the MCP to the ion beam over a temporal period until the ion detector exhibits a substantially stable gain profile.
Disclosed are systems, methods, and other implementations, including a method of operating a time-of-flight (TOF) mass analyzer, that includes introducing a plurality of ions into the mass analyzer, applying a plurality of voltage pulses to a pusher electrode of the mass analyzer to direct at least a portion of the plurality of ions into an acceleration region of the mass analyzer to generate accelerated ions, using an ion detector to detect the accelerated ions after passage thereof through a field-free region so as to generate ion detection data during a data acquisition period, and adjusting a pulse duration of the voltage pulses during the data acquisition period such that ion detection data is acquired during the data acquisition period at two or more different voltage pulse durations.
Disclosed are assemblies, systems, methods, and other implementations, including an ion lens assembly that includes one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer. The lens assembly includes a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.
Systems and methods for determining a molecular structure include obtaining mass spectrum data for an unknown parent ion. The mass spectrum data is recorded at each collision energy of a series of collision energies and includes an abundance of one or more substructures of the unknown parent ion. The molecular structure of the unknown parent ion is determined by composing the mass spectrum data into a fragmentation profile and embedding the fragmentation profile into a reduced dimension profile. The reduced dimension profile is mapped into a fragmentation space. One or more proximate molecules in the fragmentation space are identified using the mapping and a candidate for the parent ion is identified using the one or more proximate molecules.
In one aspect, a method of performing mass spectrometry is disclosed, which includes introducing a plurality of samples of a specimen into an ion source of a mass spectrometer at a sample introduction rate as fast as about 0.16 seconds per sample up to 60 seconds per sample to ionize at least a molecule (herein also referred to as an analyte) and an internal standard associated with the molecule in each sample so as to generate precursor ions corresponding to the molecule and its associated internal standard. For each sample, the following steps are performed: using a mass filter of the mass spectrometer to isolate at least the precursor ions, dissociating the isolated precursor ions to generate product ions, and generating a mass spectrum of the plurality of the product ions. The mass spectrum of the product ions can be utilized to quantify the target analyte, e.g., to determine the concentration of the target analyte in the specimen under study.
Methods and systems for performing differential mobility spectrometry-MS/MS are provided herein. In various aspects, methods and systems described herein can determine corresponding MS data from differential mobility spectrometry-MS/MS data obtained at each of a plurality of SV-COV combinations applied to the differential mobility spectrometry device, without requiring a separate differential mobility spectrometry-MS run, for example, each time the COV-combination is adjusted. Furthermore, the population of analyte ions, which are present in each of the plurality of product ion scans obtained at different SV-COV combinations, can be identified.
A mount assembly for holding a microchannel plate in an ion detector includes an input side clamping plate including a plurality of input side pads; and an output side clamping plate including a plurality of output side pads, wherein, when assembled, the input side clamping plate and the output side clamping plate are configured to allow positioning between the input side clamping plate and the output side clamping plate the microchannel plate having a plurality of microchannels each having an input side opening and an opposed output side opening; hold the microchannel plate; and position the subset of the input side pads and the subset of the output side pads in a staggered configuration such that when a microchannel of a plurality of microchannels is obstructed in a first opening, a second opening of the microchannel opposing the first opening is unobstructed.
In one aspect, a time-of-flight (TOF) mass analyzer is disclosed, which includes an input for receiving a plurality of ions (herein also referred to as "primary ions"), an ion acceleration region through which the received ions are accelerated, a push electrode for directing the received ions into the ion acceleration region, and a field-free ion drift region for receiving said accelerated ions, said field-free ion drift region having an ion detector positioned at a distal end thereof. At least one magnet is positioned relative to the electric field-free region so as to establish a magnetic field in at least a portion of the electric field-free region for deflecting electrons entering the electric field-free region so as to inhibit the electrons from reaching the ion detector.
A method for correcting detection bias includes detecting spectral data of a standard sample, the standard sample comprising two or more analytes. Each analyte has a known quantity, and the spectral data of the standard sample includes a peak for each of the two or more analytes. The method further includes determining a bias parameter for each of the two or more analytes based on the peak for each of the two or more analytes of the standard sample.
A method for scoring a bond of a polymeric compound of a sample from evidence determined from an experimental a product ion spectrum measured from the sample. At least one experimental product ion spectrum is received for the polymeric compound. One or more product ions of the at least one spectrum are assigned to at least one bond of the polymeric compound. At least two different types bond level scores are calculated for the at least one bond from the assigned matching one or more product ions. The at least two different bond level scores are combined, producing a combined bond score for the at least one bond. Additionally, a combined bond score is found for each bond of the polymeric compound and the combined bond scores are calculated as a function of the position of the bonds in the polymeric compound, producing a score profile for the polymeric compound.
A method for dissociating an oligonucleotide is disclosed. A plurality of precursor ions of one or more oligonucleotides is loaded into an ion trap. Negative radical-induced dissociation is applied to the plurality of precursor ions in the ion trap during a first time period, producing charge-reduced ions. Resonant CID is applied in the ion trap during a second time period to dissociate the charge-reduced ions. A pause without any dissociation in the ion trap is performed during a third time period to cool ions produced from the previous resonant CID or again negative radical-induced dissociation is applied in the ion trap during the third time period to again produce charge-reduced ions from the plurality of precursor ions while at a same time allowing ions produced from the previous resonant CID to be cooled. The last two steps are repeated one or more times.
patents
