Abstract: Methods and systems for conducting affinity selection by mass spectrometry in high throughput assays are disclosed herein. The methods can comprise identifying a set of hit com-pounds having a selected affinity to a binding target immobilized onto a magnetic particle. Methods can comprise forming an assay mixture within an assay vessel comprising a plurality of drug candidates and a binding target immobilized onto a magnetic particle. Methods also can comprise preparing at least a portion of the assay mixture for mass analysis transferring a sample containing the set of hit compounds to an open port sampling interface of a mass spectrometer.

Abstract: A method of ejecting a plurality of samples from a well plate includes receiving a first sample intensity prediction associated with a first sample in a first well of the well plate. A second sample intensity prediction associated with a second sample in a second well is also received. The second sample intensity prediction is less than the first sample intensity prediction. An ejection time delay value for a subsequent analysis of the first sample and the second sample is determined, based at least in part on the second sample intensity prediction. Thereafter, the first sample is acoustically ejected from the first well, and the second sample is acoustically ejected from the second well.

Abstract: In some embodiments, a method for optimizing performance of a mass spectrometer comprises using an ion source to generate ions, collisionally cooling the ions within an ion guide, directing said ions from the ion guide through at least one ion lens to a downstream mass analyzer, ramping a DC voltage applied to the ion lens, performing a mass analysis of the ions within the mass analyzer while the DC voltage applied to the ion lens is ramped, estimating performance of the mass spectrometer by measuring one or more characteristics of at least one of an ion signal and the voltage ramp, and adjusting a DC voltage applied to said at least one lens element based on said measured one or more characteristics of at least one of the ion signal and the voltage ramp so as to enhance performance of the mass spectrometer.

Abstract: Methods and systems for FTMS-based analysis having an improved duty cycle relative to conventional FTMS techniques are provided herein. In various aspects, the methods and systems described herein operate on a continuous ion beam, thereby eliminating the relatively long duration trapping and cooling steps associated with Penning traps or orbitraps of conventional FTMS systems, as well as provide increased resolving power by sequentially interrogating the continuous ion beam under different radially-confining field conditions.

Abstract: The teachings herein provide for a method of analyzing testosterone using mass spectrometry. The method entails combining in a vial or well, a tagging reagent that is reactive with testosterone, an aqueous precipitation agent that precipitate proteins from solution, and an internal standard solution, the internal standard solution containing a known concentration of an isotopically enriched testosterone and then adding to the vial or well, a sample containing or suspected to contain testosterone. The vial can then be mixed to cause simultaneous precipitation of proteins and reaction of any testosterone present with the tagging reagent to form a mixture of a precipitate and a liquid solution. The liquid solution can then be separated from any precipitate and then analyzed for testosterone using liquid chromatography tandem mass spectrometry.

Abstract: A method is disclosed for calculating and recalculating protein confidence values by recalculating peptide confidence values in proteomic analysis. A plurality of scans are performed of a sample that is proteolytically digested into surrogate peptide analytes. A plurality of spectra are obtained, and a plurality of peptides are identified. A protein database is searched for proteins matching peptides from the plurality of peptides. Peptide confidence values are determined for the set of peptides. A protein confidence value is calculated for each protein in the set of proteins. A protein from the set of proteins with a largest protein confidence value is selected, the largest protein confidence value for the protein is saved, the protein from the set of proteins is removed, and peptides corresponding to the protein is removed from the set of peptides. The protein confidence value is recalculated for each protein in the set of proteins.

Abstract: The technology relates to a system for improved mass analysis operation by proactively identifying contamination. The system includes a mass analysis instrument comprising mass analysis hardware components, a processor, and memory storing instructions that, when executed by the processor, cause the system to perform a set of operations. The set of operations include performing, by the mass analysis instrument at a first time, a predefined series of operational tests to produce first mass analysis results for a calibrant; performing, by the mass analysis instrument at a second time, the predefined series of operational tests to produce second mass analysis results for the calibrant; determining an analysis difference between the first mass analysis results and the second mass analysis results; and based on a magnitude of the analysis difference, generating at least one of a contamination indicator or a degradation indicator.

Abstract: A method for processing a fluid sample containing a first target analyte includes introducing a first batch of magnetic particles into a fluid conduit, the fluid conduit having a first open end, a second open end, and a first electromagnetic trap between the first open end and the second open end. The magnetic particles include a first receptor to bind the first target analyte in the fluid sample. The method further includes activating the first electromagnetic trap to trap and mix the magnetic particles within the first electromagnetic trap. A flow of the fluid sample is introduced through the fluid conduit from the first open end to the second open end. Deactivating first electromagnetic trap releases the magnetic particles from the first electromagnetic trap.

Abstract: Methods and systems for generating verified mass analysis results for a sample. An example method may include acquiring process data for performing a mass analysis test on the sample; performing, by a mass analysis instrument, the mass analysis test based on the acquired process data to generate mass analysis results for the sample; recording machine-level characteristics for the mass analysis instrument during the mass analysis test; generating verification data that includes at least a portion of the recorded machine-level characteristics; generating a secure analytical data file that includes the verification data and at least a portion of the mass analysis results; and transmitting the secure analytical data file.

Abstract: An electrospray ionization emitter according to various aspects described herein can include an emitter body formed using fused silica. The emitter body can comprise a fluid conduit segment that includes a liquid connection end that has been coated with polyetheretherketone (PEEK) on at least one portion thereof. The liquid connection end can have a first outer diameter that is configured to be connected to a sample source to receive a sample liquid for ionization therefrom. The emitter body can further comprise an ionization discharge segment that is fluidly connected to the fluid conduit segment. The ionization discharge segment can have an ionization discharge end that is coated with a conductive material on at least one portion thereof and configured to have a second outer diameter that allows ionization of the liquid sample.

Abstract: Intensity measurements made by electron multiplier and image-charge detectors are proportional to charge state. These intensities are used to separate detected ions into different data sets and create mass spectra from the different data sets. Ion measurements are separated by charge state using (i) a single electron multiplier detector, (ii) a single image-charge detector, or (iii) multiple electron multiplier ADC detectors. Using (i), the intensity of a peak calculated from each measured pulse is compared to predetermined intensity ranges and each peak is stored in a corresponding data set. Using (ii), each measured transient time-domain signal is converted to frequency-domain peaks, the intensity of each frequency-domain peak is compared to predetermined intensity ranges, and each peak is stored in a corresponding data set. Using (iii), each detector is adapted to measure a predetermined intensity range and store calculated peaks from the measured pulses in corresponding data sets.

Abstract: A well tray includes a base including an upper surface, a lower surface and at least one edge surface connecting the upper surface to the lower surface. The at least one edge surface defines a slot. The slot is in communication with a magnet receiver at least partially defined between the upper surface and the lower surface. The magnet receiver is configured to slidably receive a removable magnet. The tray includes a plurality of wells disposed on an upper surface of the base.

Abstract: 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.

Abstract: Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of desorption solvent within a sampling probe fluidly coupled to an ion source can be selectively controlled such that one or more analyte species can be desorbed from a sample substrate inserted within the sampling probe within a decreased volume of desorption solvent for subsequently delivery to the ion source. In various aspects, sensitivity can be increased due to higher desorption efficiency (e.g., due to increased desorption time) and/or decreased dilution of the desorbed analytes.

Abstract: In one aspect, a method of processing ions in a mass spectrometer is disclosed, which comprises trapping a plurality of ions having different mass-to-charge (m/z) ratios in a collision cell, releasing said ions from the collision cell in a descending order in m/z ratio, and receiving the ions in a mass analyzer having a plurality of rods to at least one of which an RF voltage is applied, where the RF voltage is varied from a first value to a lower second value as the released ions are received by the mass analyzer.

Abstract: In one aspect, a mass analyzer is disclosed, which comprises a quadrupole having an input end for receiving ions and an output end through which ions can exit the quadrupole, said quadrupole having a plurality of rods to at least some of which an RF voltage can be applied for generating a quadrupolar field for causing radial confinement of the ions as they propagate through the quadrupole and further generating fringing fields in proximity of said output end. The mass analyzer further includes at least a voltage source for applying a voltage pulse to at least one of said rods so as to excite radial oscillations of at least a portion of the ions passing through the quadrupole at secular frequencies thereof, where the radially-excited ions interact with the fringing fields as they exit the quadrupole such that their radial oscillations are converted into axial oscillations.

Abstract: Methods and apparatus are disclosed for reducing ion reflections between multipole segments in a mass spectrometer by matching the effective potential between the two segments. Mass spectrometers having at least two multipole segments separated from each other along a longitudinal axis of the mass spectrometer such that a boundary region exists through which ions are drawn from an upstream segment to a downstream segment, and wherein each multipole segment further includes a set of spaced-apart rod-shaped electrodes disposed around the longitudinal axis and having a field radius defined by an inscribed circle between the innermost portions of each electrode. Effective potential matching can be achieved by either supplying RF signals of different amplitudes to each segment and/or by modifying the field strength of the segments. In one embodiment, the multipole segments are configured such that the upstream multipole segment has a smaller field radius than the downstream segment.

Abstract: An analyzer and sample handling system suitable for retrieving and processing a sample housed within a suitably configured reaction vessel, and then discarding the used reaction vessel by vertically or axially pushing downward on the vessel supported in a suitably configured tray with a pressing member that forms part of an autosampler assembly are disclosed herein.

Abstract: The resolution of a TOF mass analyzer is maintained despite a loss of resolution in one or more channels of a multichannel ion detection system by selecting the highest resolution channels for qualitative analysis. Ion packets that impact a multichannel detector are converted into multiplied electrons and emitted from two or more segmented electrodes that correspond to impacts in different regions across a length of the detector. The electrons received by each electrode of the two or more segmented electrodes for each ion packet are converted into digital values in a channel of a multichannel digitizer, producing digital values for at least two or more channels. Qualitative information about the ion packets is calculated using digital values of a predetermined subset of one or more channels of the at least two or more channels known to provide the highest resolution.

Abstract: 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.