Abstract: A system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (“ADE”) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte. When the analytical instrument is a mass spectrometer or other type of device requiring the analyte to be in ionized form, the exiting droplets pass through an ionization region, e.g.

Abstract: A method and apparatus for analyzing samples using mass spectrometry are disclosed. The apparatus includes a reaction device configured to dissociate sample ions into fragments by reacting the sample ions with a charged species (e.g., electrons) such as through ECD, EID, or EIEIO. The kinetic energy of the charged species is such that the fragments may be detected and produce spectra that allow for the determination of isomeric species in the sample and the location of double bonds and/or the orientation of those double bonds within the sample molecules. The fragments may include radical fragments and non-radical fragments. Spectra resulting from analysis of the fragments may allow for the determination of the oxygen-radical fragments resulting from the dissociation of the sample molecules as confirmation of the presence of those radical fragments.

Abstract: 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 chambers of mass spectrometer 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 multipole ion guide.

Abstract: A ring stacked accelerator for use in a mass spectrometer includes a plurality of ring shaped plates arranged in a stack and is electrically coupled to a voltage divider that allows a substantially homogeneous electric field to be produced when the stack is energized. The voltage divider can include resistors and capacitors, where the capacitors are chosen to compensate for parasitic capacitances experienced by the plates. The ring stacked accelerator can be energized using an RF pulse. The ring stack accelerator can include one or more balancing capacitors for correcting effects that cause nonlinearity.

Abstract: Systems and methods are provided for calculating the area of a peak profile using information from one or more correlated peak profiles. One or more compounds are separated from a mixture over time using a separation device. Traces of the one or more compounds are monitored during the separation using a tandem mass spectrometer. A plurality of intensity measurements are received using a processor. A first peak profile for a compound of interest is detected from the plurality of intensity measurements for a first trace and one or more correlated peak profiles for the compound of interest are detected from the plurality of intensity measurements for one or more other traces using the processor. An area of the first peak profile is calculated based on the one or more correlated peak profiles using the processor.

Abstract: Methods and apparatus for processing fluids on a macro- or micro-scale are described. In various aspects, a fluid may have a plurality of elongated (i.e., substantially rod-shaped) magnetic elements disposed therein within a fluid container. An illustrative fluid container is an actuator electrode or a processing vial of a microfluidic device, such as a digital microfluidic device. A magnet component may be configured to generate a magnetic force sufficient to influence the movement of the plurality of elongated magnetic elements within the fluid to be processed. For example, the magnetic force (or magnetic force gradient) may influence the plurality of elongated magnetic elements to rotate, spin, and/or move laterally side-to-side. The shape and movements of the plurality of elongated magnetic elements facilitate the rapid and efficient processing of the fluid, such as fluid mixing and/or fluid separation.

Abstract: A system is disclosed for identifying a precursor ion of a product ion in a scanning DIA experiment. A precursor ion mass selection window is scanned across a precursor ion mass range of interest, producing a series of overlapping windows across the precursor ion mass range. Each overlapping window is fragmented and mass analyzed, producing a plurality of product ion spectra for the mass range. A product ion is selected from the spectra. Intensities for the selected product ion are retrieved for at least one scan across the mass range producing a trace of intensities versus precursor ion m/z. A matrix multiplication equation is created that describes how one or more precursor ions correspond to the trace for the selected product ion. The matrix multiplication equation is solved for one or more precursor ions corresponding to the selected product ion using a numerical method.

Abstract: In accordance with various aspects of the present teachings, methods and systems for differential mobility spectrometry are provided herein for simultaneously applying a plurality of SV/CV combinations to subsets of a population of ions generated by one or more ion sources. In various aspects, DMS devices in accordance with the present teachings can provide multiple channels (e.g., 2, 3, 4, 5, 6, or more) for operating in parallel and within which different electrical fields can be generated for filtering sample ions within those channels based on the characteristic mobilities of the ions within each channel. In this manner, devices and methods in accordance with the present teachings can, in various aspects, enable improved duty cycle, increased throughput, decreased sample consumption, increased sensitivity for a plurality of ions of interest, and/or increased resolution.

Abstract: Improvements to a side-on Penning trap include methods to stabilize ions in the trap. The ions are stabilized by injecting ions in the focusing region of the non-uniform DC fields produced by the pad electrodes of the trap. Ions are injected along an injection axis shifted from the central axis of a gap between a positively biased electrode pad and negatively biased electrode pad of the trap. Improvements also include methods to compensate for the Lorentz force that is produced when ions are injected into a side-on Penning trap. Electrodes of an ion injection device are DC biased so that the electrodes produce an electric field along the axis of the device that compensates for the Lorentz force. Finally, methods are provided to increase the m/z range of ions injected into a side-on Penning trap by pre-trapping ions just before injection of the ions into the trap.

Abstract: The present teachings relate to methods, systems, and kits for analyzing a sample containing a glycopeptide of interest that can subject the glycopeptide of interest to a plurality of parallel deglycosylation reactions that differentially cleave the glycan, with the various products resulting from the deglycosylation reactions being differentially labeled (e.g., with isobaric and/or isomeric labeling reagents) to thereby produce labeled glycopeptides or labeled fragments of the glycopeptides. The products of the various deglycosylation reactions can then be mixed together and subject to LC-MS/MS using a single injection of the mixture. In accordance with various aspects, by associating the resulting mass spectral data with a particular deglycosylation reaction (e.g., based on the presence in the MS/MS data of product reporter ions associated with the particular differential labels), the methods and systems described herein can aid in the identification of the glycan structure.

Abstract: Methods and systems are provided herein for selectively removing product ions resulting from an ECD dissociation event from the interaction region of an ECD reaction cell, while other precursor peptide ions continue to undergo ECD within the interaction region, thereby reducing or preventing the occurrence of multiple electron capture events by the product ions. In some aspects, the preferential extraction of product ions from the interaction region during the ECD reaction can occur without an auxiliary AC field being generated within the interaction region. Additionally, in some aspects, the methods and systems disclosed herein can subject the various product ions to a non-dissociative charge reduction via exposure to reagent ions of the opposite polarity so as to selectively concentrate product ions to a lower charge state.

Abstract: Protein confidence values are calculated in proteomic analysis. A protein database is searched for proteins matching peptides found from mass spectrometry of a sample producing a set of proteins and a corresponding set of peptides. Peptide confidence values for the set of peptides are determined. Protein confidence values are calculated for the set of proteins based on the peptide confidence values. A protein is selected from the set of proteins with a largest protein confidence value, the largest protein confidence value is saved for the protein, the protein is removed from the set of proteins, and one or more peptides corresponding to the protein are removed from the set of peptides. Protein confidence values are recalculated for the set of proteins based on the peptide confidence values and an effect of removing the one or more peptides from the set of peptides.

Abstract: Methods and systems for processing fluids utilizing a digital microfluidic device and transferring droplets from the digital microfluidic device to a downstream analyzer are described herein. Methods and systems in accordance with the present teachings can allow for the withdrawal of fluid from a digital microfluidic device, and can in some aspects enable the integration of a digital microfluidic device as a direct, in-line sample processing platform from which a droplet can be transferred to a downstream analyzer.

Abstract: A mass spectrometer is provided having an ion source for generating ions from a sample in a high pressure region, a first vacuum chamber having an inlet aperture, and an exit aperture. The at least one ion guide can be between the inlet and exit apertures and can include an entrance end and an exit end. The at least one ion guide can have a plurality of electrodes arranged around a central axis defining an ion channel, each of the plurality of electrodes being tapered, a planar surface of each of the plurality of tapered electrodes facing the interior of the at least one ion guide, and the surface gradually being narrowed and tilted inward to provide a smaller inscribed radius at the exit; and a power supply for providing an RF voltage to the at least one ion guide.

Abstract: A quadrupole is filled with ions and the ions are cooled by applying a pressure and gas flow within the quadrupole. Ions are trapped in the quadrupole by applying a DC voltage and an RF voltage to quadrupole rods of the quadrupole, one or more DC voltages to a plurality of auxiliary electrodes of the quadrupole, and a DC voltage and an RF voltage to an exit lens at the end of the quadrupole. The ions are coherently oscillated after the filling and cooling by applying a coherent excitation between at least two rods of the quadrupole rods. The coherently oscillating ions are axially ejected through the exit lens and to a destructive detector for detection by changing one or more voltages of the one or more DC voltages of the plurality of auxiliary electrodes and changing the DC voltage of the exit lens.

Abstract: Systems and methods are provided for compound identification using multiple spectra that are a function of a variable instrument parameter that affects the intensity of fragment ions. A plurality of acquired fragment ion spectra that are a function of a variable instrument parameter for at least one ion are received from a mass spectrometer using a processor. The at least one ion is identified by comparing rates of change of mass intensity, with respect to the variable instrument parameter, for acquired and known fragment ions using the processor. Specifically, one or more acquired rates of change calculated for acquired fragment ions from the plurality of acquired fragment ion spectra are compared with one or more known rates of change calculated for one or more stored fragment ions of one or more known compounds in a database of known compounds.

Abstract: Systems and methods described herein utilize an ion guide for use in mass spectrometer systems, which ion guide can receive ions from an ion source for transmission to downstream mass analyzers, while preventing debris (e.g., unsolvated droplets, neutral molecules, heavy charged clusters) from being transmitted into a high-vacuum chamber of the mass spectrometer system. In various aspects, systems and methods in accordance with the present teachings can increase throughput, improve the robustness of the system, and/or decrease the downtime typically required to disassemble/clean sensitive components within the high-vacuum portions of the mass spectrometer system.

Abstract: At least one product ion mass spectrum produced by a tandem mass spectrometer is received. A chemical structure of a compound that corresponds to the at least one product ion mass spectrum is received. One or more elemental compositions are assigned to at least one peak in the at least one product ion spectrum based on the chemical structure using the processor. At least one elemental composition of the one or more assigned elemental compositions is selected for the at least one peak using the processor. The mass of the at least one peak is converted to the mass of the selected at least one elemental composition using the processor, producing a product ion mass spectrum with higher mass accuracy.

Abstract: A linear ion trap includes a quadrupole having four substantially parallel conductive rods that are substantially coextensive in the axial direction. The rods include two diagonally arranged pairs including one continuous, rod pair and one pair of rods that are segmented such that the two segments in a rod are capacitively coupled to facilitate an RF drop when an RF signal is applied to one longer segment and capacitively provided to the other shorter segment. An RF signal is provided to the continuous rods and tire longer segment of the segmented rods.

Abstract: Methods and systems are provided herein for varying the CoV about a nominal CoV-apex while monitoring the ion of interest corresponding to the nominal CoV-apex as it is transmitted by a DMS. In various aspects, the CoV can be swept or stepped across a series of values during the injection of ions into the DMS such that a composite spectra of the ion of interest transmitted by the DMS (or its product ions following one or more stages of fragmentation) can be generated so as to include the transmission of the particular ion at a CoV with optimum sensitivity (i.e., if distinct from the CoV-apex), thereby improving the robustness, accuracy, and/or selectivity during experimental conditions relative to known DMS techniques, which typically used a fixed CoV value for each ion of interest.