Abstract: An apparatus and method for analyzing a sample containing multiple analytes that combines a separation device that separates the individual analytes by virtue of some physical and/or chemical characteristic other than the mass to charge ratio (m/z) interfaced with a mass spectrometer that detects the m/z of individual analytes. Separation is performed on the shorter timescale than signal detection with the mass spectrometer. A preferred embodiment utilizes an ion mobility spectrometer interfaced with an Orbitrap mass spectrometer.

Abstract: An orthogonal ion injection apparatus and process are described in which ions are directly injected into an ion guide orthogonal to the ion guide axis through an inlet opening located on a side of the ion guide. The end of the heated capillary is placed inside the ion guide such that the ions are directly injected into DC and RF fields inside the ion guide, which efficiently confines ions inside the ion guide. Liquid droplets created by the ionization source that are carried through the capillary into the ion guide are removed from the ion guide by a strong directional gas flow through an inlet opening on the opposite side of the ion guide. Strong DC and RF fields divert ions into the ion guide. In-guide orthogonal injection yields a noise level that is a factor of 1.5 to 2 lower than conventional inline injection known in the art. Signal intensities for low m/z ions are greater compared to convention inline injection under the same processing conditions.

Abstract: A collision cell is disclosed that provides ion activation in various selective modes. Ion activation is performed inside selected segments of a segmented quadrupole that provides maximum optimum capture and collection of fragmentation products. The invention provides collisional cooling of precursor ions as well as product fragments and further allows effective transmission of ions through a high pressure interface into a coupled mass analysis instrument.

Abstract: A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

Abstract: An orthogonal ion injection apparatus and process are described in which ions are directly injected into an ion guide orthogonal to the ion guide axis through an inlet opening located on a side of the ion guide. The end of the heated capillary is placed inside the ion guide such that the ions are directly injected into DC and RF fields inside the ion guide, which efficiently confines ions inside the ion guide. Liquid droplets created by the ionization source that are carried through the capillary into the ion guide are removed from the ion guide by a strong directional gas flow through an inlet opening on the opposite side of the ion guide. Strong DC and RF fields divert ions into the ion guide. In-guide orthogonal injection yields a noise level that is a factor of 1.5 to 2 lower than conventional inline injection known in the art. Signal intensities for low m/z ions are greater compared to convention inline injection under the same processing conditions.

Abstract: An apparatus and method for analyzing a sample containing multiple analytes that combines a separation device that separates the individual analytes by virtue of some physical and/or chemical characteristic other than the mass to charge ratio (m/z) interfaced with a mass spectrometer that detects the m/z of individual analytes. Separation is performed on the shorter timescale than signal detection with the mass spectrometer. A preferred embodiment utilizes an ion mobility spectrometer interfaced with an Orbitrap mass spectrometer.

Abstract: A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

Abstract: A collision cell is disclosed that provides ion activation in various selective modes. Ion activation is performed inside selected segments of a segmented quadrupole that provides maximum optimum capture and collection of fragmentation products. The invention provides collisional cooling of precursor ions as well as product fragments and further allows effective transmission of ions through a high pressure interface into a coupled mass analysis instrument.

Abstract: An ion funnel trap is described that includes a inlet portion, a trapping portion, and a outlet portion that couples, in normal operation, with an ion funnel. The ion trap operates efficiently at a pressure of ˜1 Torr and provides for: 1) removal of low mass-to-charge (m/z) ion species, 2) ion accumulation efficiency of up to 80%, 3) charge capacity of ˜10,000,000 elementary charges, 4) ion ejection time of 40 to 200 ?s, and 5) optimized variable ion accumulation times. Ion accumulation with low concentration peptide mixtures has shown an increase in analyte signal-to-noise ratios (SNR) of a factor of 30, and a greater than 10-fold improvement in SNR for multiply charged analytes.

Abstract: A method for multiplexed analysis using ion mobility spectrometer in which the effectiveness and efficiency of the multiplexed method is optimized by automatically adjusting rates of passage of analyte materials through an IMS drift tube during operation of the system. This automatic adjustment is performed by the IMS instrument itself after determining the appropriate levels of adjustment according to the method of the present invention. In one example, the adjustment of the rates of passage for these materials is determined by quantifying the total number of analyte molecules delivered to the ion trap in a preselected period of time, comparing this number to the charge capacity of the ion trap, selecting a gate opening sequence; and implementing the selected gate opening sequence to obtain a preselected rate of analytes within said IMS drift tube.

Abstract: A method for multiplexed analysis using ion mobility spectrometer in which the effectiveness and efficiency of the multiplexed method is optimized by automatically adjusting rates of passage of analyte materials through an IMS drift tube during operation of the system. This automatic adjustment is performed by the IMS instrument itself after determining the appropriate levels of adjustment according to the method of the present invention. In one example, the adjustment of the rates of passage for these materials is determined by quantifying the total number of analyte molecules delivered to the ion trap in a preselected period of time, comparing this number to the charge capacity of the ion trap, selecting a gate opening sequence; and implementing the selected gate opening sequence to obtain a preselected rate of analytes within said IMS drift tube.

Abstract: An ion funnel trap is described that includes a inlet portion, a trapping portion, and a outlet portion that couples, in normal operation, with an ion funnel. The ion trap operates efficiently at a pressure of ˜1 Torr and provides for: 1) removal of low mass-to-charge (m/z) ion species, 2) ion accumulation efficiency of up to 80%, 3) charge capacity of ˜10,000,000 elementary charges, 4) ion ejection time of 40 to 200 ?s, and 5) optimized variable ion accumulation times. Ion accumulation with low concentration peptide mixtures has shown an increase in analyte signal-to-noise ratios (SNR) of a factor of 30, and a greater than 10-fold improvement in SNR for multiply charged analytes.

Abstract: A method for analyzing analytes from a sample introduced into a Spectrometer by generating a pseudo random sequence of a modulation bins, organizing each modulation bin as a series of submodulation bins, thereby forming an extended pseudo random sequence of submodulation bins, releasing the analytes in a series of analyte packets into a Spectrometer, thereby generating an unknown original ion signal vector, detecting the analytes at a detector, and characterizing the sample using the plurality of analyte signal subvectors. The method is advantageously applied to an Ion Mobility Spectrometer, and an Ion Mobility Spectrometer interfaced with a Time of Flight Mass Spectrometer.

Abstract: A method for analyzing analytes from a sample introduced into a Spectrometer by generating a pseudo random sequence of a modulation bins, organizing each modulation bin as a series of submodulation bins, thereby forming an extended pseudo random sequence of submodulation bins, releasing the analytes in a series of analyte packets into a Spectrometer, thereby generating an unknown original ion signal vector, detecting the analytes at a detector, and characterizing the sample using the plurality of analyte signal subvectors. The method is advantageously applied to an Ion Mobility Spectrometer, and an Ion Mobility Spectrometer interfaced with a Time of Flight Mass Spectrometer.