Abstract: An apparatus for electrospray ionization of a liquid sample matrix to prepare the sample for introduction into a mass spectrometer. The inventive electrospray interface is arranged between a source of a liquid sample matrix and an electrospray ionization needle. The interface includes a central chamber which contains elements for passively mixing the liquid sample flow with a modifying liquid added to the central chamber through a side channel. The side channel is isolated from the central chamber by a flow restrictor and the modifying liquid is provided to the side channel through a valve. A second valve, side channel, and flow restrictor are used to permit introduction of a calibration fluid into the central chamber through the first side channel. The inventive interface permits mixing of a modifying liquid with the liquid sample matrix to assist in nebulization of the liquid sample by reducing the surface tension of the sample containing fluid.

Abstract: An apparatus for producing gas-phase ions from a sample compound in a carrier liquid. The electrospray needle (or capillary) of the present invention includes a central metal tube which carries the liquid containing the sample compound. The central tube is surrounded by a plurality of tubes which transport a nebulizing gas. The nebulizing gas tubes are placed symmetrically around the outside of the liquid containing tube. The nebulizer of the present invention produces a symmetric, non-annular gas flow which has variations in pressure around the circumference of the central tube. The pressure variations of the nebulizing gas flow produce additional shear forces on the liquid emerging from the central tube. This assists in forming a uniform electrospray of droplets from the liquid at lower nebulizing gas flow rates, thereby reducing the disadvantageous effects of the higher gas flow rates used in the art.

Abstract: An apparatus for efficiently removing a carrier liquid from charged liquid drops formed by electrospray ionization prior to introduction of the drops into a mass spectrometer. A central capillary tube connects a region of the low pressure vacuum system containing the mass spectrometer with a region at substantially atmospheric pressure, in which ion formation is produced by electrospray ionization. Heated, drying gas flows through a plurality of vortex forming channels symmetrically disposed about the axis of the central capillary tube which provides an entrance to the spectrometer. Gas exiting the vortex forming channels enters tangentially to the inside of a vortex drying tube with a small helix angle, causing the gas to swirl around the tube, forming a vortex. The vortex drying gas flows in a direction that is substantially transverse to the axis of the entrance capillary into the mass spectrometer.

Abstract: This invention relates to peptide-containing .alpha.-ketoamide inhibitors of cysteine and serine proteases, methods for making these compounds, and methods for using the same.

Abstract: The present invention is directed to novel benzothiazo and related heterocyclic group-containing inhibitors of cysteine or serine proteases. Methods for using the same are also described.

Abstract: An improved method of using an ion trap mass spectrometer is disclosed. According to the method an asymmetrical trapping field is applied to the trap. Preferably, the asymmetrical trapping field comprises a quadrupole field and a dipole field having the same frequency. In addition, higher order trapping field components, such as hexapole or octopole fields, may also be included, and the electrodes of the ion trap can be shaped to introduce such higher order field components. The effect of the asymmetrical trapping field of the present invention is to cause the center of the trapping field to be displaced from the mechanical center of the ion trap. A supplemental quadrupole field is then applied to the ion trap, the center of the supplemental quadrupole field being located at the mechanical center of the trap, i.e., it is displaced from the center of the trapping field. The supplement quadrupole field and the trapping field may be viewed as forming one combined field which acts upon the ions in the trap.

Abstract: The present invention is directed to novel phosphorous-containing inhibitors of cysteine or serine proteases. Methods for the use of the protease inhibitors are also described.

Abstract: A method of detecting ions of a single ion species that have been selectively stored in a quadrupole ion trap mass spectrometer is disclosed. After the selected ion species is isolated the trapping field in rapidly changed to cause ions to leave the ion trap in the axial direction where they are detected using a conventional detector. Preferably, a dipole pulse is applied to the ion trap simultaneously with the reduction of the trapping field, such that all of the ions are caused to leave the trap in a single direction, doubling the ion current over prior art methods. The method of the invention allows ejection of all of the ions in a time period which is nearly twenty times faster than the prior art resonance ejection scanning technique, and without the artifacts in the signal current caused by frequency beating.

Abstract: A method of isolating selected ion species in a quadrupole ion trap mass spectrometer is disclosed. One or more ranges of masses to be eliminated from the ion trap are ejected by applying a supplemental dipole excitation waveform, sparsely populated with frequency components, while the trapping field is modulated. The spacing of the frequency components in the supplemental excitation waveform varies across the range of frequencies in the waveform. Preferably, the frequency range is divided into a plurality of subranges, and the spacing of the frequency components in each of the subranges is constant. A method of creating a master set of frequencies used for generating a supplemental excitation waveform is also shown. Likewise, a method of calculating edge frequencies defining a gap in the mass spectrum that is excited by the supplemental waveform is also shown.

Abstract: A method of isolating selected ion species in a quadrupole ion trap mass spectrometer is disclosed. One or more ranges of masses to be eliminated from the ion trap are ejected by applying a supplemental dipole excitation waveform, sparsely populated with frequency components, while the trapping field is modulated. The spacing of the frequency components in the supplemental excitation waveform varies across the range of frequencies in the waveform. Preferably, the frequency range is divided into a plurality of subranges, and the spacing of the frequency components in each of the subranges is constant. A method of creating a master set of frequencies used for generating a supplemental excitation waveform is also shown. Likewise, a method of calculating edge frequencies defining a gap in the mass spectrum that is excited by the supplemental waveform is also shown.

Abstract: A method of isolating selected ion species in a quadrupole ion trap mass spectrometer is disclosed. One or more ranges of masses to be eliminated from the ion trap are ejected by applying a supplemental dipole excitation waveform, sparsely populated with frequency components, while the trapping field is modulated. The spacing of the frequency components in the supplemental excitation waveform varies across the range of frequencies in the waveform. Preferably, the frequency range is divided into a plurality of subranges, and the spacing of the frequency components in each of the subranges is constant. A method of creating a master set of frequencies used for generating a supplemental excitation waveform is also shown. Likewise, a method of calculating edge frequencies defining a gap in the mass spectrum that is excited by the supplemental waveform is also shown.

Abstract: A method of using a quadrupole ion trap mass spectrometer for high resolution mass spectroscopy is disclose. In the preferred embodiment, the space charge in the ion trap is controlled with high accuracy. The mass spectrum to be analyzed is divided into a plurality of contiguous mass segments and each of the segments is separately scanned. To control space charge, a broadband supplemental waveform is applied to the ion trap during the ionization period for each segment, the broadband signal being construct to eliminate all unwanted ions from the ion trap by resonance ejection such that only those ions having masses within the desired mass segment remain in the ion trap. Preferably, the ionization of each mass segment is performed under identical trapping conditions, and the ionization parameters for each segment is adjusted to optimize the space charge in the trap for that particular segment.

Abstract: A power efficient selective mass range trap filling process in which the RF trapping voltage connected to the ring electrode is slowly modulated simultaneously with: (1) e-beam ionization bombardment and (2) application of a broadband supplemental waveform containing selected secular frequencies to the QIT end caps. The modulation permits the reduction of the number of frequency components required in the broadband supplemental waveform and permits elimination of absorption by ions of energy from more than one supplemental frequency component at any one time.

Abstract: A method of using a quadrupole ion trap mass spectrometer for high resolution mass spectroscopy is disclosed. In the preferred embodiment, the space charge in the ion trap is controlled to high accuracy. This is done by using a prescan of the trap before each analytical scan, where the ionization parameters used in the prescan are not fixed, but rather are based on the previous analytical scan. The method is especially useful in connection with performance of high resolution MS/MS experiments of the type described in the inventor's prior U.S. Pat. No. 5,198,665.

Abstract: A method for using a QIT and for performing collisionally induced disassociation MS.sup.n experiments by scanning the trap potential sequentially so that the field first experiences a secular frequency of a selected parent ion and then the secular frequency of a CID produced daughter ion and then the secular frequency of a granddaughter ion and so on for each secular frequency of each progeny ion in descending mass order.

Abstract: A method of using a quadrupole ion trap mass spectrometer for high resolution mass spectroscopy is disclosed. High resolution of a mass spectrum of a desired species is achieved by first using a slow scanning rate and by first ridding the trap of unwanted ions. Accurate mass calibration is achieved by using a reference compound of known mass and using a second supplemental AC dipole voltage to eject the reference ions at nearly the same time as the sample ions of interest are ejected from the trap. This eliminates the need to scan the trap between the masses of the sample and reference ions. Space charge in the trap is held constant, thereby eliminating a major source of mass axis instability, by using the results of one scan to control the ionization time during the next scan. Preferably, during ionization a broadband supplemental dipole voltage is applied to the ion trap to rid it of unwanted ions.

Abstract: A method for efficiently filling a QIT which isolates an ion range by employing a sequential part of supplemental broadband waveforms where the first such supplemental broadband waveform is applied during the period that the e-beam ionization bombardment takes place and the second such broadband waveform is applied after the e-beam bombardment ends.

Abstract: Improved methods of using an ion trap mass spectrometer, whereby AC voltages supplemental to the AC trapping voltage are used for scanning the trap, for conducting chemical ionization experiments, and for conducting MS.sup.n experiments, are shown. In one embodiment a broadband supplemental AC voltage is applied to rid the trap of ions above or below a preselected cutoff mass. This is particularly useful in conducting chemical ionization experiments for eliminating high mass sample ions that are formed when the reagent gas is ionized by electron impact ionization. Likewise, this technique may be used to eliminate low mass reagent ions when conducting an electron impact ionization experiment in the presence of a reagent gas. In another embodiment a non-resonant, low-frequency supplemental voltage is applied to the trap causing trapped ions to undergo collision induced dissociation. Multiple generations of ion fragments may be simultaneously formed in this manner, thereby enabling MS.sup.n experiments.

Abstract: Substituted pyrazoles such as ##STR1## and their pharmaceutically suitable salts are useful as antihypertensive agents and for treatment of congestive heart failure.

Abstract: Method and apparatus for inducing collisional disassociation of isolated ions in a QIT which employs low frequency modulation of the secular frequency of oscillation of the trapped ions so as to permit sufficient frequency coincidence with the fixed frequency tickle generator to induce collisional disassociation.