Abstract: An apparatus and method is disclosed for reducing contamination in a mass spectrometer instrument system. The system includes an ion source at a first pressure for generating ions by laser desorption/ionization and an inlet aperture to a vacuum chamber at a second, lower pressure than the first pressure of the ion source. A sample plate within the ion source supports a sample deposited thereon and a laser can be configured to generate laser pulses striking at least a portion of the sample at an angle of incidence from about 0 to about 80 degrees to the center line of a first ion optical axis of a mass analyzer, producing a plume. A combination of the angle of incidence of the laser pulses and the distance between the sample plate and the inlet region aperture can reduce neutral contaminants in the plume from being drawn into the inlet aperture.

Abstract: Disclosed is a method of determining when to calibrate a time-of-flight mass spectrometer. In various embodiments, the method comprises storing within a controller a set of parameters for the mass spectrometer; providing an updated set of parameters while retaining at least one set of previously stored parameters; computing at least one rate of change of the updated set of parameters with respect to the at least one set of previously stored parameters; and determining when to calibrate the mass spectrometer from the results of computing the rate of change of at least one of the parameters. In various embodiments, a parameter stored can be a set of temperatures derived from obtaining system temperature measurements of those components whose changing temperature is an indication of mass drift.

Abstract: Disclosed are methods and apparatus for compensating for mass error for a time-of-flight mass spectrometer. A reference flight distance for a pulse of ions corresponding to a reference temperature of one or more components of an ion flight path assembly is determined, and the temperature of one or more components of the ion flight path assembly is measured. Correlating the thermal expansion of the flight path assembly with the temperature measurement allows the measured flight times to be adjusted to correspond with the reference flight distance to thereby compensate for the thermal expansion of the flight path assembly. A mass spectrum is obtained using the adjusted flight times. In various embodiments, the temperature signal is used with pre-determined thermal expansion correction factors for the flight path assembly to calculate a correction factor to control another component of the TOF MS, such as the voltage applied to a power supply system or a signal to control clock frequencies.

Abstract: In a mass spectrometer, ions from an ion source pass through an inlet aperture into a vacuum chamber for transmitting prior to mass analysis by the mass analyzer. The configuration of the inlet aperture forms a sonic orifice or sonic nozzle and with a predetermined vacuum chamber pressure, a supersonic free jet expansion is created in the vacuum chamber that entrains the ions within the barrel shock and Mach disc. Once formed, at least one ion guide with a predetermined cross-section to essentially radially confine the supersonic free jet expansion can focus the ions for transmission through the vacuum chamber. This effectively improves the ion transmission between the ion source and the mass analyzer.

Abstract: In a mass spectrometer, ions from an ion source pass through an inlet aperture into a vacuum chamber for transmitting prior to mass analysis by the mass analyzer. The configuration of the inlet aperture forms a sonic orifice or sonic nozzle and with a predetermined vacuum chamber pressure, a supersonic free jet expansion is created in the vacuum chamber that entrains the ions within the barrel shock and Mach disc. Once formed, an ion guide with a predetermined cross-section to essentially radially confine the supersonic free jet expansion can focus the ions for transmission through the vacuum chamber. This effectively improves the ion transmission between the ion source and the mass analyzer.

Abstract: Polypeptides are electroblotted through a digestion membrane to a composite capture membrane that can be directly analyzed using mass spectrometry. The molecular weights of the fragments generated by the digestion membrane are then used to identify the polypeptide from which they originated. The digestion membrane contains an immobilized protease such as trypsin, which cleaves the electroblotted polypeptides into fragments during electroblotting with such high enzyme cleavage capacity and efficiency that one pass of the polypeptide through the membrane is sufficient. The peptide fragments are collected onto a composite capture membrane that is chemically treated, for example by adding a mixture of nitrocellulose and MALDI matrix, so as to absorb peptides near the surface to facilitate desportion, thereby increasing the sensitivity of subsequent analysis by MALDI-TOF mass spectrometry. A wide variety of application are disclosed including identifying proteins separated on a gel or within a tissue sample.

Abstract: Methods using gel electrophoresis and mass spectrometry for the rapid, quantitative analysis of proteins or protein function in mixtures of proteins derived from two or more samples in one unit operation are disclosed.

Abstract: A MALDI plate construction is provided to support a sample in a manner to effect mass spectrometry of the sample. The plate construction comprises a sample receiving surface, a plate holder for retaining the sample receiving surface and an electrically conductive grid positioned adjacent to the sample receiving surface and in electrical contact with the plate holder.

Abstract: A MALDI plate suitable for MS or MS-MS analysis provided with a composite coating that comprises a hydrophobic coating and a thin layer coating of a mixture of a MALDI matrix material and an intercalating agent such as a polymer is disclosed. A MALDI plate produced in accordance with the present teachings is useful for suppression of matrix ions in the low mass region (<1,000 daltons) of a MALDI-MS spectrum.

Abstract: A microfluidic system is provided for separating components of many fluid samples in a parallel fashion through an array of capillary conduits. The system includes capillary conduits for receiving fluid samples, and for effecting separation of substituents of the sample by passing the sample through a corresponding array of capillary separation conduits containing a solid separation medium. The microfluidic circuit is made of three or more substrate layers and preferably includes etched channels in different layers that are dimensioned relative to one another to provide for retaining the solid composition within the capillary separation conduits. The system also includes an array of detector flow cells in fluid communication with the capillary separation conduits, and an array of high pressure connectors for connecting discrete capillary tubes to the fluid passages in the microfluidic circuit for introducing and removing the fluid samples from the system.

Abstract: A process and apparatus are provided for simultaneously moving a first sample plate into an analytical apparatus and a second sample plate from the analytical apparatus. The first sample plate is moved on an entry path which is vertically spaced apart from an exit path for the second sample plate. The transfer mechanism is disclosed in operation with a MALDI-TOF mass spectrometer.

Abstract: A sample plate for a MALDI process is provided which comprises an electrically conductive substrate having a hydrophobic coating whose thickness and hydrophobic character can be modified by changing the coating substrate and/or the concentration of the substrate. Different coating substances that have provided optimal performance of the sample plate for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures include synthetic waxes such as paraffin compositions, lipids, organic acids, silicon-containing compounds, silica polymers and natural waxes. Metal polishes that have been used to clean and regenerate plate surfaces have also provided a sample plate that has optimal performance for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures.

Abstract: A sample plate structure is provided including a retainer plate having a central opening, a sample insert plate which fits into the opening, an optional pressure plate and a handle. The handle applies pressure to the sample insert plate to retain it within the retainer plate. The sample insert plate is provided with a peripheral configuration, which assures that the sample insert plate is properly oriented within the sample plate support structure and is held flat. While the sample insert plate can be a consumable, the remaining portion of the apparatus can be reused.

Abstract: A sample plate structure is provided including a retainer plate having a central recess with a trough along its periphery, a sample insert plate which fits into and rests on contact surface of the recess, and a magnet that is held below the contact surface. A portion of the bottom surface of the insert is formed of a magnetic material. The magnet provides sufficient force to retain the insert plate in the retainer plate during MALDI MS analysis. The sample insert plate is provided with a peripheral configuration, which assures that the sample insert plate is properly oriented within the sample plate support structure and is held flat. A hole for a protrusion allows easy insert installation and alignment against the orientation feature in the recess as well as easy removal of the insert simply by pushing up from underneath the retainer plate. While the insert sample plate can be a consumable, the remaining portion of the apparatus can be reused.

Abstract: An array of probes is provided wherein the probes are maintained in place in bores extending through a housing by a friction force applied to the probes. The friction force can be overcome by another force applied to the probes, thereby allowing the probes to move to a new position within the bore. In one embodiment, the probes contain an internal conduit through which liquid samples are introduced into the probes. Thereafter, the probes are moved to contact a substrate surface to move the probes to a new position, the configuration of which replicates the substrate surface configuration. The housing is then raised a predetermined distance to allow sample to be accurately deposited on the substrate surface from a desired height above the substrate surface. The probes are then returned to their original position.

Abstract: The use of a segmented-ion trap with collisional damping is disclosed to improve performance (resolution and mass accuracy of single stage and tandem time-of-flight mass spectrometers. In the case of single stage spectrometers ions are directly injected from a pulsed ion source into the trap supplied with RF field and filled with gas at millitorr pressure. Subsequently, the ions are dynamically trapped by an RF-field, cooled in gas collisions and ejected out of the trap by a homogeneous electric field into a time-of-flight mass spectrometer. In the case of tandem mass spectrometric analysis the pulsed ion beam is injected into a time-of-flight analyzer to select ions-of-interest prior to injection into the trap at medium energy to achieve fragmentation in the trap.

Abstract: Regulator for precision control of pressure based on a means of measuring pressure differentials. More specifically, the present invention provides a pressure control that tracks a relatively high background pressure, and applies a positive or negative offset to create the small pressure differentials that can be utilized to transport fluids within a capillary network. The present invention is also directed to a method of controlling microfluidic elements (such as donut cavities) with a high degree of precision. In high performance liquid chromatography applications, this is accomplished using tracking pressure regulators to measure and respond to the difference between the liquid pump pressure and the regulated pneumatic pressure.

Abstract: A tandem time-of-flight mass spectrometer is described. The tandem time-of-flight mass spectrometer includes a pulsed ion source that generates a plurality of ions. A first time-of-flight mass separator accelerates the plurality of ions, fragments at least a portion of the accelerated plurality of ions, and then selects a first group of ions and fragments thereof. A second time-of-flight mass separator accelerates the first group of ions and fragments thereof, fragments at least a portion of the accelerated first group of ions and fragments thereof, and then selects a second group of ions and fragments thereof. A third time-of-flight mass separator accelerates the second group of ions and fragments thereof. An ion detector detects the second group of ions and fragments thereof from the third time-of-flight mass separator.

Abstract: A microfluidic system is provided for separating components of many fluid samples in a parallel fashion through an array of capillary conduits. The system includes capillary conduits for receiving fluid samples, and for effecting separation of substituents of the sample by passing the sample through a corresponding array of capillary separation conduits containing a solid separation medium. The microfluidic circuit is made of three or more substrate layers and preferably includes etched channels in different layers that are dimensioned relative to one another to provide for retaining the solid composition within the capillary separation conduits. The system also includes an array of detector flow cells in fluid communication with the capillary separation conduits, and an array of high pressure connectors for connecting discrete capillary tubes to the fluid passages in the microfluidic circuit for introducing and removing the fluid samples from the system.

Abstract: The use of a segmented-ion trap with collisional damping is disclosed to improve performance (resolution and mass accuracy) of single stage and tandem time-of-flight mass spectrometers. In the case of single stage spectrometers ions are directly injected from a pulsed ion source into the trap supplied with RF field and filled with gas at millitorr pressure. Subsequently, the ions are dynamically trapped by an RF-field, cooled in gas collisions and ejected out of the trap by a homogeneous electric field into a time-of-flight mass spectrometer. In the case of tandem mass spectrometric analysis the pulsed ion beam is injected into a time-of-flight analyzer to select ions-of-interest prior to injection into the trap at medium energy to achieve fragmentation in the trap.