A tandem mass spectrometer is disclosed having a collisional damping cell that slows down and adapts an ion beam, from a time-of-flight mass spectrometer (TOF MS) to a second mass spectrometer, preferably an orthogonal TOF MS. The cell provides a substantial damping of the energy of the ions in multiple collisions with a gas. An RF-only quadrupole is used to spatially focus the ion beam in the collision cell. As result, the operation of second mass spectrometer can be decoupled from the rest of the instrument, or in some cases with the energy being sufficiently damped the pulsed nature of the primary ion beam can be partially preserved and used to enhance the sensitivity of the second mass spectrometer. An ion selector passes only stable parent ions of interest, thereby introducing ions into the cell at a well controlled low energy. The ion beam can be injected into the collision cell with or without separation as well as with or without fragmentation. Thus, the results obtained with the second mass spectrometer can be used to control each individual step of the tandem MS, including ion formation in the source, ion focusing, metastable fragmentation in the first time of-flight spectrometer, primary ion selection and fragmentation in the cell as well as provide mass analysis of fragment ions. By using a high repetition rate laser at increased energy levels, the acquisition of data is significantly accelerated and adjustments on each individual step may be conveniently automated. The MS analysis can be also applied to analysis of analytes from continuous ion sources by using an orthogonal pulser in the first TOF MS to modulate the beam followed by spatial focusing of the pulsed beam.
The present invention relates to protein separation systems and methods capable of resolving and characterizing large numbers of cellular proteins. In particular, the present invention provides a novel mass mapping system and methods for the differential display of proteins. The present invention further provides novel methods for displaying differential protein expression between two samples. In particular, the present invention provides novel method of mapping differential expression of proteins in non-cancerous, pre-cancerous, and cancerous cells.
The invention relates to a time-of-flight mass spectrometer for acquiring spectra of either primary or daughter ions with high mass precision. All the periodic voltage pulse sequences used in the mass spectrometer--in the ion source, and any precursor ion selector or post-acceleration unit--are run continuously at a fixed base frequency, independently of whether a spectrum is being acquired in the relevant period, in order to avoid any disturbance of the electrical and thermal equilibrium. Ignition delay of the laser after triggering is controlled by switching the output of the clock pulse. The voltage pulse sequences, moreover--once again to avoid settling times--are to be designed in such a way that their voltages and delay times are entirely independent of the mass of the precursor ions. This feature can be achieved through appropriate forming of the delayed ion acceleration voltage pulse.
The invention relates to methods and devices for measuring daughter ion spectra (also called fragment ion spectra or MS/MS spectra) in time-of-flight mass spectrometers with orthogonal injection of the ions. The invention filters the parent ions selected to be fragmented by a mass filter before they are injected into the time-of-flight mass spectrometer, fragments the selected ions in a first stage of the time-of-flight mass spectrometer within a collision cell filled with collision gas at collision energies between one and five kiloelectron-volts, further accelerates the fragment ions and measures the fragment ions in a second stage of the time-of-flight mass spectrometer.
Techniques for simultaneously detecting direct and reflected ions in a time-of-flight tube (120) and a source (110) for generating an ion beam of ions of a sample and introducing the ion beam into a first portion of the flight tube. A reflector (126) reflects ions from the ion beam in a second portion of the flight tube. A plate (140) substantially perpendicular to an axis of the ion beam is located between the first portion of the flight tube and the second portion of the flight tube. The plate has a hole through which some ions in the ion beam may pass from the first portion to the second portion of the flight tube. Each of two opposite faces of the plate includes a set of one or more ion detectors (140). The technique allows rapid, reliable detection of complex agents in a small number of samples.
The present invention relates to an apparatus for delivering ions to a vacuum chamber. The apparatus comprises an ionization chamber, an ionization region within the ionization chamber, a vacuum interface at a vacuum interface voltage and a vacuum chamber, wherein the ionization chamber communicates with the vacuum chamber through the vacuum interface. Sample is introduced into the ionization chamber from an electrospray assembly at approximately ground potential. Two electrodes are provided within the chamber such that three electric fields are generated, a first field extending from the electrospray assembly to the first electrode, a second field extending from the second electrode to the first electrode, and a third field extending from the second electrode to the vacuum interface. Ions are forced to travel through the fields in order before entering the vacuum chamber. In addition, the invention provides a method of delivering ions to a vacuum chamber.
