Perseptive Biosystems Inc.

Anatoli Verentchikov

Marvin L Vestal

Jennifer M Campbell

Igor P Smirnov

Kevin M Hayden

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.

Preparation of ion pulse for time-of-flight and for tandem time-of-flight mass analysis

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.

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.

Tandem time-of-flight mass spectrometer with damping in collision cell and method for use

A mass spectrometer instrument for determining the molecular weight of labile molecules of biological importance, in particular heavy molecules, such as proteins, peptides or DNA oligomers, is disclosed. The instrument includes a MALDI ion source that is enclosed in a chamber with an inlet for admitting a gas and an ion sampling aperture for limiting gas flow from the chamber. The elevated pressure of the source in the range from 0.1 to 10 torr causes low energy collisions between the gas and the ions that can cause rapid collisional cooling of the excited ions, thereby improving the stability of the produced ions. The formation of clusters of ions (e.g., protein ions) with matrix materials is broken without fragmenting the ions by increasing the downstream gas temperature to between 150 and 250&deg; C. Operating the source at laser energy at least two times higher than the threshold value of ion formation and using a high repetition rate laser significantly improves sensitivity of analysis and speed of data acquisition.

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Anatoli Verentchikov