Thermo Finnigan LLC

Fei Comapny

Thermo Fisher Scientific (bremen) Gmbh

Alexander A Makarov

Wilko Balschun

Stephen Davis

Eduard V Denisov

Gerhard Jung

Stevan Roy Horning

Kun Liu

Jonathan Hughes

Viatcheslav V Kovtoun

Roger Giles

Marcus Straw

Pavel V Bondarenko

Kevin Hunter

Mikhail A Monastyrskiy

Alan S Bahm

Joseph Christian

Aaron Torok

Stephen Charles Davis

Tom Nichols

Jeff Kosmoski

Dmitry Grinfeld

Josh Gilbert

Richard Whitney Stresau

Kyle Fort

Dimitry E Grinfield

Wayne Leslie Sheils

Lee Martin Earley

Andrew David Hoffman

Systems and method for the preparation and delivery of biological samples for charged particle analysis are disclosed herein. An example system at least includes an ion filter coupled to select a sample ion from an ionized sample supply, the ion filter including a quadrupole filter to select the sample ion from the sample supply, an energy reduction cell coupled to receive the selected sample ion and reduce a kinetic energy of the sample ion, a validation unit coupled to receive the sample ion and determine whether the sample ion is a target sample ion, a substrate coupled to receive the sample, wherein the substrate is electron transparent, an ion transport module coupled to receive the sample ion from the ion filter and transport the sample ion to the substrate, and an imaging system arranged to image, with a low energy charged particle beam, the sample located on the substrate, wherein the substrate is arranged in an analysis location. The imaging system including a charge particle emitter coupled to direct coherent charged particles toward the sample; and a detector arranged to detect interference patterns formed from interaction of the coherent charged particles and the sample.

System and method for preparation and delivery of biological samples for charged particle analysis

A coupling for connecting together vacuum-based analytical systems requiring to be vibrationally isolated, comprising: a tubular connector having a longitudinal axis, the connector comprising a first end for connection to a first analytical system and a flexible portion reducing transmission of vibrations and permitting displacement of the first analytical system in a direction transverse to the longitudinal axis of the connector; and a seal longitudinally separated from the flexible portion, for vacuum sealing between the connector and a second analytical system; wherein the connector contains ion optics for transmitting ions between the first and second analytical systems.

Coupling for connecting analytical systems with vibrational isolation

An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U'(r, &#x3c6;, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U&#x2032;(r, &#x3c6;, z) is the result of a perturbation W to an ideal field U(r, &#x3c6;, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, &#x3c6;, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 &#x3a0; radians over an ion detection period T.

Electrostatic trap

A mass spectrometer includes at least one ion selector, at least one collision cell, and an ion path switching device arranged to define a looped ion path around which ions derived from a sample may be sent multiple times (without reversal of ion travel) in order to effect a desired number of isolation/fragmentation cycles for MSn analysis. When the desired number of isolation/fragmentation cycles have been completed, the ion path switching device directs the ions to a detector or a separate mass analyzer for acquisition of a mass spectrum.

Mass spectrometer with looped ion path

A method for reducing the energy spread of ions over a specific and limited mass to charge ratio range is disclosed, along with an ion deceleration arrangement for implementing such a method. An electric field, having an electric field strength E is generated by a deceleration electrode arrangement (). Ions of a specific and limited mass to charge ratio range, but having a spread of energies, are directed into the decelerating electric field generated by the deceleration electrode arrangement (). The decelerating electric field is then removed, once substantially all of the ions of the specific mass to charge ratio range have entered the decelerating electric field. By matching the electric field strength E to the energy spread of the ions upon entry into the electric field, the energy spread of the said ions is reduced. Preferred embodiments of the invention employ energy dispersion upstream of the ion deceleration arrangement. For example, an ion mirror arrangement () may be used, the ions reflecting off an ion mirror () within that ion mirror arrangement () to promote energy defocusing.

Ion energy spread reduction for mass spectrometer

A method of obtaining a mass spectrum of elements in a sample is disclosed. Sample precursor ions having a mass to charge ratio M/Z are generated, and fragmented at a dissociation site, so as to produce fragment ions of mass to charge ratio m/z. The fragment ions are guided into an ion trap of the electrostatic or 'Orbitrap' type, the fragment ions entering the trap in groups dependent upon the precursor ions M/Z. The mass to charge ratio of each group is determined from the axial movement of ions in the trap. The electric field in the trap is distorted. Ions of the same m/z, that are derived from different pre-cursor ions, are then separated, because the electric field distortion causes the axial movement to become dependent upon factors other than m/z alone.

Orbital ion trap including an MS/MS method and apparatus

An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U'(r,&#x3c6;,z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U&#x2032;(r, &#x3c6;,z) is the result of a perturbation W to an ideal field U(r, &#x3c6;,z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, &#x3c6;,z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than about 2&#x3c0; radians over an ion detection period T.

All-mass MS/MS method and apparatus

A mass spectrometer comprises an ion source which produces an ion beam from a substance to be analysed and a detector to detect a quantity of ions incident thereon. The detector includes two elements () each of which detect a part of the quantity of ions and an attenuation device attenuates the quantity of ions reaching one of the detector elements. At least one of the detector elements () is connected to a time to digital converter (TDC) to allow counting of the ions and at least one of the detector elements is connected in parallel to both a time to digital converter (TDC) and an analogue to digital converter (ADC).

High dynamic range mass spectrometer

An ion detection arrangementfor a time-of-flight (TOF) mass spectrometerincludes a beam splitter formed as a meshat the end of the TOF acceleration and detection chamber. Ions enter the detection arrangement through a common entrance window and are then divided by the beam splitter. Those ions striking the meshgenerate secondary electronswhich are detected by a microchannel plate forming a first detector. Those ions passing through the ion beam splitter are detected directly by a second detectoralso formed from a microchannel plate. The two detectors are each connected to a corresponding data acquisition systemand the data obtained by each are combined to generate a mass spectrum. The problems of detector saturation are thus avoided.

Time of flight mass spectrometer and multiple detector therefor

A mass spectrometer has an ion source () with a plurality of atmospheric pressure sample ioniser () mounted in a front face () thereof. Each sample ioniser () extends into a corresponding sample region () and the tip of each sample ioniser is mounted at right-angles to a corresponding one of a plurality of entrance cones () each having an entrance orifice () therein. Each entrance cone () in turn opens into an inlet channel having first and second parts (). The two parts of the inlet channel are separated by an electrical gate (). The inlet channels corresponding to each entrance cone () all merge into a common exit channel () to a mass spectrometer. By appropriate operation of the gates () dividing the inlet channels, rapid switching between the samples that are analysed in the mass analyser can be achieved.

Multi-inlet mass spectrometer

A time-of-flight mass spectrometer, for example, a MALDI-TOF spectrometer, measures the characteristics of the charge to mass ratio of ionized particles by measuring the time taken for the particles to travel a pre-determined distance. The spectrometer comprises an accelerator ( ) which accelerates the particles along at least two paths, which may be contained in a single beam of charged particles. Two detectors ( and ) mark the ends of the paths and are operable to detect the particles travelling therealong. The length of the path leading to the first detector ( ) differs from that of the path leading to the second detector ( ) to a sufficient extent to enable the difference in detection times of corresponding particles at the two detectors to be used to provide a measurement of said characteristics. Variations in initial velocities and/or ionization times of the particles will have similar effect on the outputs of both detectors so that one detector can, in effect, be used to calibrate or correct the output of the other detector.

Time-of-flight mass spectrometer

An ionization apparatus for connection to a mass analyzer is provided. The ionization apparatus comprises a sample slide provided with at least two channels having inner surface having samples deposited thereon, means for delivering energy such as a laser to one of the channels to release and ionize the sample to form ions, and an interfacial orifice for collecting the ions formed in the channel.

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Cheadle, United Kingdom

Alexander A Makarov