Virgin Instruments Corporation

Applera Corporation

Mds Inc.

Applied Biosystems, LLC

Dh Technologies Development Pte. Ltd.

Kevin Hayden

Marvin L Vestal

Jennifer M Campbell

Philip J Savickas

An apparatus for molecular imaging of biological samples includes a first optical port configured to receive a first pulsed optical beam that is directed in an optical path along an optical axis. A transparent target that include a first surface having an electrically conductive surface that supports a biological sample under analysis and a second surface is positioned in the optical path along the optical axis. A moveable target mount is configured to translate the transparent target to a plurality of predetermined locations. A first optical focusing element is configured to focus the first pulsed optical beam to a first predetermined diameter at the first surface of the transparent target. A second optical port is configured to receive a second pulsed optical beam that is directed in a second optical path along the optical axis. A second optical focusing element is configured to focus the second pulsed optical beam to a second predetermined diameter at the electrically conductive surface on the transparent target. A TOF mass spectrometer comprising an ion accelerator having a central axis that is substantially coaxial with the optic axis so that ions generated by the first and second pulsed optical beams are accelerated by the ion accelerator. A controller instructs the TOF mass spectrometer to acquire mass spectral data at the plurality of predetermined locations, thereby generating a molecular image of the biological sample under analysis.

Molecular imaging of biological samples with sub-cellular spatial resolution and high sensitivity

A mass spectrometer system for analysis of clinical samples includes a source of clinical samples. A controller receives the clinical samples from the source of clinical samples. A sample preparation system receives clinical sample from the controller and processes the samples to produce an extract suitable for analysis by MALDI-TOF mass spectrometry and deposits the extract on a sample plate together with a MALDI matrix. A sample plate loading mechanism transports sample plates from the sample preparation system into an evacuated ion source of a MALDI-TOF mass spectrometer. A MALDI-TOF mass spectrometer ionizes and analyzes samples on the sample plate and generates a mass spectrum of components in the clinical samples. A computer system receives data from the MALDI-TOF mass spectrometer and processes and interprets the data to generate a mass spectrum.

Mass spectrometry method and apparatus for clinical diagnostic applications

An ion accelerator for a time-of-flight mass spectrometer includes a pulsed ion accelerator positioned proximate to a sample plate and having an electrode that is electrically connected to the sample plate. An accelerator power supply generates an accelerating potential on the ion accelerator electrode that accelerates a pulse of ions generated from the sample positioned on the sample plate. An ion focusing electrode is positioned after the pulsed ion accelerator. A potential applied to the ion focusing electrode focuses the pulse of ions into a substantially parallel beam propagating in an ion flight path. A static ion accelerator is positioned proximate to the ion focusing electrode with an input that receives the pulse of ions focused by the ion focusing electrode. The static ion accelerator accelerating the focused pulse of ions.

Ion optical system for MALDI-TOF mass spectrometer

A sample plate handling system for a time-of-flight mass spectrometer includes a transport chamber and a mass spectrometer chamber that is mechanically coupled to transport chamber. A vacuum chamber is coupled through a bypass valve to the transport chamber. A two-dimensional translation stage is positioned in the mass spectrometer chamber. A sample plate transporter is mounted on the two-dimensional translation stage. A first portion of the sample plate transporter is mechanically attached to the two-dimensional translation stage. A second portion of the sample plate transporter defines a sample plate receiver that is positioned in the transport chamber. A sealing orifice located between the first and the second portions connects the transport chamber and the mass spectrometer chamber. A motion of the two-dimensional translation stage in one direction aligns the sample plate transporter with the sealing orifice and a motion of the two-dimensional translation stage in the other direction moves the sealing surface of the sample plate transporter to engage the sealing orifice, thereby preventing gas flow between the mass spectrometer chamber and the transport chamber.

Method and apparatus for transporting samples in a mass spectrometer

A sample plate handling system for a time-of-flight mass spectrometer includes a transport chamber and a mass spectrometer chamber that is mechanically coupled to transport chamber. A two-dimensional translation stage is positioned in the mass spectrometer chamber. A sample plate transporter is mounted on the two-dimensional translation stage. A first portion of the sample plate transporter is mechanically attached to the two-dimensional translation stage. A second portion of the sample plate transporter defines a sample plate receiver that is positioned in the transport chamber. A sealing surface located between the first and the second portions connects the transport chamber and the mass spectrometer chamber. A motion of the two-dimensional translation stage in one direction aligns the sample plate transporter with the sealing orifice and a motion of the two-dimensional translation stage in the other direction moves the sealing surface of the sample plate transporter to engage the sealing orifice, thereby preventing gas flow between the mass spectrometer chamber and the transport chamber.

A sample plate handling system for a time-of-flight mass spectrometer includes a sample plate for supporting samples for analysis. A first sample plate receiver is positioned in a first chamber. First and second sample plate receivers are positioned in a second chamber. A first gate valve isolates the first and second chambers when closed and allows transfer of sample plates between the first sample plate receiver in the first chamber and one of the first and second sample plate receivers in the second chamber when the first gate valve is open. A first linear extender pushes a sample plate from the first sample plate receiver in the first chamber to the first sample plate receiver positioned in the second chamber, and then retracts a second sample plate from the second sample plate receiver positioned in the second chamber and transports the second sample plate to the first sample plate receiver in the first chamber. A first sample plate receiver is positioned in a third chamber. A second gate valve isolates the third chamber from the second chamber when closed and allows transfer of sample plates between the first sample plate receiver in the third chamber and one of the first and second sample plate receivers in the second chamber when the second gate valve is open. A second linear extender pushes a sample plate from the first sample plate receiver in the third chamber to the first sample plate receiver positioned in the second chamber, and then retracts the second sample plate from the second plate receiver positioned in the second chamber and transports it into the third chamber.

Method and apparatus for transporting sample plates between chambers of a mass spectrometer

A time-of-flight mass spectrometer includes a pulsed ion source that generates a pulse of ions from a sample to be analyzed. An ion lens focuses the pulse of ions into an ion beam. An ion deflector deflects the ion beam into a deflected ion beam path. An ion mirror is positioned in the deflected ion beam path so that a plane of constant ion flight time is parallel to an input surface of the ion mirror. The ion mirror decelerates and then accelerates ions so that ions of like mass and like charge exit the ion mirror in a reflected ion beam and reach an ion detector at substantially the same time. An ion detector is positioned in the path of the reflected ion beam so that a plane of constant ion flight time is substantially parallel to an input surface of the ion detector. The ion detector detects a time-of-flight of ions from the pulsed ion source to the ion detector that is substantially independent of a path traveled.

TOF mass spectrometry with correction for trajectory error

In various embodiments, provided are methods for focusing ions for an ion fragmentor, and methods for operating an ion optics assembly. In various embodiments, the present teachings provide methods that substantially maintain the position of the focal point of the an incoming ion beam over a wide range of collision energies, and thereby provide a collimated ion beam for a collision cell over a wide range of energies. In various embodiments, the present teachings provide methods that facilitate decreasing ion transmission losses over a wide range of collision energies.

Methods of operating ion optics for mass spectrometry

The present teachings relate to MALDI-TOF instruments, instrument components, and methods of operation thereof. In various aspects, the MALDI-TOF instrument can serve and be operated as a MS/MS instrument. In various embodiments, provided are MALDI-TOF instruments, and methods of operating one or more components of a MALDI-TOF instrument, that facilitate one or more of increasing sensitivity, increasing resolution, increasing dynamic mass range, increasing sample support throughput, and decreasing operational downtime.

Mass analyzer systems and methods for their operation

Provided are ion sources, methods of forming ions and mass analyzer systems. In various embodiments, the present teachings provide ion sources, methods for focusing ions from an ion source, and methods for operating a time-of-flight mass analyzer. In various embodiments, the present teachings relate to matrix-assisted laser desorption/ionization (MALDI) ion sources and methods of MALDI ion source operation, for use with mass analyzers. In various aspects, provided are ion sources and methods of operation thereof that facilitate increasing one or more of sensitivity and resolution of a TOF mass analyzer configured for multiple modes of operation.

Ion sources for mass spectrometry

Provided are MALDI ion sources, methods of forming ions and mass analyzer systems. In various embodiments, provided are MALDI ion sources configured to irradiate a sample on a sample surface with a pulse of laser energy at angle within 10 degrees or less of the surface normal, and a first ion optics system configured to extract sample ions in a direction within 5 degrees or less of the surface normal. In various embodiments, MALDI ion sources having substantially coaxial sample irradiation and ion extraction are provided. In various embodiments, methods are provided, which produce sample ions by MALDI and extract sample ions using an accelerating electrical field to form an ion beam, such that, the angle of the trajectory at the exit from the accelerating electrical field of sample ions substantially at the center of the ion beam is substantially independent of sample ion mass.

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Newton, MA, United States of America

Kevin Hayden