Johns Hopkins University

Other

University System of Maryland

Robert J Cotter

Benjamin D Gardner

Vladimir M Doroshenko

Timothy J Cornish

Robert D English

Joseph P Steiner

Jennifer E Van Eyk

Wayne A Bryden

Avindra Nath

Scott A Ecelberger

Norman J Haughey

Catherine Fenselau

Rebekah Lynn Gundry

Serguei A Ilchenko

John F Holland

David Irani

Viatcheslav V Kovtoun

Caroline F Anderson

Methods and kits for diagnosis and prognosis using biomarkers comprising albumin-bound protein/peptide complex (ABPPC).

Albumin-bound protein/peptide complex as a biomarker for disease

Biological markers for multiple sclerosis, and their use in the diagnosis and prognosis of the disease, are described. Also described are methods for treating multiple sclerosis by administering an inhibitor of cathepsin B activity or a neuroprotective composition comprising a modified terpenoid compound. Also described are isolated polypeptide biomarkers, polynucleotides encoding the polypeptide biomarkers, and antibodies that bind specifically to the polypeptide biomarkers. Further described are kits that include the above-mentioned isolated polypeptide biomarkers, the polynucleotides encoding them, or specific antibodies against the polypeptide biomarkers.

Methods for diagnosis and optimizing treatment of multiple sclerosis

A tandem mass spectrometer includes a linear time-of-flight mass analyzer and curved field reflectron mass analyzer. The curved-field reflectron mass analyzer is disposed at an end of the linear time-of-flight mass analyzer such that ions having a plurality of ion masses formed in the linear time-of-flight analyzer such that ions having a plurality of ion masses formed in the linear time-of-flight analyzer enter the curved-field reflectron mass analyzer. The tandem mass spectrometer also includes a mass selection gate disposed between the time-of-flight mass analyzer and the curved-field reflectron mass analyzer. The mass selection gate selects an ion mass from the plurality of ion masses. Furthermore, the tandem mass spectrometer also includes a dissociating component located in a path of the ions formed in the linear time-of-flight analyzer. The dissociating component causes dissociation of the ions into a plurality of ion fragments.

Tandem time-of-flight mass spectrometer

A point-of-care mass spectrometer system has a sampling system, an ionization component structured to receive a sample for analysis from the sampling system, a mass analyzer structured to receive a source of ions for analysis from the ionization component, and a detector structured to detect ions from the mass analyzer and to generate an output signal. The sampling system selects a subset of peptides from a sample by immunopurification of multiple histocompatability complexes and concentrates the subset of peptides to provide the sample to the ionization component.

Point-of-care mass spectrometer system

A time-of-flight mass spectrometer has a first electrode, a second electrode spaced apart from the first electrode, a third electrode arranged between the first and second electrodes. The third electrode reserves a space for ions to travel between the first and second electrodes. The time-of-flight mass spectrometer further includes a sample probe disposed proximate the first electrode and adapted to hold a sample, and a detector disposed proximate the second electrode. The first electrode is adapted to be connected to a voltage source to cause a difference in voltage between the first and second electrodes to provide an electric field therebetween that changes non-linearly along an ion path between the sample probe and the detector for accelerating ions to be detected.

Non-linear time-of-flight mass spectrometer

A time-of-flight mass spectrometer which has an iron source, an evacuated tube proximate the ion source and adapted to receive ions from the ion source, and a detector disposed at an end of the evacuated tube opposite an end proximate the ion source. The ion source is constructed to generate an electric field that changes non-linearly as a function of position along a path from the ion source to the detector. The ion source is constructed to generate an electric field that changes as a function of time, the electric field being provided to accelerate ions from the ion source to the detector.

Time-of-flight mass spectrometer combining fields non-linear in time and space

A mass spectrometer is provided herein and is configured to have two ionization sources, in which a first ionization source, such as MALDI, ESI and the like, which is capable of providing in addition to ions a set of normally intractable desorbed neutrals that are ionized by a second EI source coupled with the first source.

Combined chemical/biological agent detection system and method utilizing mass spectrometry

A mass spectrometer including an ion source, a detector, a first end cap electrode arranged proximate to the ion source, a second end cap electrode arranged proximate the detector, and a ring electrode arranged between the first and the second end cap electrodes. The ring electrode can be either connected to a radio-frequency voltage source or to a constant voltage source. When the ring electrode is connected to the radio-frequency voltage the first end cap, the second end cap and the ring electrode form an ion trap and the mass spectrometer operates as an ion trap mass spectrometer. When the ring electrode is connected to a constant voltage the mass spectrometer operates as a time-of-flight mass spectrometer.

Combined chemical/biological agent mass spectrometer detector

A mass spectrometer that includes an ionizing source, a sample holder arranged in a beam path of the ionizing source, an ion detector disposed to receive ions extracted from a sample when held by the sample holder and irradiated by the ionizing source. The mass spectrometer also includes an extraction electrode arranged proximate to the sample holder, and a drift tube arranged between the extraction electrode and the ion detector. In the mass spectrometer, the extraction electrode and the drift tube are movable together relative to the sample holder, which is held at a fixed position.

Miniaturized sample scanning mass analyzer

A time-of-flight mass spectrometer includes a sample holder for a sample and an ionizer for ionizing the sample to form ions. A first element is spaced downstream from the sample holder, a second element is spaced downstream from the first element, and a drift region is downstream of the second element. An electric field is established between the sample holder and the first element at a time subsequent to ionizing the sample in order to extract the ions. A time-dependent and mass-correlated electric field is established between at least one of: (a) the first element and the second element, and (b) the sample holder and the first element. In turn, a detector detects the ions.

Method and apparatus of mass-correlated pulsed extraction for a time-of-flight mass spectrometer

The present invention provides for a reflectron time-of-flight mass spectrometer in which there exists a curved field in a portion of the reflectron that takes into account acceleration and deceleration fields in upstream (from the ion source down to the reflectron) and downstream (from the reflectron down to the ion detector) regions, which are always present in any TOF-MS. The reflectron includes a decelerating section and a correcting section, with curved electric fields in the correcting and/or decelerating sections of the reflectron being considered. Moreover, analytic expressions are provided for calculating the profiles of the curved electric field in the second (correcting) section of the reflectron, which expressions are valid for arbitrary electric field distributions in the upstream and downstream regions as well as in the first (deceleration) section of the reflectron. These profiles will depend on the electric field distributions in the upstream and downstream regions and in the first (deceleration) section of the reflectron.

Method and apparatus for correction of initial ion velocity in a reflectron time-of-flight mass spectrometer

A reflectron for use with a mass spectrometer that focuses ions having different energies contains a conductive end cap that is electrically connected to a first voltage. A conductive surface is electrically isolated from the end cap and connected to a second voltage. This conductive surface cooperates with the conductive end cap to establish an inner region in which a non-linear electric field exists. As a result, ions having different energies enter and exit the inner region at a common opening and, when within the inner region, are reflected without penetrating past the conductive surface.

End cap reflection for a time-of-flight mass spectrometer and method of

A method of operation of an ion trap mass spectrometer which isolates a first group of ions having a mass-to-charge ratio range is disclosed. The method includes producing ions from a plurality of atoms or molecules; trapping the ions in an ion trap by applying a trapping voltage to a ring electrode; applying an excitation voltage to a pair of end-cap electrodes; employing as the excitation voltage a first broadband excitation waveform and a second broadband excitation waveform, with the first waveform exciting the ions excluding substantially all of the first group and also excluding substantially all of a second group of ions having a range of mass-to-charge ratios about the first group's mass-to-charge ratio range, and the second waveform exciting the second group; applying the first waveform in order to eject the ions excluding substantially all of the first and second groups; and applying the second waveform in order to successively eject the second group of ions, according to the mass-to-charge ratios thereof, excluding substantially all of the first group of ions, thereby isolating the first group of ions. In another embodiment, the excitation voltage is a broadband excitation waveform having first, second, and third excitation portions, with the first and third portions exciting the ions excluding substantially all of the first group and also excluding substantially all of the second group, and the second portion exciting the second group. Associated apparatus is also disclosed.

Method and apparatus for isolating ions in an ion trap with increased

A method of operation of an ion trap mass spectrometer having a ring electrode and pair of end-cap electrodes in a resonance ejection mode is disclosed. The method includes producing ions from a plurality of biomolecules, applying a trapping RF voltage to the ring electrode, applying an excitation voltage to the end-cap electrodes, scanning the trapping RF voltage in order to sequentially eject the ions, controlling a ration of the amplitude of the trapping RF voltage to the amplitude of the excitation voltage in order that the ratio is generally constant, and determining a ratio of mass to charge of the ejected ions. In one embodiment, a feedback voltage which is proportional to the trapping RF voltage is sensed, and the amplitude of the excitation voltage is controlled as a function of the amplitude of the feedback voltage. In another embodiment, a first value related to the amplitude of the trapping RF voltage and a second value, which is proportional to the first value and related to the amplitude of the excitation voltage, are determined. The amplitude of the trapping RF voltage is modulated employing the first value and the amplitude of the excitation voltage is modulated employing the second value. Preferably, the determined mass-to-charge ratio (m/z) of the ejected ions is equal to a constant (.alpha.) times the trapping RF voltage (V). Associated apparatus and method of calibration are also disclosed.

Method and apparatus for scanning an ion trap mass spectrometer in the

A reflectron capable of focusing an entire mass range of product ions at substantially the same focal point, comprising a plurality of lens plates, each having an opening therein, for generating a non-linear electric field in the reflectron. To generate the non-linear electric field, the voltage applied to each successive lens plate increases non-linearly with respect to its adjacent lens plate. The voltage of the first lens plate having the opening through which the ions first enter the reflectron is set to a low potential and the voltage being applied to each successive lens plate increases in a non-linear manner with the largest voltage being applied to the lens plate furthest from the first lens plate. This non-linear voltage application, to generate the non-linear electric field, can be achieved by coupling a potentiometer between each lens plate and adjusting each potentiometer accordingly. Alternatively, to generate the non-linear electric field, the lens plates may be unequally spaced and an equal voltage may be applied to each lens plate.

Growing community of inventors

Baltimore, MD, United States of America

Robert J Cotter