Membrane detector for time-of-flight mass spectrometry
AssigneeWisconsin Alumni Research Foundation
InventorsRobert Blick, Jonghoo Park
Life of this patent
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Abstract
The invention provides methods, and related devices and device components, for detecting, sensing and analyzing analytes in samples. In some aspects, the invention provides methods, and related devices and device components, useful in combination with a mass analyzer for the mass spectrometric analysis of analytes derived from biomolecules in biological samples including biological fluids cell extracts, and cell lysates. Methods of some aspects of the invention utilize a thin membrane-based detector as a transducer for converting the kinetic energies of analytes into a field emission signal via excitation of mechanical vibrations in an electromechanically biased membrane by generation of a thermal gradient.
Claims25
A method of detecting analytes, the method comprising:
- a) providing a detector comprising:
- a membrane having a receiving surface for receiving the analytes, and an internal surface positioned opposite to the receiving surface, wherein the membrane is a material selected from the group consisting of a semiconductor, a metal and a dielectric material, and wherein the membrane has a thickness selected from the range of 5 nanometers to 50 microns;
- a holder for holding the membrane, wherein said holder contacts said membrane at one or more contact points;
- an extraction electrode positioned so as to establish an applied electric field on the internal surface of the membrane or an electron emitting layer provided on the internal surface of the membrane, thereby causing emission of electrons from the internal surface or the electron emitting layer;
- and
- an electron detector positioned to detect at least a portion of the electrons emitted from the internal surface or the electron emitting layer;
- b) generating a non-uniform temperature distribution along a thickness dimension, lateral dimension, vertical dimension or any combination of these of the membrane by contacting the receiving surface with the analytes, thereby exciting a mechanical deformation of the membrane that modulates the emission of electrons from the internal surface of the membrane or the emitting layer;
- and
- c) detecting the electrons emitted from the internal surface of the membrane or the emitting layer.
A method of detecting ions, the method comprising:
- a) providing a detector comprising:
- a membrane having an receiving surface for receiving the ions, and
- an internal surface positioned opposite to the receiving surface, wherein the membrane is a material selected from the group consisting of a semiconductor, a metal and a dielectric, and
- wherein the membrane has a thickness selected from the range of 5 nanometers to 50 microns;
- a holder for holding the membrane, wherein said holder contacts said membrane at one or more contact points;
- an extraction electrode positioned so as to establish an applied electric field on the internal surface of the membrane or an electron emitting layer provided on the internal surface of the membrane, thereby causing emission of electrons from the internal surface or the electron emitting layer;
- and
- an electron detector positioned to detect at least a portion of the electrons emitted from the internal surface or the electron emitting layer;
- b) passing the ions through a mass analyzer to achieve physical separation on the basis of mass-to-charge ratio;
- c) generating a non-uniform temperature distribution along a thickness dimension, lateral dimension, vertical dimension or any combination of these of the membrane by contacting the receiving surface with the ions, thereby exciting a mechanical deformation of the membrane that modulates the emission of electrons from the internal surface of the membrane or the emitting layer;
- d) detecting the electrons emitted from the internal surface of the membrane or the emitting layer;
- e) measuring intensities of the electrons emitted from the internal surface of the membrane or the emitting layer as a function of time, thereby generating a response signal characterized by one or more peaks at different times, wherein each peak is characterized by a maximum value;
- f) identifying a first peak corresponding to an earliest time;
- and
- g) determining the maximum value corresponding to the first peak.
Dependencies are inferred from the claim text.