Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
1999-09-24
2002-12-03
Anderson, Bruce (Department: 2881)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S282000
Reexamination Certificate
active
06489610
ABSTRACT:
FIELD
The invention concerns mass spectrometers, and more specifically tandem time-of-flight mass spectrometers.
BACKGROUND
Mass spectrometry comprises a broad range of instruments and methodologies that are used to elucidate the structural and chemical properties of molecules, to identify the compounds present in physical and biological matter, and to quantify the chemical substances found in samples of such matter. Mass spectrometers can detect minute quantities of pure substances (regularly, as little as 10
−12
g) and, as a consequence, can identify compounds at very low concentrations (one part in 10
−12
g) in chemically complex mixtures. Mass spectrometry is a powerful analytical science that is a necessary adjunct to research in every division of natural and biological science and provides valuable information to a wide range of technologically based professions, such as medicine, law enforcement, process control engineering, chemical manufacturing, pharmacy, biotechnology, food processing and testing, and environmental engineering. In these applications, mass spectrometry is used to identify structures of biomolecules, such as carbohydrates, nucleic acids and steroids; sequence biopolymers, such as proteins and oligosaccharides; determine how drugs are used by the body; perform forensic analyses, such as confirmation and quantiation of drugs of abuse; analyze environmental pollutants; determine the age and origins of geochemical and archaeological specimens; identify and quantitate components of complex organic mixtures; and perform ultrasensitive, multi-element analyses of inorganic materials, such as metal alloys and semiconductors.
Mass spectrometers measure the masses of individual molecules that have been converted to gas-phase ions, i.e., to electrically charged molecules in a gaseous state. The principal parts of a typical mass spectrometer are the ion source, mass analyzer, detector, and data handling system. Solid, liquid, or vapor samples are introduced into the ion source where ionization and volatilization occur. The form of the sample and the size and structure of the molecules determine which physical and chemical processes must be used in the ion source to convert the sample into gas-phase ions. To effect ionization, it is necessary to transfer some form of energy to the sample molecules. In most instances, this causes some of the nascent molecular ions to disintegrate (either somewhere in the ion source or just after they exit the ion source) into a variety of fragment ions. Both surviving molecular ions and fragment ions formed in the ion source are passed on to the mass analyzer, which uses electromagnetic forces to sort them according to their mass-to-charge ratios (m/z), or a related mechanical property, such as velocity, momentum, or energy. After they are separated by the analyzer, the ions are successively directed to the detector. The detector generates electrical signals, the magnitudes of which are proportional to the number of ions striking the detector per unit time. The data system records these electrical signals and displays them on a monitor or prints them out in the form of a mass spectrum, i.e., a graph of signal intensity versus m/z. In principle, the pattern of molecular-ion and fragment-ion signals that appear in the mass spectrum of a pure compound constitutes a unique chemical fingerprint from which the compound's molecular mass and, sometimes, its structure can be deduced.
Tandem Mass Spectrometers
The utility of a mass spectrometric analysis can be significantly enhanced by performing two (or more) stages of mass analysis in tandem. A two-stage instrument is referred to herein as an MS/MS instrument. An MS/MS instrument performs two (or more) independent mass analyses in sequence. In the most frequently used mode of MS/MS, ions of a particular m/z value are selected in the first stage of mass analysis (MS
1
) from among all the ions of various masses formed in the source. The selected ions (referred to as precursor ions) are energized, usually by collision with a neutral gas molecule, to induce dissociation. The product ions of these dissociations are sorted into a product-ion mass spectrum in the second stage of mass analysis (MS
2
). If the sample is a pure compound and fragment-forming ionization has been used, individual fragment ions originating in the ion source can be selected as precursor ions; their product-ion spectra (which may be thought of as mass spectra within a mass spectrum) provide much additional structural information about the compound. If the sample is a mixture and nonfragment-forming ionization is used to produce predominantly molecular ions, the second stage of mass analysis can provide an identifying mass spectrum for each component in the mixture.
Independent operation of each stage of mass analysis makes possible other MS/MS operations based on changes in mass, charge, or reactivity and on the ability of the mass spectrometer to define those changes. MS/MS also can be used to substantially improve signal-to-background ratios and, therefore, sensitivity by eliminating interferences in certain types of operations when the ion signal at the m/z of interest is produced by more than one compound. Increasingly, MS/MS is being used to probe more precisely into problems of ion structure as well as to increase resolution in analyses of complex mixtures.
Time-of-Flight Mass Spectrometers
At present, the most widely used mass analyzers are magnetic sectors, quadrupole mass filters, quadrupole ion traps, Fourier-transform ion-cyclotron resonance cells, and time-of-flight (TOF) tubes. TOF mass analyzers are fundamentally the simplest and the least expensive to manufacture. They separate ions by virtue of their different flight times over a known distance. To create these different times, an ensemble of ions of like charge are accelerated to essentially equal kinetic energies and, in a brief burst, released from the ion source into the flight tube. Since an ion's kinetic energy is equal to ½ mv
2
(where m is its mass and v its velocity) and all ions of like charge have substantially the same energy, light ions will have greater velocities and, consequently, shorter flight times to the detector than heavy ions. The m/z values of each set of ions contained in a given burst out of the ion source can be determined by measuring their successive transit times from the ion source through the flight tube to the detector (typically several tens of microseconds).
A TOF mass spectrometer is unique in that its m/z-range is theoretically unlimited, and its mass spectra are not produced by scanning. Moreover, it is a relatively simple, inexpensive instrument to manufacture and operate. These three features account in large part for the major role TOF instruments have played in the rapidly expanding usage of mass spectrometry in molecular-biological research and biotechnology.
With the other four commonly used mass analyzers, the settings of one or more parameters determines the m/z of the ions that are allowed to pass to the detector. In order for ions with a different m/z to be detected, these settings must be increased or decreased. Ultimately, some fundamental or practical characteristic of the mass analyzer limits the extent to which its m/z-determining parameters can be changed to accommodate analysis of increasingly larger ions. In a TOF mass analyzer, increasingly larger ions simply take increasingly longer times to reach the detector, and there is no limit to the length of time that can be measured. Thus, TOF mass analyzers are especially useful for the analysis of large biological molecules.
Scanning denotes a continuous increasing or decreasing of a mass analyzer's m/z-determining parameters over a predetermined range so that ions over a corresponding range of m/z-values can be detected in succession. The analytical efficiency of a mass spectrometric analysis is greatly reduced by scanning because, while the ions of one particular m/z are being detected, the ions of all other m/z-va
Barofsky Douglas F.
Håkansson Per
Katz Daniel Louis
Piyadasa C. K. Gamini
Anderson Bruce
Klarquist & Sparkman, LLP
The State of Oregon acting by and through the State Board of Hig
LandOfFree
Tandem time-of-flight mass spectrometer does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Tandem time-of-flight mass spectrometer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tandem time-of-flight mass spectrometer will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2934321