Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
2003-10-17
2004-12-07
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S3960ML, C250S294000, C250S299000, C315S500000, C315S501000, C315S502000, C315S503000, C315S504000, C315S505000
Reexamination Certificate
active
06828553
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to a compact time-of-flight mass spectrometer which enables very accurate mass determinations.
BACKGROUND OF THE INVENTION
The best choice of mass spectrometer for measuring the mass of large molecules, as undertaken particularly in biochemistry, is a time-of-flight mass spectrometer because it does not suffer from the limited mass range of other mass spectrometers. Time-of-flight mass spectrometers are frequently abbreviated to TOF or TOF-MS.
Two different types of time-of-flight mass spectrometer have been developed. The first type comprises time-of-flight mass spectrometers for measuring ions which are generated in pulses in a tiny volume and accelerated axially into the flight path, for example with ionization by matrix-assisted laser desorption, MALDI for short, a method of ionization suitable for ionizing large molecules.
The second type comprises time-of-flight mass spectrometers for the continuous injection of an ion beam, one section of which is ejected as a pulse in a “pulser” transversely to the direction of injection and forced to fly through a mass spectrometer with reflector as a linearly spread ion beam lying transverse to the direction of flight, as the schematic in
FIG. 1
shows. A ribbon-shaped ion beam is therefore generated in which ions of the same type, i.e. with the same mass-to-charge ratio, form a transverse front. This second type of time-of-flight mass spectrometer is known for short as an “Orthogonal Time-of-Flight Mass Spectrometer” (OTOF); it is mainly used in conjunction with out-of-vacuum ionization. The most frequently used type of ionization for this type of mass spectrometer is electrospray ionization (ESI). Electrospray ionization (ESI) is suitable for ionizing large molecules in much the same way as MALDI. It is also possible to use other types of ionization, for example chemical ionization at atmospheric pressure (APCI), photoionization at atmospheric pressure (APPI) or matrix-assisted laser desorption at atmospheric pressure (AP-MALDI). Ions generated in-vacuum can also be used. Before they enter the OTOF, the ions can also be selected and fragmented in appropriate devices so that the fragments can be used to improve the characterization of the substances.
In this second type of time-of-flight mass spectrometer, a large number of spectra, each with relatively low ion counts, are generated by a very high number of pulses per unit of time (up to 20,000 pulses per second) in order to utilize the ions of the continuous ion beam as effectively as possible.
As with all mass spectrometers, with a time-of-flight mass spectrometer one can only determine the ratio of the mass m of the ion to the number z of elementary charges which the ion carries. Any subsequent reference to “specific mass” or quite simply to “mass” on its own always means the ratio m/z. If, by way of exception, “mass” in the following text is to be taken to mean the physical dimension of the mass, it will be specifically called molecular mass The unit of molecular mass m is the “unified atomic mass unit”, abbreviated to “u”, usually simply termed “mass unit” or “atomic mass unit”. In biochemistry and molecular biology, the unit “Dalton” (“Da”) is still frequently used. The unit of specific mass m/z is “atomic mass unit per elementary charge” or “Dalton per elementary charge”, where the elementary charge is the charge on an electron (if negative) or proton (if positive).
FIG. 1
shows the principle of a reflector time-of-flight mass spectrometer with orthogonal ion injection. In the pulser, the ions are accelerated transversely to their direction of injection (x-direction); the direction of acceleration is called the y-direction. The ions leave the pulser through slits in slit diaphragms, which can also be used for angular focusing in a z-direction which is at right angles to the x- and y-directions. After being accelerated, however, the ions have a direction which lies between the y-direction and the x-direction, since they fully retain their original velocity in the x-direction. The angle to the y-direction is &agr;=arctan √(E
x
/E
y
), where E
x
is the kinetic energy of the ions in the primary beam in the x-direction and E
y
the energy of the ions after being accelerated in the y-direction The direction in which the ions fly after the pulsed ejection is independent of the mass of the ions.
The ions which have left the pulser now form a broad ribbon, where ions of the same type (the same specific mass m/z) are all to be found in one front, which has the width of the beam in the pulser: Light ions fly faster, heavy ones slower, but all fly in the same direction, with the exception of possible slight differences in direction which can arise as a result of the slightly different kinetic energies E
x
of the ions as they are injected into the pulser. These ions are therefore injected as monoenergetically as possible. The field-free flight path must be completely surrounded by the accelerating potential in order not to disturb the ions in flight.
As reported by W. C. Wiley and I. H. McLaren (Rev Sci Instrum 26 (1955) 1150), ions with the same specific mass which are at different locations of the beam cross section can be time-of-flight focused with respect to their different start locations by selecting the field in the pulser in such a way when switching on the outpulsing voltage that the ions furthest away are given a slightly higher acceleration energy to enable them to catch up with the leading ions again in a time-of-flight focal point. The time-of-flight focal point can be positioned as desired by means of the outpulse field strength in the pulser. This converts the initial spatial dispersion of the ions into an energy dispersion. The energy dispersion is compensated by the reflector in the known way.
To scan ion beams in time-of-flight spectrometers, instruments currently commercially available incorporate so-called channel plate secondary-electron multipliers by which the ion beams are amplified; these amplified currents are fed into fast transient recorders. The fast transient recorders digitize the amplified ion beams at the rate of one to four gigahertz in analog-to-digital converters with a signal resolution of usually eight bits.
In order to achieve a high resolution, the mass spectrometers (both axial and orthogonal time-of-flight mass spectrometers) are equipped with at least one energy focusing reflector which reflects the outpulsed ion beam toward the ion detector, thereby accurately time focusing ions of the same mass but slightly different initial kinetic energy in the y-direction onto the large-area detector. The ions fly out of the (last) reflector towards a detector which, in the case of orthogonal time-of-flight mass spectrometers, must be of the same width as the ion beam in order to be able to measure all incident ions. This detector also must be aligned parallel to the x-direction, as shown in
FIG. 1
, in order to also concurrently detect the front of flying ions of the same mass.
The resolution R and the mass accuracy of a time-of-flight mass spectrometer are proportional to the flight distance. It is therefore possible to increase the resolution by selecting a very long flight tube or by introducing several reflectors to produce multiple reflections. For example, with a flight path of one and a half meters one can achieve a mass resolution of around R=m/&Dgr;m=10,000; with around six meters, a mass resolution of R=m/&Dgr;m=40,000 (where &Dgr;m is the line width of the ion signal at half maximum, measured in mass units).
Flight tubes of several meters in length are very inconvenient because they result in unwieldy instruments. Multiple reflections are also problematic, however, because, until now, the angular focusings of the divergent ion beam, which are actually very desirable, have not been satisfactorily solved.
It is, however, also known that time-of-flight mass spectrometers exist which incorporate cylindrical capacitors in the flight path, thus enabling a small
Bruker Daltonik GmbH
Lee John R.
Souw Bernard E.
LandOfFree
Compact very high resolution 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 Compact very high resolution time-of flight mass spectrometer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compact very high resolution time-of flight mass spectrometer will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3336018