Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means
Reexamination Certificate
2003-01-08
2004-04-13
Nguyen, Kiet T. (Department: 2881)
Radiant energy
Ionic separation or analysis
Cyclically varying ion selecting field means
Reexamination Certificate
active
06720555
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to mass spectrometry and more particularly to an apparatus and method for ion mass spectrometry that detects ions via ion cyclotron resonance.
BACKGROUND OF THE INVENTION
Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS or FTMS) is a generally known instrumental method that offers higher mass resolution, greater mass resolving power, and higher mass accuracy than other currently available mass analysis methods. The principles of the FTICRMS are well described in several recent review articles and the articles referenced therein. These review articles include: A. Marshall,
Milestones in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Technique Development
, International Journal of Mass Spectrometry, Volume 200, 2000, pp. 331-356; Amster, I. J.,
Fourier Transform Mass Spectrometry
, J. Mass Spectro. 1996, 31, 1325-1337; A. Sarah, E. Lorenz, P. Maziarz III, and T. Wood,
Electrospray Ionization Fourier Transform Mass Spectrometry of Macromolecules: The First Decade
, Applied Spectroscopy, Volume 53, No. 1, 1999, pp. 18A-36A, and A. Marshall and C. Hendrickson,
Fourier Transform Ion Cyclotron Resonance Detection: Principles and Experimental Configurations
, International Journal of Mass Spectrometry, Volume 215, 2002, pp. 59-75.
The performance of the FTICRMS is achieved through the combination of electric and magnetic fields, and is based upon the principle of ion cyclotron resonance (ICR). See, Lawrence, E. O.; Livingston, M. S.,
The cyclotron
, Phys. Rev. 1932, 40, 19. Ions in the presence of a uniform static magnetic field are constrained to move in circular orbits in the plane perpendicular to the magnetic field and are unrestricted in its motion parallel to the field. The radius of this circular motion is dependent on the momentum of the ions in the plane perpendicular to the magnetic field. The frequency of the circular motion (cyclotron frequency) is a function of the mass-to-charge ratio of the ion and the magnetic field strength. Furthermore, trapping electrodes provide a static electric field, which prevent the ions from escaping along the magnetic field line. The ions are confined within the trap and as long as the vacuum is substantially high (typically <10
−9
mbar), ion
eutral collisions are minimized and the ion trapping duration is maximized. Under such conditions, ions can be contained for a long period of time, which in a general mass spectrometry experiment is typically on the order of several seconds.
When the ions are initially trapped, they have an initial low amplitude cyclotron radius defined by their thermal velocity distribution and their initial radial positions. This low amplitude motion is of random initial phase, a state called “incoherent” oscillatory motion. While these ions are trapped, an oscillating electric field can be applied perpendicular to the magnetic field causing those ions having a cyclotron frequency equal to the frequency of the oscillating electric field to resonate. The resonant ions absorb energy from the oscillating electric field, accelerate, gain kinetic energy and move to a higher orbital radii. This process, termed “ion excitation”, adds a large amplitude coherent cyclotron motion on top of the low initial thermal amplitude incoherent cyclotron. The net effect is that ions of a given cyclotron frequency, and hence mass, orbit as a packet. When the applied excitation field is switched off, the ions stop absorbing energy and the packet then orbits the chamber at the fundamental cyclotron frequency of the ions that make up this packet. The ion packet produces a signal by inducing onto nearby electrodes an image potential that oscillates at the same cyclotron frequency. This signal induced on the electrode can be amplified, detected, digitized, and stored in computer memory. The signal is typically in the form of a damped sine wave function with the characteristic frequency as described above. As long as the magnetic field in which ions are confined is relatively homogeneous, frequency can be measured very accurately and consequently, the mass-to-charge ratio can be measured with high accuracy.
U.S. Pat. No. 3,937,955, entitled “Fourier Transform Ion Cyclotron Resonance Spectroscopy Method and Apparatus”, teaches a method of detecting the signal with a broadband amplifier and subsequently performing a Fourier transformation of the signal to provide a complete mass spectrum. This technique allows for acquiring and detecting all ions simultaneously and with very high mass accuracy.
U.S. Pat. No. 4,535,235, entitled “Apparatus and method for injection of ions into an ion cyclotron resonance cell”, teaches that ions generated external of the magnet field can be injected into the ICR cell for analysis. Accordingly, prior to injecting the ions into the ICR, the ions are transmitted along an ion guide, subjected to electric fields for various functions such as mass selection and energy damping. While the ions are trapped within the ICR cell, other techniques are performed to enhance trapping and fragmentation.
It is generally known that virtually every aspect of FTICRMS performance improves at higher magnetic field. For example, if one compares a 14 Tesla magnet to the 7 Tesla instruments that are currently widely available, resolution and signal intensity will triple, mass accuracy will improve by a factor of 2, collisionally activated dissociation (CAD) fragmentation energy will increase by a factor of 4, upper m/z limit will increase by a factor of 4.
High field magnets of the type used in FTICRMS are generally electromagnets and, more specifically, due to the field strength, stability and homogeneity advantages of modern superconducting materials, they are superconducting electromagnets. Currently available superconducting magnet materials must be maintained at low temperature (variable, but typically <10K) to retain their superconductivity. Therefore, these magnets are usually cooled by immersion in liquid helium (~4.2K). Due to the relatively high cost of liquid helium, this immersion vessel, called a Dewar, is then subsequently immersed in liquid nitrogen (which is much less expensive) to decrease the helium boil-off rate. New methods of cryorefrigeration as taught by U.S. Pat. No. 5,848,532, have recently been applied to greatly decrease the boil-off of liquid nitrogen and helium cryogens, and some companies now offer superconducting magnet systems that are completely cryogen free.
Applying superconducting electromagnets to the FTICRMS experiment results in some compromises between the ideal superconducting electromagnet design and the ideal FTICRMS experiment. In general, the narrower the bore size of the magnet, the easier it is to generate higher magnetic fields with sufficient homogeneity and stability for FTICRMS. However, a narrow magnet bore diameter also means that the vacuum chamber that housed the FTICRMS experiment must also be narrow thus restricting the pumping speed of the system. Typical FTICRMS vacuum chambers currently used are in the range of 100 to 150 mm representing a tradeoff between the mutually exclusive goals of achieving high magnetic field and high vacuum simultaneously with current FTICRMS designs. If one were to design a higher magnetic field system with a bore diameter sufficient to accommodated the above-indicated vacuum chamber, and with the required magnetic field homogeneity (typically <10 ppm over a 5 cm diameter by 5 cm long cylindrical region), the magnet will require a larger number of windings and larger size magnets (and larger Dewar). This translates into a higher system cost and larger footprint. Since both lab space and funding are shrinking commodities, this approach, while workable, is undesirable.
Another approach of providing higher magnetic field is a reduction to the bore diameter while maintaining the number of windings and magnet size. The magnets used throughout the NMR field provide 0.1 ppm homogeneity over a 1 cm spherical volume (which is more than sufficient for FTM
Leydig , Voit & Mayer, Ltd.
Nguyen Kiet T.
Trustees of Boston University
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