Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means
Reexamination Certificate
2000-07-17
2002-07-09
Nguyen, Kiet T. (Department: 2881)
Radiant energy
Ionic separation or analysis
Cyclically varying ion selecting field means
C250S3960ML
Reexamination Certificate
active
06417511
ABSTRACT:
TECHNICAL FIELD
This invention relates to mass spectrometry. In particular, the invention relates to an ion beam guide apparatus, systems and method for use in mass spectrometry.
BACKGROUND ART
Mass spectrometry is an analytical methodology used for quantitative elemental analysis of materials and mixtures of materials. In mass spectrometry, a sample of a material to be analyzed, called an analyte, is broken into particles of its constituent parts and some of the particles are given an electric charge. Those particles, referred to hereinbelow as analyte ions, are typically molecular in size. Once produced, the analyte ions are separated by the spectrometer based on their respective masses. The separated analyte ions are then detected and a “mass spectrum” of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed. The mass spectrum provides information about the masses and in some cases the quantities of the various analyte particles that make up the sample. In particular, mass spectrometry can be used to determine the molecular weights of molecules and molecular fragments within an analyte. Additionally, mass spectrometry can identify components within the analyte based on the fragmentation pattern when the material is broken into particles. Mass spectrometry has proven to be a very powerful analytical tool in material science, chemistry and biology along with a number of other related fields.
Many forms of mass spectrometry produce analyte ions at relatively high pressures compared to the pressures extant in other portions of the mass spectrometer. For example, Atmospheric Pressure Matrix Assisted Laser Desorption Ionization (AP-MALDI), Field Asymmetric Ion Mobility Spectrometry (FAIMS), Atmospheric Pressure Ionization (API, including its subsets, such as Electrospray Ionization (ESI) and Atmospheric Pressure Chemical Ionization (APCI)), and Inductively Coupled Plasma (ICP) mass spectrometry, are a few forms of mass spectrometry using high pressures for ionization that are known in the art. All of these mass spectrometric methods generate ions at or near atmospheric pressure (760 Torr). Once generated, the analyte ions must be introduced or sampled into the mass spectrometer. Typically, the interior portions of a mass spectrometer are maintained at high vacuum levels (<10
−4
Torr) or even ultra-high vacuum levels (<10
−7
Torr). In practice, sampling the ions requires transporting the analyte ions in the form of a narrowly confined ion beam from the ion source to the high vacuum mass spectrometer chamber by way of one or more intermediate vacuum chambers. Each of the intermediate vacuum chambers is maintained at a vacuum level between that of the proceeding and following chambers. Therefore, the ion beam transporting the analyte ions transitions in a stepwise manner from the pressure levels associated with ion formation to those of the mass spectrometer.
At interfaces between each chamber, the ion beam passes from one chamber to the next through small apertures or orifices. The apertures are small enough that each of the intermediate vacuum chambers can maintain the desired vacuum level using a vacuum pump in spite of gas leakage that occurs between chambers at the aperture.
To be effective in mass spectrometer application, the ion beam must be able to transport the analyte ions through each of the intermediate vacuum chambers and into the mass spectrometer without significant loss of ions. Loss of ions typically occurs due to interaction with gas molecules inside the intermediate vacuum chambers. While the ion beam is passing through the intermediate vacuum chamber, analyte ions can and do collide with gas molecules present causing the ions to be slowed down or “stalled out”. Ions that are sufficiently slowed by this interaction will tend to drift to the walls of the intermediate vacuum chambers where they are “trapped” and subsequently lost from the beam.
Even if significant ion loss does not occur, the interaction between analyte ions of the beam and gas molecules present in the intermediate vacuum chambers can also cause the beam to widen or to spread. If the beam is widened too much, the number of analyte ions that will ultimately pass through the aperture at an output end of the chamber will be reduced by an unacceptable amount. Therefore, ion beams that carry the analyte ions through intermediate vacuum chambers are generally transported using “ion guides”. The use of ion guides is primarily intended to minimize the loss of ions being transported and to control the ion beam volumetric and energy characteristics.
Ion guides are devices that utilize electromagnetic fields to confine the ions radially (x and y) while allowing or even promoting ion transport axially (z). Franzen, “Electrical Ion Guides”, 1996
ASMS Conference Proceedings,
p 1170 provides a short overview of the two principal types of electrical ion guides: the electrodynamic ion guides and the electrostatic ion guides. Electrodynamic ion guides employ repellent inhomogeneous radio frequency (RF) fields to create electric pseudo-potential wells to confine the analyte ions as they travel through the guide. Common electrodynamic type ion guides include for example, RF multipoles and ring stacks. Electrostatic ion guides utilize attracting forces around a thin wire or similar mechanism to control the motion of the analyte ions in the guide.
In addition to controlling the ion beam during transport, it is often necessary to reduce the phase space volume of the ion beam at certain points during transport. Phase space volume refers to a six dimensional space of x, y and z position and x, y and z momentum. An example of this is the need to reduce the beam diameter to maximize its transmission through small diameter apertures in the vacuum chamber interfaces. Beam diameter reduction may require “collisional focusing” and/or “collisional cooling” of the ion beam. Collisional focusing/cooling is generally accomplished with the ion guide at elevated pressures.
Collisional focusing is the use of repeated collisions of ions with neutral molecules in a suitably confining electromagnetic field, thereby reducing the radial position and/or energy of the beam. That is, the ions are focused into a smaller, more parallel beam. For more information about collision focusing see, for example, D. J. Douglas and J. B. French, “Collision Focusing Effects in Radio Frequency Quadrupoles”,
J. Am. Soc. Mass Spectrom.,
3 (1992) pp. 398-408.
Collisional cooling is the use of repeated collisions of ions with neutral molecules to retard the average axial energy of the ion beam and to narrow its distribution. In other words, the beam has a lower, more uniform axial energy. To a first order, the number of collisions an ion is subjected to is dependent on the “collision cross section” of the ion and the “gas thickness”. Collision cross section is the effective area for scattering or reaction between two specified particles. Gas thickness is the product of neutral gas density and ion path length.
Generally it takes considerably more collisions to focus a beam than to cool it. It takes higher neutral gas density or longer ion path length to focus or cool ions with small cross sections. And further, it takes more collisions to cool or focus ions with larger masses. Thus, a complicated situation may result where the neutral gas pressure that yields a gas thickness high enough to guarantee adequate cooling and/or focusing of all ions may be too high for many of the ions involved. In other words, some ions, particularly low mass ions, may be overly cooled and can become “trapped” or have their axial velocities reduced below a practical or preferable level.
Also, it is sometimes desirable or even necessary to perform several stages of ionization with intermediate mass spectrometric stages, generically referred to as “MS/MS”. In one common implementation, called a “Triple Quad”, molecules are ionized (creating the “parent” ions), mass-filtered, fragmented (creating the “dau
Fischer Steven M.
Russ, IV Charles W.
Agilent Technologie,s Inc.
Nguyen Kiet T.
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