Radiant energy – Ionic separation or analysis
Reexamination Certificate
2002-04-24
2003-10-07
Nguyen, Kiet T. (Department: 2881)
Radiant energy
Ionic separation or analysis
C250S282000, C250S290000
Reexamination Certificate
active
06630662
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a method of and an apparatus for separating ions based on their mobility in a gas. More particularly, the invention is based on counteraction of forces from an axial electric field and drag of the gas flow. The invention is intended to improve the resolution of mobility separation and to facilitate coupling of a mobility separation stage to a mass spectrometer
BACKGROUND OF THE INVENTION
Mobility separation, also known as ion mobility separation, can be a useful method on its own or in combination with mass spectrometry. Mobility separation is widely used nowadays, but it suffers from some drawbacks. Firstly, mobility separation is a relatively low resolution technique; typical resolution ranges from 10 to 300. Another significant drawback is low efficiency. Ion transmission can be poor due to diffusion spreading of the ion beam as well as due to low duty cycle in sampling. Diffusion spreading can become an important problem if a mobility separation stage needs to be coupled to a mass spectrometer. The duty cycle inefficiency arises, since once a packet of ions is introduced into the drift tube of an ion mobility spectrometer, no further ions can be introduced until the first packet of ions has completely cleared the drift tube.
In many ion mobility spectrometers, the residence time is relatively short (e.g., 1-10 milliseconds) so that diffusion spreading is not significant. It can be allowed for by providing a detector with a suitably large capture area, to accept a wide beam.
One of the ways to overcome diffusion spreading is described in U.S. Pat. No. 5,487,386 and assigned to the assignee of the present invention. This patent describes an ion guide with an axial field setup or arrangement, where radial confinement is accomplished in the ion guide and mobility separation can occur along the axis, due to effect of the axial field. Still, this setup or arrangement suffers from diffusion along the axis that causes significant peak broadening and thus low resolution, with a resolution of around 10 being obtained with practical parameters. A longer ion guide and higher operating pressure allow a higher resolution to be obtained, but there are practical limits to the length and operating pressure of the ion guide. Losses due to the low duty cycle can be eliminated in this setup by using ion accumulation upstream in a dedicated trap or in a portion of the ion guide that is acting as a trap.
SUMMARY OF THE INVENTION
The present invention is based on the realization that a significant improvement can be obtained if an in guide with an axial field is combined with a counter flow of gas to carry out mobility separation. More particularly, the invention is based on the observation that there are then two forces available to drive ions along the axis of the ion guide filled with gas: the axial electric field and the drag of the gas flow. When the forces are equal and act on the ions in opposite directions, the ion position will be virtually stationary. The radial motion is confined by RF forces, and thus the ions can reside or be trapped inside the ion guide for an extended period of time, without significant losses. The ions then can be moved in one direction or another by a small change in one of the axial forces.
A further important consideration is that by applying counteracting forces, which in the limit could balance one another, ion residence times become much larger. Residence times, practically, are limited by depopulation due to chemical reaction, which in turn depends on preventing impurities being present. Residence times could be of the order of seconds.
As the magnitude of each force is specific for each type of ion, this counteraction effect can be used for separation. Mobility characteristics vary widely and can thus offer more opportunities for separating ions. The present invention selects the ions based, at least in part, on their mobility coefficients. Indeed, when two forces balance each other, it means that the velocity of the ion through the gas, in the axial direction, caused by the electric field matches the velocity of the gas flow. For a fixed velocity of the gas flow, flowing from the exit towards the inlet of the ion guide, the ions will be extracted slightly above the point where their mobility coefficient is sufficient to create the same ion velocity under the applied electric field.
The present inventor has also realized that numerous practical arrangements or setups can be developed from the basic principle. One characteristic differentiating the various arrangements is the direction of the gas flow. An arrangement will be called “forward” when the gas flow is directed away from the inlet of an ion guide to its exit; and correspondingly will be called “backward” when the gas flow directed from the exit towards the inlet of the ion guide. The magnitude of either the electrical field force of the gas drag force and be varied to accomplish separation. Each of the forces can in general have a nonlinear profile along the axis to optimize separation.
In accordance with the first aspect of the present invention, there is provided a method of separating ions, the method comprising:
a) supplying ions to a radio frequency ion guide;
b) applying an axial electric field to provide a force in one direction along the axis of the ion guide; and
(c) providing a gas flow along the ion guide to provide a drag force on ions opposing the force provided by the electric field.
While it is preferred to use a radio frequency ion guide, for some purposes, it is anticipated that the invention could be implemented using other ion guides. Accordingly, another aspect of the present invention provides a method of separating ions, the method comprising:
(a) supplying ions to an ion guide;
(b) applying an axial electric field to provide a force in one direction along the axis of the ion guide;
(c) providing a gas flow along the ion guide to provide a drag force on ions opposing the force provided by the electric field; and
(d) initially setting the electric field and the gas flow such that for at least some ions the force of the electric field and the drag force provided by the gas flow balance one another, to retain the ions within the ion guide, and subsequently adjusting at least one of the electric field and the gas flow to cause desired ions to elute from the ion guide.
A further aspect of the present invention provides an apparatus for separating ions, the apparatus comprising:
an ion guide;
means for generating an electric field along the length of the ion guide; and
means for supplying gas to at least one location of the ion guide and for exhausting gas from at least one other location of the ion guide, to generate a desired gas velocity profile along the ion guide, whereby, in use, movement of ions along the ion guide is dependent upon both an electric field force and a drag force applied to the ions.
REFERENCES:
patent: 5487386 (1996-01-01), Wakabayashi et al.
patent: 6512226 (2003-01-01), Loboda et al.
Howard R. Morris et al, High Sensitivity Collisionally-activated Decomposition Tandem Mass Spectrometry on a Novel Quadrupole/Orthogonal-acceleration Time-of-Flight Mass Spectrometer, Rapid Communications in Mass Spectrometry, vol. 10, 889-896 (1996).
Andrej Shevchenko et al, Rapid “de Novo” Peptide Sequencing by a Combination of Nanoelectrospray, Isotopic Labeling and a Quadrupole/Time-of-flight Mass Spectrometer, Rapid Communications in Mass Spectrometry, vol. 11, 1015-1024 (1997).
Bereskin & Parr
MDS Inc.
Nguyen Kiet T.
LandOfFree
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