Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
2001-12-07
2004-06-01
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S282000, C250S292000
Reexamination Certificate
active
06744043
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to mass spectrometry and ion mobility spectrometry, and more particularly is concerned with a hybrid mobility-mass spectrometry apparatus and a new method of using such a hybrid device.
BACKGROUND OF THE INVENTION
Presently, there are a wide variety of different analysis techniques known for analyzing solvents and substances of interest.
Fundamentally, all mass analysis instruments operate at low pressures, at least in the mass analysis section. As such, separation of different ions depends solely upon different mass-to-charge ratios of the ions present. A problem thus arises where one has two similar ions which happen to have an identical or similar mass-to-charge ratio. Such ions are considered to be isobaric, and cannot be separated by conventional mass spectrometry techniques.
Another known technique for analyzing substances is ion mobility spectrometry (IMS). In such a system, a substance to be analyzed is ionized, to the extent possible, as is required of the low pressure mass spectrometry technique detailed above; however, the techniques for ionization unnecessarily differ due to the different pressures and operating conditions. IMS is commonly carried out at higher pressures, even at atmospheric pressure, and can even use ambient air. However, it is often preferred to use some known, selected gas which is dry, clean and pure and has known properties. Ions are then caused to travel down a drift tube under a potential gradient, through the gas. Different ions have different mobility characteristics depending upon the size and type of the ion and its charge. Thus, different ions will have different transit times to traverse the drift tube. Ions are detected at a detector at an exit from the drift tube, and, knowing transit times for different ions, the constituent components of a sample can be determined.
A drawback with IMS is that it can provide only poor resolution (approximately 100 for example) as compared to other known mass spectrometers. The problem is related to diffusion of the gas in the drift tube. In contrast, the low pressure mass spectrometry techniques detailed above can provide high resolution (for example, approximately 10000) and consequently can distinguish between ions having close but different mass-to-charge ratios.
Again, there is a problem with IMS techniques in that one can encounter substances that have similar drift times but are in fact quite different. Such substances cannot be resolved or separated by IMS.
There are also other known separation techniques relying on quite different technologies, such as chromatography and electrophoresis. For example, liquid chromatography involves passing a sample in a liquid phase through a chromatography column. The column is provided with a packing, selected to provide different retention properties for substances of interest. Then, by analyzing substances as they leave the chromatography column and measuring the time taken to traverse the column, an initial sample can be broken down into its separate portions.
Another known separation technique, electrophoresis, in turn relies upon the fact that different ions will have different mobilities in a liquid phase. A DC voltage or potential gradient is applied to a column, typically made of a liquid or gel, and a starting substance or sample to be analyzed is injected at the entrance end of the electrophoresis column. The potential gradient causes different components of the sample to traverse through the gel at different rates, due to their different mobilities. Again, this enables different components to be detected as they leave the electrophoresis column. Alternatively, at some point the potential gradient can be turned off, so as to fix the different components at different physical locations within the gel, which then can be physically broken into separate portions for analysis.
Accordingly, it has been recognized by a number of workers in this field that there is some advantage in providing so called two-dimensional separation techniques. In liquid chromatography and electrophoresis, there have been proposals which involve taking a sample, subjecting it to a first separation technique and then another separation technique of the same type. For example, in electrophoresis, a sample can be subjected to electrophoresis separation in a gel of one type, and then a second electrophoresis separation step in a second gel having different characteristics, intended to separate out any constituents present which may have had identical characteristics in the first gel.
Such separation techniques are often considered to be “orthogonal”, since the two separation steps are wholly independent of one another. Moreover, the results can be presented as a two-dimensional chart, with orthogonal axes, where each axis represents one of the separation steps.
Moreover, there has been a proposal for combining quite different separation techniques. For instance, there has been a proposal to combine liquid chromatography or electrophoresis with some type of mass spectrometry. This can present a number of difficulties.
Firstly, a sample from liquid chromatography or electrophoresis has to be processed so as to be in a form suitable for generation of ions from mass spectrometry. For example, many modern mass spectrometers use an electrospray technique. The sample thus has to be introduced to an electrospray source, while maintaining any resolution obtained from the previous electrophoresis separation technique or the like. Earlier PCT patent application No. PCT/CA99/00868 demonstrates one proposal for such a technique.
Another fundamental problem is that the sample in capillary electrophoresis or liquid chromatography is carried out in a buffer. Once the sample is electrosprayed the mass spectrum will feature peaks related to the sample and also a wide range of peaks related to the buffer. These buffer related peaks are commonly called “chemical noise”. It is the chemical noise that often imposes limits on the detection of the minute amounts of sample. Additionally, techniques such as electrophoresis are labor intensive as a gel has to be prepared for each run.
SUMMARY OF THE PRESENT INVENTION
Low pressure mass spectrometry, which inherently depends solely on the mass-to-charge characteristics of each ion, and ion mobility spectrometry (IMS) have been considered to be two different but similar techniques. They are considerably different, since they inherently rely on different techniques to achieve separation. At the same time, there are significant similarities; IMS relies on different mobilities of ions in a gas phase; low pressure mass spectrometry while, ideally, taking place in an absolute vacuum, necessarily has some gas pressure present, and additional steps, such as collisional fragmentation, inherently require the presence of a significant gas pressure thereby providing some, superficial similarity with IMS.
U.S. Pat. No. 5,905,258 (Clemmer) discloses a Hybrid ion mobility and mass spectrometer and there have been other proposals for a hybrid spectrometer (Fuhrer et al. Anal. Chem. 2000, 72, 3965-3971). These proposals recognize that there are significant advantages in combining an IMS technique with a low pressure mass spectrometry technique. Such hybrid instruments provide the advantages of two different separation techniques, thereby enabling separation of two or more constituents or ions which, in either one of the techniques, have similar characteristics preventing separation.
The ion mobility step can be operated at a pressure much less than atmospheric pressure, so as to enable it to be fairly readily combined with a low pressure MS technique, without imposing any undue requirements with respect to pumping or maintaining separation between different chambers and the like. The main problem of a low pressure mobility separation setup is in the resultant high rate of diffusion. Losses of the ions occur when the diameter of the ion beam becomes bigger than the diameter acceptable for mass spectrometer. It has been proposed t
Bereskin & Parr
Lee John R.
Leybourne James J.
MDS Inc.
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