Radiant energy – Ionic separation or analysis – With plural – simultaneous ion generators
Reexamination Certificate
2002-12-23
2004-08-31
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
With plural, simultaneous ion generators
C250S281000, C250S288000
Reexamination Certificate
active
06784422
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to mass spectrometers. More particularly, this invention relates to ion sources for mass spectrometers, and is concerned with facilitating the handling of multiple sample inputs for mass spectrometers.
BACKGROUND OF THE INVENTION
Most mass spectrometers use a single sample input and there are a very large number of designs and configurations for single input mass spectrometers. However, in the art, there is at least one reference to spectrometer having a parallel array of mass analyzers for the purposes of increasing sample through-put (U.S. Pat. No. 5,206,506, Kirchner). However, this patent does not suggest using several sample inputs to one mass spectrometer; rather, there is a single source of ions from an ion chamber. A plurality of perforated electrode sheets form a number of different paths for ions and also a plurality of potential wells. Thus, all the ions are from the same source.
The applicant is aware of at least one reference to an electrospray mass spectrometer with two ion inlets, each associated with a separate source of ion. Jiang and Moini (Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, Dallas, Tex., 1999, pp 2560-2561) showed a system with two electrospray sources, each directed at a separate orifice into the mass spectrometer chamber. This resulted in two ion beams into the mass spectrometer. In the vacuum system, the ion beams were combined before entering the mass spectrometer. The purpose of this method was to use one sprayer to introduce the analyte (the compound to be analyzed) and the second sprayer to simultaneously introduce a mass calibration compound. The calibration compound is then selected to provide one or more distinct peaks, for calibration purposes.
A second type of multiple sample inlet system is described by Bateman et al. in European Patent Application EP 0 966 022 A2. This describes a system in which several sprayers are operated simultaneously, so as to increase the throughout of the mass spectrometer system. A different sample stream is introduced through each sprayer. All sprayers are directed toward a single orifice into the mass spectrometer, and a rotating mechanical blocking device is used to sequentially allow ions from each sample stream to be sampled into the mass spectrometer through a single orifice. The sprayers are indexed to the blocking device in order to correlate the mass spectral information with the particular sprayer.
A third system of multiple sprayers is disclosed in an abstract entitled “Dual Parallel Probes for Electrospray Source” from the Proceedings of the American Society for Mass Spectrometry, Dallas Tex., June, 1999, pp 458-459, by Shida Shen, Bruce A. Andrien Jr., Michael Sansone and Craig Whitehouse. However, this reference also does not index the sprayer to the data system in the sense of the present invention. Thus, Shen et al use a single orifice into the mass spectrometer, and produce spectra that are mixed. The practical use of this system is to introduce a known calibrant ion for use as a reference mass, to mass calibrate the ions being produced from the sample being analyzed with the other sprayer. Another potential use of this crude dual sprayer approach is when one is doing targeted analysis such as quantitation. If the following two conditions are met some practical use can be achieved: (1) the analyte mass is known and is specifically monitored by the mass spectrometer, and (2) the masses being monitored are different from the individual sprayers. This is technically a type of indexing, but is not useful in the case where composition of the sample is unknown, because then you do not know which ions are from which sample.
SUMMARY OF THE PRESENT INVENTION
The basic idea of the present invention is a method of simultaneously introducing multiple samples into an electrospray mass spectrometer for purposes of increasing the productivity of the instrument. There are potentially several ways of doing this, all of which provide some means of indexing the incoming samples with the signal produced in the mass spectrometer. A key concept is “indexing”, i.e. at any point in time the data system of the mass spectrometer of the present invention is able to associate a particular mass spectrum with a particular sprayer (or to put it another way. with a particular sample).
For example, if one were to simply mount an array of sprayers all simultaneously introducing different samples into the mass spectrometer with no way of knowing which mass spectrum came from which sprayer (or to put it another way, which mass spectrum was associated with which sample injected) the data would be useless. So in essence, the present invention sequentially allows the signal from one sprayer at a time to pass to the detector of the mass spectrometer thereby unequivocally associating a particular mass spectrum with a particular sprayer sample. Samples are injected at the same point in time into different flowing streams running in a parallel fashion into the mass spectrometer and the signal from each source is rapidly and sequentially turned on and off quickly to obtain spectra from each stream as the sample plugs pass through.
One method of doing this is to utilize a single electrospray nebulizer and, by utilizing a multiport valve, sequentially divert the desired sample into the electropsray nebulizer. This method suffers from the time delay incurred from such valves and the time required for spray stabilization during each divert period. All of these contribute to excessive duty cycle losses. In addition, there may be a memory effect whereby trace amounts of one sample remain in the tubing or sprayer, and interfere with the next sample; this again would increase duty cycle losses.
A second method is to have an array of electrospray nebulizers all introducing liquid samples into the mass spectrometer ion source simultaneously. Each nebulizer is sequentially turned on and off by cycling the high voltage to the sprayer required to give charge separation in the liquid necessary for ion production. This method suffers from the time delay incurred from the turning on and off of the high voltage power supplies and stabilization of such high voltages (kilovolt range). There is also a time delay for spray stabilization during each on/off high voltage period. All of these contribute to excessive duty cycle losses.
A third method is to have an array of electrospray nebulizers all introducing liquid samples into the mass spectrometer ion source simultaneously with the high voltage on, for all sprayers at all times. All sprayers are aimed at a single ion entrance aperture into the vacuum system. The charged droplets emitted from the sprayers are deflected by means of a mechanical blocking device. All sprayers are mechanically blocked with the exception of the one from which signal is desired at that point in time. The mechanical blocking device is situated between the sprayers and the inlet orifice of the vacuum system of the mass spectrometer; thus it is located in the atmospheric region of the mass spectrometer. This method suffers from the time delay incurred from the mechanical positioning of the blocking device resulting in a duty cycle loss and from limitations in the liquid flows that can be introduced through the sprayers. Excessive liquid impacting on a rotating mechanical shutter will result in excessive background interferences.
A fourth method of the present invention is to divert or focus the ion beam from a given sample after it has entered the first chamber of the mass spectrometer. In this case an array of sprayers is situated around an array of ion entrance apertures which in him are situated around a single mass analyzer. All sprayers simultaneously introduce the samples from their respective sources and the high voltage is on for all the sprayers, so that they are all producing ions and are never destabilized. The ions from the respective sprayers all pass through their associated ion entrance aperture into the first chamber of the mass spect
Covey Thomas R.
Jolliffe Charles L.
Thomson Bruce
Bereskin & Parr
Gill Erin-Michael
Lee John R.
MDS Inc.
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