Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
1998-09-28
2001-01-23
Arroyo, Teresa M. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S492100
Reexamination Certificate
active
06177669
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to apparatus and methods for characterizing materials using mass spectrometry, and more specifically, to an apparatus which reduces the measurement noise which results from the formation of large charged drops during use of the electrospray technique.
BACKGROUND OF THE INVENTION
Mass spectrometers have become common tools in chemical analysis. Generally, mass spectrometers operate by separating ionized atoms or molecules based on differences in their mass-to-charge ratio (m/e). A variety of mass spectrometer devices are commonly in use, including ion traps, quadrupole mass filters, and magnetic sector mass analyzers.
The general stages in performing a mass-spectrometric analysis are: (1) create gas-phase ions from a sample; (2) separate the ions in space or time based on their mass-to-charge ratio; and (3) measure the quantity of ions of each selected mass-to-charge ratio. Thus, in general, a mass spectrometer system consists of an ion source, a mass-selective analyzer, and an ion detector. In the mass-selective analyzer, magnetic and electric fields may be used, either separately or in combination, to separate the ions based on their mass-to-charge ratio. Hereinafter, the mass-selective analyzer portion of a mass spectrometer system will simply be called a mass spectrometer. Ions introduced into a mass spectrometer are separated in a vacuum environment. Accordingly, it is necessary to prepare the sample undergoing analysis for introduction into this environment. This presents particular problems for high molecular weight compounds or other sample materials which are difficult to volatilize. While liquid chromatography is well suited to separate a liquid sample matrix into its constituent components, it is difficult to introduce the output of a liquid chromatograph (LC) into the vacuum environment of a mass spectrometer. One technique that has been used for this purpose is the electrospray method.
The “electrospray” or “electrospray ionization” technique is used to produce gas-phase ions from a liquid sample matrix to permit introduction of the sample into a mass spectrometer. It is thus useful for providing an interface between a liquid chromatograph and a mass spectrometer. In the electrospray method, the liquid sample to be analyzed is pumped through a capillary tube or needle. A high electrical potential (typically, 3 to 4 thousand volts) is established between the end of the needle and an opposing wall or other structure. The stream of liquid issuing from the needle tip is broken up into highly charged drops by the electric field, forming the electrospray. An inert gas, such as dry nitrogen (for example), may also be introduced through a surrounding capillary to enhance nebulization (droplet formation) of the fluid stream.
The electrospray drops consist of sample compounds in a carrier liquid and are electrically charged by the electric potential as they exit the capillary needle. The charged drops are transported in an electric field and injected into the mass spectrometer, which is maintained at a high vacuum. Through the combined effects of a drying gas and vacuum, the carrier liquid in the drops starts to evaporate giving rise to smaller, increasingly unstable drops from which surface ions are liberated into the vacuum for analysis. The desolvated ions pass through a sample aperture and ion lenses, and are focused into the high vacuum region of the mass spectrometer, where they are separated according to mass-to-charge ratio and detected by an appropriate detector (e.g., a photo-multiplier tube). In addition to, or in place of an electrostatic ion lens, a multipole RF ion guide may be used to transport the ions to the mass spectrometer.
Although the electrospray method is very useful for analyzing high molecular weight dissolved samples, it does have some limitations. For example, commercially available electrospray devices are limited to liquid flow rates of less than 20-30 microliters/min. Higher liquid flow rates result in unstable and inefficient ionization of the dissolved sample. Since the electrospray needle is typically connected to a liquid chromatograph, this acts as a limitation on the flow from the chromatograph.
One method of improving the performance of electrospray devices at higher liquid flow rates is to utilize a pneumatically assisted electrospray needle. One example of such a needle is formed from two concentric, capillary tubes. In such a device the sample containing liquid flows through the inner tube and a nebulizing gas flows through the annular space between the two tubes. This improves the efficiency of the ionization process by improving the ability of the electrospray needle to form drops from the sample liquid. However, at high sample liquid flow rates into this type of electrospray needle, the drops formed are relatively large and can degrade the performance of the mass spectrometer (by increasing the noise) if allowed to enter the device. This makes such electrospray needles difficult to use with liquid chromatographs.
As noted, large charged drops entering a mass spectrometer degrade its performance, and it is therefore desirable to eliminate or reduce the size of these drops. One mechanism to accomplish this is to employ electrostatic dispersion of drops, which occurs when coulomb forces exceed those due to surface tension. It is known that the surface tension is reduced by reducing the drop size through evaporation. As the drop size is reduced, the relative effect of the coulomb forces increases, causing the drops to spontaneously break up into smaller drops. Evaporation of the carrier liquid(s) from the drops permits the effect of the coulomb force to dominate that of the surface tension, with the benefit of decreasing the system noise of the mass spectrometer.
Thus, one way of reducing the noise problem caused by the larger drops produced by an electrospray needle is to employ means to reduce droplet size prior to injection into the mass spectrometer. One method of accomplishing this is shown in the prior art electrospray mass spectrometer interface
100
of FIG.
1
. As shown in the figure, a liquid sample matrix flows through electrospray needle
102
and out of the needle's outlet, causing the liquid to form drops which are directed towards entrance orifice
104
of a mass spectrometer. A laminar flow of heated inert gas
106
is formed in a direction substantially counter to that of the flow from the outlet of needle
102
, with the heated drying gas placed between the outlet of the electrospray needle and capillary tube
108
which serves as the entrance to the mass spectrometer
109
. The heated inert gas facilitates evaporation of the solvent from the liquid drops, reducing their size, and acts to displace vapor formed from the evaporation process away from the entrance to the mass spectrometer. This is intended to reduce excess noise in the measurements made by the mass spectrometer.
In another prior art electrospray mass spectrometer interface
120
shown in
FIG. 2
, a drying gas
122
is arranged to flow in a transverse direction relative to entrance orifice
124
of the mass spectrometer. In addition, the direction of the sprayed drops produced by electrospray needle
126
is oriented at an angle off of the axis of the orifice. A second flow of heated drying gas
128
, in a direction different from that of drying gas
122
, intersects the droplet flow from needle
126
in a region upstream of the orifice (i.e., to the right of the orifice in the figure). Gas flows
122
and
128
mix, with the second flow
128
helping to evaporate the drops to produce ions and move the evaporating drops and ions toward the spectrometer orifice.
The prior art devices shown in
FIGS. 1 and 2
have the disadvantage of requiring a relatively large volume of drying gas flowing counter to the direction of movement of the electrospray drops (or at some angle with respect to the direction of motion of the drops). The drying gas removes the carrier liquid(s) from the smaller charged drop
Tong Roger C.
Wells Gregory J.
Yee Peter P.
Arroyo Teresa M.
Berkowitz Edward H.
Smith, II Johnnie L.
Varian Inc.
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