Radiant energy – Ionic separation or analysis
Reexamination Certificate
2000-08-16
2003-02-25
Berman, Jack (Department: 2881)
Radiant energy
Ionic separation or analysis
C250S288000, C250S425000, C250S287000
Reexamination Certificate
active
06525313
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention relates generally to electrospray ionization for mass spectrometry, and more particularly the invention relates to an apparatus and method for producing an electrospray from a sample solution for introduction into mass spectrometer.
BACKGROUND OF THE PRESENT INVENTION
Mass spectrometry is an important tool in the analysis of a wide range of chemical compounds. Specifically, mass spectrometers can be used to determine the molecular weight of sample compounds. The analysis of samples by mass spectrometry consists of three main steps—formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass, and detection of the ions. A variety of means exist in the field of mass spectrometry to perform each of these three functions. The particular combination of means used in a given spectrometer determine the characteristics of that spectrometer.
The present invention relates to the first of these steps the formation of gas phase ions from a sample material. More particularly, the present invention relates to electrospray ionization (ESI), one such means for producing gas phase ions from a sample material. Electrospray ionization, was first suggested by Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice,
J. Chem. Phys.
49, 2240, 1968). Generally, in the electrospray technique, analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the tip of the needle and a counter electrode. Specifically, a voltage of several kilovolts is applied between, for example, a metal capillary and a flush surface separated by a distance of approximately 20 to 50 millimeters. Under the effect of the electric field, a liquid in the capillary is dielectrically polarized at the end of the capillary. The liquid is then pulled out into a cone, known as the Taylor cone. The surface tension of the liquid at the pointed end of the cone is no longer able to withstand the attraction of the electric field, and this causes a small electrically charged droplet to be detached. The charged droplet flies with great acceleration to the flush counter electrode, effected by the inhomogeneous electric field. During the flight of the liquid, evaporation occurs and the droplets are slowed down. The spray results in the formation of finely charged droplets of solution containing analyte molecules. The larger ions become ionized, and move towards the counter electrode to be transferred into the vacuum system of a mass spectrometer, for example, through a narrow aperture or capillary very large ions can be formed in this way. For example, ions as large as 1 MDa have been detected by ESI in conjunction with mass spectrometry (ESMS).
Electrospray, as in the present invention, facilitates the formation of ions from sample material. It should be noted that the size of the droplets produced in the ESI technique is dependant upon the size of the sprayer used. The terms nanospray or micro spray are used to indicate the use of very small sprayers in electrospray technique. In other words, a sprayer having an opening of less than about 10 &mgr;m (microns) will produce a nanospray, a sprayer having an opening of between approximately 10-100 &mgr;m (microns) will produce a micro spray, and a sprayer having an opening of greater than 100 &mgr;m (microns) will produce an electrospray. For convenience, all three are referred to generally as “electrospray,” in as much as the present invention can be used with each.
Referring to
FIG. 1
, depicted is an ionization source of co-pending application Ser. No. 09/570,797 which shows an API source for generating ions from a sample for subsequent analysis. As shown, the ionization source
101
comprises spray chamber
1
, transfer region
2
, first pumping region
5
, second pumping region
4
, hinge
9
, flange
10
, and source block
16
. During normal operation of the ionization source
101
incorporating an ESI source it is anticipated that numerous other elements may be used within ionization source
101
as shown in FIG.
1
. These may include vacuum pump
15
, ion transfer devices such as capillary
6
having an entrance end
7
, and exit end
19
and inner channel
8
, multipole devices such as pre-hexapole
11
and hexapole
12
, as well as other ion optic devices such as skimmers
13
and
14
and exit electrodes
17
.
Initially, sample solution is formed into droplets at atmospheric pressure by spraying the sample solution from a spray needle
20
into spray chamber
1
. The spray may be induced by the application of a high potential between the tip of spray needle
20
and the capillary entrance end
7
within spray chamber
1
. Then, these sample droplets evaporate while in the spray chamber
1
thereby leaving behind sample ions. These sample ions are accelerated or directed toward capillary entrance
7
and into channel
8
by the electric field generated between spray needle
20
and capillary entrance
7
. These ions are then transported through capillary
6
to capillary exit
19
, due to the flow of gas created by the pressure differential between spray chamber
1
and first transfer region
2
.
The present invention relates particularly to the sprayers used within electrospray ionization. Presently, known electrospraying techniques teach that it is necessary to take active steps to ionize the solution for analysis in the mass spectrometer. For instance,
FIG. 2
depicts a typical prior art electrospray needle
21
. As shown, needle
21
comprises an elongated capillary structure tapered at one end to form tip
22
. Needle
21
includes a plenum
24
to receive the liquid sample. Plenum
24
is shown having an interval region larger than that of the capillary section of needle
21
. Liquid sample flows from plenum
24
through upstream inlet
25
into the capillary section of ejection through tip
26
. Plenum
24
may be electrically conductive so that a voltage applied to the plenum
24
will allow for the transfer of charge into the liquid stream. Alternatively, a charge can be imposed on the capillary section of needle
21
. The applied voltage produces an electrical field which is arranged such that it is at its highest at the tip
26
such that the charge and field at tip
26
are high enough to form the electrospray (i.e. charged droplets) . Such a prior art apparatus consists only of a single needle which, is a very thin capillary, producing flow rates on the order of 20 nL/min. Further, such a needle must be loaded through its back end (i.e. the plenum
24
, as shown in FIG.
2
), not through the tip
25
. This can be a very time consuming process.
Typically, nanospray needles are produced by taking a glass capillary having a relatively large diameter and pulling and/or machining it to a tip. Then a metal coating is vapor deposited onto its outer surface, as disclosed in Mann U.S. Pat. No. 5,504,329 (Mann). The needle shown in
FIG. 3
is the result of such a process. Needles such as this are formed by using heat to soften glass capillary tubing and pulling the tip end to form the needle's tapered tip
27
. These needles are generally single use, and must be loaded with sample solution using micropipettes or some other means for loading sample solution through the end
28
of the needle—the end opposite the spray tip—using a micropipette.
Such needles are generally single use, and require the sample to be reloaded through its back end after each use. The prior art needles breed inaccuracy because the conditions have to be replicated with each removal and replacement. In addition, the fragile nature of the needles, combined with their limited use, makes replacement costs a significant expense for their users. Also, because these needles are extremely fragile, replacement is frequent, which is both costly and time consuming.
Once these prior art needles are formed, a means of making electrical contact is required. Prior art need
Berman Jack
Brucker Daltonics Inc.
Fernandez Kalimah
Ward & Olivo
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