Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2000-10-27
2003-03-18
Anderson, Bruce (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S282000, C250S42300F
Reexamination Certificate
active
06534765
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to liquid chromatography (LC) and mass spectrometry (MS). More particularly, this invention is concerned with both a method and apparatus for providing improved creation and detection of ions by use of photoionization (PI), in conjunction with LC and MS.
BACKGROUND OF THE INVENTION
While atmospheric pressure photoionization (APPI) is known, it has not previously been applied to liquid chromatography-mass spectrometry (LC-MS). Furthermore, there have been very few reports of PI combined with LC, despite the longstanding use of photoionization detection (PID) with gas chromatography (GC).
Photoionization detection in GC typically involves the use of a discharge lamp that generates vacuum-ultraviolet (VUV) photons. If one of these photons is absorbed by a molecule in the column eluant with a first ionization potential (IP) lower than the photon energy, then single photon ionization may occur. The photoions thereby generated are detected as current flowing through a suitable collection electrode; a chromatogram can be obtained by plotting the current detected during a chromatographic run versus time. For PID-GC, the discharge lamp is normally selected such that the energy of the photons is greater than the IP of the analyte, but below the IP of the carrier gas. (Most organic molecules have ionization potentials in the range of 7-10 eV; the common GC carrier gases have higher values, e.g. helium, 23 eV). Ionization of the analyte can then occur selectively and low background currents may be achieved.
There are a few earlier reports in the literature of combining LC and PI. (Schermund, J. T., Locke, D. C. Anal. Lett. 1975, 8, 611-625; Locke, D. C., Dhingra, B. S., Baker, A. D. Anal. Chem. 1982, 54, 447-450; Driscoll, J. N., Conron, D. W., Ferioli, P., Krull, I. S., Xie, K.-H. J. Chromatogr.
1984, 302, 43-50
; De Wit, J. S. M., Jorgenson, J. W. J. Chromatogr. 1987, 411, 201-212). However, these also relied upon direct detection of the photoion current, without mass analysis. Selective ionization was possible in these experiments, too, because the common LC solvents also have relatively high IP's (water, IP=12.6 eV; methanol, IP=10.8 eV; acetonitrile, IP=12.2 eV). Thus, these methods were similar to photoionization detection as used with GC. In the majority of cases the liquid eluant from the LC column was completely vaporized before it entered the ionization region, and ionization took place in the vapour phase. However, one of these studies involved direct photoionization of the liquid-phase eluant (Locke, D. C., Dhingra, B. S., Baker, A. D. Anal. Chem. 1982, 54, 447-450.)
When trace levels of analyte must be detected in the presence of a great excess of carrier gas or solvent, and ion current alone is being measured, it is essential that photoionization be selective. Otherwise, ions generated from the carrier gas or solvent could overwhelm the analyte ions of interest. However, this requirement may be obviated if a mass analyzer is used to separate the photoions prior to detection, i.e. so as to separate desired analyte ions from other ionized species, such as those arising from solvent molecules or any impurities.
There is also a small number of reports of APPI combined with mass spectrometry. The inventors are aware of only three reports of true mass analysis of photoions created at atmospheric pressure (Revel'skii, I. A.; Yashin, Vosnesenskii, V. N.; Y. S.; Kurochkin, V. K.; Kostyanovksii, R. G.; Izv. Akad. Nauk SSSR, Ser. Khim. 1986, (9) pp. 1987-1992; Revel'skii, I. A.; Yashin, Y. S.; Kurochkin, V. K.; Kostyanovksii, R. G.; Chemical and Physical Methods of Analysis 1991, 243-248 translated from Zavodskaya Laboratoiya 1991, 57, 1-4; Revel'skii, I. A.; Yashin, Y. S.; Voznesenskii, V. N.; Kurochkin, V. K.; Kostyanovksii, R. G. USSR Inventor's certificate 1159412, 1985), although there have been numerous examples of APPI coupled with ion mobility spectrometry (IMS) (Baim, M. A., Eatherton, R. L., Hill Jr., H. H. Anal. Chem. 1983, 55, 1761-1766; Leasure, C. S., Fleischer, M. E., Anderson, G. K., Eiceman, G. A. Anal. Chem. 1986, 58, 2142-2147; Spangler, G. E., Roehl, J. E., Patel, G. B., Dorman, A., U.S. Pat. No. 5,338,931, 1994; Doering, H.-R.; Arnold, G.; Adler, J.; Roebel. T.; Riemenschneider, J.; U.S. Pat. No. 5,968,837, 1999). In the three papers describing APPI-MS experiments that established the feasibility of the combination, direct analysis was performed of a gaseous mixture of samples in a flow of helium carrier gas. A hydrogen discharge lamp (hn=10.2 eV) was utilized to create ions from the gaseous mixture for analysis by a quadrupole mass spectrometer. Significantly, the relative abundance of sample ions in the spectra obtained of the sample mixture was found to depend upon sample concentration. At high sample concentrations, ion-molecule reactions, particularly charge (electron) transfer, distorted the appearance of the mass spectra: this charge transfer caused the majority of charge to be transferred to the species with the lowest IP. Another finding was that predominantly molecular or quasi-molecular ions are created by PI at atmospheric pressure, indicating that little fragmentation occurs during the ionization step. Finally, when solvent vapour (water or methanol) was introduced into the sample mixture carried in the helium stream, a decrease in sensitivity for the method was observed.
With regard to the prospect of combining APPI with LC-MS, the finding that the presence of solvent vapour decreases the efficiency of ion formation is troublesome. This effect was known to the last researchers to study PID-LC, who described how vaporized solvent molecules absorb the photons, thereby decreasing the flux available to create photoions from the sample (De Wit, J. S. M., Jorgenson, J. W. J. Chromatogr. 1987, 411, 201-212). Another interesting observation from the early APPI-MS studies is the effect that charge-transfer reactions have on the final appearance of the spectra. This observation tells of the fact that the relative abundance of ions in an APPI spectrum will depend upon the reactions that the original photoions undergo prior to mass analysis. As is generally true for atmospheric pressure ionization methods, the high collision frequency insures that species with high proton affinities and/or low ionization potentials tend to dominate the positive ion spectra acquired, unless special measures are taken to sample the ions from the source before significant reactions occur. (In the case of negative ion atmospheric pressure ionization, molecules with high gas phase acidity or high electron affinity dominate the negative ion spectra.)
Many conventional LC-MS instruments rely on a corona discharge to promote ionization. A common configuration provides a heated nebulizer, known to those skilled in the art, for nebulization and vaporization of a sample solution, with the sample being introduced subsequent to a liquid chromatography step. The sample may also be introduced subsequent to a different liquid phase separation method, or from a liquid feeding device not involving a separation step (see the discussion of the preferred embodiment below).
A corona discharge (CD) has its own unique requirements. In the CD source, a high potential is necessary to create and maintain the discharge, which imposes restrictions on the use of separate ion transport mechanisms. A tube cannot be used to transport ions from the CD, because in order for a transport tube to have any effect it must be in close proximity to the ion source; in fact, it must enclose it. However, in order for the CD source to function, a strong electric field must be present at the needle tip, and if this field is maintained by applying the potential between the needle and the transport tube, then the ions produced will be quickly lost to the tube, due to the acceleration from the electric field; conversely, if the tube is held at a potential close to that of the needle, then ion loss from the above mechanism will be
Bruins Andries Pieter
Robb Damon B.
Abeles Daniel C.
Anderson Bruce
Eckert Seamans Cherin & Mellott , LLC
MDS Inc.
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