Patent Application
20080067352
The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:
a and 1b are schematic illustrations of a combined ambient desorption and ionization source for a mass spectrometer, in accordance with the principles of the present invention. A heated gas-jet probe desorbs the sample on a substrate. The desorbed molecules are reacted with charged solvent ions of an electrospray to form ions.
a and 2b are schematic illustrations of another combined ambient desorption and ionization source for a mass spectrometer, in accordance with the principles of the present invention. A heated solvent stream probe desorbs the sample on a substrate. The desorbed molecules are ionized by a corona discharge.
The present invention provides a combined ambient desorption and ionization sources for a mass spectrometer. Sample ions generated by sources in ambient conditions are introduced into the mass spectrometer via a vacuum interface.
Two exemplary combined desorption and ionization sources for mass spectrometry under ambient conditions are described herein. For convenience in description and in understanding the invention, only positive ion generation is described in the context of the two examples.
a and 1b show an exemplary combined desorption and ionization source 10 for mass spectrometry. Source 10, which is operable under ambient conditions, is based on electrospray ionization. (ESI). In conventional ESI technique, ionization is effected by the use of the emitter, i.e. a metal needle or a metal capillary tube, at a controlled distance from a counter electrode. A DC voltage is applied, either to the emitter or to the solvent, to produce a strong electrical field at the emitter tip. The electric field interacts with ions in solution as they leave the tip. This interaction results in electro hydrodynamic disintegration of the fluid, generation of droplets, and formation of an aerosol jet. A drying gas is often used to expedite desolvation and droplet shrinkage. By solvent evaporation and repeated disintegration, the process proceeds by progressive droplet diminution. Differential solvent loss reduces droplet size, which in turn in turn increases electrical surface charge. Finally, when the charge repulsion forces of the ion exceed the surface tension of the droplet, the latter bursts apart by Coulomb explosion. When the droplet diameter diminishes in radius, ion emission to the gas phase occurs under the conditions in which the solvation energy of the ion exceeds the attraction between the ion and polarizable droplet. The molecular ions are usually multiply charged. Electrospray ionization is the method of choice for proteins, peptides and oligonucleotides. However, the sample must be soluble in low boiling solvents (e.g., acetonitrile, MeOH, CH3Cl, water, etc.) and electro sprayed with solvent through the needle or emitter.
In the present invention, however, sample molecules or analytes are not in a solution with a solvent that can be sprayed together. Instead, the sample molecules, which are placed on a substrate, are desorbed by a heated gas jet and then ionized by an electro sprayed solvent in an electrospray process. Sample molecule ions are generated through reaction between desorbed molecules and charged solvent ions.
Combined desorption and ionization source 10 includes a heated gas-jet probe 100, an electrospray probe, a sample substrate 102 for carrying a sample 103. The electrospray probe includes a thin capillary 104 and a tune 105. Thin capillary tube 104 carries a flowing solvent while tube 105 carries nebulizing gas for generating a solvent spray. A vacuum interface 106, which also serves as a counter electrode, allows passage of sample molecule ions into the body of mass spectrometer 120 for analysis. Heated gas-jet probe 100 and the electrospray probe are located above the sample substrate 102 at suitable angles and distances to the substrate. Nebulizing gas such as nitrogen gas, streams through the gas-jet probe 101 and is directed onto sample 103. A heating unit 101, heats the flowing gas stream. The energetic gas stream impacts sample 103 and desorbs sample molecules into gas phase. Simultaneously, a solvent is pumped through thin capillary 104, which may have an internal diameter of about 0.1 mm. The solvent is pumped through thin capillary 104 and sprayed by assisted nebulizing gas through the tube 105. Further, thin capillary 104 is raised to a high potential of about a few kV. Small charged solvent droplets are sprayed from the end of thin capillary 104 into a bath gas at atmospheric pressure and travel towards an orifice of vacuum interface 106 leading into mass spectrometer 120. As the charged droplets traverse this path, they become desolvated and reduced in size to such an extent that surface-columbic forces overcome surface-tension forces. Then, the charged droplets break up into even smaller charged droplets. The small charged droplets react with the desorbed sample molecules. The reaction between the small charged solvent and the desorbed sample molecules may include proton transfer from charged solvent to sample molecule and sample molecule fusion into charged solvent droplet. The electrospray process leads to even smaller charged droplets. The further droplet shrinkage leads to gas-phase ion generation.
The gas-phase ions are sampled by mass spectrometer 120, which may include a suitable analyzer such as a quadrupole mass filter or quadrupole ion trap (QIT) or quadrupole linear ion trap (LIT); a Fourier Transformation Ion Cyclotron Resonance (FT-ICR), a Time-of-flight (TOF), a triple quadrupole or a Q-TOF mass spectrometer.
A more detailed theoretical description of the traditional electrospray process is found in: Electrospray Ionization Mass spectrometry, edited by Richard B. Cole, John Wile $Sons, Inc, New York, 1997. However, the traditional electrospray ionization source is related to a solution (solvent with sample) spray from the capillary.
The desorption and ionization source 10 shown in
The desorption and ionization source 10 shown in
a and 2b show another exemplary combined desorption and ionization source 20 for mass spectrometry. Source 20 uses a corona discharge (APCI) for ion formation.
Source 20, which is operable under ambient conditions, is based on APCI process, which is related to the electrospray ionization process (ESI). Source 20 uses a heated nebulizing solvent beam for desorption of sample molecules. Source 20 includes a heated solvent stream probe 200, a corona discharge needle 201, a vacuum interface 106, which is also a counter electrode, and a sample substrate 102 (with sample 103 on it). Heated solvent stream probe 200 and corona discharge needle 201 are located above sample substrate 102 at appropriate angles and distances to the substrate.
In operation of source 20, a solvent (e.g. water, organic liquid or water/organic mixture and a small amount of acid) flows through probe 200, and is directed on to sample 103. A heating unit 101 heats the flowing solvent. The energetic solvent stream impacts sample 103 and desorbs sample molecules into the gas phase mixed with the solvent. Corona discharge needle 201 is maintained at potential of a about few kilovolts. The corona effect describes the partial discharge around a conductor placed at a high potential. This leads to ionization and electrical breakdown of the atmosphere surrounding the conductor. As in the case of an APCI source, the atmosphere surrounding the corona electrode consists mainly in the vapors from desorption. The vapors are ionized by the corona effect, and react chemically with the sample molecules in the gas-phase.
Source 20 may be operated in a positive mode or a negative mode. For positive mode operation, the proton affinity of the analyte must be higher than the proton affinity of the eluent (in other words, the analyte can capture a proton from the protonated solvent):
SH++M→S+MH+
where S is solvent, H+is proton and M is sample molecule.
For negative mode operation, the gas phase acidity of the analyte must be lower than the gas phase acidity of the eluent (in other words, the analyte can give a proton to the deprotonated solvent):
[S−H]−+M→S+[M−H]−
In either mode, the result is the formation of sample molecule ions. The sample molecule ions flow into the orifice of the vacuum interface 106 and are analyzed by a mass spectrometer 120 as mention above.
The desorption and ionization source 20 shown in
The desorption and ionization source 20 shown in
Another exemplary combined desorption and ionization source merges features of sources 10 and 20 that are shown in
It will be understood that in the inventive sources, desorption and ionization processes are separated. The separation of the two processes allows each process to be independently optimized. The two processes may be optimized to obtain optimal molecular ion yield for mass spectrometry and to eliminate chemical noise peaks.
Numerous modifications and alternative embodiments of the present invention will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode for carrying out the present invention. Details of the structure may vary substantially without departing from the spirit of the invention, and exclusive use of all modifications that come within the scope of the invention is reserved.
