Classifications

• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/02—Details
  • H01J49/10—Ion sources; Ion guns
  • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
  • H01J49/161—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
  • H01J49/164—Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/02—Details
  • H01J49/06—Electron- or ion-optical arrangements
  • H01J49/067—Ion lenses, apertures, skimmers

Definitions

• TITLE METHOD AND APPARATUS FOR GENERATING IONS
• the applicants' teachings relate to a method and apparatus for generating ions by laser desorption/ionization for analysis by mass spectrometry.
• Mass spectrometry is a prevalently used analytical method that identifies molecules in compounds based on the detection of the mass-to- charge ratio of ions generated from molecules that have been electrically charged. Numerous methods exist to ionize molecules. One such method is laser desorption/ionization.
• MALDI matrix-assisted laser desorption/ionization
• samples are typically mixed with a UV-adsorbing compound known as a MALDI matrix, deposited on a surface, and ionized with a laser pulse.
• the energy of the laser is absorbed by the matrix molecules and transferred to the sample molecules, causing them to vaporize and ionize.
• a plume of ions is created, and the ions are then analyzed by a mass spectrometer. Docket No. 6087WO - 2 -
• an ion source at a first pressure for generating ions by laser desorption/ionization for analysis by a mass analyzer that has an inlet aperture to a vacuum chamber at a second, lower pressure than the first pressure of the ion source.
• the ion source comprises a surface (e.g., a sample plate) for supporting a sample deposited thereon and a laser configured to generate laser pulses striking at least a portion of the sample.
• the laser pulses can be at an angle of incidence from about 0 to about 80 degrees to the center line of the ion path of the mass analyzer, which is referred to herein as a first ion optical axis of the mass analyzer.
• the laser pulse strikes the sample plate at an angle of greater than about 20 degrees with respect to the first ion optical axis of the mass analyzer.
• the normal of the sample plate can be positioned at an angle from about 0 to about 45 degrees relative to the first ion optical axis of the mass analyzer.
• the normal of the sample plate can be tilted at an angle from about 20 to about 45 degrees relative to the first ion optical axis of the mass analyzer.
• mass analyzer through an inlet aperture in a structure separating the inlet region from the mass analyzer.
• the distance between the sample plate and the inlet region aperture is selected to reduce neutral molecules from being drawn into the inlet region of the mass analyzer due to the gas flow that results from the pressure difference between the ion source region and the mass analyzer.
• the center of the plume is substantially directed away from the inlet region as it leaves the sample plate surface, and an electric field is applied to draw analyte ions into the inlet region of the mass analyzer.
• the combination of the angle of incidence of the laser pulses and the distance between the sample plate and the inlet region aperture is configured such that the plume is substantially directed away from the inlet region of the mass analyzer as it leaves the sample plate surface and neutral contaminants are not drawn into the mass analyzer.
• the distance between the sample plate and the inlet aperture is selected so that gas drag forces resulting from the pressure difference between the ion source and the mass analyzer result in the effect of such gas drag forces being considerably reduced so as not to draw a substantial proportion of the neutral contaminants through the inlet aperture.
• the laser pulses strike the sample plate at an angle of incidence that is greater than about 20 degrees relative to the first ion optical axis of the mass analyzer.
• an electric field is applied to draw analyte ions into the inlet region of the mass analyzer.
• a system for generating analyte ions by laser desorption/ionization of a sample for mass analysis.
• the system comprises an ion source at a first pressure for generating analyte ions and a mass analyzer having an inlet aperture for receiving the analyte ions into a vacuum chamber at a second, lower pressure than the first pressure of the ion source.
• the ion source comprises a surface (e.g., a sample plate) for supporting a sample deposited thereon and a laser configured to generate Docket No. 6087WO - 4 -
• the normal of the sample plate can be positioned at an angle from about 0 to about 45 degrees relative to a first ion optical axis of the mass analyzer, and the laser pulses can be at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis of the mass analyzer.
• the normal of the sample plate can be tilted at an angle from about 20 to about 45 degrees relative to a first ion optical axis of the mass analyzer, and the laser pulses can be at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis of the mass analyzer.
• a plume that can contain analyte ions of the sample and neutral contaminants is produced.
• the distance between the sample plate and the inlet aperture is selected so that gas drag forces resulting from the pressure difference between the ion source and the mass analyzer result in the effect of such gas drag forces being considerably reduced so as not to draw a substantial proportion of the neutral contaminants through the inlet aperture.
• an electric field is applied to draw analyte ions into the mass analyzer.
• a method of generating analyte ions by laser desorption/ionization of a sample for mass analysis comprises providing an ion source at a first pressure having a surface for supporting sample deposited thereon and a laser adapted to generate laser pulses striking at least a portion of the sample on the surface to create a plume that comprises analyte ions.
• the method further comprises providing a mass analyzer having an inlet aperture to a vacuum chamber at a second, lower pressure than the first pressure of the ion source for receiving at least a portion of the analyte ions, wherein the distance between the ion source and the inlet aperture is selected to reduce the influence of gas flow velocity effects that result from the difference in pressure between the ion source and the mass analyzer and that draw molecules from the source to the inlet region.
• the surface can be a sample plate positioned at an angle from about 0 to about 45 degrees relative to a first ion Docket No. 6087WO - 5 -
• the laser can be configured to generate pulses of energy at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis of the mass analyzer.
• the surface can be a sample plate whose normal can be tilted at an angle from about 20 to about 45 degrees relative to the first ion optical axis of the mass analyzer, and the laser can be configured to generate pulses of energy at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis of the mass analyzer.
• the method comprises providing an electric field that is applied to draw analyte ions into the mass analyzer.
• Figure 1 schematically illustrates an ion source in accordance with various embodiments of the applicants' teachings.
• Figure 2 schematically illustrates a mass analyzer system with a tilted sample plate in accordance with various embodiments of the applicants' teachings.
• FIG. 3 schematically illustrates a mass analyzer system in accordance with various embodiments of the applicants' teachings.
• Figure 4 shows a typical contamination pattern on a lens located within the vacuum region of a prior art mass analyzer having a MALDI source after approximately 30,000 samples have been analyzed. Docket No. 6087WO - 6 -
• Figure 5 compares the sensitivity of a prior art ion source and the applicants' ion source as a function of the amount of sample material analyzed.
• Figure 6 shows a measurement of the instrument sensitivity as a function of the potential between an electrode and the inlet cone of a mass analyzer when the potential on the sample plate with respect to the inlet cone is 60 V in accordance with the applicants' teachings.
• Figure 7 schematically illustrates a prior art mass analyzer system, showing the influence of the gas drag region on the ions and neutrals in the plume.
• Figure 8 schematically illustrates a mass analyzer system in accordance with various embodiments of the applicants' teachings, showing the separation of the gas drag region from the plume.
• Figure 9 schematically illustrates a mass analyzer system in accordance with various embodiments of the applicants' teachings, showing the parameters that can be varied to minimize contamination.
• FIG. 1 schematically illustrates an ion source 10 for generating ions for mass analysis in accordance with the applicants' teachings. Gas can be bled into the ion source 10 to maintain a pressure of about 1 Torr, such that ion or neutral Docket No. 6087WO - 7 -
• the ion source 10 having an aperture 11 comprises a sample plate 14 that can support a sample 16 comprising an analyte.
• the sample 16 can, but is not limited to, include a MALDI matrix.
• the matrix material can be, but is not limited to, a-cyano-4-hydroxy-cinnamic acid (CHCA), 2,5- dihydroxybenzoic acid (DHB), sinapinic acid (SA), 3-hydroxypicolinic acid, nicotinic acid-N-oxide, 2,6-dihydroxyacetophenone, and ferulic acid.
• CHCA a-cyano-4-hydroxy-cinnamic acid
• DVB 2,5- dihydroxybenzoic acid
• SA sinapinic acid
• 3-hydroxypicolinic acid 3-hydroxypicolinic acid
• nicotinic acid-N-oxide 2,6-dihydroxyacetophenone
• ferulic acid ferulic acid.
• the normal of the sample plate 14 can be positioned at an angle from about 0 to about 45 degrees relative to a first ion optical axis 18 that corresponds to the center line of the ion path of a mass analyzer 20, and in Figure 1 the normal of the sample plate is tilted at an angle of
• An inlet region 26 of the mass analyzer 20 can comprise an inlet cone 28 having an inlet aperture 28a and a vacuum chamber 12, which can be at a pressure lower than the ion source pressure, for example, between about 3 and about 50 mTorr. In various embodiments, the pressure in the vacuum chamber is about 8 mTorr.
• a laser 22 generates laser pulses that strike at least a portion of the sample 16 on the sample plate 14 at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis 18 of the mass analyzer 20.
• the laser can be a high repetition laser and can have a pulse rate from about 500 Hz and up to about 1500 Hz.
• At least a portion of the sample can be depleted by the laser pulses of a high repetition laser in under one second.
• a plume 24 comprising analyte ions and neutral contaminants such as matrix material can be produced which follows the trajectory of the incident laser pulses and thus the center of the plume is directed away from the inlet region 26 of the mass analyzer 20.
• the cone 28 comprises an aperture 28a and in various embodiments the aperture 28a can be 4 mm in diameter.
• the pressure difference between the ion source 10 and the vacuum chamber 12 can produce gas flow that can induce gas drag forces through the inlet region 26 of the mass analyzer 20. Gas flow under such Docket No. 6087WO - 8 -
• conditions of pressure difference can be the dominant mode of plume transport and can thus entrain analyte ions, neutral particles, and matrix molecules (either neutral or charged) in the vicinity of the inlet region 26 and draw them through the aperture 28a into the vacuum chamber 12 of the mass analyzer 20 as is well known in the art.
• the region influenced by gas flow will be referred to throughout the application as the gas drag region and is indicated by reference numeral 29 in Figure 1.
• the subsequent gas expansion injects both the analyte ions and neutral contaminants well into (e.g., several centimeters) the vacuum chamber at roughly sonic velocities.
• Positioning the sample plate close to the cone aperture assures efficient transfer of ions with the disadvantage of allowing neutral contaminants, along with analyte ions, Docket No. 6087WO - 9 -
• the target can be spaced outside the immediate influence of the gas drag region and electric fields can be used to direct the ions toward the gas flow streams, thereby presenting an opportunity to discriminate between ions and neutrals.
• Measuring the extent of neutral particle discrimination involved laser ablation of a large number of samples and tracking the deposition of neutral material on a lens located within the vacuum chamber by both visual inspection and by measuring a loss of signal intensity due to charging of the ion optics. This charging effect can create distorted potentials due to the build up of insulating layers on the ion optics over time. Defining "one sample” as the laser ablation of a portion of material from one Docket No. 6087WO - 10 -
• the first experiment used laser pulses striking the sample plate at an angle of incidence of 25 degrees relative to the center line of the first ion optical axis of the mass analyzer, an inlet aperture diameter of 4 mm, and a 2 mm spacing between the sample plate and the inlet aperture, where the entire plume would be within the gas drag region and showed the highest efficiency of ion transfer.
• this configuration was also the most susceptible to contamination, showing distinctly visible deposits surrounding the inlet aperture and the quadrupole rods of the QO region of the vacuum chamber, and heavy contamination surrounding the exit aperture of the QO region after only 30,000 sample ablations at which point a 50% signal reduction was observed. Evidence of this contamination is shown in Figure 4.
• the third experiment used laser pulses striking the sample plate at an angle of incidence of 80 degrees relative to the center line of the first ion optical axis of the mass analyzer, a sample plate tilted at an angle of 20 degrees, an inlet aperture diameter of 4 mm and a 16 mm spacing between sample plate and the inlet aperture. Optics contamination was significantly reduced relative to the other experiments. Greater than 200,000 sample ablations occurred before a 50% signal reduction was recorded. The drift potential between the sample plate and the cone used higher voltages than the experiment using 4 mm spacing, a range of 50 to 150 V. This experiment demonstrated good ability to discriminate between neutrals and ions, with ions traveling through the drift region with few losses or spreading between desorption at the source and travel to the cone aperture. Neutrals were pumped away before reaching the strong vacuum draw of the gas drag region close to the aperture.
• a mass analysis system comprises an ion source 30 having a sample plate 34 and a mass analyzer 40 for receiving ions generated by the ion source 30.
• the pressure in the source can be between about 100 mTorr and about 2 Torr and can be about 1 Torr.
• the ion source comprises a source aperture 58.
• the sample plate 34 can contain a sample 36 comprising an analyte.
• the sample 36 can, but is not limited to, include a MALDI matrix.
• the matrix material can be, but is not limited to, a-cyano-4- hydroxy-cinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (DHB), sinapinic acid (SA), 3-hydroxypicolinic acid, nicotinic acid-N-oxide, 2,6- dihydroxyacetophenone, and ferulic acid.
• CHCA a-cyano-4- hydroxy-cinnamic acid
• DVB 2,5-dihydroxybenzoic acid
• SA sinapinic acid
• 3-hydroxypicolinic acid nicotinic acid-N-oxide
• 2,6- dihydroxyacetophenone 2,6- dihydroxyacetophenone
• ferulic acid ferulic acid.
• the normal of the sample plate 34 can be positioned at an angle from about 0 to about 45 degrees relative to a first ion optical axis 38 that corresponds to the center line of the ion path of the mass analyzer 40 and in Figure 2 the normal of the sample plate is tilted
• a laser 42 generates laser pulses that strike at least a portion of the sample 36 on the sample plate 34 at an angle of incidence from about 0 to about 80 degrees to the center line of the first ion optical axis 38 of the mass analyzer 40.
• the laser 42 can be a high repetition laser and can have a pulse rate from about 500 Hz and up to 1500 Hz.
• at least a portion of the sample 36 can be depleted by the laser pulses of a high repetition laser in under one second.
• a plume 44 comprising analyte ions and neutral contaminants such as matrix material can be produced which follows the trajectory of the incident laser pulses and thus the center of the plume is substantially directed away from the inlet region 46 of the mass analyzer 40.
• the gas pressure of the vacuum chamber 48 can be between about 3 mTorr and about 50 mTorr. In various embodiments, the gas pressure of the vacuum chamber 48 can be about 8 mTorr.
• An electric field can be generated to direct the analyte ions of interest along the first ion optical axis 38 into the inlet region 46 of the mass analyzer 40. The electric field strength can be defined by the following equation:
• E represents an electric field strength
• V represents a first electrical potential applied on the sample plate 34 measured relative to the electrical potential applied on the cone 54
• d represents the distance between the sample plate 34 and the aperture 54a of the mass analyzer 40.
• gas drag and electric field forces available to accelerate the ions toward the inlet of the mass analyzer each have distinct properties with respect to particle movement within the analyzer system, that is, gas drag will move both charged and neutral particles whereas electric fields will move charged particles alone. Gas drag forces can have a stronger influence on charged particles than can electric Docket No. 6087WO - 13 -
• instrument geometry including spacing between the ion source and the inlet aperture can be configured such that the ablation plume can remain at a sufficient distance away from the inlet region and thus gas drag forces do not substantially draw the charged and the neutral contaminant particles into the mass analyzer.
• an electric field can be applied to separate the charged analyte ions from the neutral contaminant particles which can be present in the plume.
• the electric field can direct only the charged analyte ions into the vicinity of the gas drag region such that the gas drag forces can draw the analyte ions into the mass analyzer, thereby reducing contamination of the system.
• the combined effects of these two forces can be used to determine appropriate instrument geometry to achieve high transfer efficiency for ions while maintaining some degree of discrimination between ions and neutral particles.
• the influence of electric field forces depends on the distance of the sample plate 34 from the inlet region 46 of the mass analyzer 40 and the potential applied on the sample plate 34 with respect to the potential applied to the cone 54.
• the applied electric field can be used to direct the ions toward the inlet region 46 of the mass analyzer 40.
• the electrical potential can be from 10 V to 250 V.
• the sample plate 34 can be positioned at least 16 mm from the inlet cone 54a of the mass analyzer 40, and the electrical potential on the sample plate 34 can be 60 V, providing an electric field strength of 60 V/16 mm which is 3.75 V/mm or 3,750 V/m.
• the gas "pull through” effect can be approximated by the gas velocity reduction further away from the inlet aperture. This reduction can be approximated by the ratio of the area of the inlet aperture to the area of the semi-sphere at a given distance r.
• the surface area of the semi-sphere can be given by 2/7T 2 .
• the relative gas velocity reduction can be determined as follows:
• D is the diameter of the inlet aperture and r is the distance from the inlet aperture.
• the foregoing analysis represents a qualitative approach in configuring instrument geometry to determine how to minimize the effect of neutrals entering the mass analyzer from the ablation plume.
• a more rigorous analysis of the geometry required for the plume to substantially remain outside of the gas drag region takes into effect other parameters including the angle of incidence of the laser pulses, the pressure of the source gas and the diameter of the inlet aperture and is provided below.
• ⁇ represents proportionality.
• m is the mass flow of source gas into the inlet aperture and r is the distance from the inlet aperture.
• m is the mass flow of source gas into the orifice
• M is the molecular weight of the source gas
• T 0 is the temperature of the source gas
• po is the pressure of the source gas
• D is the diameter of the inlet aperture
• Equation 4 [0048] Substituting Equation 4 into Equation 3 gives the following equation:
• V G ⁇ S oc —- o ⁇ cc 00..7744— ⁇ V - J — -Po (Equation 5) r 2 r 2 i T n
• VGAS VGAS.
• the relationship between VPLUME and VGAS can be described as follows:
• A is a constant of proportionality with an approximate value of 1.
• Equation 5 [0053] Substituting Equation 5 into Equation 6 gives the following equation:
• Equation 2 which is similar to Equation 2, where p 0 , T 0 , and M are constants.
• ⁇ is the angle between the center line of the ion path of the instrument and the plume
• R is a given radius of the gas flow dominated region
• L is the distance between the sample plate and the inlet aperture
• Equation 8 [0060] Substituting Equation 8 into Equation 9 gives the following equation:
• contamination can be reduced, compared to the prior art, by increasing the angle ⁇ or by increasing the distance between the sample plate and the inlet aperture, L, or by decreasing the diameter of the inlet aperture, D, or decreasing the source pressure, p 0 .
• an electrode 50 can be positioned between the sample plate 34 and the inlet region 46 of the mass analyzer 40, and a second electrical potential with respect to the potential applied to the cone 54 can be applied to the electrode 50 to direct the analyte ions away from the laser beam 42 and along a second ion optical axis 52 into the inlet region 46 of the mass analyzer 40.
• An electrode can be a conducting element on which a potential is provided and can include, but is not limited to, a plate, ring, rod or tube.
• the electrode 50 can be positioned in various ways and locations, as known in the art, between the sample plate 34 and the inlet region 46 of the mass analyzer 40 to direct analyte ions into the inlet region 46 of the mass analyzer 40.
• the second electrical potential between the potential of the cone 54 and the potential of the plate 34 can be varied.
• the second potential can be from 20 to 250 V, and, in various aspects, the electrode 50 can be at the same potential as the sample plate 34.
• the second electrical potential can be applied in conjunction with the electrical potential between the sample plate or independently from the first electrical potential.
• the electrical potential between the sample plate and the cone can be applied independently without enabling the second electrical potential between electrode 50 and the cone 54 to direct the analyte ions into the inlet region 46 of the mass analyzer 40.
• a mass analysis system comprises an ion source 60 having a sample plate 64 that can contain a sample 66 comprising an analyte and a mass analyzer 70 for receiving ions generated by the ion source 60.
• the ion source comprises an aperture 62 and in various embodiments the pressure in the source can be between about 100 mTorr and about 2 Torr and can be about 1 Torr.
• the sample plate 64 typically is substantially orthogonal relative to a first ion optical axis 68 of the mass analyzer 70 to form a tilt angle relative to the first ion optical axis of 0 degrees.
• the mass analyzer 70 can comprise a cone 84 having an aperture 84a and a vacuum chamber 78.
• the pressure difference between the ion source 60 and the vacuum chamber 78 can produce gas flow that can induce gas drag forces through the inlet region 76 of the mass analyzer 70.
• a laser 72 generates laser pulses that strike at least a portion of the sample 66 on the sample plate 64.
• a laser ablation plume 74 comprising analyte ions, can be produced.
• a gas drag region 86 can thus entrain analyte ions, neutral particles, and matrix molecules (either neutral or charged) in the vicinity of the inlet region 76 and draw them through the aperture 84a into the vacuum chamber 78 of the mass analyzer 70.
• instrument geometry including spacing between the ion source and the inlet aperture can be configured such that the laser ablation plume can remain at a sufficient distance away from the gas drag region and thus gas drag forces do not substantially draw the charged and the neutral contaminant particles into the mass analyzer.
• an electric field can be applied to separate the charged analyte ions from the neutral contaminant particles which can be present in the plume by directing the analyte ions of interest along the first optical axis 68 into the inlet region 76 of the mass analyzer 70.
• the neutral contaminant particles will not be influenced by the electric field.
• Figure 4 shows a photo of the severe contamination 80 that can accumulate on a lens (such as the lens 82 shown in Figure 3) within a prior art mass analyzer after approximately 30,000 samples have been analyzed in accordance with the prior art system. Since the lens typically has an aperture of only 1.5 mm, even small contaminant deposits on the lens can greatly decrease the flow of ions through the mass analyzer and therefore the contamination seen in Figure 4 can be considered to be severe.
• the dark circle in the middle of the photograph is the lens aperture and the build up of contaminants that have entered the system (designated by reference numeral 80) surrounds the aperture. It should be noted that the four dark rings positioned symmetrically about the lens aperture represent the ends of the quadrupole rods in the QO region of the mass analyzer.
• Figure 7 illustrates the gas drag region 186 of a prior art mass analyzer that can entrain analyte ions 188, neutral particles and matrix molecules 187 in the vicinity of the inlet region 176 of the mass analyzer 170 and can pull them into the mass analyzer 170 through the cone 184.
• Figure 8 illustrates that the gas drag region 156 can be separated from the plume 144 in accordance with various embodiments of the applicants' teachings. Also shown in Figure 8 are the parameters provided in Equations 1 and 2.
• the analyte ions 145 can be pulled into the mass analyzer 140 and the neutral particles 143 can follow the plume 144 in the direction of the laser beam 142.
• Figure 5 shows an example comparing the sensitivity of a prior art ion source and the applicants' ion source as a function of the number of samples processed using the compound Haloperidol.
• the relative signal represents signal that has been normalized to the signal obtained from a clean system in which the sample number is equal to one.
• sensitivity decreases in the prior art system as the number of samples analyzed increases and sensitivity substantially decreases after approximately 30,000 samples are analyzed.
• a system configured in accordance with the Docket No. 6087WO - 24 -
• a laser which can be, but is not limited to, a high-repetition rate solid state laser, strikes a portion of a sample, comprising an analyte, on a tilted sample plate.
• a plume comprising analyte ions can be generated and moves toward the incoming laser beam and away from the inlet region of the mass analyzer.
• the analyte ions are typically produced at pressures of about 0.2 to about 2 Torr in high pressure MALDI applications, as known in the art.
• Neutral and matrix particles which can be present in the plume can contaminate the system if they enter the inlet region of the mass analyzer and deposit in locations that can influence the performance of the system, generally close to ion trajectories.
• both ions and neutral and matrix particles if present, follow an initial trajectory towards the incoming laser beam and away from the inlet region of the mass analyzer. This allows the neutrals and contaminants Docket No. 6087WO - 25 -
• An electric field generated by applying a first electrical potential, can direct the analyte ions into the inlet region of the mass analyzer.
• a second electrical potential can be applied either independently or in conjunction with the first electrical potential to direct the analyte ions in the vicinity of the gas drag region where gas drag forces can draw the analyte ions into the inlet aperture of the mass analyzer.
• the distance between the sample plate and the inlet aperture can be 5 mm or greater. In various embodiments, the distance between the sample plate and the inlet aperture can be 6 mm or greater. In various embodiments, the distance between the sample plate and the inlet aperture can be 10 mm or greater. In various embodiments, the distance between the sample plate and the inlet aperture can be between 5 and 20 mm. In various embodiments, the distance between the sample plate and the inlet aperture can be between 12 and 20 mm. In various embodiments, the distance between the sample plate and the inlet aperture can be 16 mm.
• the use of a high repetition laser can allow data to be acquired rapidly and a speed of approximately one second or less for each sample point on the sample plate can be achieved.
• a high repetition laser several thousand laser shots per sample can be obtained in a Docket No. 6087WO - 26 -
• samples can be analyzed quicker and build up of contaminants can occur in a short period of time. For example, after analysis of approximately 30,000 samples in a prior art system, performance can be noticeably reduced such that cleaning of the system is necessary. When cleaning of the system is required, vacuum needs to be broken which can result in significant down time of the system.
• the applicants' teachings can reduce the frequency of system cleaning, and therefore down time, which is especially important for high-throughput applications.
• the sample can comprise a
• a matrix-free sample can also be used, especially for samples in which the mass range is limited by matrix interference.
• An example of a matrix-free technique is desorption/ionization on silicon (DIOS) where analyte molecules are trapped within a porous silicon surface from which they are laser desorbed and ionized (Nature, 1999, 399, 243-246). The absence of matrix interference can allow for the analysis of small molecules below 300 m/z.
• DIOS desorption/ionization on silicon
• the absence of matrix interference can allow for the analysis of small molecules below 300 m/z.
• a matrix-free sample can be used, neutrals as well as other contaminants can still be present and can form deposits that can contaminate the system.
• sample plate illustrated in the figures is representative of a typical plate, but the applicants' teachings are not limited to such a configuration.
• Other configurations of the sample plate as known in the art can be used.
• the sample plate can contain topological features, as known in the art.
• the sample plate can be a curved, disc shape or can comprise other materials such as tape.
• an electrode can be a conducting element on which a potential is provided.
• An electrode can include, but is not limited to, a plate, ring, rod or tube. Docket No. 6087WO - 27 -
• the mass analyzer can be, but is not limited to, a mass spectrometric instrument which can employ single MS, tandem (MS/MS) or multi-dimensional (MS n ) mass spectrometry.
• Mass spectrometers can include, but are not limited to, a triple quadrupole, an ion trap, a hybrid linear ion trap, a time-of-flight, quadrupole time-of-flight, an RF multipole, a magnetic sector, an electrostatic sector, and an ion mobility spectrometer.
• Mass analyzers can include, but are not limited to, mass filters, mass selectors, ion focusing and/or ion steering elements, for example, ion guides.
• Mass analyzers also can include, but are not limited to ion reflectors and/or ion fragmentors, for example, collision cells, photodissociation cells, and surface dissociation fragmentors.

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