WO2006089449A2 - Dispositif et procede d'analyse et d'imagerie par spectrometrie de masse hautement localisees - Google Patents

Dispositif et procede d'analyse et d'imagerie par spectrometrie de masse hautement localisees Download PDF

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Publication number
WO2006089449A2
WO2006089449A2 PCT/CH2006/000117 CH2006000117W WO2006089449A2 WO 2006089449 A2 WO2006089449 A2 WO 2006089449A2 CH 2006000117 W CH2006000117 W CH 2006000117W WO 2006089449 A2 WO2006089449 A2 WO 2006089449A2
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Prior art keywords
molecules
ion trap
sample
atoms
sample surface
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PCT/CH2006/000117
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English (en)
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WO2006089449A3 (fr
Inventor
Renato Zenobi
Thomas Schmitz
Patrick Setz
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Eidgenössische Technische Hochschule Zürich
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Publication of WO2006089449A2 publication Critical patent/WO2006089449A2/fr
Publication of WO2006089449A3 publication Critical patent/WO2006089449A3/fr

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0459—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components for solid samples
    • H01J49/0463—Desorption by laser or particle beam, followed by ionisation as a separate step
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0004—Imaging particle spectrometry

Definitions

  • the present invention generally relates to the field of mass spectrometry.
  • the present invention relates to a device and a method for localized mass spectrometric analysis of a sample surface.
  • LDMS localized laser desorption mass spectrometry
  • an intense, highly focused laser beam is applied to the sample surface, whereby the surface spot hit by the laser beam is partially vaporized and ionized (this process is well known as "laser desorption and ionization", LDI).
  • LDI laser desorption and ionization
  • the resulting ions are transferred to a mass spectrometer by applying electric fields and analyzed therein. By scanning the laser beam over the sample surface, information about the local chemical composition is obtained (B. Spengler, M. Hubert, J. Am. Soc. Mass Spectrom. 13 (2002) 735-748).
  • MALDI matrix-assisted laser desorption ionization
  • a focused laser beam acts to ablate neutral sample molecules from a sample sur- face in a special ablation chamber. These neutral species are transferred by a gas stream into the ionizer of a mass spectrometer of the ion-trap kind.
  • SIMS secondary ion mass spectrometry
  • a high-energy primary ion beam is used to irradiate a sample surface.
  • secondary ions are liberated from the sample surface, transferred to a mass spectrometer by application of electric fields, and mass analyzed.
  • the achievable spatial resolution is primarily determined by the spot size of the primary ioh beam. In practice, the spot size can be brought down to approximately 100 nanometers, and therefore SIMS can offer a better spatial resolution than localized LDMS.
  • SIMS the sample must be investigated in ultrahigh vacuum, and the ionization process in SIMS leads to a relatively high degree of undesired fragmentation of the sample molecules, which further increases with molecular size. Therefore, SIMS is only of limited usefulness for localized chemical analysis, especially when applied to biological materials.
  • SNOM scanning near-field optical microscopy
  • STM scanning tunneling microscopy
  • AFM atomic force microscopy
  • the device of the present invention comprises a setup for providing a localized light field for ablating/desorbing sample atoms and/or molecules at an impact spot on the sample surface.
  • This setup comprises a light source, preferably a laser, more preferred a pulsed laser (having a wavelength in the UV 1 VIS or IR range), for generating light.
  • the light either has a single predeter- mined wavelength (in the preferred case of a coherent light source like a laser) or a - preferably narrow - distribution of wavelengths with a mean wavelength corresponding to a predetermined wavelength.
  • the device further comprises field localization means for concentrating the light to a field region with lateral dimensions on the range of the predetermined wavelength.
  • the field localization means serve for generating a localized optical field which is essentially confined to a region on the sample surface whose lateral dimensions are on the range of the predetermined wavelength.
  • lateral dimensions on the range of a predetermined wavelength is to be understood as meaning that the intensity of the light field falls off to below 50% of the peak intensity within a lateral range of less than ten times, better five times the predetermined wavelength, more preferred less than two times the wavelength, even more preferred less than the wavelength itself, most preferred less than 50% of the wavelength.
  • the field localization means comprise a scanning near-field optical microscopy (SNOM) setup.
  • the lateral dimensions of the field region are preferably less than two times the predetermined wavelength, more preferred less than the predetermined wavelength itself.
  • the field localization means comprise an optical probe, preferably an optical fiber, coupled to the light source, the probe having a probe tip with an aperture which is smaller than the predetermined wavelength in all lateral directions, i.e., a so-called sub- wavelength aperture.
  • the field localization means comprise a dielectric or conducting (generally metallic) tip, which serves as a means for localized field enhancement. This tip is irradiated by the light from the light source. The light may be focused to the tip by any conventional means (e.g., a lens arrangement).
  • Positioning means are provided for positioning the field localization means relative to the sample surface.
  • these means are preferably adapted to position the field localization means and the sample surface relative to each other such that the sample surface is within the field region of the narrowly concentrated light field generated by the field localization means.
  • the positioning means are adapted to position the field localization means and the sample surface relative to each other at a distance which is smaller than the predetermined wavelength.
  • the region of the sample surface irradiated by the concentrated light field will be called the impact spot of the light. Irradiation of the impact spot with the light field will lead to highly localized ablation (desorp- tion) of atoms and/or molecules from the sample surface, in neutral form, in (partially) ionized form or both.
  • atom refers to an atom in an arbitrary electronic state (neutral or singly or multiply charged/ionized, positively or negatively).
  • molecule refers to a molecule in an arbitrary electronic state. While the field localization provides for high lateral spatial resolution, the amount of sample atoms and/or molecules ablated during each laser pulse event is extremely small, often only in the attomole range. Therefore, efficient means for collecting the atoms and/or molecules and sensitive means for analyzing them are required.
  • the invention therefore suggests to further provide an ion trap for storing the sample atoms and/or molecules ablated from the surface in ionized form, trans- fer means for transferring the sample atoms and/or molecules from the sample surface, specifically, from the vicinity of the impact spot, to the ion trap, and an additional mass analyzer coupled to the ion trap for analyzing the sample atoms and/or molecules.
  • an ion trap By providing an ion trap, atoms and/or molecules ablated from the sample surface can be collected and accumulated efficiently and can be analyzed once a sufficient number of atoms and/or molecules have accumulated. This overcomes the sensitivity problems known in the prior art.
  • the device is adapted for keeping the sample at a pressure different from, specifically, higher than, the pressure within the ion trap and/or the mass spectrometer.
  • the device further comprises vacuum generating means (usually one or more suitable pumps, preferably diffusion pumps) for creating a vacuum within the mass spectrometer and within the ion trap.
  • the levels of vacuum may be different in the mass spectrometer region, the ion trap region, and in the transfer means.
  • the device is adapted for keeping the sample at ambient pressure. This allows even the analysis of live biological samples, which is impossible with any methods requiring the sample to be in vacuum.
  • the transfer means advantageously comprise a transfer tube extending from a first end disposed near the sample surface (specifically, the impact spot) to a second end. Transfer occurs by the effect of a positive pressure difference between the first and second ends.
  • an electromagnetic field may be applied to the transfer tube for accelerating and guiding atoms and/or molecules in ionized form into and/or within the transfer tube.
  • the transfer tube preferably comprises a capillary portion near its first end having an inner diameter which is significantly smaller than an inner diameter of a portion of the transfer tube near its second end, preferably smaller by a factor of at least 10, more preferred at least 50.
  • the inner diameter of the capillary portion is preferably in the range of 25 to 400 micrometers.
  • the transfer means advantageously comprise heating means for heating the transfer tube.
  • the transfer means comprise an intermediate vacuum chamber and tube means connecting said intermediate vacuum chamber to the ion trap, and the second end of the transfer tube is disposed in the intermediate vacuum chamber.
  • the transfer means comprise an intermediate vacuum chamber and tube means connecting said intermediate vacuum chamber to the ion trap, and the second end of the transfer tube is disposed in the intermediate vacuum chamber.
  • a skimmer cone with a central through-hole is disposed in the intermediate vacuum chamber, wherein the through-hole is connected to the tube means which connect the intermediate vacuum chamber to the ion trap.
  • a "push-pull" method may be applied, meaning that another capil- lary opposite the (suction) capillary of the transfer tube provides a continuous flow of an auxiliary gas (e.g., nitrogen), directing the ablated material towards the suction capillary.
  • an auxiliary gas e.g., nitrogen
  • the device For positioning the inlet end (first end) of the transfer tube close to the impact spot of the laser beam on the sample surface, the device preferably comprises tube positioning means, preferably a micromanipulator, for positioning the first end of the transfer tube relative to the sample surface and/or relative to the field localization means.
  • tube positioning means preferably a micromanipulator
  • the distance from the first end of the transfer tube to the impact spot (or to the field localization means) is of the same order as the inner diameter of the first end.
  • this distance is less than three times the diameter of the first end of the transfer tube, since the effect of active suction is limited in distance to only two to three times of the diameter of a capillary.
  • the mass spectrometer is a time-of-flight (TOF) mass spectrometer.
  • the TOF mass spectrometer may advantageously be of the linear or of the re- flectron type. TOF mass spectrometers are preferred since they provide for high sensitivity and short repetition rates for spectral acquisition (high duty cycles).
  • the direction of entry of the sample atoms and/or molecules into the ion trap and the direction of exit of the ionized sample atoms and/or molecules into the mass spectrometer are preferably not collinear.
  • the long axis of the mass spectrometer in other words, the drift direction of the ionized atoms and/or molecules in the mass spectrometer
  • the direction of entry of sample atoms and/or molecules into the ion trap are preferably not collinear.
  • these directions subtend an angle of at least 30 degrees, more preferred at least 60 degrees. It is most preferred that this angle is 90 degrees, i.e., that the sample atoms and/or molecules enter the ion trap in a direction that is perpendicular to the direction of transfer of the ionized sample atoms and/or molecules into the mass spectrometer.
  • the sample atoms and/or molecules are transferred into the ion trap in neutral or partially ionized form and ionized at least partially (preferably as efficiently as possible) after they have entered the ion trap.
  • the device advantageously comprises ionizing means adapted for ionizing the sample atoms and/or molecules after entry into the ion trap.
  • a particularly high efficiency of ionization may be achieved by employing chemical ionization (Cl) directly in the storage region of the ion trap.
  • the ionizing means preferably comprise gas supply means for supplying a chemical ionization gas to the ion trap and auxiliary ionizing means, e.g., an electron source, for at least partially ionizing the chemical ionization gas.
  • the chemical ionization gas may be ionized within the ion trap or externally.
  • the chemical ionization gas in ionized form is adapted for transferring charge to the sample atoms and/or molecules by chemical ionization.
  • the field positioning means advantageously comprise a piezo stage and a tuning fork.
  • the tuning fork is advantageously excited at or near its eigenfrequency, and its damping is monitored. A measure of the damping is employed for monitoring the distance of the tip end to the sample surface.
  • any type of ion trap may be used.
  • a cylindrical or hyperbolic RF ion trap is preferred.
  • the inventive method comprises the following steps: (a) Providing a light source, for generating light having a predetermined wavelength or having a distribution of wavelengths whose mean is at a predetermined wavelength, and field localization means for concentrating said light into a localized optical field having an intensity distribution which is essentially confined to a field region with lateral dimensions in the range of said predetermined wavelength;
  • each mass distribution recorded by the mass analyzer or mass information derived thereof is correlated with the lateral position of the field localization means for which the mass distribution has been determined.
  • the mass spectra may be correlated with additional data obtainable from the SNOM directly and/or through other observations. Such additional data may comprise, e.g.:
  • Fig. 1 shows a highly schematic view of a device according to the present invention
  • Fig. 2 shows a schematic detail view of a scanning near-field optical microscope
  • Fig. 3 shows a schematic perspective sectional view of a time-of-flight mass spectrometer coupled to an ion trap
  • Fig. 4 shows a schematic side sectional view of a time-of-flight mass spectrometer coupled to an ion trap
  • Fig. 5 shows an enlarged schematic perspective sectional view of the ion trap
  • Fig. 6 shows an enlarged schematic side sectional view of the ion trap
  • Fig. 7 shows a schematic view of a differentially pumped transfer system and a micromanipulator coupled to the transfer system
  • Fig. 8 shows a schematic partial side sectional view of a transfer tube
  • Fig. 9 shows a flow diagram of a process according to the present invention.
  • Fig. 10 shows a mass spectrum obtained with a device according to the present invention.
  • Fig. 1 shows a schematic diagram of a device according to a preferred embodiment of the present invention.
  • the device comprises several key units inter- faced with each other: a SNOM setup 2 for highly localized laser desorption or ablation; an ion trap system 4 comprising an ionizer 440 and a trap 410; a transfer system 5 for transferring desorbed atoms or molecules into the ion trap system 4; and a TOF mass spectrometer 3 interfaced with the ion trap system 4.
  • a common control unit 1 the device will be described in more detail, followed by a description of its operation.
  • the control unit 1 comprises a computer 100 with CPU and storage means, an input device (keyboard) 110 and a visual output device (monitor) 111.
  • the inter- face between the computer and the units to be controlled may be achieved in any of the usual ways, e.g., by an I/O card present in the computer 100 providing for external analog or digital input and output lines, by Ethernet connection, by serial bus connection etc.
  • the SNOM setup 2 comprises a laser 201 (in the UV 1 VIS or IR wavelength range) for generating a pulsed laser beam, which is coupled into an optical fiber 202.
  • the fiber has a tapered tip 203 with a sub-wavelength aperture facing a sample surface 204.
  • the fiber 202 may be positioned relative to the sample surface 204 and scanned over the surface. To this end, it is connected to a tuning fork 211 which is mounted on a first piezo stage 212.
  • the sample itself is mounted on a second piezo stage 205 for lateral scanning.
  • the whole SNOM setup 2 is kept at ambient pressure, which provides for easy access and handling of the setup as well as for great versatility and allows analysis of delicate samples (i.e. live cells).
  • Fig. 2 shows a more detailed, yet schematic view of the SNOM setup 2.
  • the tuning fork 211 is employed.
  • the tuning fork 211 is excited at or near its eigenfrequency by a transducer 213 driven by an oscillator unit 222, and the damping of the tuning fork by shear forces is monitored in a position control unit 221 via pickup transducers (not shown in Figs. 1 and 2) and an amplifier 214.
  • the tip 203 ap- proaches the sample surface 204 to within atomic dimensions, shear forces strongly increase, leading to a strong increase in damping of the tuning fork 211.
  • the damping signal is used in the position control unit 221 , which drives the piezo stages 205 and 212. In this way, precise positioning in the z direction may be achieved. Operation of such a tuning-fork mechanism is well-known in the art.
  • a CCD camera (not shown in Figs. 1 and 2) allows observation of the sample during scanning and analysis.
  • the SNOM is mounted on an inverted micro- scope which allows simultaneous acquisition of emission spectra of the sample (i.e., fluorescence) as a complementary imaging contrast.
  • the ion trap system 4 comprises a vacuum chamber which contains the actual ion trap 410 and the ionizer 440.
  • the trap 410 is op- erated by a trap operating unit 401 , while the ionizer is operated by a HV power supply 402 and a filament power supply 403.
  • a gas reservoir in the form of a gas cylinder 421 contains an chemical ionization gas, which may be fed into the vacuum chamber by means of a valve 422 and a gas supply line 423.
  • An appropriate vacuum is maintained in the vacuum chamber by means of a pump 430.
  • the TOF mass spectrometer 3 comprises a vacuum chamber which contains a flight tube 310 and a detector 320.
  • a pump 330 maintains high vacuum, typically below 10 '5 mbar, in the vacuum chamber of the mass spectrometer 3.
  • Figs. 3 and 4 illustrate the setup of the ion trap system 4 interfaced with the mass spectrometer 3 in more detail. For simplicity, only the most important of those parts are shown in a schematic way which are situated inside the respective vacuum chambers.
  • Figs. 5 and 6 show the region of the ion trap on a mag- nified scale.
  • the ion trap is a radiofrequency (RF) ion trap as it is well known in the art. It comprises a central metallic ring electrode 416 whose interior defines the storage region of the trap. On both sides of the ring electrode, axial end plates 411 , 413 are disposed, which are electrically insulated from the ring electrode 416. In the ring electrode 416, two radial bores are provided. Through the first of these bores, an inlet tube 520 is guided into the interior of the ring electrode 416, while the second bore serves to guide the supply line 423 for the chemical ionization gas into this region.
  • the ion trap chamber can also be filled with a buffer gas for collisional cooling (i.e.
  • the first (left) end plate 411 which is the end plate more distant from the mass spectrometer, has a central opening 412 for admitting an electron beam into the interior of the central ring electrode 416.
  • the second (right) end plate 413 which is the end plate facing the mass spectrometer, also has an opening 414, which serves to allow the ions stored in the trap to exit the trap.
  • An electron beam 444 whose spatial distribution is illustrated in Fig. 6, is generated by an ionizer 440, comprising an electron source in the form of a filament (not shown in Figs. 3 to 6) and plates 441 , 442, 443 for accelerating, gating and focusing the electrons released from the filament.
  • the mass spectrometer comprises a flight tube 310 which is closed off towards the ion trap by a front end plate 311. Ions are accelerated into the flight tube by a HV potential on a pressure orifice 312 in the front end plate 311 and drift through the flight tube 310 as an ion beam 340. At the far end of the flight tube 310, they are guided through a pair of focusing (steering) plates 313, 314 before hitting a dual MCP detector assembled in a Chevron stack 320 (i.e., the direction of the channel bias angle in the first MCP is opposite to the one in the second MCP).
  • the ion extraction region of the mass spectrometer is formed by the end plates 411 , 413 of the ion trap 410.
  • the pumps 330 and 430 shown in Fig. 1 are preferably pumps with a low level of vibration, such as oil diffusion pumps.
  • the inlet tube 520 constitutes a leak of the vacuum chamber of the ion trap system 4 towards the outside environment, and the pressure orifice 312 constitutes a leak of the vacuum chamber of the mass spectrometer 3 towards the vacuum chamber of the ion trap system 4. Therefore, the pumps need to have a sufficient capacity to keep the required level of vacuum despite these leaks.
  • a backing pump such as a rotary pump may be provided; however, this pump should be kept at a certain distance from the setup and physically well-separated from it, e.g., in a different room. Because the backing pump does not need to obtain a high level of vacuum (a residual pressure of, say, below 0.1 mbar will often be sufficient), the associated need of longer piping pre- sents no limitation.
  • the level of vacuum to be attained in the vacuum chamber of the TOF mass spectrometer is in the high vacuum range, e.g., below 10 "5 mbar, preferably below 10 ⁇ 6 mbar, in order to avoid collisions between residual gas molecules and the ions to be analyzed when they drift through the flight tube.
  • the ion trap system In the ion trap system, however, requirements are less stringent, and a vacuum level of better than 10 ⁇ 2 mbar is sufficient.
  • the pressure in the ion trap region is higher than in the TOF region since ion traps exhibit more favorable operation characteristics at elevated pressures.
  • only one single vacuum pump might be employed for both vacuum chambers.
  • This pump is then connected to the vacuum cham- ber of the mass spectrometer 3.
  • the transfer system comprises a capillary 512 mounted in a transfer tube 511.
  • the transfer tube may be closed by means of a valve 514.
  • the transfer tube 511 leads into a tee piece 516 (e.g., DN 25 ISO-KF) which serves as an intermediate vacuum chamber of the transfer system.
  • a vacuum is generated by a backing pump 530 (merely symbolized by an arrow in Fig. 7).
  • This pump with a flow capacity of preferably at least around 10 liters per second, generates a vacuum in the range of approximately 0.01 - 1 mbar. This is sufficient to suck atoms and/or molecules present at the tip of capillary 512 (on the left of Fig. 7) into the tee piece 516.
  • This arrangement of capillary 512, transfer tube 511 and intermedi- ate vacuum chamber (tee piece) 516 may be regarded as a first stage of the transfer system 5.
  • the tee piece 516 is closed off towards the ion trap system 4 by a flange 519 (e.g., DN 100 ISO-K).
  • a skimmer cone 518 is mounted on the flange 519. It has a central through-hole which leads into an inlet tube 520 leading, in turn, into the central ring electrode 416 of the ion trap 410.
  • the atoms/molecules which have been sucked into the tee piece 516 are enriched with respect to the ambient air by passing through the skimmer cone 518.
  • the skimmer cone 518 with its through-hole and the inlet tube 520 may be regarded as a second stage of the transfer system 5.
  • the long axis of the inlet tube 520 extends in a perpendicular direction to the long axis of the flight tube 310 of the mass spectrometer.
  • Fig. 8 shows a schematic partial side sectional view of an end portion of the transfer tube 511 with the capillary 512 mounted in it.
  • the transfer tube is ta- pered at its end.
  • the capillary 512 is attached to inside of the transfer tube 511.
  • the inner diameter D of the transfer tube is approximately 1 to 5 mm, while the inner diameter d of the capillary is in the range of 25 to 400 micrometers. There is a factor of at least approximately 10 between these inner diameters.
  • the transfer tube is made of AT steel, a stainless steel specially coated in that sense to suppress adsorption of the molecules to be transported. This successfully avoids fractionated sampling of the analyte.
  • the capillary 512 may be welded into the transfer tube 511 , or it may be held in the transfer tube by other suitable means, e.g., a fixing bushing on the transfer tube into which the capillary is inserted, facilitating re- placement of the capillary.
  • the transfer system is heated.
  • the capillary 512, the transfer tube 511 and the inlet tube 520 are surrounded by electric heating elements 513, 515, 517 and 521 , as they are well known in the art.
  • the transfer system may additionally comprise means for applying electric voltages (e.g., between the tip of the capillary 512 and the sample holder) for accelerating and/or steering ionized species and thus efficiently transporting them into the ion trap.
  • electric voltages e.g., between the tip of the capillary 512 and the sample holder
  • a first step 901 the device is prepared for operation. In particular, it is ensured that a proper vacuum is maintained in the vacuum chamber of the mass spectrometer 3, and that the vacuum chamber of the ion trap system 4 is filled with the chemical ionization gas at a suitable pressure.
  • the sample is placed onto the sample holder of the SNOM setup 2.
  • the optical fiber 202 is positioned relative to the sample surface such that its tip 203 faces a first spot on the sample surface which is to be analyzed. This positioning is achieved by appropriately operating the piezo stages 205 and 212. In this way, the distance between aperture of the fiber tip and the sample surface may be precisely adjusted to below the near-field range of the aperture.
  • the near-field range is defined as less than the wavelength of the laser, preferably less than 20% of the wavelength; typically only a few nanometers distance are employed.
  • a strong laser pulse is generated by the laser 201.
  • This laser pulse is coupled into the fiber 202.
  • the laser beam illuminates the sample spot on the surface.
  • atoms and/or molecules at the sample spot are brought into the gas phase (i.e., ablated or desorbed).
  • step 903 these atoms/molecules are sucked into the ion trap 410 by means of the transfer system.
  • a pressure difference is present between the end of the capillary 512 which faces the sample spot and the end of the transfer tube 511 in the intermediate vacuum chamber (tee piece) 516.
  • a pressure difference is present between the tip of the skimmer cone 518 and the end of the inlet tube 520 which is near the ion trap 410.
  • a chemical ionization gas (Cl gas) is present in the ion trap 410 at a suitable pressure. Since the capillary acts as a leak for the vacuum chamber of the ion trap, it is important that the pump 430 has sufficient capacity to maintain a proper vacuum level in the chamber, i.e., to efficiently remove the incoming gas. Since in this process the pump will also continuously remove some of the Cl gas, it is furthermore important that the Cl gas is replenished in sufficient amounts that a suitable partial pressure of the Cl gas is maintained during the ionization step 904.
  • the Cl gas is bombarded by electrons from the ionizer 440 and is thereby ionized.
  • the CI gas then transfers charge to the sample atoms/molecules entering the ion trap 410 through the transfer tube 511.
  • the appropriate partial pressure of the Cl gas depends on its exact nature. Suitable pressure ranges for chemical ionization are well known in the art.
  • the trap For trapping the ionized sample atoms/molecules within the trap (step 905), the trap is operated by applying an AC voltage in the RF frequency range on the central ring electrode 416.
  • the principles of operation of such an RF trap are well known in the art. The parameters of operation are chosen such that the trap is operated in a mass-selective manner resulting in that only ions with a mass in a predetermined mass window are efficiently held in the trap. It is well known in the art how such a mass selectivity may be obtained.
  • By choosing the low mass cut-off higher than the mass of the Cl gas ions only the ionized sample atoms/molecules are stored while Cl gas ions are not held in the trap.
  • the low mass cut-off is chosen to be, say, 30 amu. If desired, it is also possible to ionize and trap the Cl gas before the laser ablation is performed; in this case an Cl gas with a mass above the low mass cut-off is used. Suitable parameters for either trapping or rejecting the chemical ionization gas can be chosen for operation of the ion trap.
  • the arrival times inevitably spread over a certain time range, which is typically in the range of 100 to 200 msec.
  • the atoms/molecules After having been ionized, are accumulated and held in the trap for a certain amount of time in step 905.
  • sample atoms/molecules Once a sufficient number of sample atoms/molecules have accumulated in the ion trap 410, they are extracted and accelerated from the ion trap 410 by means of a voltage pulse applied to the end plates 411 and 413 of the trap, accelerated further by a constant HV potential on the pressure orifice 312 and transferred into the flight tube 310 of the TOF mass spectrometer 3 (step 906). Alternatively, more atoms/molecules may be collected by further laser pulses, thereby repeating steps 902 to 905 a certain number of times.
  • the ion trap 410 serves as an initial ion accelerator (ion extraction device) for the mass spectrometer 3, i.e., it takes over functions which normally would be as- sociated with the mass spectrometer 3. Still, the main acceleration occurs by the potential difference to the end plate 311 of the mass spectrometer containing the pressure orifice 312.
  • the detector 320 is of the well-known multi-channel plate (MCP) type, yielding electrical sig- nals which depend on the rate of ions hitting the detector.
  • MCP multi-channel plate
  • the fiber tip is moved to the next desired sample spot (step 908), and the procedure is repeated, starting from step 902.
  • a region of the sample surface may be systematically scanned, and an image of the chemi- cal composition of the surface may be obtained.
  • all voltage potentials and pulses that are required for the operation of the ion trap 4 and the mass spectrometer 3 are supplied by the MS operating unit 301.
  • the unit also acquires the electrical signal of the MCP detector 320 with high time resolution.
  • the unit parameters and timing are controlled by the central control unit 1 , to which the acquired raw data is also sent for further processing.
  • the MS operating unit 301 can be designed as an integrated unit, comprising all the power supplies, high-voltage RF generator, timing circuits, hardware acqui- sition and communication boards and a real-time operating software, or a group of different stand-alone units may be provided, such as digital delay pulse generators, different power supplies, high-voltage pulsers/switches, a RF exciter and high-voltage RF amplifier and a digital oscilloscope.
  • the MS operating unit is configured to operate the ring electrode of the ion trap at a constant RF frequency and a given RF amplitude while the axial end plates 411 and 413 are kept at ground potential and no electrons of the ionizer 440 are allowed to pass into the interior of the ion trap.
  • Each MS acquisition cycle starts as soon as the MS operating unit 301 receives a trigger signal from the control unit 1 (at the same time the laser 201 is also triggered by the control unit).
  • RF frequency and amplitude RF frequency and amplitude
  • a trigger is sent to the RF generator which turns off the RF output (i.e., by gradually decreasing the RF amplitude to 0 Volts within a RF cycle).
  • the phase of the RF signal is constantly being monitored in order to start the clamp-down of the RF amplitude at a defined phase angle. This also allows to synchronize the HV extraction pulses on the axial end plates 411 , 413 with the RF phase and amplitude.
  • the time of extraction in respect to the RF signal is a critical parameter in ion trap operation as it has a large influence on the obtained ion yield.
  • An opti- mized extraction is typically achieved at phase angles between 90 - 140°.
  • the extraction voltage on the plate 411 is switched in 200 ns from ground to a positive voltage, and on plate 413 from ground to a negative voltage.
  • the time when the extraction is initiated also serves as the start time for the acquisition of the time-of-flight MS signal. After all the ions have reached the detector 320, acquisition is stopped, the MS time signal transferred to the control unit 1 , and all operating parameters of the MS operating unit are restored back to the idle state.
  • Fig. 10 shows a mass spectrum obtained with a setup according to the present invention. Intensity at the MCP is recorded as a function of the mass/charge ratio m/z.
  • the sample is kept at ambient pressure
  • the sample may equally well be kept at any different pressure, including reduced pressures.
  • SNOM setup comprises an etched and metallized optical fiber
  • different kinds of optical probes with sub-wavelength apertures may be used, specifically, hollow optical waveguides of the capillary type.
  • the SNOM setup may be different from the one presently described, as long as it allows to generate a localized optical field with preferably sub-micrometer lateral resolution.
  • a dielectric or conducting (e.g., metallic or metallized) tip or AFM cantilever is provided near the sample surface, and a laser beam is directed at the tip by conventional focusing techniques.
  • the field in the immediate vicinity of the tip will be strongly enhanced by the presence of the tip, thus leading to strong localization of the optical field.
  • the transfer system of the above-described embodiment comprises a transfer tube through which the sample atoms/molecules are transported by a gas stream, preferably in neutral form. It is also possible to adjust the laser operating parameters (pulse energy, etc.) in a way that ions are produced directly during the ablation event. In this case the transport can be assisted by electromag- netic fields, specifically, by applying an electric field between the sample holder and the end of the transfer capillary facing the sample surface. While the setup of the transfer system as described above in connection with Fig. 7 is preferred, the transfer system may be simplified by leaving away the intermediate vacuum chamber (tee piece) 516 with its skimmer cone.
  • the sample atoms/molecules are ionized by chemical ionization. While this method is preferred due to the high efficiency of the method, different methods are possible, including direct ionization of the sample atoms/molecules by an electron beam, a laser beam or by impact on a heated surface. Ionization of the ablated neutrals is also possible before they enter the ion trap by different means, i.e. by a laser beam directed perpendicular through the transfer tube or by photoionization (i.e. with UV light). If chemical ionization is employed, any suitable Cl gas may be used, including methane, propane, isobutane, water, ammonia, helium, hydrogen, and many other well described in the prior art.
  • any other type of ion trap as they are well- known in the art, may be used, including other types of quadrupolar RF ion traps.
  • TOF mass spectrometer While a TOF mass spectrometer is preferred for mass analysis, other types of mass analyzers may be used, as they are well known in the art. Mass analyzers which are generally of the TOF type are however preferred due to their achievable high mass range, ease and speed of operation (especially if compared to mass analyzers of the ion-trap kind) and high detection efficiency. In particular, instead of a linear TOF mass spectrometer, a TOF mass spectrometer of the reflectron type may be used, which may lead to improved mass resolution by a refocusing of an initial spatial spread of the ions to be analyzed. A further advantage of TOF mass spectrometers is that the ion trap may serve as the ion extraction region of the mass spectrometer, such that no further specific means for this purpose are needed.
  • UV Ultraviolet VIS Visible (wavelength range)

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  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Electron Tubes For Measurement (AREA)

Abstract

La présente invention se rapporte à un dispositif et à un procédé permettant d'effectuer une analyse par spectrométrie de masse localisée d'une surface d'échantillon (204). Le dispositif selon l'invention comprend un système optique, de préférence une installation de microscopie optique à champ proche à balayage (SNOM) (2), qui sert à ablater des atomes/molécules d'échantillon de la surface d'échantillon avec une résolution spatiale élevée, de préférence à pression atmosphérique. Lesdits atomes/molécules sont transférés vers un piège à ions (410) par des moyens de transfert (5) appropriés, avantageusement à travers un tube de transfert sous l'action d'une différence de pression. Les atomes/molécules sont ionisés, de préférence par ionisation chimique, et s'accumulent dans le piège à ions (410). Une fois qu'un nombre suffisant d'ions se sont accumulés, ces derniers sont analysés par un analyseur (3), de préférence du type à temps de vol.
PCT/CH2006/000117 2005-02-28 2006-02-23 Dispositif et procede d'analyse et d'imagerie par spectrometrie de masse hautement localisees WO2006089449A2 (fr)

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Cited By (3)

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CN102662086A (zh) * 2012-04-20 2012-09-12 中国科学院半导体研究所 基于微纳操作臂的多自由度近场光学显微镜
US20130206738A1 (en) * 2012-02-10 2013-08-15 First Solar, Inc. In situ inductive ablation meter
KR101850304B1 (ko) 2015-02-09 2018-04-19 도레이 리서치 센터 인코포레이티드 분석방법 및 그것을 구비하는 분석장치

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FR2797956A1 (fr) * 1999-08-26 2001-03-02 Univ Metz Dispositif de detection et d'analyse par ablation laser et transfert vers une trappe ionique d'un spectrometre, procede mettant en oeuvre ce dispositif et utilisations particulieres du procede
WO2001078106A2 (fr) * 2000-04-10 2001-10-18 Perseptive Biosystems, Inc. Preparation d'un pulse d'ions pour analyse de masse a temps de vol simple et en tandem
WO2002084577A1 (fr) * 2001-04-17 2002-10-24 Large Scale Proteomics Corporation Systeme permettant d'optimiser l'alignement d'un faisceau laser avec des points selectionnes sur des echantillons dans un spectrometre maldi
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130206738A1 (en) * 2012-02-10 2013-08-15 First Solar, Inc. In situ inductive ablation meter
CN102662086A (zh) * 2012-04-20 2012-09-12 中国科学院半导体研究所 基于微纳操作臂的多自由度近场光学显微镜
KR101850304B1 (ko) 2015-02-09 2018-04-19 도레이 리서치 센터 인코포레이티드 분석방법 및 그것을 구비하는 분석장치
KR20180041252A (ko) * 2015-02-09 2018-04-23 도레이 리서치 센터 인코포레이티드 분석방법 및 그것을 구비하는 분석장치
KR102240589B1 (ko) 2015-02-09 2021-04-15 도레이 리서치 센터 인코포레이티드 분석방법 및 그것을 구비하는 분석장치

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