WO2008148557A2

WO2008148557A2 - Sample holder device for ionization chambers for mass spectometry

Info

Publication number: WO2008148557A2
Application number: PCT/EP2008/004499
Authority: WO
Inventors: Gaetano Corso; Dott.Ssa Oceania D'apolito; Dott. Giuseppe Paglia
Original assignee: Universita' Degli Studi Di Foggia
Priority date: 2007-06-05
Filing date: 2008-06-05
Publication date: 2008-12-11
Also published as: WO2008148557A3; ITRM20070312A1

Abstract

A sample holder device for ionization chambers is disclosed. The sample holder device of the present invention allows to perform DESI measurements (desorption electrospray ionization mass spectrometry) in ionization chambers equipped with facilities for other mass spectrometry ionization techniques such as ESI (electrospray ionization mass spectrometry) and APCI (atmospheric pressure chemical ionization). By simply and easily inserting the sample holder device according to the present invention in a ionization chamber equipped for instance with ESI or APCI facilities, it is possible to work with a further ionization technique (DESI) in the same ionization chamber without costly and time-consuming modifications of the chamber. It is thus possible to profit of all the advantages of the DESI technique and, at the same time, to compare the results obtained with those obtained with other ionization techniques such as ESI or APCI.

Description

SAMPLE HOLDER DEVICE FOR IONIZATION CHAMBERS FOR MASS SPECTROMETRY

FIELD OF THE INVENTION

The present invention relates to the field of mass spectrometry. In particular, the present invention relates to a sample holder device for mass spectrometry. More in particular, the present invention relates to a sample holder device for ionization chambers for desorption electrospray ionization mass spectrometry (DESI).

BACKGROUND OF THE INVENTION

Mass spectrometry is an analytical technique based on the measurement of the mass-to- charge ratio (m/z) of charged particles coming from the sample to be analyzed (analyte). There are several approaches to mass spectrometry allowing to measure several kinds of samples (organic compounds, inorganic elements, biologic material etc.) in different physical states (gas, liquid and solid phases) both in a vacuum environment or under ambient conditions. Because of the wide spectrum of samples and sample conditions accessible by mass spectrometry, this technique is relevant for a wide range of applications such as fundamental research, clinical research, industrial research, forensics and the like. Among the approaches developed in the field of mass spectrometry, particularly relevant are the electrospray ionization mass spectrometry (ESI) and the desorption electrospray ionization mass spectrometry (DESI).

The ESI technique was first proposed by Malcolm Dole in 1968 [1] and it was further developed, in particular with respect to the measurement of biological macromolecules, by John Fenn [2] who was awarded, for this reason, with the Chemistry Nobel Prize in 2002. In the ESI technique, the charged particles are obtained from the sample to be analyzed (analyte) in the liquid phase. The liquid comprising the analyte diluted in a solvent is pushed through a capillary tube (internal diameter in the order of 100 μm) ending with a narrow metallic tip usually held at high voltage. The capillary tube and the narrow tip form the so called electrospray source. The liquid coming out of the electrospray source forms an aerosol, i.e. a mist of droplets containing charged molecules of the analyte. Because of the continuous evaporation of the solvent and of the Coulomb repulsion between the charged molecules of the analyte, the droplets forming the aerosol undergo a series of breaking up processes leading to smaller and smaller droplets and ultimately to single charged molecules of the analyte. Sometimes, an inert carrier gas such as nitrogen or argon is employed to improve the nebulization process. The single charged molecules of the analyte are detected by the typical analyzers of the mass spectrometers such as quadrupole mass filters, quadrupole ion traps, ion cyclotron resonance instruments and magnetic sector instruments. More details about the ESI technique could be found for instance in [3]. Although the ESI technique is particularly advantageous with respect to other mass spectrometry techniques, and it is for this reason commonly used in analytical laboratories all over the world, it has a major drawback due to the limited success of the automation of the method. In particular, due to carry over problems of the samples, the shortest achievable time per analysis in the ESI technique is 20 - 40 seconds. Atmospheric Pressure Chemical Ionization (APCI) is similar to ESI but it takes place at atmospheric pressure and involves a gas phase ionization process instead of the liquid phase ionization process typical for ESI measurements. Typically, APCI measurements are performed in modified ESI facilities. More details about the APCI technique could be found for instance in reference [4].

The DESI technique has been recently introduced, and it is described for instance in references [5] and [6] and in the International Patent Application PCT/US2005/011212. In the DESI technique, an electrospray source similar to the one employed in the ESI technique is used to produce the so called DESI-active spray (i.e. an aerosol of charged droplets) which is directed towards a sample to be analyzed (analyte). The impingement and the subsequent interaction of the charged droplets of the DESI-active spray with the surface of the analyte result in the desorption and ionization of molecules of the analyte. These charged molecules of the analyte are then detected by the analyzer of the mass spectrometer. In particular, the DESI spectrometers known in the art are provided with an ion transfer line adapted to collect the ions of the analyte desorbed from the sample and to drive them to the analyzer. The DESI technique has been successfully applied on solid samples, both conductive and insulating, on liquid samples and even on living organisms. In particular, this technique allows to analyze intact samples that have not undergone any kind of preparation procedure or samples rapidly pre-treated. The DESI technique is for these reasons particularly advantageous, and it is currently being developed in several fields of application such as medical and biological research, environmental sciences, pharmaceutical industry, toxicology and forensics. Contrary to the ESI technique, the DESI technique allows to obtain rates of up to 10 analysis per second [6]. Moreover, several kinds of DESI-based imaging techniques have been developed in order to create, for example, a map of the distribution of constituents of a sample, as described, for instance, in the International Patent Application PCT/US2005/011212.

The DESI apparatuses known in the art are provided with classical ion trap analyzers or with linear ion trap analyzers coupled with electrospray sources customized in order to provide desorption and ionization of the analyte molecules. Moreover, it is necessary to provide the system with an ion transfer line to drive the analyte ions to the analyzer. For these reasons, it is extremely complex to adapt DESI sources to already operating mass spectrometers. Consequently, the DESI sources known in the art are not easy-fitting to every kind of mass spectrometry analyzers and, even if they are manual and not automatic, they are extremely costly. It is thus necessary to provide a solution allowing mass spectrometers based on other ionization techniques to easily switch to the DESI technique. Moreover, since it is necessary that the environment where the ionization occurs is at the same temperature as the ion source and the collector, most of the mass spectrometers known in the art are provided with a cylindrical ionization chamber. Since these cylindrical chambers are generally small, they allow to accommodate only small devices. It results, therefore, that inserting and extracting the devices from the ionization chambers is particularly difficult and time-consuming. Moreover, there are no easy-fitting devices suitable, at the same time, for several kinds of ionization techniques for mass spectrometry.

OBJECT OF THE INVENTION

In view of the mentioned problems incurred in operating the DESI technique, it is an object of the present invention to provide a sample holder device for ionization chambers allowing to overcome these problems. In particular, it is an object of the present invention to provide a sample holder device for ionization chambers that allows to easily adapt a

ESI or a APCI apparatus to operate also in the DESI mode.

It is a further object of the present invention to provide a sample holder device that is easily and rapidly inserted and extracted from the ionization chamber.

Moreover, it is an object of the present invention to provide a sample holder device that allows to easily regulate the position of the sample inside the ionization chamber. More in particular, it is an object of the present invention to provide a sample holder device that allows to easily calibrate the spectrometer and to optimize the operating parameters of the system in relation with the position of the sample.

It is a further object of the present invention to provide a sample holder device that allows to easily orient the sample with respect to the source and the ion collector in the ionization chamber.

It is a further object of the present invention to provide an automated sample transfer system for mass spectrometers that allows the system to operate at high time-per- analysis rate.

SUMMARY OF THE INVENTION

In a preferred embodiment of the present invention, a sample holder device for ionization chambers is provided, said sample holder device comprising a base comprising a curved portion adapted to match the internal surface of a ionization chamber so that said sample holder device can be translated in at least one translation direction inside said ionization chamber, and that said sample holder device can be rotated around an axis of rotation being parallel to said translation direction.

In a further preferred embodiment of the present invention, a sample holder device for ionization chambers is provided wherein said curved portion is adapted to match the internal surface of a cylindrical ionization chamber so that said sample holder device can be translated in a direction parallel to the axis of the ionization chamber.

In yet a further preferred embodiment of the present invention, a sample holder device for ionization chambers is provided, said sample holder device comprising a base comprising a curved portion whose curvature radius corresponds to the curvature radius of the ionization chamber.

In a particularly advantageous embodiment of the present invention, a sample holder device is provided, wherein said sample holder device comprises a base and a sample holder, and wherein said base further comprises supporting means for supporting said sample holder. In yet another embodiment of the present invention, the position of the sample holder on the supporting means is adjustable.

In a further embodiment of the present invention, the sample holder comprises an inclined portion. The slope angle of said inclined portion could be predefined and fixed or, alternatively, it could be adjustable so as to add a further degree of freedom in the choice of the position and orientation of the sample in the ionization chamber.

In a further embodiment of the present invention, the sample holder comprises a protruding portion located at the bottom of the inclined portion. In alternative embodiments of the present invention, said protruding portion is provided with a notch. In a particularly advantageous embodiment of the present invention, said notch has a semicircular shape. In yet another embodiment of the present invention, said notch is located in the centre of said protruding portion.

The sample holder device according to the present invention may further comprise other devices suitable for several kinds of measurements.

In a preferred embodiment of the present invention, the sample holder devices is provided with means for measuring the temperature of the sample. Several kinds of measuring temperatures means such as sensors, thermocouples and the like could be integrated in the sample holder device of the present invention.

In yet another embodiment of the present invention, the sample holder device is provided with means for regulating the temperature of the sample. Heating means such as heating filaments or cooling means such as liquid nitrogen means could be integrated in the sample holder device of the present invention.

In a further embodiment of the present invention, the sample holder device is provided with a mask for selecting the area of the sample to be probed.

In a further preferred embodiment of the present invention, the sample holder device is provided with a grid located above the position of the sample. In yet a further embodiment of the present invention, a mass spectrometer is provided, as defined in claim 19.

In a further embodiment of the present invention, an automated transfer system for mass spectrometers is provided, as defined in claim 20 and in the following specification.

BRIEF DESCRIPTION OF THE FIGURES

Fig. 1 schematically represents a sample holder device for ionization chambers according to a preferred embodiment of the present invention.

Fig. 2 schematically displays a ionization chamber comprising a source, a collector and a sample holder device according to a preferred embodiment of the present invention.

Fig. 3 shows the mass spectrum of the amino acid Methionine (quasi-molecular ion, m/z: 150) obtained employing a sample holder device for ionization chambers according to a preferred embodiment of the present invention and the optimized parameters listed in Table 1 in the experimental section.

Fig. 4 shows the neutral loss mass spectra of an amino acids mixture obtained with the DESI technique employing a sample holder device according to a preferred embodiment of the present invention (upper spectrum), and with the ESI technique in the same ionization chamber (lower spectrum).

Fig. 5 shows the mass spectra of blood samples (normal and pathological-MSUD) obtained with the DESI technique employing a sample holder device according to a preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In the following, the present invention is described with reference to a preferred embodiment as illustrated in the following detailed description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the present invention. Fig. 1 schematically displays a sample holder device for ionization chambers according to a preferred embodiment of the present invention. The sample holder device comprises a base (2) and a sample holder (1). The sample holder (1) is shown in perspective in the upper part of the figure. The bottom part of the figure shows a cross-sectional view of the sample holder device in its entirety (base (2) and sample holder (1)). The base (2) comprises a curved portion (2¹). The presence of the curved portion is particularly advantageous in order to adapt the sample holder device to be supported on the internal surface of a ionization chamber. Moreover, the sample holder device provided with a base (2) comprising a curved portion (2') can be easily translated inside the ionization chamber in a direction perpendicular to the cross-sectional direction of Fig. 1 , and it can be easily rotated around an axis of rotation parallel to the translation direction.

The base (2) of the sample holder device of Fig. 1 further comprises supporting means (2", 2'") for supporting the sample holder (1). In the embodiment shown in Fig. 1, supporting mean 2" forms a surface connected at one end with the curved portion (2') and oriented along a radius of said curved portion (2'). Supporting mean 2'" connects the curved portion (2¹) with the second end of the supporting mean 2" so as to form in the cross-sectional view an angle β of 90°. In alternative embodiments of the present invention, the angle β formed by the supporting means 2" and 2'" can be arbitrarily fixed to any value, for instance to any value comprised between 0° and 90°, but also to values higher than 90".

The sample holder (1) is placed on the surface formed by the supporting mean 2". The sample holder (1) can be fixed to the surface formed by the supporting mean 2" by any kind of fixing means known to those skilled in the art. Alternatively, the sample holder (1) can be simply placed on the base (2) without being fixed to it, so that it can be moved on the surface formed by the supporting mean 2" in order to easily and finely adjust the position of the sample holder (1) with respect to the base (2). Moreover, if the sample holder (1) is not fixed to the base (2), it is possible to insert and extract the sample form the ionization chamber by inserting and extracting only the sample holder (1) while leaving the base (2) inside the ionization chamber.

The sample holder (1) is formed by an inclined plane (8) with a slope angle α. The slope angle α could be fixed. Alternatively, the slope angle α could be adjustable so as to add a further degree of freedom to the orientation of the sample.

The sample is placed on the inclined plane (8). The sample could be directly placed on the inclined plane (8), for instance in the case of a solid sample. Moreover, the sample could be attached to the plane (8) by any mean known to those skilled in the art, for instance by adhesive means. Alternatively, the sample could be positioned on a plate (3) placed on the inclined plane (8). The inclined plane (8) could be provided with supporting means for supporting said plate (3). The plate (3) could be made of glass, PTFE, stainless steel, paper or any other solid material. The sample can be positioned on the plate (3) by any known method known to those skilled in the art. A sample in the solid phase could be for instance fixed to the plate (3) by adhesive means; a sample in the liquid phase could be sprayed or deposited on the plate (3); a sample in the gas phase could be sprayed on the plate (3).

The sample holder (1) further comprises a protruding portion (4) located at the bottom of the inclined plane (8). The protruding portion could serve to prevent the sample or the plate (3) to slip off the inclined plane (8).

The protruding portion (4) is further provided with a notch (5) located at the centre of said protruding portion (4) and having a semicircular shape. The notch (5) could house the ending portion of the ion collector so as to allow to position the sample close to the ion collector and to improve the collection of analyte ions.

In alternative embodiment of the present invention, the sample holder device could be provided with several devices suitable for several kinds of measurements, such as DESI- based imaging measurements, reactions measurements, temperature-dependent measurements and so on.

The sample holder device could be provided with means for measuring the temperature of the sample. Several kinds of means such as sensors, thermocouples and the like could be integrated in the sample holder device according to the present invention. These means could be for instance integrated in the sample holder (1).

Moreover, the sample holder device of the present invention could be provided with means for heating and/or cooling the sample. Examples of heating means suitable to be integrated in the sample holder device of the present invention are heating filaments. Example of cooling means suitable to be integrated in the sample holder device of the present invention are liquid nitrogen based means. Heating or cooling the sample during the measurements could be important for several kinds of studies such as reaction mechanisms studies, activation energies studies and the like. The sample holder device of the present invention could be provided with a mask for selecting the area of the sample to be probed. The mask delimits the area of the sample targeted by the DESI-active spray so that the analyte ions are collected from a predefined area of the sample. This could be employed, for instance, to create a map of the distribution of constituents of the sample.

The mask could be for instance fixed to the protruding portion (4) located at the bottom of the inclined plane (8), and it could be placed parallel to said inclined plane (8) so as to create a space between said mask and said inclined plane (8). A plate (3) comprising a sample (10) could be placed on the inclined plane (8) in the space comprised between said inclined plane (8) and the mask.

The sample holder device could be provided with a grid located above the position of the sample. A grid positioned between the sample and the source of the DESI-active spray allows to improve the resolution of DESI-based imaging techniques. The grid could be for instance fixed to the protruding portion (4) located at the bottom of the inclined plane (8), and it could be placed parallel to said inclined plane (8) so as to create a space between said grid and said inclined plane (8). A plate (3) comprising a sample (10) could be placed on the inclined plane (8) in the space comprised between said inclined plane (8) and the grid.

The sample holder device of the present invention could be employed for several kinds of DESI-based imaging measurements.

The system could be for instance provided with a needle held at a predefined voltage and employed to finely select the area of the sample to be probed. The needle could be housed for instance in the notch (5) of the protruding portion (4) located at the bottom of the inclined plane (8) of the sample holder (1).

Moreover, the sample could be scanned with a laser spot in order to perform high resolution DESI-based imaging measurements. Moreover, the laser spot could be employed to heat the sample, in particular to heat predefined regions of the sample. The laser spot could be driven through the notch (5) of the protruding portion (4) located at the bottom of the inclined plane (8) of the sample holder (1). Fig. 2 shows a cross-sectional view of a cylindrical ionization chamber (9) provided with a sample holder device according to a preferred embodiment of the present invention. The sample holder device comprises a base (2) and a sample holder (1). The sample (10) is located on a plate (3) placed on the inclined plane of the sample holder (1). The ionization chamber is provided with an active spray source (6) and with an ion collector (7).

The curvature radius of the curved portion of the base (2) of the sample holder device corresponds to the curvature radius of the ionization chamber (9). The position of the sample holder device with respect to the spray source (6) and the ion collector (7) can be easily adjusted. The sample holder device can be translated in the direction parallel to the axis of the ionization chamber; at the same time, it can be rotated around this axis, for instance by sliding the curved portion of the base (2) along the internal surface of the ionization chamber (9).

The sample holder device can be fixed to the internal surface of the ionization chamber (9) at any predefined position. Alternatively, the sample holder device can be simply leaned on the internal surface of the ionization chamber (9). In this case, inserting and extracting the device from the ionization chamber (9) is extremely easy and not time- consuming. Moreover, the sample holder device could be provided with an automated system for the adjustment of the position and orientation inside the ionization chamber

(β).

The position of the sample (10) inside the ionization chamber (9) and, in particular, with respect to the position of the spray source (6) and of the ion collector (7) can be easily adjusted. More in particular, it is possible to precisely control and optimize several parameters particularly relevant for the measurements such as the distance from the spray source (6) to the sample (10), the distance from the sample (10) to the ion collector (7), the angle of incidence γ of the DESI-active spray on the sample (10) and the ion collection angle δ of the ion collector (7) with respect to the sample (10). γ and δ could be, for instance, easily and precisely adjusted by rotating the sample holder device around the axis of the ionization chamber by sliding the curved portion of the base (2) along the internal surface of the ionization chamber (9). Alternatively, in particular embodiments of the present invention, γ and δ could be adjusted by adjusting the slope angle α of the inclined plane (8) of the sample holder (1).

The distances of the sample (10) from the spray source (6) and from the ion collector (7) can be adjusted for instance by translating the sample holder device inside the ionization chamber. Alternatively, they can be adjusted by rotating the sample holder device inside the ionization chamber. In particular embodiments of the present invention, these distances could be adjusted by adjusting the position of the sample holder (1) on the supporting means (2") of the base (2).

The adjustments mentioned above can be performed manually or, in particularly advantageous embodiments of the present invention, they can be performed by automated systems.

The position of the sample (10) could be varied also during the measurements in order to desorb ionized molecules of the analyte from different areas of the sample, to create, for instance, a map of the distribution of constituents of a sample.

The arrangement of the system shown in Fig. 2 shows that the sample holder device according to the present invention allows to perform DESI measurements in a ionization chamber equipped with spray source (6) and ion collector (7) for standard ESI measurements without structural modifications of the ionization chamber itself. By inserting the sample holder device of the present invention in the ionization chamber, it is possible to precisely position any kind of sample (10) inside the chamber with respect to the spray source (6) and the ion collector (7). The spray source (6) provides the DESI- active spray: several kinds of substances can be employed to form the DESI-active spray and the operation of the spray source is similar to the operation for the ESl measurements. For instance, several parameters regulating the spray formation process can be adjusted as listed in Table 1 below. The droplets of the DESI-active spray impinge on the surface of the sample (10) causing the desorption and ionization of the molecules of the sample. The ionization of the molecules of the sample can take place before or after the desorption. The ionized molecules are collected by the ion collector (7) and analyzed in the mass spectrometer analyzer according to the standard procedures employed for instance for the analysis during the ESI measurements. The measurements can be performed in ambient conditions, for instance at atmospheric pressure, or under vacuum conditions by properly establishing a vacuum environment in the ionization chamber by any kind of vacuum means known to the skilled person.

In a particularly advantageous embodiment of the present invention, an automated sample transfer system for mass spectrometers is provided. The automated sample transfer system comprises sample holder devices according to the present invention. The automated sample transfer system may comprise flexible supporting means such as a conveyor belt. The distances between the samples on the supporting means are adjusted according to the kind of samples to be analyzed and to the duration of the measurement process. The automated sample transfer system may be controlled by a software. The employment of such an automated sample transfer system allows to minimize the time-per-analysis and, thus, to improve the time-per-analysis rate and, at the same time, to guarantee the high quality and precision of the analysis.

EXPERIMENTAL

This section describes the experimental results obtained with a sample holder device for ionization chambers according to a preferred embodiment of the present invention.

The ionization chamber employed is a standard ionization chamber equipped with the facilities to perform ESI measurements (electrospray source, ion collector, triple quadrupole analyzer) and it has a cylindrical shape. A sample holder device according to the present invention has been inserted in the ionization chamber in order to perform DESI measurements on the sample carried by the sample holder device.

In a first step of the experimental procedure, several measurements parameters have been optimized as shown in table 1. For each parameter (column 1) a wide range of values has been tested (column 2) and the optimum value inside said range has been registered (column 3). The sample employed for this step is an amino acids mixture with the following amino acids concentrations: Phe 70 μM; Leu 160 μM; VaI 30 μM; Tyr 100 μM; Met 35 μM.

Table 1.

In a second step of the experimental procedure, different materials for the plates (3) employed to support the sample (10) are tested. The sample employed for this step is an amino acids mixture with the following amino acids concentrations: Phe 70 μM; Leu 160 μM; VaI 30 μM; Tyr 100 μM; Met 35 μM. The measuring parameters correspond to the optimal settings listed in Table 1. The results are shown in Table 2.

Table 2.

In a third step of the experimental procedure, the DESI-mass spectrum of the amino acid Methionine (quasi-molecular ion, m/z: 150) employing a sample holder device for ionization chambers according to a preferred embodiment of the present invention has been measured. The measurement parameters employed correspond to the optimal settings listed in Table 1. The results are shown in Fig. 3. The main peak at m/z = 150 is visible and the spectrum show the typical fragmentation features of the amino acid Methionine.

In a fourth step of the experimental procedure, the results of the DESI measurements performed on an amino acids mixture employing a sample holder device according to the present invention are compared with the ESI measurements performed in the same ionization chamber on the same amino acids mixture. The analysis has been performed with the "neutral loss" function and the results are shown in Fig. 4. The spectra obtained with both techniques display an excellent agreement showing that the sample holder device of the present invention allows for the easy and, at the same time, reliable switching between the two measuring techniques in the same ionization chamber.

In a fifth step of the experimental procedure, normal and pathological-MSUD blood samples have been analyzed with the DESI technique employing a sample holder device according to a preferred embodiment of the present invention. The blood samples are rapidly extracted from the patients and deposited on the sample holder without any further preparation procedure. The results are shown in Fig. 5. Asterisks (*) show the internal standard signals. The differences between the two spectra are clearly visible showing that the sample holder devices according to the present invention allow for the quick, easy, reliable and high quality analysis of biological samples.

The results described in this experimental section show that the sample holder device according to the present invention is particularly advantageous. It is in fact possible to perform DESI measurements by simply inserting the sample holder device according to the present invention in a ionization chamber equipped with ESI facilities. No further modifications (neither structural, nor instrumental) of the mass spectrometer are required. Similarly, it is also possible to perform DESI measurements by simply inserting the sample holder device according to the present invention in a ionization chamber equipped with APCI (Atmospheric Pressure Chemical Ionization) facilities. By simply and easily inserting the sample holder device according to the present invention in a ionization chamber equipped with ESI or APCI facilities, it is possible to obtain desorption and ionization of molecules of any analyte supported by said sample holder device. It is, thus, possible to work with a further ionization technique (DESI) in the same ionization chamber without costly and time-consuming modifications of the chamber. It is therefore possible to profit of all the advantages of the DESI technique and, at the same time, to eventually compare the results obtained with those obtained with other ionization techniques such as ESI or APCI.

REFERENCES

[1] M. Dole et al., Journal of Chemical Physics 49 (1968), 2240 - 2247.

[2] J. Fenn et al., Science 246 (1989), 64 - 71.

[3] J. Fenn et al., Mass Spectrometry Reviews 9 (1990), 37 - 70.

[4] V. G. Zaikin et al., European Journal of Mass Spectrometry 12 (2006), 79 - 115.

[5] Z. Takats et al., Science 306 (2004), 471 - 473.

[6] R. G. Cooks et al. Science 311 (2006), 1566 - 1570.

Claims

1. A sample holder device for ionization chambers, characterized in that: said sample holder device comprises a base (2), said base comprising a curved portion (2¹) adapted to match the internal surface of a ionization chamber so that said sample holder device can be translated in at least one translation direction inside said ionization chamber, and that said sample holder device can be rotated around an axis of rotation, said axis of rotation being parallel to said translation direction.

2. The sample holder device of claim 1 , wherein said curved portion (2') is adapted to match the internal surface of a cylindrical ionization chamber so that said translation direction is parallel to the axis of the ionization chamber.

3. The sample holder device of any one of the preceding claims, wherein the curvature radius of said curved portion (2') corresponds to the curvature radius of the ionization chamber.

4. The sample holder device of any one of the preceding claims, wherein said sample holder device further comprises a sample holder (1) and wherein said base (2) further comprises supporting means (2", 2'") for supporting said sample holder (1).

5. The sample holder device of claim 4, wherein said supporting means (2", 2'") of said base (2) are connected so as to form an angle β, and said supporting means (2", 2'") are further connected to said curved portion (2¹).

6. The sample holder device of claim 5, wherein said angle β measures 90°.

7. The sample holder device of any one of claims 4 to 6, wherein the position of said sample holder (1) on the supporting means (2", 2'") is adjustable.

8. The sample holder device of any one of claims 4 to 7, wherein said sample holder (1) comprises an inclined portion (8).

9. The sample holder device of claim 8, wherein the slope angle α of said inclined portion (8) is adjustable.

10. The sample holder device of any one of claims 8 and 9, wherein said inclined portion (8) comprises supporting means for supporting a plate (3), said plate (3) comprising the analyte (10).

11. The sample holder device of any of claims 8 to 10, wherein said sample holder (1) further comprises a protruding portion (4) located at the bottom of said inclined portion (8).

12. The sample holder device of claim 11 , wherein said protruding portion (4) further comprises a notch (5).

13. The sample holder device of claim 12, wherein said notch (5) has a semicircular shape.

14. The sample holder device of any of claims 12 and 13, wherein said notch (5) is located in the centre of said protruding portion (4).

15. The sample holder device of any one of the preceding claims, further comprising means for measuring the temperature of the sample.

16. The sample holder device of any one of the preceding claims, further comprising means for regulating the temperature of the sample.

17. The sample holder device of any one of the preceding claims, further comprising a mask for selecting the area of the sample to be probed.

18. The sample holder device of any one of the preceding claims, further comprising a grid located above the position of the sample.

19. A mass spectrometer comprising a ion collector (7), a spray source (6) and a ionization chamber (9), characterized in that: said ionization chamber (9) is provided with a sample holder device according to one of claims 1 to 18.

20. An automated sample transfer system for mass spectrometers, characterized in that: said automated sample transfer system comprises sample holder devices according to one of claims 1 to 18.