Apparatus and method for generating an ionized sample

Abstract

There is provided an apparatus for generating ionized samples, also referred to in the art as an "ion source", a method for generating ionized samples, and a sample support for use in such an apparatus or method. The sample support has at least one sample-bearing membrane reversible between a concave and a convex configuration. The sample-bearing membrane is adapted to receive a source sample thereon when in the concave configuration, and to be reversed to the convex configuration for desorption of the sample. The apparatus includes a receptacle defining a gas pressurizing chamber traversed by a transfer tube. The gas pressurizing chamber has a gas input for receiving a carrier gas flow and a nozzle portion surrounding the transfer tube, directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample to an ionizing device.

Description

[0001] APPARATUS AND METHOD FOR GENERATING AN IONIZED SAMPLE

[0002] TECHNICAL FIELD

[0003] The technical field generally relates to an apparatus and a method for generating an ionized sample and / or molecules, more particularly from laser diode thermal desorption of a source sample on a reversible sample-bearing membrane.

[0004] BACKGROUND

[0005] The analysis of samples by combining high resolution separation techniques and mass spectrometry is a widely used technique. This combination of scientific instruments has become important in different domains such as those requiring a high quantity of analyses, due partly to the development of new molecules. This is particularly true for fields such as the clinical, toxicological, forensic, food analysis, pharmaceutical, environmental and proteomic industries.

[0006] Different coupling and ionisation techniques have been developed using liquid chromatography and mass spectrometry. One such technique is called Atmospheric Pressure Chemical Ionization (hereinafter APCI). According to this technique, the sample and the mobile phase are first nebulized and dried at atmospheric pressure and then ionized by a corona discharge. One drawback of this technique is the use of a liquid mobile phase which can introduce cross-contamination of the samples. Another well-known type of ionization source is called Matrix-Assisted Laser Desorption / lonization, or MALDI. In this case, desorption and ionization of a solid-state target material are induced simultaneously by irradiating the sample directly with a laser. The ionization process is carried out at atmospheric pressure or under vacuum via a matrix. Again, crosscontamination is often introduced in the sample from the matrix. For both of these techniques, sample preparation and analysis are time consuming and contribute to most of the analysis cost.

[0007] U.S patent 7.321.116 (PICARD et al.) presented an ionization source at atmospheric pressure, generally interfaced with mass spectrometry. This ionization source is based on a process of laser diode thermal desorption and thus has been named LDTD (Laser Diode Thermal Desorption). Thermal desorption is induced indirectly by a laser beam without a support matrix-unlike the MALDI technique-and ionization is achieved by a corona discharge without liquid mobile phase-unlike the APCI technique. The LDTD technique being matrix and mobile phase free, cross contamination of samples is virtually eliminated compared to other prior art techniques.

[0008] While LDTD has been broadly adopted in the industry, there remains a need in the art for further improvements on this technique.

[0009] SUMMARY

[0010] In accordance with one aspect, there is provided an apparatus for generating an ionized sample, comprising:

[0011] - a sample support comprising at least one sample-bearing membrane reversible between a concave and a convex configuration, the sample-bearing membrane being adapted to receive a source sample thereon when in the concave configuration;

[0012] - a heater for heating the sample-bearing membrane when in the convex configuration to cause heating of the source sample, thereby producing a desorbed sample through desorption of the source sample;

[0013] - a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end;

[0014] - a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and

[0015] - an ionizing device provided proximate the second end of the transfer tube for ionizing said desorbed sample to thereby obtain said ionized sample.

[0016] In some implementations, the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes. The sample support may comprise a plurality of sections arranged in a 2D array, each section provided with one of the sample-bearing membranes. The sample support may also comprise a main body made of an insulating material. The main body may comprise a top plate and a bottom plate extending one over the other and holding a periphery of each sample-bearing membrane of the plurality of sample-bearing membranes therebetween.

[0017] In some implementations, each of the at least one sample-bearing membrane is made of a chemically inert and heat conductive materials, such as stainless steel or aluminum.

[0018] In some implementations, each of the at least one sample-bearing membrane has a portion forming a well when the sample-bearing membrane is in the concave configuration and a protuberance when the sample-bearing membrane is in the convex configuration.

[0019] In some implementations, each of the at least one sample-bearing membrane has a front surface adapted to receive a source sample thereon and a back surface opposite the front surface. Each of the at least one sample-bearing membrane may comprise a coating deposited on the front surface thereof.

[0020] In some implementations, the heater comprises a laser source generating a radiation beam directed so as to impinge on the rear surface of the sample-bearing membrane.

[0021] In some implementations, the transfer tube is in a fixed position with respect to the receptacle.

[0022] In some implementations, the gas pressurizing chamber extends symmetrically around the transfer tube.

[0023] In some implementations, the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that provides gas dynamics favoring the transport of the desorbed sample into the transfer tube.

[0024] In some implementations, the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that minimizes flow stagnation zones in a gas flow path around the first end of the transfer tube.

[0025] In some implementations, the gas pressurizing chamber comprises a tubular portion to which the gas input is connected, the tubular portion having a diameter larger than a diameter of the nozzle portion and larger than a diameter of the transfer tube. The surface area of the tubular portion of the gas pressurizing chamber may be about 85 times the surface area of the transfer tube.

[0026] In some implementations, the gas pressurizing chamber comprises a transition portion in which the diameter of the gas pressurizing chamber transitions from the diameter of the tubular portion to the diameter of the nozzle portion. The receptable may have an inner wall having a rounded cross-sectional shape within the transition portion of the gas pressurizing chamber.

[0027] In some implementations, the apparatus comprises a compressed air source providing the carrier gas flow and a gas conduit connecting the compressed air source to the gas input.

[0028] In some implementations, the apparatus comprises a non-pressurized air source providing the carrier gas flow a fan connected to the gas input to push the carrier gas into the gas pressurizing chamber.

[0029] In accordance with one aspect, there is provided an apparatus as defined in any of the implementations above combined with a reversing tool configured to reverse the samplebearing membrane with the source sample thereon from the concave to the convex configuration.

[0030] In some implementations, the reversing tool comprises a pushing pin shaped and sized to engage the rear surface of the sample-bearing membrane.

[0031] In accordance with another aspect, there is provided a sample support for use in an apparatus for generating an ionized sample, comprising:

[0032] - a main body made of an insulating material; and

[0033] - at least one sample-bearing membrane reversible between a concave and a convex configuration, each of the at least one sample-bearing membrane having a front surface adapted to receive a source sample thereon when the sample-bearing membrane is in the concave configuration and a back surface opposite the front surface.

[0034] In some implementations, the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes. The sample support may comprise a plurality of sections arranged in a 2D array, each section provided with one of the sample-bearing membranes. The sample support may also comprise a main body made of an insulating material. The main body may comprise a top plate and a bottom plate extending one over the other and holding a periphery of each sample-bearing membrane of the plurality of sample-bearing membranes therebetween.

[0035] In some implementations, each of the at least one sample-bearing membrane is made of a chemically inert and heat conductive materials, such as stainless steel or aluminum.

[0036] In some implementations, each of the at least one sample-bearing membrane has a portion forming a well when the sample-bearing membrane is in the concave configuration and a protuberance when the sample-bearing membrane is in the convex configuration.

[0037] In accordance with yet another aspect, there is provided a method for generating an ionized sample, comprising:

[0038] - providing a sample support comprising at least one sample-bearing membrane reversible between a concave and a convex configuration, the sample support being provided with the sample-bearing membrane in the concave configuration;

[0039] - loading a source sample on the sample-bearing membrane;

[0040] - reversing the sample-bearing membrane with the source sample thereon from the concave to the convex configuration;

[0041] - heating the sample-bearing membrane to cause heating of the source sample, thereby producing a desorbed sample through desorption of the source sample;

[0042] - transporting the desorbed sample though a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end, the transfer tube being surrounded by a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and ionizing the desorbed sample with an ionizing device provided proximate the second end of the transfer tube, thereby obtaining the ionized sample.

[0043] In some implementations, the method further comprises mounting the sample support to the receptacle prior to the heating of the sample-bearing membrane.

[0044] In some implementations, the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes and the sample support comprises a plurality of sections arranged in a 2D array, each section provided with one of the sample-bearing membranes. The sample support may comprise a main body made of an insulating material, the main body comprising a top plate and a bottom plate extending one over the other and holding a periphery of each sample-bearing membrane of the plurality of sample-bearing membranes therebetween.

[0045] In some implementations, loading the source sample on the sample-bearing membrane comprises using a deposition technique selected from the group comprising manual pipetting, acoustic deposition, deposition by automated liquid handler and deposition from a syringe needle.

[0046] In some implementations, reversing the sample-bearing membrane comprises pushing on a surface of the sample-bearing membrane opposite the source sample using a reversing tool.

[0047] In some implementations, heating the sample-bearing membrane comprises projecting a radiation beam from a laser source onto a surface of the sample-bearing membrane opposite the source sample.

[0048] In accordance with another aspect, there is provided an apparatus for generating an ionized sample for use with a sample support comprising at least one sample-bearing membrane adapted to receive a source sample thereon, the apparatus comprising:

[0049] - a heater for heating the sample-bearing membrane, thereby producing a desorbed sample through desorption of the source sample; - a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end;

[0050] - a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and

[0051] - an ionizing device provided proximate the second end of the transfer tube for ionizing said desorbed sample to thereby obtain said ionized sample.

[0052] In some implementations, the heater comprises a laser source generating a radiation beam directed so as to impinge on the rear surface of the sample-bearing membrane.

[0053] In some implementations, the transfer tube is in a fixed position with respect to the receptacle.

[0054] In some implementations, the gas pressurizing chamber extends symmetrically around the transfer tube.

[0055] In some implementations, the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that provides gas dynamics favoring the transport of the desorbed sample into the transfer tube.

[0056] In some implementations, the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that minimizes flow stagnation zones in a gas flow path around the first end of the transfer tube.

[0057] In some implementations, the gas pressurizing chamber comprises a tubular portion to which the gas input is connected, the tubular portion having a diameter larger than a diameter of the nozzle portion and larger than a diameter of the transfer tube. The surface area of the tubular portion of the gas pressurizing chamber may be about 85 times the surface area of the transfer tube. In some implementations, the gas pressurizing chamber comprises a transition portion in which the diameter of the gas pressurizing chamber transitions from the diameter of the tubular portion to the diameter of the nozzle portion. The receptable may have an inner wall having a rounded cross-sectional shape within the transition portion of the gas pressurizing chamber.

[0058] In some implementations, the apparatus comprises a compressed air source providing the carrier gas flow and a gas conduit connecting the compressed air source to the gas input.

[0059] In some implementations, the apparatus comprises a non-pressurized air source providing the carrier gas flow a fan connected to the gas input to push the carrier gas into the gas pressurizing chamber.

[0060] Other features and advantages will be better understood upon reading of detailed embodiments with reference to the appended drawings.

[0061] BRIEF DESCRIPTION OF THE DRAWINGS

[0062] FIG. 1 is a schematic representation of an apparatus according to one implementation.

[0063] FIG. 2A shows a sample support with a sample-bearing membrane in the concave configuration; FIG. 2B shows the sample support of FIG. 2A with the sample-bearing membrane being reversed to the convex configuration by a reversing tool.

[0064] FIG. 3 is a top view of a sample support with a plurality of sample-bearing surfaces according to one implementation.

[0065] FIG. 4 is a schematic representation of an apparatus according to another implementation.

[0066] FIGs. 5A to 50 illustrate the steps of a method according to one implementation.

[0067] DETAILED DESCRIPTION

[0068] To provide a more concise description, some of the quantitative expressions given herein may be qualified with the term "about". It is understood that whether the term "about" is used explicitly or not, every quantity given herein is meant to refer to an actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including approximations due to the experimental and / or measurement conditions for such given value.

[0069] In the present description, the term “about” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e. the limitations of the measurement system. It is commonly accepted that a 10% precision measure is acceptable and encompasses the term “about”.

[0070] In the present description, when a broad range of numerical values is provided, any possible narrower range within the boundaries of the broader range is also contemplated. For example, if a broad range value of from 0 to 1000 is provided, any narrower range between 0 and 1000 is also contemplated. If a broad range value of from 0 to 1 is mentioned, any narrower range between 0 and 1 , i.e. with decimal value, is also contemplated.

[0071] The present invention first provides an apparatus for generating ionized samples, also referred to in the art as an “ion source”, a method for generating ionized samples, and a sample support for use in such an apparatus or method. In some implementations, the apparatus and method described herein may be used in conjunction with a mass spectrometer providing a mass spectrometry analysis of the ionized samples according to techniques know in the art. It will however be readily understood that the ionized samples generated by the present apparatus or method may alternatively be destined for analysis by a different technique, such as ion mobility spectrometry, spectrophotometry, nuclear magnetic resonance, and the like.

[0072] Ion sources such as described herein may be of use in a variety of contexts, such as in toxicology and in forensic testing, for example for Substance-Abuse or Prescription Drug Monitoring (PDM) testing, in clinical diagnostics relying on accurate measurements to precisely quantify biomarkers in patients, or for toxicology and therapeutic drug monitoring (TDM). Pharmaceutical applications are also of interest. For instance, in early drug discovery, a new chemical entity (NCE) must undergo rigorous evaluations based on the Absorption-Distribution-Metabolism-Excretion-Toxicology (ADMET) system. Characterization and quantification of pathogens both in food and in the environment are other examples of applications which are of paramount importance for the control or avoidance of public health issues. The present technique may also be used in the context of the analysis of explosives in a quick and convenient way without requiring sample preparation. It will however be understood that the present apparatus and method may be used in any other context where ionization of a sample is desired.

[0073] In various implementations, the apparatus and method described herein may include one or more features described in U.S patent 7.321.116 (PICARD et al.), the entire contents of which is incorporated herein by reference.

[0074] Referring to FIG. 1 , there is shown an apparatus 10 for generating ionized samples according to one embodiment.

[0075] With additional reference to FIG. 2A, the apparatus 10 may include a sample support 22. The sample support 22 may be a single-sample or multi-sample plate onto which source samples 25 are loaded. The sample support 22 includes one or more sample-bearing membranes 24, each having a front surface 27a and a back surface 27b. Each samplebearing membrane 24 is destined to receive one source sample 25 on its front surface 27a, until heating of the sample-bearing membrane 24 causes the desorption of the corresponding source sample 25, as explained further below. Typically, each source sample 25 is deposited onto one of the sample-bearing membranes 24 of the sample support 22 and may be adsorbed or dried thereon or adhere to the sample-bearing membrane 24 via other mechanisms. In some implementations, the source samples may be embodied by biological liquids, buffer solutions, environmental samples, diluted swabbed samples to name a few examples. By way of example, deposition techniques such as manual pipetting, acoustic deposition, deposition by automated liquid handler, syringe needles or the like may be used.

[0076] Referring to FIG. 3, in some implementations, the sample support 22 preferably has different sections each provided with one of the sample-bearing membranes 24. In the illustrated embodiment, the sample-bearing membranes 24 are arranged in a 2D array. In some implementations, the sample support 22 includes a main body 21 made of polypropylene or other insulating material. As shown in FIG. 2A, the main body 21 may include a top plate 21a and a bottom plate 21b extending one over the other and holding the periphery of each sample-bearing membrane 24 therebetween. In some multi-sample implementations, the sample-bearing membranes 24 may be sections of a single sheet of material extending across the entire sample support 22.

[0077] The sample-bearing membranes 24 are preferably metallic in construction. In some implementations, the sample-bearing membranes 24 may be made of chemically inert and heat conductive materials such as stainless steel or aluminium. In some variants, a coating (not shown) may be deposited on the front surface 27a of the membrane 24 prior to loading the source samples 25 thereon. This coating may for example promote desorption of the source samples and / or improve ionization of the desorbed samples. In one embodiment, as the sample-bearing membranes 24 are surrounded by plastic or other insulating material of the main body 21 of the sample support 22, the heat conductive property of the sample support 22 is therefore to a large extent limited to the sample-bearing membranes 24 alone, and thus the heating of one source sample 25 loaded onto one sample-bearing membrane 24 does not heat adjacent source samples sufficiently to cause premature desorption of those surrounding samples.

[0078] Referring to FIGs. 2A and 2B, in accordance with one aspect, each sample-bearing membrane 24 is reversible between a concave (FIG. 2A) and a convex (FIG. 2B) configuration. By convention, the concave or convex configurations are determined from the front of the sample-bearing membranes 24, that is, the side on which the source samples 25 are loaded. The concave configuration, in which the sample support is adapted to receive a source sample 25 thereon, is shown in FIG. 2A. As will be readily understood by one skilled in the art, in the concave configuration the sample-bearing membrane 24 or a portion thereof defines a well 24’ in which the source sample 25 can be deposited according to known techniques, as explained above. In typical implementations, the sample support 22 is manufactured and provided with the samplebearing membrane 24 or membranes in the concave configuration, that is, pre-shaped to form a well 24’. The well-shape configuration is of particular interest to receive source samples in liquid form. In other implementations where the source sample is already in a solid or dry form, for example deposition using a transfer from a swab, the sample-bearing membrane could receive the source sample while already in the convex configuration. FIG. 2B illustrates the convex configuration. As one skilled in the art will also readily understand, in the convex configuration the desorption of the source sample 25 into a desorbed sample and subsequent extraction of the desorbed sample are improved, as further explained below.

[0079] Referring to FIG. 2B, in some implementations the apparatus 10 further includes or is combined with a reversing tool 100 configured to reverse the sample-bearing membrane 24 with the source sample 25 thereon from the concave to the convex configuration. The reversing tool preferably includes a pushing pin 102 shaped and sized to engage the rear surface 27b of the membrane 24 at the portion thereof forming the well 24’ in which the source sample is deposited. By gently pushing the membrane 24 towards the front, the well 24’ is reversed, the source sample 25 now extending on a protuberance 24” projecting over the remainder of the membrane 24. The reversing tool may for example rotate to induce uniformity of the convex shape.

[0080] In some embodiments, the sample-bearing membrane 24 is made of a chemically inert and conductive material, such as stainless steel or aluminium, having a specific ductility with hardness in the range of about 75 on the Rockwell B scale. Preferably, the material of the membrane 24 and shape of the well 24’ are selected to ensure the self centering of liquid prior drying of the source sample 25. Preferably, the membrane 24 has a ductility that enables the change of form once the source sample 25 is completely dried from the concave to the convex configuration without sample loss.

[0081] Referring back to FIG. 1 , the apparatus 10 may further include a heater 12 for heating the sample-bearing membrane 24 when in the convex configuration to cause heating of the source sample 25, thereby producing a desorbed sample 42 through desorption of the source sample 25. The induced desorption of the loaded source sample implies that the source sample is “unloaded” by desorption and / or vaporization or another release mechanism.

[0082] In some implementations, the heater 12 is embodied by a laser source generating a radiation beam 14. The laser source may for example be embodied by a laser diode. In some embodiments, the laser source 12 may emit infra-red light with a wavelength between 800 and 1040 nm, and preferably about 980 nm, at a power of about 1 to 50 W. Alternatively, a laser wavelength in the visible spectrum, for example at about 450 nm may be used if the material of the sample-bearing membrane 24 exhibits sufficient absorption at this wavelength to generate thermal desorption. In some implementations, an optical arrangement (not shown) for shaping, directing and / or focusing the radiation beam 14 may also be provided, and includes any appropriate optical component apt to focus the radiation beam 14 and direct it to its target. Although the present description relates to a LDTD implementation, implicitly based on laser heating of the membrane, it will readily understand by one skilled in the art that other sources of heating may used in different implementations, such as pre-heated point that is moved to contact the well, or a flow of heated gas, or the like.

[0083] In the illustrated embodiment, the radiation beam 14 is directed so as to impinge on the rear surface 27b of the sample-bearing membrane 24, therefore not directly affecting the source sample 25 which is loaded on the opposite surface (front surface 27a) of the sample-bearing membrane 24. In this manner, the source sample 25 is heated indirectly, unlike with the MALDI technique, and the heating process only acts to desorb the sample without ionizing it.

[0084] Still referring to FIG. 1 , the apparatus 10 may further include a transfer tube 26 having a first end 28 opening proximate the sample-bearing membrane 24 to receive the desorbed sample 42 therefrom, and a second end 30 opposite the first end 28. As explained further below, a carrier gas flows through the transfer tube 26 to transport the desorbed sample 42 from the first end 28 to the second end 30.

[0085] The apparatus 10 may also include a receptacle 60 defining a gas pressurizing chamber 62 traversed by the transfer tube 26. The gas pressurizing chamber 62 has a gas input 64 for receiving a carrier gas flow 66, and a nozzle portion 68 surrounding the first end 28 of the transfer tube 26. In the illustrated embodiment, the transfer tube 26 and receptacle 60 are fixed in place, as opposed to the piston-mounted system shown in U.S patent 7.321.116 (PICARD et a ), and a mechanical seal (not shown) may be provided around and above the sample-bearing membrane 24 to optimize sample capture. Fixing the transfer tube may increase the flow stability from well to well (sample to sample) while maintaining the seal around each well of the sample holder. It will however be understood that in other embodiments a piston-mounted system or other mobile configuration could be used for the transfer tube 26. The sample support 22 is preferably mounted on a translation stage (not shown), which moves the support 22 so that each sample-bearing membrane 24 is sequentially positioned with its back end 25 in alignment with the radiation beam 14 and its front end 27 in alignment with the transfer tube 26. In some embodiments, the translation stage may translate the sample support 22 along orthogonal axes (X-Y) in a plane perpendicular to the radiation beam 14, in a pre-programmed sequence. Standard or adapted software may be used to this effect.

[0086] The transfer tube 26 extends concentrically to the gas pressurizing chamber 62. In other words, the gas pressurizing chamber extends symmetrically around the transfer tube 26. In some implementations, the receptacle 60 is designed with a geometry at the interface between the transfer tube 26 and the sample-bearing membrane 24 that provides gas dynamics favoring the transport of the desorbed sample 42. Flow stagnation zones in the gas flow path around the first end 28 of the transfer tube 26 are preferably minimized, such that the carrier gas flow is directed efficiently into the transfer tube 26 to carry therewith the desorbed sample 42 from the first end 28 to the second end 30.

[0087] In the illustrated embodiment, the gas pressurizing chamber 62 has a tubular portion 63 to which the gas input 64 is connected. The tubular portion 63 has a diameter several times larger than a diameter of the transfer tube 26. In one example, the area ratio may be of about 85. Still in the illustrated embodiment, the gas pressurizing chamber 62 includes a transition portion 65 in which the diameter of the gas pressurizing chamber transitions from the larger diameter of the tubular portion 63 to the smaller diameter of the nozzle portion 68. In some variants, the receptable 60 has an inner wall 61 having a rounded cross-sectional shape within the transition portion 65, which avoids dead zones and turbulence areas within the gas pressurizing chamber 62.

[0088] As one skilled in the art will readily understand, the gas pressurizing chamber 62 as described herein can favor an even distribution of the carrier gas flow 66 within the chamber 62, in particular in the nozzle portion 68 surrounding the first end 28 of the transfer tube 26, uniformizing the pressure therein. This in turn favors a more optimal transport of the desorbed sample 42 into and through the transfer tube 26. In one example of implementation of the apparatus, the transfer tube has an internal diameter of 6 mm and a length adjusted to the dimensions of the apparatus; the tubular portion of the gas pressurizing chamber has an internal diameter of 30 mm and the nozzle portion a diameter of 12 mm; the gas pressurizing chamber has an height of 40 mm; and the transfer tube guide has a length of 30 mm.

[0089] The carrier gas may for example be nitrogen, compressed air or CO2. The carrier gas may also include a reactive gas for promoting the ionization of the desorbed sample.

[0090] The apparatus 10 may include or be connected to a compressed air carrier gas source 70. In some implementations, the carrier gas is preheated in a gas heater so that its temperature is controlled. In the embodiment of FIG. 1 , the carrier gas source 70 is a compressed air source connected to the gas input 64 of the receptacle 60 through a gas conduit 72 transporting the pressurized carrier gas from the carrier gas source 70 to the gas input 64 of the receptacle 60.

[0091] Referring to FIG. 4, in another embodiment, a fan 74 may be provided and connected to the gas input 64 to push the carrier gas into the gas pressurizing chamber 62. Advantageously, in this embodiment the carrier gas does not need to be pressurized. In some embodiment, a minimum gas pressure differential of about 0.68 inches of water between the exterior and the interior of the gas pressurizing chamber 62 is preferred to enable the desired even gas distribution within the nozzle portion 68 of the gas pressurizing chamber 62.

[0092] As seen in both FIG. 1 and FIG. 4, the apparatus 10 may further include an ionizing device 80 provided proximate the second end 30 of the transfer tube 26 for ionizing the desorbed sample 42 to obtain the ionized sample 82. The ionized sample 82 may be coupled into a mass spectrometer (not shown) or the like using techniques known in the art.

[0093] In some implementations, the ionization device 80 may be embodied by an ionizing needle for generating a corona discharge. The ionizing needle may be made of conductive material such as stainless steel or tungsten. The corona discharge (0-10 kV) may be carried out through the ionizing needle by a process of electronic cascades. In some variants, the ionizing needle may be controlled by constant current mode or by constant voltage mode, and the voltage applied thereto may be controlled by the mass spectrometer software or by an electronic control box. In other implementations, the ionizing device 80 may alternatively or additionally include a LIV source for ionizing the desorbed samples through photoionization. In one embodiment, both ionizing techniques may be provided, and an operator may either choose a single mode of ionization or both modes simultaneously. Other modes of ionization of the desorbed sample may also be envisioned without departing from the scope of protection.

[0094] Referring to FIGs. 4 and 5A to 5C, a method for generating an ionized sample according to one implementation is schematically illustrated.

[0095] With reference to FIG. 5A, the method first includes providing a sample support 22 comprising a sample-bearing membrane 24 reversible between a concave and a convex configuration. The sample support 22 initially has the sample-bearing membrane 24. in the concave configuration. The method next includes loading a source sample 25 on a front surface 27a of the sample-bearing membrane 24. As explained above, any relevant source sample and deposition technique may be used. Furthermore, one skilled in the art will readily understand that the loading of the source sample may be performed prior to the mounting of the sample support 22 into an apparatus such as described therein.

[0096] With reference to FIG. 5B, the method next includes reversing the sample-bearing membrane 24 with the source sample 25 thereon from the concave to the convex configuration. This may for example be accomplished with the use of a reversing tool 100 such as described above. Again, in some implementations the reversing of the samplebearing membrane 24 may be performed prior to the mounting of the sample support 22 into an apparatus such as described therein.

[0097] With reference to FIG. 5C, the method next includes heating the sample-bearing membrane 24 to cause heating of the source sample 25, thereby producing a desorbed sample 42 through desorption of the source sample. This heating may for example be accomplished by projection a radiation beam 14 from a laser source onto a back surface 27b of the sample-bearing membrane, opposite the sample. Referring now to FIG. 4, the method next includes transporting the desorbed sample 42 though a transfer tube 26 having a first end 28 opening proximate the sample-bearing membrane 24 to receive the desorbed sample 42 therefrom, and a second end 30 opposite the first end 28. The transfer tube 26 is surrounded by a receptacle 60 defining a gas pressurizing chamber 62 traversed by the transfer tube 26. The gas pressurizing chamber 62 has a gas input for receiving a carrier gas flow 66 and a nozzle portion 68 surrounding the first end 28 of the transfer tube 26 directing the carrier gas flow 66 into the transfer tube 26 to carry therewith the desorbed sample 42 from the first end 28 to the second end 30.

[0098] Finally, the method includes ionizing the desorbed sample 42 with an ionizing device 80 provided proximate the second end 30 of the transfer tube 26, thereby obtaining the ionized sample 82.

[0099] In some implementations of the apparatus and method described above, measurements showed improvement in the signal intensity with LDTD standard solution by 17%. The loss on the wall in the stagnation region, at the inlet of the transfer tube, was reduced by 63%.

[0100] Of course, numerous additional modifications could be made to the embodiments described above without departing from the scope of protection as defined in the appended claims.

Claims

Claims:1 . An apparatus for generating an ionized sample, comprising:- a sample support comprising at least one sample-bearing membrane reversible between a concave and a convex configuration, the sample-bearing membrane being adapted to receive a source sample thereon when in the concave configuration;- a heater for heating the sample-bearing membrane when in the convex configuration to cause heating of the source sample, thereby producing a desorbed sample through desorption of the source sample;- a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end;- a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and- an ionizing device provided proximate the second end of the transfer tube for ionizing said desorbed sample to thereby obtain said ionized sample.

2. The apparatus according to claim 1 , wherein the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes.

3. The apparatus according to claim 2, wherein the sample support comprises a plurality of sections arranged in a 2D array, each section provided with one of the samplebearing membranes.

4. The apparatus according to claim 2 or 3, wherein the sample support comprises a main body made of an insulating material.

5. The apparatus according to claim 4, wherein the main body comprises a top plate and a bottom plate extending one over the other and holding a periphery of each samplebearing membrane of the plurality of sample-bearing membranes therebetween.

6. The apparatus according to any one of claims 1 to 5, wherein each of the at least one sample-bearing membrane is made of a chemically inert and heat conductive materials.

7. The apparatus according to any one of claims 1 to 6, wherein each of the at least one sample-bearing membrane is made of stainless steel or aluminum.

8. The apparatus according to any one of claims 1 to 7, wherein each of the at least one sample-bearing membrane has a portion forming a well when the sample-bearing membrane is in the concave configuration and a protuberance when the samplebearing membrane is in the convex configuration.

9. The apparatus according to any one of claims 1 to 8, wherein each of the at least one sample-bearing membrane has a front surface adapted to receive a source sample thereon and a back surface opposite the front surface.

10. The apparatus according to claim 9, wherein each of the at least one sample-bearing membrane comprises a coating deposited on the front surface thereof.

11. The apparatus according to claim 9 or 10, wherein the heater comprises a laser source generating a radiation beam directed so as to impinge on the rear surface of the sample-bearing membrane.

12. The apparatus according to any one of claims 1 to 11 , wherein the transfer tube is in a fixed position with respect to the receptacle.

13. The apparatus according to any one of claims 1 to 12, where the gas pressurizing chamber extends symmetrically around the transfer tube.

14. The apparatus according to any one of claims 1 to 13, wherein the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membranethat provides gas dynamics favoring the transport of the desorbed sample into the transfer tube.

15. The apparatus according to any one of claims 1 to 13, wherein the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that minimizes flow stagnation zones in a gas flow path around the first end of the transfer tube.

16. The apparatus according to any one of claims 1 to 15, wherein the gas pressurizing chamber comprises a tubular portion to which the gas input is connected, the tubular portion having a diameter larger than a diameter of the nozzle portion and larger than a diameter of the transfer tube.

17. The apparatus according to claim 16, wherein the surface area of the tubular portion of the gas pressurizing chamber is about 85 times the surface area of the transfer tube.

18. The apparatus according to claim 16 or 17, wherein the gas pressurizing chamber comprises a transition portion in which the diameter of the gas pressurizing chamber transitions from the diameter of the tubular portion to the diameter of the nozzle portion.

19. The apparatus according to claim 18, wherein the receptable has an inner wall having a rounded cross-sectional shape within the transition portion of the gas pressurizing chamber.

20. The apparatus according to any one of claims 1 to 19, comprising a compressed air source providing the carrier gas flow and a gas conduit connecting the compressed air source to the gas input.

21. The apparatus according to any one of claims 1 to 19, comprising a non-pressurized air source providing the carrier gas flow a fan connected to the gas input to push the carrier gas into the gas pressurizing chamber.

22. The apparatus according to any one of claims 9 to 11 , combined with a reversing tool configured to reverse the sample-bearing membrane with the source sample thereon from the concave to the convex configuration.

23. The combination of claim 22, wherein the reversing tool comprises a pushing pin shaped and sized to engage the rear surface of the sample-bearing membrane.

24. A sample support for use in an apparatus for generating an ionized sample, comprising:- a main body made of an insulating material; and- at least one sample-bearing membrane reversible between a concave and a convex configuration, each of the at least one sample-bearing membrane having a front surface adapted to receive a source sample thereon when the sample-bearing membrane is in the concave configuration and a back surface opposite the front surface.

25. The sample support according to claim 24, wherein the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes.

26. The sample support according to claim 25, comprising a plurality of sections arranged in a 2D array, each section provided with one of the sample-bearing membranes.

27. The sample support according to claim 25 or 26, wherein the main body comprises a top plate and a bottom plate extending one over the other and holding a periphery of each sample-bearing membrane of the plurality of sample-bearing membranes therebetween.

28. The sample support according to any one of claims 24 to 27, wherein each of the at least one sample-bearing membrane comprises a coating deposited on the front surface thereof.

29. The sample support according to any one of claims 24 to 28, wherein each of the at least one sample-bearing membrane is made of a chemically inert and heat conductive materials.

30. The sample support according to any one of claims 24 to 29, wherein each of the at least one sample-bearing membrane is made of stainless steel or aluminum.

31. The sample support according to any one of claims 24 to 30, wherein each of the at least one sample-bearing membrane has a portion forming a well when the samplebearing membrane is in the concave configuration and a protuberance when the sample-bearing membrane is in the convex configuration.

32. A method for generating an ionized sample, comprising:- providing a sample support comprising at least one sample-bearing membrane reversible between a concave and a convex configuration, the sample support being provided with the sample-bearing membrane in the concave configuration;- loading a source sample on the sample-bearing membrane;- reversing the sample-bearing membrane with the source sample thereon from the concave to the convex configuration;- heating the sample-bearing membrane to cause heating of the source sample, thereby producing a desorbed sample through desorption of the source sample;- transporting the desorbed sample though a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end, the transfer tube being surrounded by a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and- ionizing the desorbed sample with an ionizing device provided proximate the second end of the transfer tube, thereby obtaining the ionized sample.

33. The method according to claim 32, further comprising mounting the sample support to the receptacle prior to the heating of the sample-bearing membrane.

34. The method according to claim 32 or 33, wherein the at least one sample-bearing membrane comprises a plurality of sample-bearing membranes and the sample support comprises a plurality of sections arranged in a 2D array, each section provided with one of the sample-bearing membranes.

35. The method according to claim 34, wherein the sample support comprises a main body made of an insulating material, the main body comprising a top plate and a bottom plate extending one over the other and holding a periphery of each sample-bearing membrane of the plurality of sample-bearing membranes therebetween.

36. The method according to any one of claims 32 to 35, wherein loading the source sample on the sample-bearing membrane comprises using a deposition technique selected from the group comprising manual pipetting, acoustic deposition, deposition by automated liquid handler and deposition from a syringe needle.

37. The method according to any one of claims 32 to 36, wherein reversing the samplebearing membrane comprises pushing on a surface of the sample-bearing membrane opposite the source sample using a reversing tool.

38. The method according to any one of claims 32 to 36, wherein heating the samplebearing membrane comprises projecting a radiation beam from a laser source onto a surface of the sample-bearing membrane opposite the source sample.

39. An apparatus for generating an ionized sample for use with a sample support comprising at least one sample-bearing membrane adapted to receive a source sample thereon, the apparatus comprising:- a heater for heating the sample-bearing membrane, thereby producing a desorbed sample through desorption of the source sample;- a transfer tube having a first end opening proximate the sample-bearing membrane to receive the desorbed sample therefrom, and a second end opposite the first end;- a receptacle defining a gas pressurizing chamber traversed by the transfer tube, the gas pressurizing chamber having a gas input for receiving a carrier gas flow and a nozzle portion surrounding the first end of the transfer tube directing the carrying gas flow into the transfer tube to carry therewith the desorbed sample from the first end to said second end; and- an ionizing device provided proximate the second end of the transfer tube for ionizing said desorbed sample to thereby obtain said ionized sample.

40. The apparatus according to claim 39, wherein the heater comprises a laser source generating a radiation beam directed so as to impinge on a surface of the samplebearing membrane opposite the source sample.

41. The apparatus according to claim 39 or 40, wherein the transfer tube is in a fixed position with respect to the receptacle.

42. The apparatus according to any one of claims 39 to 41 , where the gas pressurizing chamber extends symmetrically around the transfer tube.

43. The apparatus according to any one of claims 39 to 42, wherein the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that provides gas dynamics favoring the transport of the desorbed sample into the transfer tube.

44. The apparatus according to any one of claims 39 to 42, wherein the receptacle has a geometry at an interface between the transfer tube and the sample-bearing membrane that minimizes flow stagnation zones in a gas flow path around the first end of the transfer tube.

45. The apparatus according to any one of claims 39 to 44, wherein the gas pressurizing chamber comprises a tubular portion to which the gas input is connected, the tubular portion having a diameter larger than a diameter of the nozzle portion and larger than a diameter of the transfer tube.

46. The apparatus according to claim 45, wherein the surface area of the tubular portion of the gas pressurizing chamber is about 85 times the surface area of the transfer tube.

47. The apparatus according to claim 45 or 46, wherein the gas pressurizing chamber comprises a transition portion in which the diameter of the gas pressurizing chamber transitions from the diameter of the tubular portion to the diameter of the nozzle portion.

48. The apparatus according to claim 47, wherein the receptable has an inner wall having a rounded cross-sectional shape within the transition portion of the gas pressurizing chamber.

49. The apparatus according to any one of claims 39 to 48, comprising a compressed air source providing the carrier gas flow and a gas conduit connecting the compressed air source to the gas input.

50. The apparatus according to any one of claims 39 to 48, comprising a non-pressurized air source providing the carrier gas flow a fan connected to the gas input to push the carrier gas into the gas pressurizing chamber.

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