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    • 专利摘要:
    The invention relates to an analysis plate (10) comprising at least one analysis zone intended to receive a sample to be analyzed by mass spectrometry according to the MALDI-TOF technique, of the type comprising at least one test face (12). ) on which is delimited at least one analysis zone, of the type in which the plate comprises a plane support (18), characterized in that the support (18) comprises at least one sheet (20) of paper material comprising fibers cellulosic, and in that the analysis plate (10) comprises at least one layer (24) of metallic material.
    公开号:FR3065652A1
    申请号:FR1753705
    申请日:2017-04-27
    公开日:2018-11-02
    发明作者:Patrick Broyer；Nadine Perrot；Jerome Blaze；Jean-Maire Baumlin
    申请人:Biomerieux SA；Arjo Wiggins Fine Papers Ltd；
    IPC主号:
    专利说明:

    Holder (s): BIOMERIEUX Limited company, ARJO WIGGINS FINE PAPERS LIMITED.
    Extension request (s)
    Agent (s): CABINET BEAU DE LOMENIE Civil society.
    (54) MALDI-TOF ANALYSIS PLATE WITH PAPER SUPPORT AND USE THEREOF.
    FR 3 065 652 - A1 _ The invention relates to an analysis plate (10) comprising at least one analysis zone intended to receive a sample to be analyzed by mass spectrometry according to the MALDI-TOF technique, of the type comprising at least a test face (12) on which is defined at least one analysis zone, of the type in which the plate comprises a flat support (18), characterized in that the support (18) comprises at least one sheet (20 ) of paper material comprising cellulosic fibers, and in that the analysis plate (10) comprises at least one layer (24) of metallic material.
    , 0 ^

    The present invention relates to the field of microbiology. More specifically, the invention relates to the analysis of a biological sample using mass spectrometry, and in particular, mass spectrometry by matrix-assisted desorption-ionization and measurement of the flight time called MALDI-TOF.
    The MALDI-TOF technique has been used for a few years to carry out a rapid identification of microorganisms, at the level of the species.
    The identification of a microorganism is carried out from the MALDI-TOF mass spectrum of the most abundant proteins in the microorganism, by comparison with reference data allowing (identification of the family, genus and most often of the species of the microorganism). Routinely, the protocol implemented includes the deposition of at least one colony portion of the microorganism on a MALDI plate, the addition of a matrix adapted to the MALDI technique, the acquisition of the mass spectrum and the identification of the species by comparison with reference data stored in a database. More recently, the MALDI technique has also been used to detect the resistance of a microorganism to an antibiotic, and in particular to identify a phenotype, responsible for the hydrolysis of beta-lactam antibiotics, due to the secretion of enzymes of the beta-lactamase type, and in particular of the carbapenemase type.
    Various devices adapted to such a characterization are marketed by the applicant, and by the companies Bruker Daltonics and Andromas in particular, these devices notably comprising a laser ionization source and a time-of-flight mass spectrograph. These devices are therefore designed to operate with an analysis plate on which is deposited, on at least one analysis area, a biological sample to be analyzed which is then covered with the matrix suitable for the MALDI technique. Then, the assay plate is inserted into one of the device analysis chamber that is brought to a level relatively high vacuum with a pressure which is e.g., less than 10 -5 millibar, for example in the range ranging from 10 ' 6 to 10' 9 millibars.
    Under these vacuum conditions, the population of microorganism (s) placed within the MALDI matrix is subjected to gentle ionization by laser. The laser beam used for ionization may have any type of wavelength favorable for sublimation or for vaporization of the matrix. Preferably, an ultraviolet or even infrared wavelength will be used. This ionization could, for example, be carried out with a nitrogen laser emitting a UV ray at 337.1 nm.
    The matrix then absorbs photonic energy and the restitution of this energy leads to the sublimation of the matrix, the desorption of the molecules present in the population of micro-organism (s) and the appearance of matter in a qualified state of plasma. Within this plasma, charge exchanges occur between molecules from the matrix and molecules from microorganisms. For example, protons can be torn from the matrix and transferred to proteins, peptides and organic compounds present in the analysis area. This step allows gentle ionization of the molecules present without inducing their destruction. The population of microorganism (s) thus releases ions of different sizes. The latter are then accelerated by an electric field and fly freely in a tube under reduced pressure, called the flight tube. The smaller ions will then “travel” faster than the larger ions, allowing their separation. At the terminal end of the flight tube is located a detector. The time of flight (or TOF for “Time Of Flight”) put by the ions is used to calculate their mass. Thus, a mass spectrum is obtained, representing the intensity of the signal corresponding to the number of ionized molecules of the same mass on charge [m / z], as a function of the m / z ratio of the molecules which strike the detector. The mass-to-charge ratio [m / z] is expressed in Thomson [Th]. After the analysis plate has been inserted into the mass spectrometer and the required vacuum level has been reached, the spectrum can be obtained very quickly, usually in less than a minute.
    In the context of the invention, the analysis by MALDI-TOF can be a simple MALDI-TOF analysis, or even an analysis by MALDI-TOF TOF MALDI TOF-TOF.
    A MALDI analysis plate has at least one and, in general, several analysis zones. The analysis zones form a spot, most often circular in shape. In order to promote subsequent ionization, the surface of the plate is generally conductive, at least at the level of the analysis zone or zones. By way of example, such an analysis plate is generally formed from a metal, or formed from a polymer such as polypropylene, said polymer being covered with a layer of stainless steel. The polymer may contain a conductive material such as carbon black. Such a plate may be, for example, that sold by the company Shimadzu, under the reference Fleximass ™ DS disposable MALDI targets.
    Various MALDI plates are commercially available such as VITEK® MS plates from BioMérieux (disposable) and Maldi Biotarget plates from Bruker Daltonics (reusable). Such plates generally include 48 to 96 analysis zones or spots, and at least one, or even two or three reference analysis zones, which can be of size different from the analysis zones.
    In general, it is considered that the analysis plates intended for an analysis by MALDI-TOF must have very rigorous geometric characteristics, in particular characteristics of thickness of the analysis plate and flatness of the test face. perfectly mastered. Indeed, the MALDI-TOF analysis is based in particular on the comparison of the flight times of the different particles resulting from ionization. It is easy to see that the flight time is affected by the distance to be covered, and therefore by good control of the initial position of the sample. Document EP-2,106,858 describes an analysis plate, the surface of which is structured to modify the wetting. This analysis plate is intended to allow analysis by mass spectrometry, but the nature of the analyzer envisaged for this analysis is not specified. Those skilled in the art would therefore certainly not consider using such a structured analysis plate for a mass spectrometry analysis in which the analysis is based on the measurement of a time of flight of the ionized particles.
    Document EP-1,814,137 describes an analysis plate comprising a separate substrate and a measuring element which are in electrical contact. Document EP-2,792,471 describes a MALDÏ analysis plate made of polymer material, with a hydrophobic agent. The analysis plate is also coated with a layer of metallic material. Document EP-2,808,887 describes an analysis plate intended for MALDI-TOF analysis which comprises a base plate of metallic material covered with a layer of strongly oriented graphite, which is assembled to the base plate by a electrically conductive adhesive.
    Some MALDI-TOF analysis plates are reusable. This implies that the analysis plate must be cleaned and decontaminated, for example with a solvent, between two uses. It is therefore necessary that the plate supports the cleaning / decontamination process without alteration, which increases the manual procedure for using this type of analysis plate and the time necessary for the complete process of using the MALDI-TOF, in particular in requiring a longer preparation time and more labor-intensive. Other analysis plates are for single use, for example made of polymer material. So far, the unit cost of such plates remains high. There appears to be a need to reduce the cost of manufacturing such analysis plates.
    To this end, the invention provides an analysis plate comprising at least one analysis zone intended to receive a sample to be analyzed by mass spectrometry according to the MALDI-TOF technique, of the type comprising at least one test face on which is delimited at least one analysis zone, and of the type in which the plate comprises a flat support, characterized in that the support comprises at least one sheet of paper material comprising cellulosic fibers, and in that the plate analysis includes at least one layer of metallic material.
    According to other optional features of the invention, taken alone or in combination:
    - The layer of metallic material is added to the sheet of paper material on the side of the test face.
    - The layer of metallic material is added to the sheet of paper material by vacuum metallization of the sheet of paper material.
    -The layer of metallic material is attached to the sheet of paper material by transfer metallization.
    - The layer of metallic material has a thickness of less than 0.5 microns.
    - The layer of metallic material includes aluminum.
    -The sheet of paper material comprises, as fibers, exclusively cellulose fibers.
    - The sheet of paper material comprises cellulosic fibers and synthetic fibers, in particular synthetic polymer fibers.
    - The sheet of paper material comprises cellulosic fibers and synthetic fibers, with, by mass, more cellulosic fibers than synthetic fibers.
    The paper material of the paper material sheet comprises at least one hydrophobic agent.
    - The sheet of paper material has a grammage greater than or equal to 120 grams per square meter, preferably greater than or equal to 150 grams per square meter.
    - The sheet of paper material has a grammage less than or equal to 400 grams per square meter, preferably less than or equal to 300 grams per square meter.
    - The support consists exclusively of paper material.
    - The support comprises at least one support blade on which the sheet of paper material is attached.
    - The support comprises at least one support blade of polymer material on which the sheet of paper material is attached.
    - The support comprises two blades of superimposed polymeric material, and the sheet of paper material is attached to one face of one of the two superimposed blades.
    - The blade of polymer material has a thickness in the range from 0.2 to 2 millimeters.
    - The sheet of paper material has a basis weight in the range from 60 grams per square meter to 200 grams per square meter.
    - The sheet of paper material is glued to the support blade.
    - The sheet of paper material comprises at least one deformation obtained mechanically along the contour of at least one analysis zone, thus delimiting the at least one analysis zone.
    At least one analysis zone on the sheet of paper material comprises a deformation obtained mechanically, over the entire extent of said analysis zone.
    - The analysis plate includes a marking with an ink delimiting at least one analysis zone.
    The invention also relates to the use of an analysis plate having any of the preceding characteristics as a sample support in a method of analyzing the sample by mass spectrometry according to the MALDI-TOF technique. .
    In such use, the analysis plate can be used with an adapter which holds the sheet of paper material by its periphery. Such an adapter may include a plate, a frame and a clamping mechanism which causes the analysis plate to be clamped between the frame and the plate, the frame cooperating with the periphery of the analysis plate and comprising an opening revealing at least one analysis area of the analysis plate.
    Various other characteristics will emerge from the description given below with reference to the appended drawings which show, by way of nonlimiting examples, embodiments of the subject of the invention.
    Figure 1 is a schematic perspective view of an analysis plate according to the invention.
    Figures 2, 3A and 3B schematically illustrate, in cross section, three alternative embodiments of an analysis plate according to the invention, without a support blade.
    Figures 4A and 4B schematically illustrate, in cross section, two alternative embodiments of an analysis plate according to the invention, with one and two support blade (s) respectively.
    Figure SA is a top view of a portion of the test face of an analysis plate according to the invention, more particularly illustrating a first embodiment of a marking of a test area.
    FIG. 5B is a partial schematic view in cross section, with cutaway, illustrating the production by mechanical deformation of the marking of FIG. HER.
    Figures 6A and 6B are views similar to those of Figs. 5A and SB, illustrating an alternative embodiment.
    Figures 7A and 7B are views similar to those of Figs. 5A and SB, illustrating another alternative embodiment.
    Figure 8 schematically illustrates the production of several analysis plates by cutting a strip.
    FIG. 9A is a schematic exploded perspective view illustrating the use of an analysis plate according to the invention with an adapter, the elements being seen from the side of their lower face, in particular from the side of the bearing face of the analysis plate.
    FIG. 9B is a schematic perspective view illustrating the use of an analysis plate according to the invention with the adapter of FIG. 9A, side view of the test face of the analysis plate.
    FIG. 10 is a schematic exploded cross-sectional view of the assembly of FIG. 9B.
    Figure 11 is a schematic cross-sectional view illustrating the assembly of FIG. 9B in use configuration.
    Figures 12A to 12E are schematic views illustrating different variants of structuring of the analysis plate.
    Various other characteristics will emerge from the description given below with reference to the appended drawings which show, by way of nonlimiting examples, embodiments of the subject of the invention.
    Illustrated in Figs. 1 and 2 a first example of an analysis plate 10 produced according to the invention.
    The analysis plate 10 has for example in known manner a planar shape in an extension plane. The analysis plate 10 has a thickness in the direction perpendicular to its extension plane which is for example less than one tenth of the smallest dimension of the plate measured in the extension plane, commonly called width. The analysis plate 10 thus has a test face 12 and a support face 14 which extend parallel to the extension plane. The test face 12 is that on which at least one analysis zone is provided, in the illustrated example several analysis zones 16 each intended to collect a biological sample to be analyzed. In the example illustrated, the analysis plate 10 thus presents 48 analysis zones arranged in four columns of twelve analysis zones. However, thanks to the low cost of an analysis plate 10 according to the invention, provision can be made for it to have a reduced number of analysis zones, for example one, two, four, five or eight analysis zones 16 .
    For example, the analysis plate 10 may have, in its extension plane, a smaller dimension between 10 and 50 millimeters, for example 25 millimeters, and a larger dimension between 50 and 100 millimeters, for example 75 millimeters.
    By convention, it is considered for the remainder of the text that the analysis plate 10 extends in a horizontal plane, and that the test face 12 is an upper face and that the bearing face 14 is a lower face of the analysis plate 10.
    Preferably, each analysis zone 16 is visually delimited from the rest of the test face 12 of the analysis plate 10. In the example illustrated, each analysis zone 16 is substantially circular in shape.
    The analysis plate 10 can also include reference analysis zones (not shown in the figures), which can for example be used for the calibration of the apparatus in the context of the MALDI-TOF analysis.
    According to the invention, the analysis plate 10 comprises a flat support 18, which comprises at least one sheet of paper material 20 comprising cellulosic fibers. The sheet of paper material 20 therefore has an extension plane corresponding to the extension plane of the analysis plate 10.
    The paper material is a material which consists of agglomerated fibers, the fibers comprising cellulosic fibers. The cellulosic fibers are for example of vegetable origin. The agglomeration of the fibers of the paper material is obtained by the paper technique. According to this technique, the fibers are dispersed in an aqueous solution, possibly with the addition of auxiliary materials (fillers, dyes, glue, etc.), thus forming a paper pulp. The paper pulp is placed in a thin sheet on an openwork table allowing the drainage of a large part of the water contained in the paper pulp. Various operations of pressing and drying the web allow the fibers to agglomerate, giving the sheet of paper material 20 its cohesion. In a known manner, a sheet of paper material 20 can undergo surface treatments aimed for example at depositing, on the surface of the sheet, one or more layers of additive materials making it possible to modify the surface condition of the sheet of paper material. The sheet of paper material can also undergo mechanical treatments, in particular calendering, embossing, etc., again aimed at modifying the surface condition of the sheet of paper material.
    In certain embodiments of the invention, the sheet of paper material 20 may comprise, as fibers, exclusively cellulosic fibers. By this is meant that the sheet of paper material 20 comprises, as fibers, only cellulosic fibers, except however for the possible presence of fibrous impurities. Preferably, the mass of these fibrous impurities represents less than 2% of the mass of paper material. This quantity can be measured according to the TAPPI T401 standard.
    In the present application, the mass per square meter of the sheet of paper material, also called grammage, is measured according to standard ISO 536.
    However, in certain embodiments, provision may be made for the sheet of paper material to comprise cellulosic fibers and non-cellulosic fibers, in particular glass fibers and / or synthetic polymers. Fibers of synthetic polymers can in particular comprise fibers of polyester, polyethylene or polyiactic acid. One of the advantages of adding non-cellulosic fibers as envisaged above is to allow the paper layer to retain less moisture in the event of exposure to a humid atmosphere. Among the noncellulosic fibers, one can for example provide:
    - glass microfibers from the company Lauscha Fiber International, for example fibers B-08-F having a diameter of 0.8 microns made of borosilicate;
    - Cyphrex synthetic polymer fibers from the company Eastman, for example Cyphrex tm 10001 with a diameter of 2.5 microns and a length of 2.5 millimeters in PET
    - synthetic polymer fibers from the company Advansa, for example Advansa 328 NSD fibers of length 6mm and with a dtex of 1.7 in polyester or Advansa PLA fibers of length 3 mm having a dtex of 1.7 in PLA.
    Indeed, it appeared that, when using the analysis plate according to the invention, comprising at least one sheet of paper material 20, the moisture absorbed by the sheet of paper material 20 could slow down the step of placing the analysis chamber under vacuum in which the analysis sheet is introduced for the MALDI-TOF analysis. This slowdown can be offset by an increase in the pumping capacity of the MALDI-TOF installation. It can also be counterbalanced by an adequate conditioning of the analysis plate before its use. Thus, an analysis plate 10 according to the invention will advantageously be kept in a moisture-proof packaging. It is for example possible to form a packaging comprising an aluminum foil completely enclosing the analysis plate 10. It can be provided that the analysis plate is packed under a controlled atmosphere, preferably by providing that the atmosphere internal to the packaging as dry as possible, and possibly by providing a desiccant inside the packaging. In particular, an internal atmosphere with a relative humidity of less than 5% will advantageously be provided. The relative humidity measurement can be made using a calibrated hygrometer. The relative humidity can then be calculated from the formulas defined in standard NF X 15-110.
    Thus, by constructing the sheet of paper material 20 so that it is less likely to retain moisture when exposed to a humid atmosphere, the characteristics of the analysis plate 10 comprising such a sheet are improved. of paper material, in particular by reducing the vacuuming time for carrying out the analysis.
    However, in the case of the presence of synthetic fibers, it will preferably be provided that, for the sheet of paper material, the ratio between the mass of non-cellulosic fibers and the total mass of the fibers of the sheet of paper material is less than 50%. This value can be measured for a given paper according to the Tappi 401 method.
    The resistance of the sheet of paper material to moisture absorption can also be obtained by other means.
    Alternatively, provision may be made to treat a sheet of paper material, previously formed, by impregnating it with a hydrophobic material, for example a material containing paraffin. Among the hydrophobic materials that can be envisaged, mention may be made of:
    - Vapor Coat® 2200.E from Michelman;
    - Diofan® A050 from the company Solvay based on Polyvinylidene Chloride (PVDC). ;
    - Aquacer 497 from BYK Additives & Instruments, which is a paraffin-based wax emulsion.
    According to another variant, provision may be made to treat a sheet of paper material, previously formed, for example by dipping in an acid, for example sulfuric acid. On contact with the acid, part of the cellulose of the cellulose fibers is transformed, which results in greater resistance of the sheet of paper material thus treated to the absorption of moisture.
    As will be seen below, the analysis plate 10 may include elements other than the sheet of paper material 20.
    The analysis plate 10 can comprise several sheets of paper material. In this case, the sheets of paper material are advantageously superimposed on each other, preferably on the whole of the extent of the analysis plate 10 in its extension plane. The different sheets of paper material can be joined together, for example by gluing. Preferably, a one-component polyurethane adhesive or a two-component polyurethane adhesive based on solvent (preferably non-aqueous) or without solvent will be used in this case.
    The adhesive can be applied by spraying or by roller coating. It is possible to use an ultraviolet activatable adhesive. It is also possible to use a double-sided adhesive film. We therefore prefer a film of the smallest possible thickness.
    In the case of an analysis plate 10 comprising several sheets of paper material, the sheets of paper material may or may not be identical. The paper materials constituting these sheets of paper material, their grammage, and / or their thickness, etc. may be identical or different. Likewise, the sheets of paper material may have different dimensions, for example at least one different dimension in the extension plane of the analysis plate 10.
    In some cases, as illustrated in Figs. 2, 3A and 3B, the support 18 of the analysis plate 10 consists exclusively of paper material. This case does not prevent the analysis plate 10 furthermore comprising additional layers or strata as will be described later. However, it is considered in this case that the support 18, which gives most of its mechanical rigidity to the analysis plate, consists exclusively of paper material. In the case of a support consisting exclusively of several sheets of paper material, the presence of an adhesive, in particular an adhesive, or other means of assembly between the different sheets of paper material will not prevent consideration the support as consisting exclusively of paper material.
    In the case where the support 18 of the analysis plate 10 consists of a single sheet of paper material 20, as illustrated in Figs. 2 and 3A, this preferably has a grammage greater than or equal to 120 grams per square meter, more preferably greater than or equal to 150 grams per square meter. In the case where the support 18 of the analysis plate comprises several sheets of paper material, as illustrated in FIG. 3B, the sum of the grammages of the sheets of paper material of the support is preferably greater than or equal to 120 g per square meter, more preferably greater than or equal to 150 grams per square meter. It has in fact been observed that this grammage makes it possible to obtain sufficient rigidity for easy manipulation of the analysis plate in the context of its use in a MALDI-TOF analysis, but above all to thus guarantee a sufficiently flat geometry. , including after handling, so as not to disturb the measurements by MALDI-TOF.
    Preferably, the analysis plate 10 has a grammage of paper material less than or equal to 400 grams per square meter, preferably less than or equal to 300 grams per square meter, in one sheet or distributed among several sheets. Indeed, it appears that, even in the presence of a single sheet of paper material and / or even in the case where the support of the analysis plate 10 consists exclusively of paper material, such a grammage makes it possible to obtain a more than sufficient rigidity of the analysis plate. Beyond such a grammage, there is a risk of increasing the susceptibility of the analysis plate 10 to store moisture, which we have seen was a brake on use, by requiring an increase in the evacuation time of the analysis chamber in a MALDI-TOF analysis apparatus.
    Thus, the sheet of paper material 20 used in the analysis plate 10 according to the invention preferably has a thickness which can be between 100 and 450 microns, measured according to standard NF EN ISO 534. In the case of a analysis plate comprising several sheets of paper material, the cumulative thickness of the sheets of paper material, after their assembly to form the analysis plate, is preferably between 100 and 1000 microns, measured according to standard NF EN ISO 534 .
    Preferably, the sheet of paper material 20 has, at least on its face turned towards the side of the test face 12 of the analysis plate 10, a low roughness. For example, this roughness, measured according to the Bendtsen method defined in standard ISO 8791-2: 2013, can have a value less than 750 milliliters per minute, preferably less than 500 milliliters per minute.
    In certain embodiments of the invention, it is possible to provide that the support 18 comprises at least one support blade 22 on which the sheet of paper material 20 is attached. In this case, the support 18 thus comprises at least two elements, to namely the support blade 22 and the sheet of paper material 20, as illustrated for example in FIG. 4A.
    In such a case, the support blade 22 preferably has a planar shape extending parallel to the extension plane of the analysis plate 1Θ. The support blade 22 has a thickness in the direction perpendicular to its extension plane which is for example less than one tenth of the smallest dimension of the plate measured in the extension plane.
    Preferably, considering the convention set out above, the support blade 22 is arranged below the sheet of paper material 20 or of the plurality of sheets of paper material. Thus, the support blade 22 preferably has a lower face which forms the bearing face 14 of the analysis plate 10.
    The support blade 22 is for example made of polymer material, for example polypropylene or polypropylene-based material. According to an example, the support blade is a plate of Polypropylene Priplak® Classic black 800, of thickness 800 micron.
    Such a support plate can be laminated with a plate of the same type using a Super-Lok® 364 adhesive from the company National Starch.
    Particles and / or fibers or other additives can be embedded in the polymer material, in particular particles and / or fibers which conduct electricity, in particular particles and / or fibers which are metallic or based on metal and / or particles and / or carbon fibers.
    Advantageously, the support blade 22 can come from a strip of material obtained by extrusion. Advantageously, the support blade 22 can thus be obtained in a very long strip, packaged in a roll or in a plate, therefore in a presentation similar to the paper material obtained at the output of a paper machine.
    Advantageously, the sheet of paper material 20 and the support blade 22 can be assembled together, for example by gluing. Preferably, in this case, a one-component polyurethane colony or a two-component polyurethane shell, solvent-based (preferably non-aqueous) or solvent-free, will be used. The adhesive can be applied by spraying or by roller coating or by direct etching. I! it is possible to use an ultraviolet activatable adhesive. It is also possible to use a double-sided adhesive film. We therefore prefer a film of the smallest possible thickness.
    As illustrated in Fig. 4B, the support 18 may comprise several support blades, in particular two support blades made of superimposed polymeric material, and the sheet of paper material 20 is attached to one face of the two superimposed blades.
    The support blade 22 of polymer material, or the plurality of support blades, have (s), for example, a thickness in the range from 0.2 to 2 millimeters. In this case of the presence of at least one support blade 22, the sheet of paper material 20 may have a lower grammage than that envisaged in the case where the support 18 consists exclusively of paper material. For example, the sheet of paper material may have a basis weight in the range from 60 grams per square meter to 200 grams per square meter.
    The analysis plate 10 comprises at least one layer of metallic material. A stratum is understood to be an element or a part of an element of the analysis plate 10 which extends in the extension plane of the analysis plate 10. Metallic materials include metals and their alloys.
    The layer 24 of metallic material is attached to the sheet of paper material 20.
    Preferably, the layer 24 of metallic material can be attached directly to the sheet of paper material 20, with only the interposition of a possible layer of adhesive material te! than an adhesive or an adhesive film, without interposing any other support layer, as illustrated in FIG. 2.
    Preferably, a layer of metallic material can be added to the sheet of paper material 20, on the side of the test face 12.
    The layer 24 of metallic material may for example be an aluminum layer, or an aluminum alloy. However, other metallic materials can be envisaged, for example silver or silver alloys.
    A stratum 24 of metallic material can be added to the sheet of paper material 20 by vacuum metallization of the sheet of paper material 20. In this case, the stratum 24 of metallic material can form the surface of the test face 12 of the analysis plate 10. The vacuum metallization technique is a thin layer deposition technique widely used in the paper industry. The metal to be deposited is evaporated from a solid metal source, by heating at high temperature in a vacuum deposition chamber into which a substrate, for example a strip of paper material, is introduced in a continuous process. The particles resulting from evaporation are deposited directly on the paper material on which they condense in the solid state. Such vacuum metallization is typically obtained in a vacuum metallizer.
    According to another technique, such a layer 24 of metallic material can be attached to the sheet of paper material 20 by transfer metallization. An exemplary embodiment of transfer metallization is described in detail in document FR-2,406,523 to which a person skilled in the art can refer. Note that in this case, as illustrated in Figs. 3A and 3B, the analysis plate 10 can include, starting from the test face 12:
    - a resin layer, for example an acrylic or epoxy-acrylic resin 26;
    - the layer of metallic material 24;
    a layer of glue 28, for example a one-component polyurethane glue in the solvent phase;
    - the sheet of paper material 20.
    An example of an embodiment of an analysis plate 10 according to the invention, in the variant of FIG. 3A, is constructed as follows. A sheet of paper material 20 made of cellulose fiber is obtained using a paper machine of the Foudrinier type. The paper 20 preferably comprises at least one hydrophobic agent which is mixed with the paper pulp before the formation of the sheet. The hydrophobic agent which was used is an aqueous emulsion of Alkyl Ketene Dimer (AKD).
    This sheet of paper is coated on both sides with a pigment solution (not visible in the drawings), for example a solution of calcium carbonate and Kaolin, by the air knife coating technique. The deposit is approximately 10 g / m 2 per side. This sheet of paper material 20 has a grammage of 250 g / m 2 . On a top face of this sheet of paper material 20, a metallization by transfer metallization is applied according to the teaching of document FR-2,406,523. A laminated complex is formed consisting of a base film PET (polyethylene terephtaiate), a separation layer (release), a layer of acrylic resin 26 of approximately 2 microns and a deposit of aluminum alloy 24 ( with a thickness of 10 to 100 nanometers, preferably 15 to 50 nanometers, preferably about 20 nanometers), deposited under vacuum on the resin layer 26 to form the layer of metallic material 24. This metallic layer can be measured by commercial thickness measurement devices, in particular those using radiometric methods (X fluorescence or β backscatter) allowing access to measurement resolutions between 100 nanometers and a few Angstroms. This complex is assembled, with the layer of metallic material 24 facing the sheet of paper, using a layer of one-component solvent glue 28, against the upper face of the sheet of paper 20. The glue 28 can be one of the above. The amount of glue used can be, for example, from 3 to 12 grams per square meter. Subsequently, thanks to the separation layer, for example based on stearo-chromium chloride, the base film is detached in order to leave the adhesive layer 28, the metallization 24 and the resin layer 26 on the paper. Note that, in this embodiment, the surface of the test face 12 of the analysis plate 10 is formed by the layer of resin 26, non-electrically conductive, which covers the layer 24 of metallic material .
    Of course, such an analysis plate 10 may include, as indicated above, other sheets of paper material and / or possibly one or more support blades.
    Thus, it has been illustrated in FIG. 3B an alternative embodiment which includes all the elements of the embodiment of FIG. 3A, except that the sheet of paper material 20 has a grammage of 80 g / m 2 , and which comprises a sheet of additional paper material 20 ′ assembled against the underside of the sheet of paper material 20, therefore the face opposite to the one to which the stratum 24 of metallic material is attached. The assembly can be done by gluing using a layer of glue 28 '. The glue 28 ′ can be one of the one mentioned above. The sheet of additional paper material 20 ′ has for example a grammage of 170 g / m 2 .
    In another embodiment, a PET film previously coated with a non-stick layer based on chromium stearo-chloride is coated with an Epoxy / Acrylic resin which is dried. This coated face is introduced into a metallizer in order to receive an aluminum deposit of about 20 nanometers there. The metallized face is coated with a one-component polyurethane adhesive in the solvent phase by a coating in direct etching. It is dried before being laminated with Satimat® 90 g / m 2 paper from the company Arjowiggins. The next day, the PET film is peeled from the surface of the paper leaving the metallic deposit visible on the paper. This assembly is then bonded to a support assembly comprising at least support blade, for example using a Super-Lok® 364 adhesive from the company National Starch. Preferably, the support assembly comprises two support blades, each of which is formed from a plate of black Polypropylene Priplak® Classic 800, of thickness 800 microns. The two support blades are for example glued using a Super-Lok® 364 adhesive from the company National Starch.
    In general, tests have shown that an analysis plate 10 comprising a layer of metallic material, in particular aluminum or aluminum alloy, attached to an upper face of a sheet of paper material 20, as illustrated in Figs. 3A or 3B, can form a perfectly satisfactory analysis plate 10 making it possible to obtain analysis results with the same reliability as a reference plate.
    In particular, satisfactory results have been obtained with a layer of metallic material, in particular aluminum or aluminum alloys, having a thickness of less than 0.5 micron, or even less than 0.1 micron, see less than 0 0.05 micron.
    This layer of thin metallic material may be the only electrically conductive layer of the analysis plate 10, including in the possible presence, above the layer of metallic material 24, of a layer of non-conductive material. , in this case the resin layer 26.
    However, tests have shown that a layer 24 of metallic material, and more particularly of aluminum or of aluminum alloy, preferably has a thickness greater than 0.01 micron. Such a thickness notably allows the stratum not to be degraded during the vacuuming of the analysis chamber.
    It will be noted that tests carried out in the absence of a layer of metallic material have not made it possible to obtain satisfactory results during the analysis by mass spectrometry according to the MALDI-TOF technique.
    For example, an analysis plate constituted exclusively by a sheet of Powercoat HD 230 paper from the company Arjowiggins, which is an extremely smooth coated paper whose thickness is 222 microns and the grammage 219 g / m 2 , has no not satisfactory, with only a few peaks detected but with a spectrum without quality. Other tests with analysis plates not comprising a layer of metallic material attached to its test surface were not satisfactory, including with a sheet of paper material having a grammage of 300 g / m 2 .
    Preferably, each analysis zone 16 of the test face 12 is identified at least visually on the test face 12.
    For this, an analysis zone can be delimited on the test face by the presence of a mechanical deformation of the analysis plate 10, in particular by a mechanical deformation of the sheet of paper material 20.
    For example, in the example illustrated in Figs. SA and SB, in order to delimit at least one analysis zone 16, the sheet of paper material 20 is mechanically deformed along the contour of the analysis zone, in this specific case depending on part of the contour of the analysis zone. In fact, it can be seen that the analysis zone 16 is a circular zone the contour of which is delimited in part by a groove 29. The groove 29 is here in two parts, each in the form of an arc of a circle, and the two parts face each other. This groove 29 can be obtained by pressing the test face 12 in the thickness direction of the analysis plate 10, with plastic deformation of the sheet of paper material 20, thus obtaining permanent mechanical deformation.
    In the variant illustrated in Figs. 6A and 6B, the sheet of paper material is mechanically deformed over the entire extent of the analysis zone, in the form of a dish with a flat bottom.
    In the variant illustrated in Figs. 7A and 7B, the sheet of paper material is mechanically deformed over the entire extent of the analysis zone 16, and also around the analysis zone 16 to leave a raised bead 30 which extends in the example illustrated in a circle along the contour of the analysis area 16. The analysis area 16 is thus hollow relative to the top of the bead 30, forming a bowl as in the previous example.
    In the examples illustrated in Figs. 5B, 6B and 7B, the sheet of paper material 20 is surmounted by a stratum 24 of metallic material forming the test face 12, and this stratum of metallic material 24 is also deformed to form the groove 29 or the cuvette flat bottom or bead 30. The same result is obtained with an analysis plate having the structure illustrated in FIG. 3 in which the layer 24 of metallic material is obtained by transfer metallization, including with the possible optional presence of one or more support blades 22 as mentioned above.
    The depth of the permanent mechanical deformation is for example between 10 and 300 microns.
    It is understood that, in both cases, the mechanical deformation which delimits the analysis zone 16 not only makes it possible to delimit it visually, but also makes it possible to form a barrier to the propagation of the sample, and / or of the reagent (s) , and / or the matrix during deposition on the analysis plate 10.
    Thanks to the low mechanical strength of the sheet of paper material 20 in the direction of a recess according to its thickness, this mechanical deformation can easily be carried out according to the conventional embossing techniques used in the paper industry. In particular, such an embossing can be carried out online, for example when the support is still in the form of a continuous strip.
    Furthermore, to delimit at least one analysis zone 16, the analysis plate can include an ink marking. Such marking is preferably affixed to the test face 12.
    The marking may for example have a geometry analogous to the mechanical deformation illustrated in the examples of Figs. SA, 6A or 7A.
    According to an advantageous embodiment, the marking can be carried out on the test face 12, preferably over the entire extent of the analysis zone 16, with an ink having, once dried, a wetting angle for the the sample and / or the matrix which is different from the wetting angle of the surface of the material constituting the test face 12, for the sample and / or the matrix. Preferably, the wetting angle between the ink and the sample and / or the matrix is smaller than the wetting angle between the surface of the material constituting the test face 12 and the sample and / or the matrix, for example with AGFA Orgacon ™ ELP3145 ink sold by AGFA GEVAERT NV or its affiliates. In other words, the surface of the ink, when dry, is more hydrophilic than the surface of the test face 12. In this way, the ink makes it possible to facilitate the deposition of the sample and or the matrix in liquid phase, but the difference in wetting angle between the ink and the surface of the material constituting the test face 12 forms a barrier which will prevent, or at least limit, the extension of the deposit, in confining it inside the analysis zone 16 marked by the ink.
    However, it is also possible to provide for the ink to be deposited not on the analysis zone 16, but around it, and it is then possible, for example, to provide for the wetting angle between the ink and the sample and / or the matrix is greater than the wetting angle between the surface of the material constituting the test face 12 and the sample and / or the matrix. For example, this is done with DuPont ™ 5064H ink sold by EI du Pont de Nemours and Company or its affiliates, which has a higher wetting angle with water or formic acid than the surface of the metallic transfer paper backing. This ink is electrically conductive. The values below are wetting angles in degrees versus time measured with a Dynamic Absorption Tester from Testing Machines, Inc. (TMI) which uses the TAPPI 558 method.
    Paper n netali type Fig. 3A DuPont ™ 5064H ink on metallized paper type Fig. 3A t = 0, l s t = l s t = 10 s t = 0, l s t = ls t = 10 s H2O 83.8 82.3 80.4 113.8 111.8 111.5 Acidformic 41.8 38.2 29.8 68.2 64.8 47.6
    According to an advantageous embodiment, the marking can be carried out on the test face 12, preferably over the entire extent of the analysis zone 16, with an electrically conductive ink.
    Marking by ink deposition can be carried out by any known technique, in particular any technique used in the printing industry such as, for example, printing by electrophotography, printing by ink jet, by screen printing, by flexography or offset printing.
    Of course, it is possible to combine the delimitation of the analysis zone by mechanical deformation of the sheet of paper material and the delimitation of the analysis zone by marking with an ink. Thus, in the example described illustrated in FIG. 5A, provision may be made to mark with an ink the circular zone delimited by the groove 28. In the examples illustrated in FIGS. 6A and 7A, provision can be made to mark the flat bottom of the bowl with ink.
    In the examples mentioned above, the analysis zone 16 is a smooth surface, for example having a roughness comparable to, or even less than, that of the sheet of paper material 20.
    However, to facilitate the deposition step, it is possible to provide for the surface of the analysis zone 16 to be structured. Preferably, this structuring will be obtained by mechanical deformation of the surface, and in particular by mechanical deformation of the sheet of paper material 20. This structuring can thus form, on the surface of the analysis zone 16, hollows and reliefs according to regular or irregular geometry. The relative depth between the hollows and the reliefs of the surface of the structured analysis zone can for example be between 10 and 300 microns. The geometry and the relative depth of the hollows and the reliefs of the surface of the structured analysis area 16 can be scalable over the extent of an analysis area 16, for example by variation of shape, size, pitch and / or depth of the hollows or reliefs.
    In Figs. 12A to 12F, various possible structures have been illustrated.
    In Fig. 12A, the structuring is formed of concentric circular lines 52, hollow or in relief with respect to the surface of the analysis area 16. The circular lines are for example equidistant from each other, but they could have an evolving spacing, not constant. The circular lines 52 are for example distributed over the entire extent of the analysis zone 16. The circular lines are for example concentric with a circular contour 54 of the analysis zone 16.
    In Fig. 12B, the structuring is formed by radial lines 56 coming from the same central point of the analysis zone 16, in hollow or in relief with respect to the surface of the analysis zone 16. The radial lines are for example separated angularly from one another at a constant angle, but they could have an evolving, non-constant spacing. The radial lines are for example distributed over the entire extent of the analysis area 16. The radial lines for example come from the center of a circular contour 54 of the analysis area 16.
    In Fig. 12C, the structure is formed of concentric circular lines 52, as described in FIG. 12A, and radial lines 56, as described in Fig. 12B.
    In Fig. 12D, the structuring is formed of lines, in hollow or in relief with respect to the surface of the analysis area 16, forming a grid 54. The grid 58 can be a square grid formed by two perpendicular series of parallel straight lines, but one can also envisage two non-perpendicular series of parallel straight lines, or more than two series of parallel lines, each series each having a different orientation. Within a series of parallel lines, the lines are for example equidistant from each other, but they could have an evolving, non-constant spacing. The grid 58 extends for example over the entire extent of the analysis zone 16. However, the grid could be limited to only part of the analysis zone 16, for example to a peripheral crown, of the zone analysis 16.
    In Fig. 12E, the structuring is formed by a multitude of repeated geometric elements, forming a repeating pattern 60, in hollow or in relief relative to the surface of the analysis zone 16. In FIG. 12F, the structuring is formed of a repeating checkerboard pattern 60, in hollow or in relief relative to the surface of the analysis area 16. In both cases, the pattern 60, 62 extends for example over all the extent of the analysis zone 16. However, the pattern could be limited to only part of the analysis zone 16, for example to a peripheral ring of the analysis zone 16.
    It can be provided that, on the active face 12 of the analysis plate 10, only the analysis zone or zones are provided with a structure as described above. However, it is also possible to provide that at least part of the active face 12 of the analysis plate 10, outside of the analysis zone 16 or of the analysis zones 16, is also provided with a structure such as described above, or even that the entire active face 12 of the analysis plate 10 is provided with a structure as described above.
    The exemplary embodiments of an analysis plate 10 according to the invention make it possible to produce the analysis plate 10 using materials and techniques commonly used in the paper industry, making it possible to obtain a analysis 10 at very low cost, both from the point of view of the cost of the materials used and, even more importantly, from the point of view of the cost of the manufacturing processes used.
    Indeed, the cost of paper materials and their production and their implementation for the manufacture of analysis plates according to the invention is very low compared to the cost of materials and production of analysis plates known up to now. The metal analysis plates used until now are indeed expensive to produce. The analysis plates of polymer material known up to now, generally produced by injection molding of individual analysis plates, are also relatively expensive.
    The manufacture of an analysis plate 10 according to the invention can be carried out, as illustrated in FIG. 8, by cutting individual analysis plates 10 starting from a strip of material 32 produced at very low cost. This strip of material 32 can include all of the sheet (s) of paper material 20, support blade (s) 22, stratum 24 of metallic material, etc. envisaged for producing the analysis plate 10 according to the invention. 'invention, pre-assembled in a laminate complex obtainable online in long strip. Likewise, the operations of marking by mechanical deformation or the operations of marking by ink deposition can use the corresponding techniques used in the printing industry, again implemented online for strips of great lengths.
    Thus, an operation can be provided for cutting the analysis plate 10 to its final dimension in such a preassembled laminate complex, as being an ultimate step in the manufacturing process, at least a step subsequent to the production of the laminate complex. . Of course, certain steps such as marking by mechanical deformation or by ink deposition can be carried out after such a cutting operation.
    This results in a very low cost of producing an analysis plate, in particular in the case of the use of mass production methods derived from paper techniques, in particular “Roll to Roll” type processes, allowing a automation of the manufacturing process, without human intervention or with minimal human intervention.
    Contrary to all expectations, it appeared that analysis plates produced in accordance with the teachings of the invention make it possible to obtain, in a standard apparatus, a characterization of the samples in accordance with what is generally obtained with pre-existing analysis plates .
    Indeed, with analysis plates as described above with reference to FIG. 3A, it was possible to detect by MALDI-TOF analysis, with the same precision as with a reference plate of the prior art, many bacterial strains, peptides or proteins. In particular, the identification on the analysis plates according to the invention was as good as the identification on the VITEK® MS analysis plates sold and were 100% correct. The identification probabilities were similar with an average of 98.4%, for the reference, 96.5% for an analysis plate according to the invention, as described in relation to FIG. 3A, in a smooth version, and 98% for an analysis plate according to the invention, also as described in relation to FIG. 3A, but in a structured version. The MS spectra were also comparable, exhibiting the same resolution, ie the same number of peaks and the same dynamic range.
    All the peptides and proteins tested with the different matrix were detected on an analysis plate according to the invention, in a smooth version, with the same quality as on the reference target. The tests covered 22 bacterial species and yeasts, with masses between 2000 and 20,000 Daltons, and with peptides and proteins whose mass was between 300 and 46,000 Daltons.
    A plate according to the invention is therefore advantageously used as a sample support in a method of analyzing the sample by mass spectrometry according to the MALDI-TOF technique.
    For use in a standard mass spectrometry apparatus according to the MALDI-TOF technique, the inventors have designed an adapter 34 which makes it possible to use the analysis plates 10 according to the invention, in particular the analysis plates according to the Figs. 3A and 3B described above, which have a reduced thickness compared to conventional analysis plates.
    The adapter 34 holds the analysis plate 10 by its periphery and makes it possible to position this sheet of paper material 20 in the analysis chamber of the apparatus so that the test face 12 of the analysis plate 10 is located at an equivalent position, in the direction perpendicular to its extension plane, to that of a conventional analysis plane, despite the difference in thickness between the two.
    According to an example of an adapter 34, illustrated in Figs. 9A, 9B, 10 and 11 the adapter 34 comprises a plate 36 and a frame 38.
    The plate 36 has a planar shape, and its dimensions are equal to that of the analysis plate 10 in the plane of extension of the plate. The plate 36 has an upper face 40 intended to receive the bearing face 14 of the analysis plate 10, and a lower face 41.
    The frame 38 is in the form of a profile which extends in a plane parallel to the plane of extension of the analysis plate 10, along the periphery of the analysis plate 10. The frame 38 thus has a upper face 42 and a lower face 44. In the lower face 44, a clearance 45 is arranged which presents the exact contour of the analysis surface 10. The depth of the clearance 45, in the direction perpendicular to the plane of extension of the analysis surface 10, is preferably greater than the thickness of the analysis plate 10. In the example illustrated, this depth corresponds substantially to the sum of the thickness of the analysis plate 10 with the thickness of plateau 36, leque! can also be received, at least in part, in the clearance 45. The frame 38 delimits, in its upper face 42, an opening 46 whose dimensions in the extension plane are sufficient to reveal all of the zones analysis 16 of the analysis plate 10 through this opening 46 when the analysis plate 10 is engaged in the clearance 45 of the lower face 44 of the frame 38, the test face 12 upwards. On the other hand, the opening 46 has, in the plane of extension of the plate 10, dimensions smaller than that of the plate 10 so that the bottom of the clearance 45 of the frame 38 forms an abutment surface 48 against which comes lean on the periphery of the test face 12 of the analysis plate 10.
    According to an advantageous embodiment, the adapter 34 also includes a tightening mechanism which causes the tightening of the analysis plate 10 between the frame 38 and the plate 36. In the example illustrated, the tightening mechanism is a mechanism magnetic comprising a series of magnets 50. In the example illustrated, the magnets 50 are carried by the frame 38, so that the plate 36 is made at least partly of ferromagnetic material, for example ferromagnetic metal and / or comprises also corresponding magnets arranged with their reverse magnetic polarity. Of course, the reverse arrangement could be provided. Other clamping mechanisms could be envisaged, for example with clamps or with screws. However, the magnetic mechanism has the advantage of very easy implementation and provides a sufficient clamping force to hold the plate 10 without damaging it, in particular by avoiding excessive tightening and adapting to a variable range of paper thickness without modification of the adapter.
    Depending on the depth provided for the clearance 45, either the underside 44 of the plate 38, or the underside of the plate 36 is capable of coming to rest against a reception face of the analysis chamber. The depth of the clearance 45 of the frame 38 and the thickness of the plate 36 therefore determine, depending on whether one or the other rests against the reception face of the analysis chamber, the position of the test face 12 of the analysis plate 10 in the analysis chamber, in a direction perpendicular to the plane of extension of the plate 10. Also, the depth of the clearance 45 of the frame 38 and the thickness of the plate 36 are calculated so that the test face 12 of the analysis plate 10 is arranged, in a direction perpendicular to the plane of extension of the plate 10, at an altitude desired for the proper functioning of the apparatus.
    The use of an adapter 34 makes it possible to avoid any damage to the analysis plate 10 during its handling, in particular during its introduction into the mass spectrometry apparatus. I! It is thus thus possible to handle only the adapter 34, which can be made of plastic material and / or metal. This especially avoids the risk of folding the analysis plate 10 when it is thin, for example with a support 18 consisting only of one or more sheets of paper material 20, 20 ', without the presence of a blade additional support.
    In addition, when the dimensions of the adapter 34 are provided to position the test face 12 of the analysis plate 10 at the height, with respect to the reception face of the analysis chamber, identical to that from the test face of a conventional analysis plate, the same apparatus can be used either with a conventional analysis plate or with an analysis plate according to the invention without requiring registration of the mass peaks.
    The invention is not limited to the examples described and shown since various modifications can be made thereto without departing from its scope.
    权利要求:
    Claims (25)
    [1" id="c-fr-0001]
    1 - Analysis plate (10) comprising at least one analysis zone (16) intended to receive a sample to be analyzed by mass spectrometry according to the MALDI-TOF technique, of the type comprising at least one test face (12 ) on which is defined at least one analysis zone (16), of the type in which the plate comprises a flat support (18), characterized in that the support (18) comprises at least one sheet (20) of paper material comprising cellulosic fibers, and in that the analysis plate (10) comprises at least one layer (24) of metallic material.
    [2" id="c-fr-0002]
    2 - Analysis plate according to claim 1, characterized in that the layer (24) of metallic material is attached to the sheet of paper material (20) on the side of the test face (12).
    [3" id="c-fr-0003]
    3 - Analysis plate according to any one of the preceding claims, characterized in that the layer (24) of metallic material is attached to the sheet of paper material (20) by vacuum metallization of the sheet of paper material (20 ).
    [4" id="c-fr-0004]
    4 - Analysis plate according to any one of the preceding claims, characterized in that the layer (24) of metallic material is attached to the sheet of paper material (20) by transfer metallization.
    [5" id="c-fr-0005]
    5 - Analysis plate according to any one of the preceding claims, characterized in that the layer of metallic material (24) has a thickness of less than 0.5 microns.
    [6" id="c-fr-0006]
    6 - Analysis plate according to any one of the preceding claims, characterized in that the layer of metallic material (24) comprises aluminum.
    [7" id="c-fr-0007]
    7 - Analysis plate according to any one of the preceding claims, characterized in that the sheet of paper material (20) comprises, as fibers, exclusively cellulose fibers.
    [8" id="c-fr-0008]
    8 - Analysis plate according to any one of claims 1 to 6, characterized in that the sheet of paper material (20) comprises cellulose fibers and synthetic fibers, in particular synthetic polymer fibers.
    [9" id="c-fr-0009]
    9 - Analysis plate according to claim 8, characterized in that the sheet of paper material (20) comprises cellulosic fibers and synthetic fibers, with, by mass, more cellulosic fibers than synthetic fibers.
    [10" id="c-fr-0010]
    10 - Analysis plate according to any one of the preceding claims, characterized in that the paper material of the sheet of paper material (20) comprises at least one hydrophobic agent.
    [11" id="c-fr-0011]
    11 - Analysis plate according to any one of the preceding claims, characterized in that the sheet of paper material (20) has a grammage greater than or equal to 120 grams per square meter, preferably greater than or equal to 150 grams per meter square.
    [12" id="c-fr-0012]
    12 - Analysis plate according to any one of the preceding claims, characterized in that the sheet of paper material (20) has a grammage less than or equal to 400 grams per square meter, preferably less than or equal to 300 grams per meter square.
    [13" id="c-fr-0013]
    13 - Analysis plate according to any one of the preceding claims, characterized in that the support (18) consists exclusively of paper material.
    [14" id="c-fr-0014]
    14 - Analysis plate according to any one of claims 1 to 10, characterized in that the support (18) comprises at least one support blade (22) on which is attached the sheet of paper material (20).
    [15" id="c-fr-0015]
    15 - Analysis plate according to claim 14, characterized in that the support (18) comprises at least one support blade (22) of polymeric material on which is attached the sheet of paper material (20).
    [16" id="c-fr-0016]
    16 - Analysis plate according to any one of claims 14 or 15, characterized in that the support (18) comprises two blades of polymeric material (22) superimposed, and in that the sheet of paper material (20) is attached to one face of one of the two superimposed blades (22).
    [17" id="c-fr-0017]
    17 - Analysis plate according to claim 15, characterized in that the blade of polymer material (22) has a thickness in the range from 0.2 to 2 millimeters.
    [18" id="c-fr-0018]
    18 - Analysis plate according to any one of claims 14 to 17, characterized in that the sheet of paper material has a basis weight in the range from 60 grams per square meter to 200 grams per square meter.
    [19" id="c-fr-0019]
    19 - Analysis plate according to any one of claims 14 to 18, characterized in that the sheet of paper material (20) is glued to the support blade (22).
    [20" id="c-fr-0020]
    20 - Analysis plate according to any one of the preceding claims, characterized in that the sheet of paper material comprises at least one deformation obtained mechanically along the contour of at least one analysis zone (16), thus delimiting the 'at least one analysis zone (16).
    [21" id="c-fr-0021]
    21 - Analysis plate according to any one of the preceding claims, characterized in that at least one analysis zone (16) on the sheet of paper material (20) comprises a deformation obtained mechanically, over the entire extent of said analysis area (16).
    [22" id="c-fr-0022]
    22 - Analysis plate according to any one of the preceding claims, characterized in that the analysis plate (10) comprises a marking by an ink delimiting at least one analysis zone (16).
    [23" id="c-fr-0023]
    23 - Use of an analysis plate according to any one of claims 1 to 22 as a sample support in a method of analyzing the sample by mass spectrometry according to the MALDI-TOF technique.
    [24" id="c-fr-0024]
    24 - Use according to claim 23, characterized in that the analysis plate is used with an adapter (34) which holds the sheet of paper material (20) by its periphery.
    [25" id="c-fr-0025]
    25 - Use according to claim 24, characterized in that the adapter (34) comprises a plate (36), a frame (38) and a clamping mechanism (50) which causes the clamping of the analysis plate between the frame (38) and the plate (36), the frame (38) cooperating with the periphery of the analysis plate (10) and comprising an opening (46) revealing at least one analysis zone (16) of the analysis plate (10).
    1/10
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    FR3105024A1|2019-12-20|2021-06-25|Commissariat à l'Energie Atomique et aux Energies Alternatives|Pneumatically actuated paper-based substrate device|
    法律状态:
    2018-02-28| PLFP| Fee payment|Year of fee payment: 2 |
    2018-11-02| PLSC| Publication of the preliminary search report|Effective date: 20181102 |
    2020-03-18| PLFP| Fee payment|Year of fee payment: 4 |
    2021-03-11| PLFP| Fee payment|Year of fee payment: 5 |
    2022-02-24| PLFP| Fee payment|Year of fee payment: 6 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1753705A|FR3065652B1|2017-04-27|2017-04-27|MALDI-TOF ANALYSIS PLATE WITH PAPER SUPPORT AND ITS USE|
    FR1753705|2017-04-27|FR1753705A| FR3065652B1|2017-04-27|2017-04-27|MALDI-TOF ANALYSIS PLATE WITH PAPER SUPPORT AND ITS USE|
    US16/603,687| US20200114346A1|2017-04-27|2018-04-26|Maldi-tof analysis plate with paper support and use thereof|
    EP18723575.9A| EP3615218A1|2017-04-27|2018-04-26|Maldi-tof analysis plate with paper support and use thereof|
    CN201880027902.0A| CN110997146A|2017-04-27|2018-04-26|MALDI-TOF analysis plate with paper support and use thereof|
    PCT/FR2018/051056| WO2018197814A1|2017-04-27|2018-04-26|Maldi-tof analysis plate with paper support and use thereof|
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