Matrix film deposition system

Abstract

A system capable of depositing a matrix film containing a low amount of impurities (e.g. neutral particles) is provided. The system includes: a first plate electrode 120 having an attachment surface on which a sample plate P is to be attached; a second plate electrode 130 arranged so as to face the attachment surface; a nozzle 110 for spraying a liquid containing a matrix substance into the space between the two electrodes 120 and 130 by an electrospray method, the nozzle 110 arranged so that none of the electrodes 120 and 130 lies on the central axis A of a spray flow of the liquid; and an electric field creator 140 for creating, between the two electrodes 120 and 130, an electric field for forcing electrically charged droplets contained in the spray flow of the liquid containing the matrix substance to move toward the attachment surface.

Claims

1. A matrix film deposition system for depositing a film containing a matrix substance on a surface of a sample plate, the system comprising: a) a first plate electrode having an attachment surface on which the sample plate is to be attached; b) a second plate electrode arranged so as to face the attachment surface; c) an electrostatic spray nozzle for spraying a liquid containing a matrix substance into a space between the first plate electrode and the second plate electrode, the electrostatic spray nozzle being arranged so that neither the first plate electrode nor the second plate electrode lies on a central axis of a spray flow of the liquid; d) an electric field creator for creating, between the first plate electrode and the second plate electrode, an electric field for forcing electrically charged droplets of the liquid containing the matrix substance contained in the spray flow to move toward the attachment surface, by applying DC voltage between the first plate electrode and the second plate electrode; e) an electrode driver for arranging the first plate electrode and the second plate electrode so that the distance between these two electrodes decreases or increases with an increase in the distance from the electrostatic spay nozzle, wherein the nozzle includes: f) a capillary having a tubular shape for allowing the liquid containing the matrix substance to flow from a proximal end to a droplet-spraying hole formed at a distal end, and the system further includes: g) a facing electrode located at a position facing a tip of the nozzle; and h) a voltage supplier for applying DC voltage between the capillary and the facing electrode.

2. The matrix film deposition system according to claim 1, further comprising: i) a droplet size regulator for regulating a size of the droplets of the liquid containing the matrix substance to be adhered to the sample plate, by changing a potential difference between the first plate electrode and the second plate electrode.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a schematic configuration diagram of a matrix film deposition system according to the first embodiment of the present invention.

(2) FIG. 2 is a diagram showing a modified example of the matrix film deposition system according to the first embodiment.

(3) FIG. 3 is a schematic configuration diagram of a matrix film deposition system according to the second embodiment of the present invention.

(4) FIG. 4 is a diagram showing a modified example of the matrix film deposition system according to the second embodiment.

(5) FIG. 5 is a diagram showing another example of the configuration of the matrix film deposition system according to the present invention.

(6) FIG. 6 is a diagram showing still another example of the configuration of the matrix film deposition system according to the present invention.

(7) FIG. 7 is a diagram showing a modified example of the system of FIG. 5.

(8) FIG. 8 is a diagram showing a modified example of the system of FIG. 6.

(9) FIG. 9 is a model diagram for explaining a conventional method for depositing a matrix film on a sample plate by the ESD method.

DESCRIPTION OF EMBODIMENTS

First Embodiment

(10) FIG. 1 is a configuration diagram showing the main section of a matrix film deposition system according to one embodiment of the present invention. This matrix film deposition system includes a nozzle 110 for spraying a liquid containing a matrix substance (matrix liquid), a first plate electrode 120 on which a sample plate P is to be attached, and a second plate electrode 130 arranged so as to face the first plate electrode 120.

(11) The area surrounded by the circle in the right area of FIG. 1 is an enlarged view of a longitudinal section of the tip portion of the nozzle 110. As shown, the nozzle 110 is a double-tube structure having a capillary 111 and a nebulizer gas tube 112 which is coaxial with the capillary 111 and which is arranged so as to serve as the external cylinder surrounding the capillary 111. The capillary 111 is supplied with a matrix liquid from a matrix liquid supplier 113. Meanwhile, inert gas (normally, nitrogen gas) which acts as a nebulizer gas is supplied from a nebulizer gas supplier 114 into the space between the outer circumferential surface of the capillary 111 and the inner circumferential surface of the nebulizer gas tube 112. A high DC voltage of a few kV to several tens of kV is applied from a spray voltage supplier 115 to either the capillary 111 itself or a metal cylinder (not shown) surrounding the capillary 111.

(12) The first and second plate electrodes 120 and 130 are flat metal plates arranged parallel to each other with a gap of approximately 15 to 30 mm. A DC voltage of approximately ±1 kV to ±3 kV is applied between the two electrodes by a deposition voltage supplier 140 (which corresponds to the electric field creator in the present invention). A sample plate P, which is normally made of an electrically conductive material, is attached to the surface of the first plate electrode 120 facing the second plate electrode 130 (plate attachment surface). For example, the sample plate P may be a plate shaped like a slide glass which approximately measures 26 mm×76 mm or a MALDI plate with the one-side length of approximately 80 mm to 130 mm. The plate attachment surface is provided with a claw-shaped holding member made of an insulator or similar material. With this holding member, the sample plate P with a sample (e.g. a slice of biological tissue) previously put on its surface is fixed on the first plate electrode 120.

(13) The spray voltage supplier 115 and the deposition voltage supplier 140 operate under the command of a controller 150, which consists of a computer and other devices. An input unit 151 composed of buttons, dials, keyboards or other elements for allowing users to enter commands is connected to the controller 150.

(14) In the matrix film deposition system of the present embodiment, the nozzle 110 is positioned so that its tip is directed downward. The first and second plate electrodes 120 and 130 are located below the nozzle 110 and arranged parallel to each other as well as facing each other across the central axis A of the spray flow produced by the nozzle 110.

(15) In the film deposition process by the matrix film deposition system of the present embodiment, when the matrix liquid supplied from the matrix liquid supplier 113 reaches the tip of the capillary 111, the liquid becomes either positively or negatively charged (in the present example, positively) due to the influence of the electric field created by the voltage applied from the spray voltage supplier 115. The matrix liquid thus electrically charged are broken into droplets and ejected with the aid of the nebulizer gas jetted from the tip of the nebulizer gas tube 112. The ejected droplets are split into even smaller sizes by the Coulomb repulsive force of the electric charges. Thus, the matrix liquid is sprayed from the tip of the nozzle 110 downward. This spray flow, spreading in a roughly conical form, enters the space between the first and second plate electrodes 120 and 130. Meanwhile, DC voltage is applied between the first and second plate electrodes 120 and 130 by the deposition voltage supplier 140, with the first plate electrode 120 acting as the cathode. Therefore, the positively charged droplets of the matrix liquid which have entered the space are attracted toward the first plate electrode 120 due to the effect of the electric field created by this voltage application, and deviate from the spray flow, to eventually adhere to the surface of the sample plate P. By contrast, neutral particles without any electric charges are not attracted toward the first plate electrode 120; they are carried by the spray flow, travel downward and directly pass through the space. Therefore, the neutral particles will not adhere to the sample plate P.

(16) Thus, in the matrix film deposition system according to the present embodiment, only the electrically charged droplets of the matrix liquid are deposited on the sample plate P, so that a matrix film containing a lower amount of impurities than conventional films will be formed. Furthermore, according to a command entered by the user through the input unit 151, the controller 150 can change the magnitude of the voltage applied from the deposition voltage supplier 140 so as to limit the maximum size of the droplets of the matrix liquid to be adhered to the sample plate P (in this case, the controller 150 corresponds to the droplet size regulator in the present invention). More specifically, decreasing the magnitude of the voltage applied from the deposition voltage supplier 140 results in a smaller maximum size of the droplets of the matrix liquid to be adhered to the sample plate P.

(17) In the previously described example, the electric field created by voltage application from the deposition voltage supplier 140 has an approximately uniform strength along the central axis A of the spray flow within the space between the first and second plate electrodes 120 and 130. However, the present invention is not limited to this form. For example, the electric field may be created in such a manner that its strength within that space changes with the distance from the nozzle 110. One example of such a configuration is shown in FIG. 2.

(18) In the present example, a plurality of electrodes 121a-d and 131a-d are attached to the outer surfaces of the first and second plate electrodes 120 and 130 (i.e. on the surfaces facing away from the spray flow), respectively, in the direction parallel to the central axis A of the spray flow. Furthermore, deposition voltage suppliers 141a-d are individually provided between each pair of the electrodes located at the corresponding positions on the plate electrodes 120 and 130. The controller 150 regulates the magnitudes of the voltages applied to the electrodes, for example, so as to make the potential difference between the first and second plate electrodes 120 and 130 smaller on the side closer to the nozzle 110 and larger on the side farther from the nozzle 110.

(19) More specifically, in FIG. 2, the deposition voltage supplier 141a is provided between the electrodes 121a and 131a which are the closest pair to the nozzle, the deposition voltage supplier 141b is provided between the second closest pair of the electrodes 121b and 131b, the deposition voltage supplier 141c is provided between the third closest pair of the electrodes 121c and 131c, and the deposition voltage supplier 141d is provided between the electrodes 121d and 131d which are the farthest pair from the nozzle. Letting Va, Vb, Vc and Vd respectively denote the magnitudes of the voltages applied from these deposition voltage suppliers 141a, 141b, 141c and 141d, the voltage values are regulated so that Va<Vb<Vc<Vd. According to this configuration, the force acting on the electrically charged droplets ejected from the nozzle 110 to move them toward the first plate electrode 120 within the space between the first and second plate electrodes 120 and 130 is weak on the side close to the nozzle 110 and becomes stronger with an increase in the distance from the nozzle 110. This has the effect of preventing the situation in which a greater amount of matrix liquid adheres to a region close to the nozzle 110 and causes the matrix film formed on the sample plate PI to be uneven in thickness.

(20) Alternatively, in the configuration shown in FIG. 2, the magnitude of the voltage applied between each pair of the electrodes may be controlled in the opposite way (i.e. Va>Vb>Vc>Vd) so that the potential difference between the first and second plate electrodes 120 and 130 will be larger on the side closer to the nozzle 110 and smaller on the side farther from the nozzle 110. For example, such a configuration is useful if the velocity of the spray flow from the nozzle 110 is comparatively high and the electrically charged droplets cannot easily adhere to the region close to the nozzle 110 on the sample plate P. Other voltage configurations are also possible; for example, the voltages applied along the central axis A may be controlled so that the thereby created potential difference becomes relatively larger or smaller in a region near a predetermined region (e.g. central region) of the sample plate P than in the other regions. In these examples, the electrodes 121a-d and 131a-d, the deposition voltage suppliers 141a-d and the controller 150 correspond to the field strength difference creator in the present invention.

(21) In the configuration in which the field strength along the central axis A of the spray flow is varied according to the distance from the nozzle 110 in the previously described way, it is preferable to provide a film thickness monitor 160 for measuring the thickness of the matrix film at a plurality of points on the sample plate P in real time during the film deposition process, and to control the magnitude of each voltage applied from the deposition voltage suppliers 141a-d by a feedback process based on the film thicknesses measured at the plurality of points so that the film will have the same thickness at all the points. For example, a laser displacement sensor (displacement gauge) capable of a contactless measurement of the thickness of an object may be used as the film thickness monitor 160. In this case, laser light is cast from the laser displacement sensor onto the sample plate P and the thickness of the matrix film is determined based on the difference in the optical path length between a laser light which returns after being reflected by the surface of the matrix film and a laser light which returns after penetrating through the matrix film and being reflected by the surface of the sample plate P.

(22) In the previously described examples, the tip of the nozzle 110 is directed downward, and the first and second plate electrodes 120 and 130 are located below the nozzle 110. The direction of the nozzle 110 as well as the position of the two plate electrodes 120 and 130 relative to the nozzle 110 in the present embodiment are not limited to those examples; the minimal requirement is that the first and second plate electrodes 120 and 130 face each other across the spray flow produced by the nozzle 110. For example, it is also possible to direct the tip of the nozzle 110 upward and place the first and second plate electrodes 120 and 130 above the nozzle 110, or to direct the tip of the nozzle 110 laterally (e.g. to the right) and place the first and second plate electrodes 120 and 130 to the right of the nozzle 110.

Second Embodiment

(23) A matrix film deposition system according to the second embodiment of the present invention is hereinafter described. FIG. 3 is a configuration diagram showing the main section of the matrix film deposition system according to the present embodiment. Each component which has an identical or corresponding counterpart in the already described matrix film deposition systems of the first embodiment (FIG. 1) will be denoted by a numeral whose last two digits are common to the previously described component, and its description will be appropriately omitted.

(24) The matrix film deposition system according to the present embodiment uses the so-called “nano-electrospray” process, a kind of electrospray method, to spray the matrix liquid. In the present matrix film deposition system, the nozzle 210 is not provided with the nebulizer gas tube; alternatively, a facing electrode 270 is provided at a position facing the nozzle 210 across the space between the first and second plate electrodes 220 and 230. Furthermore, the matrix film deposition system according to the present embodiment is provided with evacuating means (not shown) including a vacuum pump and other elements below the facing electrode 270, since the spray flow from the nozzle 210 would otherwise stay within that space due to the absence of the stream of the nebulizer gas. The capillary 211 for spraying the matrix liquid is either a thin glass tube coated with a thin metallic layer or a thin metallic tube, with its tip tapered. Between the facing electrode 270 and the capillary 211, high DC voltage is applied from the spray voltage supplier 215.

(25) In the film deposition process by the matrix film deposition system of the present embodiment, when the matrix liquid supplied from the matrix liquid supplier 213 reaches the tip of the capillary 211, the liquid becomes either positively or negatively charged (in the present example, positively) due to the influence of the electric field created by the voltage applied from the spray voltage supplier 215. This liquid, which contains a large amount of similarly charged ions, is stretched into a thin, conical shape (called the “Taylor cone”) due to the effect of the electric field created in the space between the capillary 211 and the facing electrode 270 by the voltage applied from the spray voltage supplier 215. The charge density increases with the progress of the formation of the Taylor cone. When the density reaches the critical point, a Coulomb explosion occurs, whereby the electrically charged drop of the matrix liquid is broken into droplets and ejected from the tip of the capillary 211. While being progressively split into smaller sizes by the Coulomb repulsive force of the electric charges, those droplets are attracted by the facing electrode 270 and move downward. Thus, the matrix liquid is sprayed from the tip of the nozzle 210 downward. This spray flow, spreading in a roughly conical form, enters the space between the first and second plate electrodes 220 and 230. Meanwhile, DC voltage is applied between the first and second plate electrodes 220 and 230 by the deposition voltage supplier 240, with the first plate electrode 220 acting as the cathode. Therefore, the positively charged droplets of the matrix liquid which have entered the space are attracted toward the first plate electrode 220 due to the effect of the electric field created by the aforementioned voltage, and deviate from the spray flow, to eventually adhere to the surface of the sample plate P. By contrast, neutral particles (the drops without any electric charges) ejected from the tip of the capillary 211 along with the ejection of the drops of the matrix liquid are not attracted toward the first plate electrode 220; due to the gravity force combined with the operation of the evacuating means, those particles travel downward and directly pass through the space. Therefore, the neutral particles will not adhere to the sample plate P.

(26) Thus, in the matrix film deposition system according to the present embodiment, only the electrically charged droplets of the matrix liquid are deposited on the sample plate P, so that a matrix film containing a lower amount of impurities than conventional films will be formed. Furthermore, according to a command entered by the user through the input unit 251, the controller 250 can change the magnitude of the voltage applied from the deposition voltage supplier 240 so as to limit the maximum size of the droplets of the matrix liquid to be adhered to the sample plate P (in this case, the controller 250 corresponds to the droplet size regulator in the present invention). More specifically, decreasing the magnitude of the voltage applied from the deposition voltage supplier 240 results in a smaller maximum size of the droplets of the matrix liquid to be adhered to the sample plate P.

(27) Similarly to the case of the first embodiment, the system according to the present embodiment may be configured so that the strength of the electric field created by voltage application from the deposition voltage supplier 240 changes with the distance from the nozzle 210 along the central axis A of the spray flow. One example of such a configuration is shown in FIG. 4.

(28) In this example, once again, a plurality of electrodes 221a-d and 231a-d are attached to the outer surfaces of the first and second plate electrodes 220 and 230 (i.e. on the surfaces facing away from the spray flow), respectively, in the direction parallel to the central axis A of the spray flow. Furthermore, deposition voltage suppliers 241a-d are individually provided between each pair of the electrodes located at the corresponding positions on the plate electrodes 220 and 230. The controller 250 regulates the magnitudes of the voltages applied to these electrodes so that the potential difference between the first and second plate electrodes 220 and 230 will be smaller in a region closer to the nozzle 210 (or a region farther from the nozzle 210 or an intermediate region) and larger in the other regions. Such a voltage configuration prevents the situation in which a greater amount of matrix liquid adheres to a specific region on the sample plate P and causes the matrix film to be uneven in thickness. In the present example, the electrodes 221a-d and 231a-d, the deposition voltage suppliers 241a-d and the controller 250 correspond to the field strength difference creator in the present invention.

(29) Additionally, it is preferable to provide a film thickness monitor 260 (e.g. laser displacement sensor) for measuring the thickness of the matrix film on the sample plate P in real time during the film deposition process and to control the magnitudes of each voltage applied from the deposition voltage suppliers 241a-d by a feedback process based on the film thicknesses measured at a plurality of points on the sample plate P by the film thickness monitor 260 so that the film will have the same thickness at all the points.

(30) It should be noted that the present invention can be carried out in various forms and is not limited to the embodiments described thus far using specific examples. The previous embodiments can be appropriately changed within the spirit of the present invention. For example, the arrangement of the first and second plate electrodes can be changed: In the first and second embodiments, the two plate electrodes are arranged so that their respective inner surfaces (i.e. the surfaces facing the spray flow produced by the nozzle) are parallel to the central axis A of the spray flow. FIGS. 5 and 6 show different examples of the arrangement, in which one or both of the inner surfaces of the first and second electrodes 320 and 330 are inclined from the central axis A (each component which has an identical or corresponding counterpart already shown in FIGS. 1-4 is denoted by a numeral whose last two digits are common to the previously described component, and its description will be appropriately omitted).

(31) In both FIGS. 5 and 6, the first and second plate electrodes 320 and 330 are arranged so that the distance between these two electrodes decreases with an increase in the distance from the nozzle 310. FIGS. 7 and 8 each show the opposite configuration, in which the distance between the two electrodes increases with an increase in the distance from the nozzle 310. Any of these configurations having the first plate electrode 320 and/or the second plate electrode 330 inclined from the central axis A of the spray flow is advantageous in that the potential gradient formed between the first and second plate electrodes 320 and 330 by the voltage applied from the deposition voltage supplier 340 can be varied with the distance from the nozzle 310 without providing a number of electrodes for each of the two plate electrodes 320 and 330 as in the previous embodiments. In the present examples, the first plate electrode 320 and/or the second plate electrode 330 inclined from the central axis A of the spray flow corresponds to the field strength difference creator in the present invention.

(32) In the present configurations, it is preferable to provide a plate electrode driver 380 having a motor and other elements for changing the angle of one or both of the plate electrodes 320 and 330 as well as a film thickness monitor 360 (e.g. laser displacement sensor) for measuring the thickness of the matrix film at a plurality of points on the sample plate P in real time during the film deposition process, and to control the operation of the plate electrode driver 380 by a feedback process based on the film thicknesses measured by the film thickness monitor 360 during the deposition process so that the film will have the same thickness at all the points. In this case, the first plate electrode 320 and/or the second plate electrode 330 inclined from the central axis A of the spray flow, the plate electrode driver 380 and the controller 350 correspond to the field strength difference creator in the present invention.

REFERENCE SIGNS LIST

(33) 110, 210, 310 . . . Nozzle 111, 211 . . . Capillary 112 . . . Nebulizer Gas Tube 113, 213, 313 . . . Matrix Liquid Supplier 114, 314 . . . Nebulizer Gas Supplier 115, 215, 315 . . . Spray Voltage Supplier 120, 220, 330 . . . First Plate Electrode 130, 230, 330 . . . Second Plate Electrode 121a-d, 131a-d, 221a-d, 231a-d . . . Electrode 140, 141a-d, 240, 241a-d, 340 . . . Deposition Voltage Supplier 150, 250, 350 . . . Controller 151, 251, 351 . . . Input Unit 160, 260, 360 . . . Film Thickness Monitor 270 . . . Facing Electrode 380 . . . Plate Electrode Driver A . . . Central Axis of Spray Flow P . . . Sample Plate