JP2004003950A - Method for manufacturing ink jet head and probe array - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ink jet head suitable for jetting a biosample. <P>SOLUTION: The ink jet head (10) is provided with a constitution, in which a pressure chamber substrate (11) made of silicon; an electrode substrate (12) made of glass; and a channel substrate (13) made of glass are laminated. The lower end part of the electrode substrate (12) is anodically bonded so as to be opposed to the pressure chamber substrate (11), with a very small gap in-between. A solution containing the biosample is filled in a pressure chamber (20) from a common cavity (18) via an orifice (19). When a pulse voltage is impressed on an electrode (15), a diaphragm (16) is elastically deformed by electrostatic force, to increase or reduce the pressure inside the pressure chamber (20) and jet a droplet (30) from a nozzle (22) toward a glass slide (40) via an orifice (21). <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a technique for manufacturing a probe array, and more particularly to an inkjet head suitable for spotting a probe on a solid phase.
[0002]
[Prior art]
In recent years, with the progress of the genome project, the genetic structure of each organism has been clarified one after another. In order to link this result to the analysis of life phenomena, decoding of DNA base sequences and functional analysis of genetic information are issues. It has become. A DNA microarray is used as a system for simultaneously monitoring the expression levels of all genes in a cell. The array performs a reverse transcription reaction from mRNA and total RNA extracted from cells and tissues, prepares probe DNA, and spots it on a substrate such as a slide glass at high density. The target DNA having a base sequence complementary to the probe DNA is hybridized and the gene expression level is evaluated by observing the fluorescence pattern. The size of the array is usually 1cm ² -10cm ² Therefore, it is necessary to spot thousands to tens of thousands of types of probe DNA at a high density in this region. As a method for this, a method of synthesizing the probe DNA on a solid phase and a method of solidifying the probe DNA synthesized in advance are used. There is a technique of fixing on the phase. The latter method is widely used from the viewpoint of, for example, ease of probe purification, and conventionally, probe DNA has been fixed using a contact pin or an ink jet head. The technique of spotting probe DNA on a solid phase using an ink jet head is described in detail in Patent Document 1.
[Patent Document 1] JP-A-11-187900
[Patent Document 2] Japanese Patent Publication No. 2000-500946
[0003]
[Problems to be solved by the invention]
However, in the method using the contact pin, the supply amount of the droplet supplied onto the solid phase is unstable, the spot shape on the solid phase becomes irregular, and the contact pin is not sufficiently cleaned. Has the disadvantage that cross-contamination can occur. In addition, the operation requires a long time, and is not efficient.
[0004]
On the other hand, according to the method using an inkjet head, the probe can be quickly and densely fixed on the solid phase, and a stable spot shape can be formed. Since the nozzle plate or diaphragm is attached using an epoxy resin-based or acrylic resin-based adhesive, it absorbs into the sample solution filled in the orifice or cavity when absorbing moisture. As a result of elution of the contained curing agent and the like, there is a possibility that various biological samples such as target DNAs and proteins contained in the sample solution may be damaged.
[0005]
Further, as disclosed in Patent Literature 1, a heating resistor is installed in a thin tube communicating with a nozzle, and electric energy is applied to the heating resistor to instantaneously foam a liquid, and a droplet is discharged from the nozzle. In the bubble jet (registered trademark) method of discharging DNA, instantaneous high temperature may cause denaturation of DNA or protein.
Further, when handling a biological sample, the biological sample is easily contaminated by bacteria and the like, and is liable to be decomposed and deteriorated. Usually, when such a biological sample is filled in the head, sterilization is performed in advance by ultraviolet irradiation or the like. Furthermore, some biological samples are easily decomposed and deteriorated by light, and it may be preferable to shield the head from light after sterilization by ultraviolet irradiation. However, attaching a shielding film or the like to the head after sterilization requires many steps, and the yield is poor.
In addition, since the inkjet head is a consumable item, a large amount of waste is generated each time it is replaced.However, materials that require special treatment or materials that need to be separated at the time of disposal may be integrally formed. Alternatively, a large number of steps may be required for recycling.
[0006]
Therefore, an object of the present invention is to provide an ink jet head (droplet ejection head) suitably used for a biological sample.
More specifically, an object of the present invention is to propose a method for manufacturing an ink jet head and a probe array that can easily and quickly fix a probe on a solid phase without damaging a biological sample.
Another object of the present invention is to provide an ink jet head that can easily shield the head during use.
Still another object of the present invention is to provide an ink jet that can be easily disassembled and that can be easily recycled or disposed.
[0007]
[Means for Solving the Problems]
In order to solve the above problems, an ink jet head of the present invention is an ink jet head for discharging a solution containing a biological sample onto a solid phase, comprising: a glass electrode substrate having electrodes on its surface; The pressure in the pressurized chamber is adjusted by the displacement of the vibration plate which is opposed to the substrate with a small gap and is elastically deformed by an electrostatic force corresponding to the potential difference with the electrode, and is filled in the pressurized chamber. A pressure chamber substrate made of silicon for discharging the solution from the nozzle hole.
[0008]
Both the glass substrate constituting the electrode substrate and the silicon substrate constituting the pressurized chamber substrate have a high affinity with the biological sample such as nucleic acid and protein, and have a so-called bubble jet (registered trademark) method (thermal type). Since it is an electrostatic drive system that does not generate heat as in the case of an ink jet system, stable ejection onto a solid phase surface can be achieved without damaging a biological sample.
Note that, in this specification, an inkjet head refers to a droplet discharge head that discharges droplets by an inkjet method. Hereinafter, the inkjet head is also referred to as a droplet discharge head.
[0009]
Preferably, the electrode substrate and the pressure chamber substrate are anodic bonded.
[0010]
Since the electrode substrate and the pressure chamber substrate can be joined without using an adhesive or the like, the biological sample is not damaged.
[0011]
Preferably, the inner wall surface of the pressure chamber is hydrophilically treated with a silicon oxide film.
[0012]
Accordingly, the pressurizing chamber has excellent affinity for an aqueous solution containing a biological sample such as a nucleic acid or a protein, so that a stable biological sample can be discharged.
[0013]
Preferably, a glass flow path substrate having a common cavity for storing the solution to be supplied to each of the pressurizing chambers and an orifice communicating from the cavity to the pressurizing chamber is provided.
[0014]
By making the flow path substrate made of glass, it is possible to ensure the affinity of the common cavity or orifice directly in contact with the biological sample with the biological sample.
[0015]
Preferably, the flow path substrate and the pressure chamber substrate are anodic bonded.
[0016]
Since the flow path substrate and the pressure chamber substrate can be joined without using an adhesive or the like, the biological sample is not damaged.
[0017]
Preferably, the electrode substrate and the flow path substrate are made of a borosilicate glass substrate.
[0018]
The borosilicate glass substrate contains a large amount of alkali ions and is not only suitable for anodic bonding, but also has a thermal expansion coefficient substantially equal to that of the silicon substrate, so that reliable bonding with less distortion at the bonding surface of the substrate can be obtained.
[0019]
Preferably, the pressurizing chamber substrate and the flow path substrate are at least one of a pressurizing chamber shape, a common cavity shape, a nozzle diameter, and an orifice diameter, and a mask designed in advance so as to be suitable for the physical properties of the biological sample. It is manufactured through a lithography process using.
[0020]
By employing the lithography process, the dimensions of the pressurizing chamber, such as the shape and nozzle diameter, can be easily changed by changing the mask.
The droplet discharge head according to the present invention is a droplet discharge head for discharging a solution containing a biological sample onto a solid phase, wherein a first substrate having an electrode on a surface thereof and the first substrate having one surface side are formed of the first substrate. The pressure in the pressurized chamber is adjusted by the displacement of the vibration plate which is arranged via a minute gap and is elastically deformed by an electrostatic force corresponding to the potential difference with the electrode, and the pressure in the pressurized chamber is filled. A second substrate having a pressurized chamber for discharging a solution from a nozzle hole; and a third substrate bonded to the other surface of the second substrate, wherein the first to third substrates are provided. At least one of the substrates is made of an ultraviolet-transparent material, or all of the first to third substrates are made of a heat- and moisture-resistant material, so that sterilization by ultraviolet or steam heat treatment is possible.
Since at least one of the first to third substrates is made of an ultraviolet-transparent material, or all of the first to third substrates are made of a heat- and moisture-resistant material, the biological sample is placed in the head. The head can be subjected to ultraviolet sterilization using a high-pressure mercury lamp for sterilization or steam heat sterilization using an autoclave or the like, which is required before introduction or disposal. In addition, the steam heating sterilization by an autoclave is performed by, for example, treating with high-temperature and high-pressure steam of 121 ° C. for 20 minutes. In the case of a system using a piezoelectric element such as PZT, the piezoelectric element may be damaged by steam heating sterilization or the like. Productivity can be improved.
Examples of the above-mentioned ultraviolet transmitting material or heat and moisture resistant material include a silicon-based substrate such as silicon or glass (eg, borosilicate glass and quartz glass), and a resin substrate such as epoxy resin, acrylic resin, or Teflon (registered trademark). Such a material is used.
It is preferable that the ultraviolet ray transmitting material or the heat and moisture resistant material is a silicon-based substrate.
As described above, since the material of the substrate is unified to the silicon-based substrate, recycling is facilitated, and it is possible to provide environmentally friendly products.
Preferably, the silicon-based substrate is a quartz substrate or a glass substrate. By using a quartz substrate or a glass substrate as the material of the substrate, it is possible to easily recycle the raw material of the glass only by melting. Further, if the substrate is made of quartz or glass, it has excellent affinity with a biological sample.
Preferably, the silicon-based substrate is a silicon substrate. Since all the substrates are silicon substrates, it can be easily recycled to additives of metal materials such as steel and aluminum. Further, when the substrate is made of silicon, the substrate has excellent durability and excellent affinity with a biological sample.
Note that each silicon-based substrate is preferably bonded by anodic bonding or dilute hydrofluoric acid. When the anodic bonding or the bonding with diluted hydrofluoric acid is performed in this manner, the bonding can be performed without using an adhesive or the like, so that the biological sample is not damaged. Is preferable because it does not contain any extra impurities.
Preferably, the electrode is formed of any one of ITO, gold, copper and aluminum. If a conductive material that is not specified as a specially controlled industrial waste such as ITO, gold, or copper is used for the electrode, no special treatment is required at the time of disposal, so that the cost at the time of disposal can be reduced.
In a droplet discharge head in which a plurality of substrates are stacked, at least one substrate is formed using a shape memory material, and by applying a predetermined temperature, the shape memory material is deformed into a memory shape. To facilitate separation from other substrates. Since the shape memory material is used, the substrate can be easily separated. In addition, separation and disposal can be facilitated, and furthermore, ultraviolet irradiation sterilization processing and heat sterilization processing at the time of disposal can be more reliably performed.
A droplet discharge head according to still another aspect of the present invention is a droplet discharge head in which a plurality of substrates are stacked, and a thermal expansion coefficient or a thermal contraction rate of at least one set of bonded substrates is different from each other. The bonding is released by applying a predetermined temperature.
Since different materials having different coefficients of thermal expansion or thermal contraction are used for the adjacent substrates, for example, by rapidly cooling the substrate with liquid nitrogen and giving a sudden temperature change, by applying a predetermined temperature, Adjacent substrates can be easily separated. In addition, since the substrate can be easily separated, the sterilization treatment by ultraviolet irradiation and the heat sterilization treatment at the time of disposal can be made more reliable, and the disposal treatment such as pulverization treatment can be facilitated.
The plurality of substrates are arranged on a first substrate having an electrode on a surface thereof, and one surface of the plurality of substrates is arranged via a minute gap with respect to the first substrate, and is elastically deformed by electrostatic force corresponding to a potential difference between the first substrate and the first substrate. A second substrate having a pressurized chamber for discharging the solution filled in the pressurized chamber from the nozzle hole by adjusting the pressure in the pressurized chamber by the displacement of the plate; Preferably, the third substrate is bonded to the surface side.
Since the droplet discharge head is of an electrostatic drive type, stable discharge onto the solid phase surface is possible without damaging the biological sample.
A droplet discharge head according to still another aspect of the present invention is a droplet discharge head that discharges droplets in response to an applied signal, using a photosensitive material or a photochromic material on the outer periphery of the droplet discharge head, At least a part thereof can be shielded from light.
By using a photosensitive material or a photochromic material on the outer periphery, light can be shielded, so that the sample can be suitably used even when a sample which is easily affected by light is used.
As the photochromic material, for example, a photochromic glass that is transparent at the time of fading and darkens (colors or changes color) by irradiation with ultraviolet light or visible light can be used. By using photochromic glass, light can be shielded, and since it is made of glass, it has excellent affinity for aqueous solutions containing biological samples such as nucleic acids and proteins.
As the photochromic glass, a material containing a photosensitive material such as silver halide may be used, or a material containing no photosensitive material that causes coloring due to generation of light-induced defects (CdO-based, ZnO-based, CaO-Al ₂ O ₃ (System glass). More preferably, the photochromic material is a photochromic glass to which silver halide is added, and by adjusting the composition of the photochromic glass and the particle size of the silver halide, the photochromic glass is formed using the photochromic glass. The fading time of the outer wall can be adjusted.
By adjusting the composition of the photochromic glass and the particle size of the silver halide, the bleaching time of the outer wall can be adjusted, so that the shading time of the head can be adjusted to a desired time, and a biological sample or the like can be adjusted. It is possible to more reliably suppress the influence of light on the light.
Preferably, the photosensitive material is a photosensitive glass to which a photosensitive metal, a photosensitizer, and a thermal reducing agent are added, and the outer wall is irreversibly darkened.
This makes it possible, for example, to sterilize the surface of the head made of photosensitive glass to darken the color by performing a sterilization process using, for example, ultraviolet light. Therefore, the sample in the head can be more reliably protected from the influence of light with a simple process.
A first substrate having an electrode on a surface thereof, a vibrating plate arranged on one surface thereof with a minute gap from the first substrate, and elastically deformed by electrostatic force corresponding to a potential difference between the electrode and the first substrate; And a second substrate having a pressurized chamber for discharging the solution filled in the pressurized chamber from a nozzle hole, and the other surface of the second substrate And a third substrate bonded to the side, and is preferably driven by electrostatic force.
Since the droplet discharge head is of an electrostatic drive type, stable discharge onto the solid phase surface can be performed without damaging the biological sample.
[0021]
In the method for producing a probe array of the present invention, a solution containing a probe that specifically binds to a target molecule is discharged onto a solid phase using the inkjet head (droplet discharge head) of the present invention, and the solution is discharged onto the surface of the solid phase. Fix the probe.
[0022]
By using the ink jet head (droplet ejection head) of the present invention, it is possible to form a droplet spot at a predetermined position on the solid phase surface accurately and efficiently without damaging a biological sample. .
[0023]
Preferably, a different probe is discharged for each nozzle.
[0024]
As a result, a probe array containing various biological samples can be manufactured, which is convenient for manufacturing a DNA microarray for performing a large amount of gene analysis at once.
[0025]
Preferably, the number of ejections is adjusted according to the physical properties of the solution containing the probe, and the weight of the droplet spot formed on the surface of the solid phase is made substantially uniform.
[0026]
Since physical properties such as viscosity, surface tension, and contact angle of a solution containing nucleic acids and proteins differ significantly depending on the type of protein, etc. It is effective to increase or decrease the number of ejections in consideration of characteristics.
[0027]
Preferably, the driving voltage for each nozzle is adjusted according to the physical properties of the solution containing the probe, and the weight of the droplet spot formed on the solid phase surface is made substantially uniform.
[0028]
Since physical properties such as viscosity, surface tension, and contact angle of a solution containing nucleic acids and proteins differ significantly depending on the type of protein, etc., these properties must be used to equalize the weight of droplet spots formed on a solid phase. It is effective to adjust the drive voltage in consideration of characteristics
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present embodiment will be described with reference to the drawings.
[0029]
[First Embodiment]
FIG. 1 is a sectional view of the inkjet head according to the first embodiment of the present invention. The ink jet head 10 has a three-layer structure in which a pressure chamber substrate 11 made of silicon is laminated between an electrode substrate 12 and a flow path substrate 13 so as to sandwich both sides thereof in the thickness direction. At the center and lower end of the pressurizing chamber substrate 11, a pressurizing chamber 20 having a boat-shaped cross section, which is anisotropically etched with a potassium hydroxide solution or the like, is etched in a surface facing the flow path substrate 13. ing. Assuming that the plane orientation of the silicon substrate is (110), the pressurizing chamber 20 has a boat shape composed of an inclined surface that forms an angle of about 35 degrees with a plane perpendicular to the silicon substrate. This pressurizing chamber 20 can also be called a pressure chamber, a discharge chamber, or simply a cavity. Further, a silicon oxide film 14 having a thickness of about 1 μm is formed on the front and back surfaces of the substrate by a thermal oxidation method.
[0030]
In a preferred embodiment of the present invention, the pressurized chamber 20 filled with various biological samples such as probe DNA and protein is made of a material having an excellent affinity for the biological material, that is, a material harmless to the biological material. When the pressure chamber substrate 11 is formed of a silicon substrate, it is preferable to treat the surface of the pressure chamber substrate 11 with a silicon oxide film. The silicon oxide film is rich in hydrophilicity and is suitable for discharging an aqueous solution containing nucleic acids and proteins, and there is no possibility of damaging a biological sample.
[0031]
Such a silicon substrate may be any of a single crystal silicon substrate, a polycrystalline silicon substrate, and an SOI substrate. Further, the method of forming a silicon oxide film is not limited to the thermal oxidation method, but may be a sputtering method, a vapor deposition method, or the like. Various film-forming techniques such as an ion plating method, an ion plating method, a sol-gel method and a CVD method can be used. Although only a single pressurizing chamber 20 is shown in FIG. 1 for convenience of explanation, a plurality of pressurizing chambers 20 are actually defined at a predetermined arrangement pitch in a direction orthogonal to the paper surface. .
[0032]
On the other hand, the flow path substrate 13 has a common cavity 18 for storing a biological sample to be supplied to each pressurizing chamber 20, an orifice 19 communicating each pressurizing chamber 20 and the common cavity 18, and An orifice 21 communicating with a nozzle 22 opened at the lower end of the substrate is etched in a concave shape on a surface facing the pressure chamber substrate 11. At the upper end of the substrate, a supply pipe 17 for a biological sample is inserted at a position communicating with the common cavity 18. In a preferred embodiment of the present invention, the common cavity 18 and the orifice 19 in contact with the biological sample , The orifice 21 is desirably made of a material having an excellent affinity for a biological material, and borosilicate glass is particularly preferable. By forming the flow path substrate 13 from a borosilicate glass substrate, the affinity with the biological sample is ensured and the processability is excellent. Therefore, it is suitable as a material of the inkjet head for discharging the biological sample.
[0033]
On the surface of the electrode substrate 12 facing the pressurizing chamber substrate 11, a recess 23 is formed by etching so as to form a substantially constant minute gap from the upper end to the lower end of the electrode substrate 12. The interval of the minute gap needs to be a necessary and sufficient interval for electrostatically driving the inkjet head 10, and for example, 0.2 μm is preferable. On the bottom surface of the concave portion 23, an elongated electrode 15 for forming an electrostatic force with the pressurized chamber substrate 11 is formed. In order to form the electrode 15, a film of indium tin oxide having a thickness of about 0.1 μm may be formed by using, for example, a sputtering method. Although only a single electrode 15 is shown in the figure for convenience of explanation, a plurality of electrodes 15 are actually formed in a direction perpendicular to the paper surface in correspondence with the arrangement pitch of the pressurizing chambers 20. As a desirable mode of the present invention, it is preferred that the pressurized chamber substrate 11, the electrode substrate 12, and the flow path substrate 13 are joined to each other by a joining means having excellent affinity with the biological sample. This is because, when bonded with an adhesive or the like, the biological sample may be damaged due to elution of the curing agent or the like. As such bonding means, anodic bonding is particularly desirable. According to the anodic bonding, since strong bonding can be performed by the attraction of static electricity, there is no inconvenience such as elution of the components contained in the adhesive into the biological sample, and the anodic bonding is excellent in affinity with the biological sample. In view of such circumstances, a borosilicate glass substrate is suitable as a material of the electrode substrate 12 for anodic bonding with the pressurized chamber substrate 11 made of a silicon substrate. When a borosilicate glass substrate is used, it contains a large amount of alkali ions and is suitable not only for anodic bonding, but also has a thermal expansion coefficient substantially equal to that of a silicon substrate, so that reliable bonding with little distortion at the bonding surface of the substrate can be obtained. .
[0034]
In order to perform anodic bonding between the electrode substrate 12 and the pressure chamber substrate 11, while accurately positioning the lower end thick portion of the electrode substrate 12 having a U-shaped cross section and the lower end of the pressure chamber substrate 11, The two are superimposed on each other with an appropriate pressure, and the temperature is raised to about 300 ° C. to about 500 ° C., and 1 × 10 ^-4 Under a vacuum of about Torr or a nitrogen atmosphere, a DC voltage of 200 V to 1000 V is applied between the two substrates so that the silicon substrate has a positive potential. Then, sodium ions, which are alkali metal ions contained in the borosilicate glass substrate, segregate on the surface on the opposite side (left side in the figure) of the borosilicate glass substrate. On the other hand, a large amount of negative ions remaining in the substrate form a space charge layer on the bonding surface with the silicon substrate, and induce strong electrostatic attraction between the silicon substrate and the borosilicate glass substrate. Strongly bond. The same procedure can be used to join the flow path substrate 13 made of a borosilicate glass substrate and the pressure chamber substrate 11 made of a silicon substrate. If the pressurizing chamber substrate 11 and the electrode substrate 12 are anodically bonded, a supporting member 24 having an appropriate elasticity and an excellent insulating property such as epoxy resin is attached to the upper end of the substrate in order to maintain a small gap therebetween. In the above, it is inserted between the small gaps.
[0035]
When a borosilicate glass substrate is used for the anodic bonding, MgO, Al ₂ O ₃ , CaO or the like may be added to adjust the thermal expansion coefficient of the glass substrate to the thermal expansion coefficient of the silicon substrate so as to reduce the thermal stress during anodic bonding. It is preferable that the temperature of the borosilicate glass substrate is set to be slightly higher to reduce the difference in the amount of deformation of the substrate due to thermal stress and to minimize the occurrence of warpage at the bonding surface. Further, the electrode substrate 11 and the flow path substrate 13 are not limited to the borosilicate glass substrate, and may be a silicon substrate whose surface is oxidized. In particular, when a silicon substrate is used as the electrode substrate 12, a p-type or n-type impurity is diffused at a position where the electrode 15 is to be formed, so that an electrode layer serving as the electrode 15 is formed. it can.
[0036]
In order to drive the inkjet head 10 configured as described above, a common electrode 26 made of gold or platinum formed on the upper end surface of the pressure chamber substrate 11 and an electrode 15 formed on the electrode substrate 12 are formed. And an output voltage from the external power supply 25 is applied. The output voltage is a rectangular pulse wave having an amplitude of 0 V to 35 V. Then, while the surface of the electrode 15 is positively charged, the surface of the opposing pressure chamber substrate 11 is negatively charged. As a result, an electrostatic force acts on both, but the bottom of the pressurizing chamber 20 which is a thin portion of the pressurizing chamber substrate 11 slightly bends toward the electrode substrate 12 and is elastically deformed. That is, the plastic silicon oxide film 14 located at the bottom of the pressurizing chamber 20 is elastically deformed by electrostatic drive and functions as a diaphragm 16 for adjusting the pressure in the pressurizing chamber 20. Next, when the voltage applied to the electrode 15 is turned off, the electrostatic force is released and the diaphragm 16 is restored to the original position, so that the pressure in the pressurizing chamber 20 suddenly increases, and the orifice 21 After that, the biological sample is ejected from the nozzle 22 as a dot-shaped micro droplet 30. The droplet 30 is a micro dot of about several picoliters. The vibrating plate 16 bent toward the pressurizing chamber 20 is bent again toward the electrode substrate 12 by the reaction thereof, and the pressure in the pressurizing chamber 20 is suddenly reduced. Replenish the biological sample.
[0037]
A slide glass 40 as a support (solid phase) of the probe is disposed in the discharge direction of the droplet 30, and the droplet 30 containing various biological samples such as probe DNA and protein is discharged onto the slide glass 40, By adsorbing these probes on the same substrate, a highly integrated probe array can be manufactured. As the solvent containing the probe, it is preferable to use a solvent in which the spot shape when adhered onto the transparent glass substrate 40 becomes circular and the discharge spot spreads so that cross-contamination between adjacent discharge spots does not occur. desirable. Such a solvent is not particularly limited as long as stable droplet ejection can be performed without denaturing a biological sample. In order to enable stable droplet ejection, it is desirable that the viscosity is 1 cPs to 20 cPs and the surface tension is 30 mN / m to 50 mN / m. In order to stably fix the probe on the surface of the slide glass 40, it is preferable to introduce a functional group or the like that is easily chemically adsorbed to the surface of the solid phase. For example, in order to immobilize a single-stranded DNA fragment, a thiol group is introduced into the end of the DNA chain, while a maleimide group is introduced into the surface of the slide glass 40 so that the probe can be bonded through the bond between the two. DNA can be stably immobilized.
[0038]
FIG. 3 is a graph showing the relationship between the viscosity of droplets ejected from the inkjet head 10 and the ejection weight per shot. As shown in the figure, the experiment by the present inventor confirmed that the ejection weight per shot was about 100 ng when the viscosity was 10 cPs, while the ejection weight per shot was about 30 ng when the viscosity was 30 cPs. I have. Since the viscosity of a solution containing probe DNA or various proteins varies significantly depending on the type of nucleic acid or protein, when a different protein solution is discharged for each nozzle using the same inkjet head, the discharge amount per shot is reduced. Different for each nozzle. As described above, if the weight of the ejection liquid differs for each nozzle, the integration density of the probes differs for each spot, so that a uniform probe array cannot be manufactured. For this reason, in the present invention, when protein solutions and the like having different viscosities are ejected from different nozzles using the same inkjet head, the number of ejections of the droplets is set in advance for each nozzle, so that the number of droplets ejected on the slide glass is reduced Is adjusted so that the discharge weight to the nozzle becomes substantially uniform.
[0039]
FIG. 2 is a diagram for explaining a procedure for manufacturing a probe array. In the figure, reference numerals 31, 32, and 33 denote droplet spots formed by ejecting a predetermined weight of a solution containing various biological samples such as nucleic acids and proteins onto a slide glass 40 and landing them thereon so as to have a substantially circular spread. . These droplet spots 31, 32, 33 are arranged in a line at a predetermined pitch along the scanning direction (right direction in the figure) of the inkjet head. Nucleic acids, proteins, and the like contained in these droplet spots are different from each other, so that the viscosities are also significantly different. Therefore, for example, by changing the number of ejections for each nozzle, such as one droplet spot 31, one droplet spot 32, and two droplet spots 33, the weight of each droplet spot is almost equal. It has been adjusted to be.
[0040]
In addition, in order to make the weight of the droplet spot uniform, in addition to the method of adjusting the number of ejections according to the viscosity of the droplet as described above, the setting of the driving voltage for each nozzle is changed in advance, so that the droplet spot is changed. May be made uniform in weight. In addition, the probe immobilized on the solid phase is not limited to a probe DNA having a base sequence complementary to the target DNA, and includes, for example, a ligand that specifically binds to a receptor, an antibody that specifically binds to an antigen, and an enzyme. Various proteins, such as a substrate that specifically binds, can be used as a probe.
[0041]
As described above, according to the present embodiment, by configuring the inkjet head 10 with the borosilicate glass substrate and the silicon substrate, the inkjet head 10 having an affinity for various biological samples such as nucleic acids and proteins can be realized. It is suitable for manufacturing a probe array. In addition, since the inkjet head 10 has a borosilicate glass substrate and a silicon substrate as main constituent members, it can be easily designed and processed using a lithography process used in a semiconductor manufacturing process and the like. This is convenient for changing the design because only the pattern of the photomask needs to be changed. In particular, the viscosity of a solution containing a protein or the like is significantly different from that of a normal ink in physical properties such as viscosity and surface tension depending on the type of the protein or the like. However, it is convenient because the design can be easily changed only by changing the pattern of the photomask. Further, according to the semiconductor manufacturing process, high-precision fine processing can be performed, so that dimensional accuracy is good and there is no variation in the size of a droplet spot when manufacturing a probe array. Further, since the semiconductor manufacturing process is diverted, the cost is low and the productivity is excellent.
[0042]
Further, since anodic bonding is used as a bonding means between the borosilicate glass substrate and the silicon substrate, there is no need to use an adhesive or the like harmful to a biological sample, and the biocompatibility is extremely excellent. When a borosilicate glass substrate and a silicon substrate are bonded with an adhesive or the like, the adhesive may be eluted by acid cleaning, heat treatment, ultraviolet irradiation, or the like. The process is not harmful to the biological sample even if the above process is performed, and can be reused repeatedly by washing, so that it is very economical. In addition, since the device is driven by electrostatic force, there is no possibility of denaturing proteins and the like unlike Bubble Jet (registered trademark), and the apparatus configuration can be extremely simplified, so that the inkjet head can be downsized and the dead volume can be reduced. . In addition, a high-density spot can be formed by reducing the pitch of the nozzles. Further, according to the electrostatic drive, the actuator has high reliability and a long life, and can be driven at a high frequency, thereby enabling high-speed ejection.
[Second embodiment]
In the second embodiment, a supply pipe 17 for supplying a discharged liquid such as a biological sample-containing solution is not provided on the side wall, but is provided on the opposite side to the discharge port (nozzle 22), that is, on the upper part. Have been.
4 and 5 are diagrams for explaining a specific example of the droplet discharge head according to the second embodiment in which a supply port for a biological sample is provided on the opposite side to such a discharge port.
As shown in FIGS. 4A and 4B, a droplet discharge head 110 according to the second embodiment has a second substrate 111 made of silicon having a pressure chamber and a first substrate made of glass having electrodes. And a third substrate 113 made of glass provided so as to cover the pressurizing chamber and a third substrate 113 so as to sandwich both sides thereof in the thickness direction.
FIG. 5A shows a top view of the droplet discharge head according to the second embodiment, and FIGS. 5B and 5C respectively show the AA direction in FIG. 5A. 2 and a cross-sectional view in the BB direction.
As shown in FIG. 5A, the terminal of the first electrode 115 provided on the first substrate 112 is an electrode extraction portion that can be connected to an external power supply (not shown). The periphery of the portion is protected by a seal 127 made of a heat-resistant resin. The heat-resistant resin used for the seal 127 is not particularly limited, but from the viewpoint that no special treatment is required at the time of disposal, it is preferable to use a resin containing no chlorine or the like such as polyester and polypropylene.
Next, each substrate constituting the droplet discharge head 110 will be described with reference to FIG.
As shown in FIG. 5B, the surface of the first substrate 112 facing the second substrate 111 has a concave portion 123 for forming a substantially constant minute gap with the second substrate. Is formed. A first electrode 115 for forming an electrostatic force with the second substrate 111 is formed on the bottom surface of the concave portion 123. The first electrode 115 may be formed using indium tin oxide (ITO) to a thickness of about 0.1 μm by a sputtering method. Note that a conductive material other than ITO can be used for the first electrode 115. As other conductive materials, it is preferable to use conductive materials that are not specified as specially controlled industrial waste, such as gold, copper, and aluminum. When such a material is used, no special treatment is required at the time of disposal, and the cost at the time of disposal can be reduced.
On the second substrate 111, a nozzle 122, a pressurized chamber 120 having a boat-shaped cross section, an orifice 119, and a cavity 118 are provided so as to communicate linearly on a surface facing the third substrate 113. Further, a silicon oxide film 114 having a thickness of about 1 μm is formed on the back and front surfaces of the substrate by a thermal oxidation method or the like. A liquid such as a biological sample-containing solution supplied from the outside is once received by the cavity 118, introduced into the pressurizing chamber 120 through the orifice 119, and discharged from the nozzle 122. In addition, the second substrate has a concave portion corresponding to an electrode lead-out portion at the end of the first electrode 115 provided on the first substrate 112, so that the first electrode 115 can be easily connected to an external power supply. It is designed to be. On the side of the pressurizing chamber 120 provided on the second substrate 111, near the concave portion corresponding to the electrode extraction portion of the first electrode 115, the first electrode 115 and the first electrode 115 on the first substrate are connected. A second electrode 126 for applying a predetermined voltage between them is provided. For such a second electrode 126, a conductive material such as gold or platinum can be used, for example. Although a heavy metal can be used as the electrode, it is preferable to use a conductive material other than the heavy metal from the viewpoint of environmental friendliness.
The third substrate 113 makes it easy to connect an external power source to the electrode extraction portion of the first electrode 115 provided on the first substrate 112 and the second electrode 126 provided on the second substrate 111. For this reason, the first substrate 112 and the second substrate 111 are formed to have a width smaller than that of the first substrate 112 and the second substrate 111 by an amount corresponding to the first electrode 115 and the second electrode 126. The third substrate 113 is desirably made of a material having an excellent affinity for a liquid for ejection such as a biological sample-containing solution, and borosilicate glass is particularly preferable. Borosilicate glass contains a large amount of alkali ions and is not only suitable for anodic bonding, but also has a thermal expansion coefficient substantially equal to that of a silicon substrate, so that reliable bonding with little distortion at the bonding surface of the substrate can be obtained.
The first substrate 112, the second substrate 111, and the third substrate 113 are bonded by anodic bonding. Note that the bonding may be performed using a diluted hydrofluoric acid solution.
In order to drive the head 110 configured as described above, as shown in FIGS. 5A and 5C, a first substrate made of gold or platinum formed on a part of the upper surface of the second substrate 111 is used. An output voltage from an external power supply 125 is applied between the second electrode 126 and the first electrode 115 formed on the first substrate 112. Then, the bottom of the pressurizing chamber 120, which is a thin portion of the second substrate 111, is slightly bent toward the first substrate 112 and elastically deforms. Other detailed operation mechanisms are as described above.
In addition, in the droplet discharge head 110 of the present invention, as shown in FIG. 4C, the liquid storage tank 150 may be integrally formed with the holder 160 interposed therebetween. Further, the tank 150 may be provided with a cap 170 having a ventilation hole.
In the first and second embodiments, a glass substrate is used as the first substrate (electrode substrate) and the third substrate (flow path substrate) from the viewpoint of particularly excellent affinity with a biological sample. A silicon substrate was used as the second substrate (pressurizing chamber substrate). However, the material is not limited to the above materials from the viewpoint of the ultraviolet sterilization treatment or the steam overheat sterilization treatment of the head. The first to third substrates may be substrates capable of performing an ultraviolet sterilization process or a steam overheat sterilization process, for example, a silicon-based substrate such as silicon or glass (eg, borosilicate glass or quartz glass), or an epoxy resin. A substrate made of an ultraviolet-transmissive material or a heat- and moisture-resistant material, such as a resin substrate made of acrylic resin or Teflon (registered trademark) can be used. As a substrate made of such an ultraviolet light transmitting material or a heat and moisture resistant material, a silicon substrate is preferable. By unifying the material of all the substrates to the silicon-based substrate, recycling becomes easy and it becomes possible to provide environmentally friendly products.
Specifically, in the first and second embodiments, a silicon substrate is used as the second substrate. However, like the first and third substrates, the second substrate is formed of a glass substrate. Alternatively, it may be formed using a quartz substrate. Since all the substrates constituting the head are formed from a glass or quartz substrate, they can be easily melted and recycled as a raw material for glass, and are excellent in affinity with a biological sample. At this time, the substrates may be joined by dilute hydrofluoric acid. By melting and bonding the substrate with dilute hydrofluoric acid in this way, the substrate can be bonded without using an adhesive, etc., so that the biological sample is not damaged, and the glass material can be recycled. It is preferable because additives such as an adhesive do not mix.
Further, the first substrate and the third substrate may be formed of a silicon substrate instead of the glass substrate. Since the substrate constituting the head is entirely formed of a silicon substrate, it can be easily recycled into additives such as steel and aluminum. Further, it has excellent durability and excellent affinity with a biological sample. At this time, each substrate may be joined by dilute hydrofluoric acid. Since the bonding can be performed without using an adhesive or the like, the biological sample is not damaged, and unnecessary impurities are not mixed during recycling.
In the above embodiment, glass is used as a material for forming the first substrate 112 and the third substrate 113. However, instead of such a normal glass, a photosensitive material or a photochromic material, for example, a photosensitive glass is used. Alternatively, photochromic glass may be used. As the photochromic glass, a material containing a photosensitive material such as silver halide may be used, or a material containing no photosensitive material that causes coloring due to generation of light-induced defects (CdO-based, ZnO-based, CaO-Al ₂ O ₃ (System glass). Among these, in particular, a photochromic glass made of borosilicate glass to which silver halide is added, wherein the discoloration time is adjusted by adjusting the composition of the borosilicate glass and the particle size of the silver halide. Is preferred. In addition, as the photosensitive glass, for example, a small amount of gold, silver, copper, and palladium ions as the photosensitive metal, cerium ions as the photosensitizer, and antimony oxide and tin oxide as the thermal reducing agent are added. Photosensitive glass is also preferably used. By using such a photochromic glass or photosensitive glass, the head can be sterilized by, for example, ultraviolet irradiation using a high-pressure mercury lamp, and the effect on the sample by light other than at the time of sterilization can be more reliably determined. It becomes possible to suppress to. Needless to say, a glass material other than borosilicate glass, for example, aluminosilicate glass or the like may be used as a glass material of the photochromic glass or the photosensitive glass.
Further, the relationship between the composition of the borosilicate glass, the particle size of the silver halide and the fading time can be specifically adjusted by the method described in Glass Handbook (Asakura Shoten).
Further, the photochromic glass is not particularly limited, but in consideration of the wavelength of about 253.7 nm used for sterilization, it is preferable that the main component be silver chloride having sensitivity to short wavelengths, and that bromine or iodine be used. , It is possible to adjust the sensitivity to the longer wavelength side.
In the above embodiment, quartz glass may be used as the third substrate. When quartz glass is used for the third substrate, the coefficient of thermal expansion of the quartz glass is significantly smaller than that of the silicon substrate constituting the second substrate, so that the quartz glass can be easily separated by rapid cooling with liquid nitrogen or the like. It becomes. The second substrate and the third substrate were separated from each other by dilute hydrofluoric acid. ₂ You may join by melting a component. More specifically, after the second substrate and the third substrate are brought into close contact with each other at a predetermined position, a very small amount of dilute hydrofluoric acid is added to the interface, whereby the dilute hydrofluoric acid is applied to the entire bonding surface by a capillary phenomenon. You can spread it. It is considered that the bonding between the second substrate and the third substrate is performed by the following reaction.
SiO ₂ + 6HF → H ₂ SiF ₆ + 2H ₂ O
[Third Embodiment]
FIG. 6A is a sectional view illustrating a droplet discharge head according to the third embodiment of the present invention. The droplet discharge head 210 according to the third embodiment has a laminated structure in which both sides of a second substrate 211 are sandwiched in a thickness direction between a third substrate 213 and a first substrate 212 made of a shape memory resin. Have. Further, the second substrate 211 is formed shorter than the third substrate 213 and the first substrate 212 in order to form a nozzle port 222 and a flow path connecting the nozzle port and the pressurizing chamber 220. . A member 211 ′ for forming a nozzle 222 having a desired diameter is further joined to the third substrate 213 and the first substrate 212. Further, a holder 229 formed of a shape memory resin may be further formed outside the first substrate as needed. By joining such a holder 229, for example, it is possible to easily store it in the housing of the droplet discharge device.
The third substrate 213 is formed using a shape memory resin, and is integrally formed with a flow path 228 for supplying a liquid to the head. As such a shape memory resin, for example, a polyurethane resin or the like is used. Further, a liquid storage tank for storing liquid may be formed integrally with the flow path 228.
On the surface of the second substrate 211 facing the third substrate 213, a cavity 218, a pressure chamber 220, and an orifice 219 communicating the cavity 218 with the pressure chamber 220 are formed. The bottom of the pressurizing chamber 220 is thin and functions as a diaphragm 216. In addition, one end of a concave portion forming the pressurizing chamber 220 is open, and the pressurizing chamber 220 communicates with the nozzle 222 through a flow path formed by the member 211 ′ and the first substrate 212.
The first substrate 212 is provided with a concave portion 223 for forming a substantially constant minute gap between the first substrate 212 and the diaphragm 216 formed at the bottom of the pressurizing chamber 220. The interval of the minute gap needs to be a necessary and sufficient interval for electrostatically driving the droplet discharge head 210, and for example, is preferably 0.2 μm. A first electrode 215 for forming an electrostatic force with the second substrate 211 is formed on the bottom surface of the concave portion 223. For the first electrode 215, the above description is referred to as appropriate.
When a biological sample is used as a liquid to be discharged, the second substrate 211 and the first substrate 212 are preferably bonded to each other by a bonding means having excellent affinity with the biological sample. As such means, the above description is appropriately referred to. The joined body of the second substrate 211 and the first substrate 212 thus joined, and the member 211 ′ forming the nozzle 222 are further joined by being press-fitted into the third substrate 213. Since the third substrate 213 is formed of a shape memory resin (for example, polyurethane resin) as described above, it is restored to the stored shape when heated to a predetermined temperature after use, and FIG. As shown in (3), the third substrate 213 portion integrally formed with the flow path 228 is easily separated. As described above, the flow path substrate formed of a resin, the second substrate 211 and the first substrate 212 formed of a glass member or the like can be easily separated. Environmentally friendly. The shape return temperature of the shape memory resin can be adjusted by adjusting the composition and the degree of polymerization of the resin, and for example, can be set higher than the autoclave treatment temperature (for example, 121 ° C.). .
Note that the material of the first substrate 212 and the second substrate 211 can be, for example, a silicon substrate, a glass substrate, a resin substrate, or the like, and is not particularly limited as long as the effects of the present embodiment can be achieved. is not. However, when a biological sample-containing solution is used as the liquid to be discharged, the second substrate 211 is preferably made of, for example, a silicon substrate, a glass substrate, or the like that has a high affinity for the biological sample.
In the droplet discharge head according to the present embodiment, the first electrode 215 provided on the first substrate 212 and the second electrode (not shown) provided on the second substrate 211 are connected to an external power supply (not shown). ), And can be driven by applying a predetermined voltage. For the details of the driving mechanism, the above description can be appropriately referred to.
The description of the method of manufacturing the probe array in the first embodiment is appropriately referred to in the droplet discharge heads of the second and third embodiments.
[0043]
【The invention's effect】
According to the present invention, an ink-jet head is composed of a glass electrode substrate and a silicon pressurizing chamber substrate, so that it has a high affinity for biological samples such as nucleic acids and proteins and has good compatibility with bubble jets. Since the method is an electrostatic drive method that does not generate heat as in the case of the (registered trademark) method, stable ejection onto a solid phase surface can be performed without damaging a biological sample. Further, by anodically bonding the electrode substrate and the pressure chamber substrate, the electrode substrate and the pressure chamber substrate can be bonded without using an adhesive or the like, so that the biological sample is not damaged. In addition, since the inner wall surface of the pressurized chamber is hydrophilically treated with a silicon oxide film, the pressurized chamber has excellent affinity for aqueous solutions containing biological samples such as nucleic acids and proteins, and is stable. The discharged biological sample can be discharged.
[0044]
In the probe array manufacturing method of the present invention, the droplet spot is formed at a predetermined position on the solid phase surface accurately and efficiently without damaging a biological sample by using the inkjet head of the present invention. Becomes possible. In addition, since a probe array including various biological samples can be manufactured by discharging different probes for each nozzle, it is convenient for manufacturing a DNA microarray for performing a large amount of gene analysis at once. In addition, the number of ejections or the drive voltage is adjusted according to the physical properties of the solution containing the probe, and the weight of the droplet spot formed on the solid phase surface can be made substantially uniform.
[0045]
Further, the inkjet head of the present invention is not limited to the use of discharging a solution containing a probe, for example, the use of synthesizing a probe DNA on a solid phase or the use of dispensing a biological sample or a reagent. effective.
[Brief description of the drawings]
FIG. 1 is a cross-sectional view of an inkjet head according to an embodiment.
FIG. 2 is an explanatory diagram of a manufacturing process of a probe array.
FIG. 3 is a graph of the ejection weight per shot with respect to the viscosity of a droplet.
FIG. 4 is an explanatory diagram showing a specific example of a droplet discharge head according to a second embodiment of the present invention.
5A and 5B are a top view and a cross-sectional view illustrating a specific example of a droplet discharge head according to a second embodiment of the present invention.
FIG. 6 is a sectional view illustrating a droplet discharge head according to a third embodiment of the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 10 ... Ink-jet head, 11 ... Pressurization chamber substrate, 12 ... Electrode substrate, 13 ... Channel substrate, 14 ... Silicon oxide film, 15 ... Electrode, 16 ... Vibration plate, 17 ... Supply pipe, 18 ... Common cavity, 19 ... Orifice, 20 ... Pressure chamber, 21 ... Orifice, 22 ... Nozzle, 23 ... Concave part, 24 ... Support member, 25 ... Power supply, 26 ... Common electrode, 30 ... Droplet, 40 ... Slide glass, 110 ... Inkjet head, 111 ... second substrate, 112 ... first substrate, 113 ... third substrate, 114 ... silicon oxide film, 115 ... first electrode, 116 ... vibration plate, 118 ... cavity, 119 ... orifice, 120 ... pressure Chamber, 122 nozzle, 123 recess, 126 second electrode, 127 seal, 150 liquid storage tank, 160 holder, 170 cap, 171 vent, 2 0: inkjet head, 211: second substrate, 212: first substrate, 213: third substrate, 214: silicon oxide film, 215: first electrode, 216: diaphragm, 218: cavity, 220 ... Pressurizing chamber, 222 nozzle, 223 recess, 228 channel, 229 holder

Claims (23)

An inkjet head for discharging a solution containing a biological sample onto a solid phase,
A glass electrode substrate having electrodes on the surface,
The pressure in the pressurized chamber is adjusted by the displacement of the vibration plate which is disposed opposite to the electrode substrate with a minute gap and is elastically deformed by an electrostatic force corresponding to the potential difference with the electrode, and is filled in the pressurized chamber. And a pressure chamber substrate made of silicon for discharging the solution from a nozzle hole. The ink jet head according to claim 1, wherein the electrode substrate and the pressure chamber substrate are anodic-bonded. 3. The ink jet head according to claim 1, wherein an inner wall surface of the pressurizing chamber is hydrophilically treated with a silicon oxide film. 4. The glass flow path substrate according to claim 1, further comprising: a glass flow path substrate having a common cavity for storing the solution to be supplied to each of the pressure chambers, and an orifice communicating from the cavity to the pressure chamber. The inkjet head according to any one of the above. The ink jet head according to claim 4, wherein the flow path substrate and the pressure chamber substrate are anodic-bonded. The inkjet head according to claim 4, wherein the electrode substrate and the flow path substrate are made of a borosilicate glass substrate. The pressurizing chamber substrate and the flow path substrate use a mask that is designed in advance to be suitable for the physical properties of the biological sample with respect to at least one of the pressurizing chamber shape, the common cavity shape, the nozzle diameter, and the orifice diameter. The inkjet head according to claim 6, which is manufactured through a conventional lithography process. A droplet discharge head for discharging a solution containing a biological sample onto a solid phase,
A first substrate having electrodes on its surface;
One side is disposed with a minute gap between the first substrate and the diaphragm, which is elastically deformed by an electrostatic force corresponding to the potential difference between the electrodes, and adjusts the pressure in the pressurizing chamber by displacement to fill the pressurizing chamber. A second substrate having a pressurized chamber for discharging the solution from the nozzle hole,
A third substrate bonded to the other surface of the second substrate,
At least one of the first to third substrates is made of a UV-transmissive material, or all of the first to third substrates are made of a heat- and moisture-resistant material, and sterilized by UV or steam heat treatment. Droplet discharge head made possible. 9. The droplet discharge head according to claim 8, wherein the ultraviolet light transmitting material or the heat and moisture resistant material is a silicon-based substrate. The droplet discharge head according to claim 9, wherein the silicon-based substrate is a quartz substrate or a glass substrate. The droplet discharge head according to claim 9, wherein the silicon-based substrate is a silicon substrate. The droplet discharge head according to any one of claims 8 to 11, wherein the electrode is formed of one of ITO, gold, copper, and aluminum. In a droplet discharge head in which a plurality of substrates are stacked, at least one substrate is formed using a shape memory material, and by applying a predetermined temperature, the shape memory material is deformed into a memory shape. Droplet discharge head that facilitates separation from other substrates. A droplet discharge head in which a plurality of substrates are stacked, wherein the at least one set of bonded substrates has different coefficients of thermal expansion or thermal contraction from each other, and the bonding is released by applying a predetermined temperature. Droplet discharge head. The plurality of substrates,
A first substrate having electrodes on its surface;
One surface side is arranged via the minute gap with the first substrate, and the pressure in the pressurizing chamber is adjusted by the displacement of the vibration plate which is elastically deformed by an electrostatic force corresponding to the potential difference with the electrode to fill the pressurizing chamber. A second substrate having a pressurized chamber for discharging the solution from the nozzle hole,
A third substrate joined to the other surface of the second substrate,
The droplet discharge head according to claim 13. A droplet discharge head that discharges droplets in response to an applied signal, wherein a photosensitive material or a photochromic material is used on the outer periphery of the droplet discharge head, and at least a part of the droplet discharge head can be shielded from light. . The photochromic material is a photochromic glass to which silver halide is added,
17. The droplet discharge head according to claim 16, wherein the fading time of the outer wall formed using the photochromic glass can be adjusted by adjusting the composition of the photochromic glass and the particle size of the silver halide. 17. The droplet discharge head according to claim 16, wherein the photosensitive material is a photosensitive glass to which a photosensitive metal, a photosensitizer, and a thermal reducing agent are added, and the outer wall darkens irreversibly. The droplet discharge head,
A first substrate having electrodes on its surface;
One surface side is arranged via the minute gap with the first substrate, and the pressure in the pressurizing chamber is adjusted by the displacement of the vibration plate which is elastically deformed by an electrostatic force corresponding to the potential difference with the electrode to fill the pressurizing chamber. A second substrate having a pressurized chamber for discharging the solution from the nozzle hole,
A third substrate joined to the other surface of the second substrate,
19. The droplet discharge head according to claim 16, wherein the droplet discharge head is driven by electrostatic force. The solution according to any one of claims 1 to 7, wherein the solution containing a probe that specifically binds to a target molecule is the solution according to any one of claims 1 to 7. A method for manufacturing a probe array, wherein the probe is ejected onto a solid phase using a droplet ejection head, and the probe is fixed to the surface of the solid phase. The method for manufacturing a probe array according to claim 20, wherein a different probe is discharged for each nozzle. 22. The method of manufacturing a probe array according to claim 21, wherein the number of ejections is adjusted according to the physical properties of the solution containing the probe, and the weight of the droplet spot formed on the solid phase surface is made substantially uniform. 22. The probe array according to claim 21, wherein the drive voltage for each nozzle is adjusted in accordance with the physical properties of the solution containing the probe, and the weight of the droplet spot formed on the solid surface is made substantially uniform. Production method.

Images