JP2007051883A - Method of manufacturing microarray, and liquid drop discharge unit - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of manufacturing efficiently a high performance microarray, by filling quickly a sample liquid into an ink jet head without contaminating a bubble, irrespective of kinds of the sample liquids and properties thereof. <P>SOLUTION: This method of manufacturing the microarray in the present invention includes the first process for filling a ready-to-discharge liquid from a supply port 16 of a liquid drop discharge head 10 to a tip of a nozzle 22, the second process for immersing the each supply port into the sample liquid supplied to each liquid storage part, the third process for approaching a liquid holding means 212 having water holding property to the nozzle 22, the fourth process for filling the sample liquid up to the tip of the nozzle, by operating a pressurizing means under the condition where the the supply port is immersed into the sample liquid, and by discharging all the ready-to-discharge liquid from the nozzle into the liquid holding means 212 having the water holding capacity, and the fifth process for operating the pressurizing means to discharge the sample liquid into a microarray substrate 202. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a microarray manufacturing method and a droplet discharge device.

  In recent years, a method for detecting and measuring a target substance in a sample using a so-called microarray in which biological molecules such as nucleic acids, proteins, and cells are immobilized on a substrate as a probe, and utilizing the specificity of binding between biological molecules Is widely used.

  In Japanese Patent Application Laid-Open No. 11-187900 (Patent Document 1), a liquid containing a probe that can specifically bind to a target substance is ejected to a solid surface by an ink jet method, and the probe is placed on the solid surface. A method of spotting a probe on a solid phase, which is characterized by being attached, is disclosed.

In such a microarray, in order to detect a target substance with high throughput, it is necessary to immobilize many kinds of probe molecules in a minute region. Japanese Patent Laying-Open No. 2004-160904 (Patent Document 2) discloses a first substrate having a plurality of liquid storage portions and a second substrate having a plurality of flow paths independently communicating with the plurality of liquid storage portions. And an ink-jet head that includes a plurality of nozzles that communicate with the plurality of flow paths independently and have a plurality of nozzles that discharge droplets. According to this, since the liquid storage section on which a plurality of samples are mounted and the plurality of nozzles corresponding to the arrangement of the spots of the microarray to be manufactured are communicated with each other through the flow path, a large number of probes are fixed in a minute region. A microarray can be produced at high speed.
JP 11-187900 A JP 2004-160904 A

  However, when the above-described ink jet head is used, it is necessary to fill each liquid reservoir with a different sample liquid prior to ejection, and this filling process takes time. Since the discharge process itself can be performed in a very short time, it is important to shorten the filling process time in order to improve the productivity of the microarray.

  In addition, filling the liquid into the fine flow path in the inkjet head means that the interface between the liquid and the gas moves in the fine flow path. In such a process, the viscosity of the sample liquid to be filled is used. Depending on the surface tension, air bubbles can easily enter the fine flow path and cause clogging. If air bubbles enter, it can be removed by performing so-called blanking and discarding the discharge liquid for several times. However, in general, sample solutions for microarrays are expensive and difficult to obtain. It is desirable to avoid wasting sample solution as much as possible.

  Therefore, the present invention provides a method for manufacturing a high-performance microarray with high efficiency by quickly filling the inkjet head with the sample liquid so that bubbles do not enter and the sample liquid is not wasted. For the purpose.

  In order to solve the above-described problems, a microarray manufacturing method according to the present invention includes a nozzle formed on a first main surface, and a pressurizing chamber including a pressurizing unit for pressurizing a liquid discharged from the nozzle. , A liquid storage part communicating with the pressurizing chamber, and a supply port for supplying a liquid to the liquid storage part, wherein the supply port is opposed to the first main surface. A method of manufacturing a microarray using a droplet discharge device equipped with a droplet discharge head provided so as to protrude from a nozzle, wherein the droplet is discharged from the supply port of the droplet discharge head to the nozzle tip A first step of filling the preparation liquid, a second step of immersing each of the supply ports in a sample liquid containing a sample fixed to the microarray substrate, and a liquid holding means having water retention capacity close to the nozzle A third step of The pressurizing means is operated while the supply port is immersed in the sample liquid, and the discharge liquid is completely discharged from the nozzle into the water-retaining liquid holding means, thereby allowing the sample liquid to reach the tip of the nozzle. A fourth step of filling, and a fifth step of operating the pressurizing means to discharge the sample liquid onto the microarray substrate.

  In this manner, first, the discharge preparation liquid is filled in the fine flow path from the supply port to the tip of the nozzle, and then the discharge preparation liquid is discharged from the nozzle while the supply port is immersed in the sample liquid. For example, the sample liquid is sucked up from the supply port by the volume of the discharged preparation liquid. Since the discharge process is performed in a very short time, the sample liquid is filled from the supply port to the nozzle tip in a very short time by discharging all of the discharge preparation liquid.

  In addition, when filling the sample liquid, the interface between the sample liquid and the gas does not move in the fine flow path, but the interface between the sample liquid and the discharge preparation liquid, that is, the interface between the liquids moves in the fine flow path. As a result, bubbles do not enter the sample liquid. Therefore, the sample liquid is not wasted due to empty shots. Since the discharge preparation liquid is all discharged from the nozzle as the sample liquid is filled, the quality of the microarray is not affected.

  Furthermore, when the discharge preparation liquid is discharged, the liquid holding means having water retention is placed close to the nozzle, so that the discharged discharge preparation liquid is absorbed by the liquid holding means. Accordingly, it is possible to prevent the first main surface from being contaminated by the discharged discharge preparation liquid. Note that the order of the second step and the third step may be interchanged.

  In the liquid droplet ejection head used in the microarray manufacturing method according to the present invention, the liquid storage portion and the supply port may be formed independently, or may be integrally formed in a tube shape. By adopting a configuration in which the supply port protrudes from the second main surface, the supply port can be directly immersed in liquid in a small container such as each well of a microtiter plate, for example. There is an advantage that the holding portion is not contaminated by contacting the sample liquid.

  In the microarray manufacturing method according to the present invention, the first step includes a step of immersing the supply port in the discharge preparation liquid, and a gas or a liquid in the droplet discharge head is sucked from the nozzle to prepare the discharge preparation. And filling the liquid up to the tip of the nozzle.

  According to such a method, the ejection preparation liquid can be filled up to the tip of the nozzle efficiently in a short time.

  As the discharge preparation liquid used in the microarray manufacturing method according to the present invention, any liquid can be selected and used as long as it does not affect the sample liquid. For example, the viscosity and the surface easily pass through the fine flow path. It is preferable to have a tension and be inexpensive. Examples of such a liquid include pure water and a buffer solution. In particular, pure water is preferable without causing solids to precipitate and clogging after the liquid has dried.

  In order to solve the above problems, the present invention also provides a nozzle formed on the first main surface, a pressurizing chamber having a pressurizing means for pressurizing the liquid discharged from the nozzle, and the pressurizing chamber. A liquid holding portion communicating with the pressure chamber; and a supply port for supplying a liquid to the liquid holding portion, the supply port protruding from a second main surface facing the first main surface. A droplet discharge apparatus that is used by mounting a droplet discharge head that is provided as described above, the fixing means capable of fixing the droplet discharge head with the nozzle facing upward or downward; There is also provided a droplet discharge device comprising a water-retaining liquid holding means capable of approaching the nozzle when the nozzle is fixed upward.

  According to such a droplet discharge device, after filling the droplet discharge head with the discharge preparation liquid, first, the droplet discharge head is fixed with the nozzle facing upward, and the supply port is immersed in the sample liquid. Since the discharge preparation liquid is discharged in this state, the sample liquid is sucked up from the supply port. At this time, since the water-holding liquid holding means is close to the nozzle, the discharge preparation liquid discharged from the nozzle does not drop due to gravity and contaminates the nozzle surface. Subsequently, if the droplet discharge head is fixed with the nozzle facing downward, the sample liquid can be efficiently discharged toward the microarray substrate or the like.

  In addition, when the nozzle is fixed upward, the droplet discharge device according to the present invention covers the nozzle and adheres closely to the first main surface, and the gas or liquid in the droplet discharge head is discharged from the nozzle. It is preferable to provide suction means capable of suction.

  If the gas or liquid in the droplet discharge head is sucked by the suction means from the nozzle while the supply port is immersed in the discharge preparation liquid, the discharge preparation liquid can be efficiently filled up to the tip of the nozzle.

  Furthermore, it is preferable that the droplet discharge device according to the present invention includes a rotating unit that reverses the top and bottom of the droplet discharge head.

  With such a configuration, the step of sucking the liquid from the supply port and the step of discharging droplets from the nozzle to the microarray substrate or the like can be performed alternately and efficiently.

Embodiments according to the present invention will be described below with reference to the drawings.
(Droplet ejection head)
FIG. 1 is a perspective view showing an inkjet head 10 which is an example of a droplet discharge head used in a microarray manufacturing method according to the present invention.

  The droplet discharge head 10 includes a nozzle at the center of the first main surface 12 and has a pressure chamber, a liquid holding portion, and a flow path that allows the pressure chamber and the liquid holding portion to communicate with each other. Yes. The nozzle, pressurizing chamber, liquid holding unit, and flow path will be described later. Further, the droplet discharge head 10 has a supply port 16 for supplying a liquid to each liquid holding unit. The supply port 16 is provided so as to protrude from the second main surface facing the first main surface 12 as illustrated.

  The droplet discharge head 10 in this embodiment includes 96 nozzles, pressurization chambers, liquid holding units, and supply ports 16 each, and fills each liquid holding unit with liquid from a 96-hole microtiter plate. By discharging from each nozzle, 96 spots can be simultaneously formed on the microarray substrate.

  FIG. 2 is a schematic cross-sectional view of the droplet discharge head 10 taken along line II-II in FIG.

  A head chip 20 having a nozzle is provided in the center of the first main surface 12 of the droplet discharge head 10. In the head chip, 96 nozzles 22 are provided in an arrangement of 48 rows × 2 columns, but only two nozzles 22c and 22j are shown in the cross-sectional view, and the pressurizing chamber also includes the nozzles 22c and 22c. Only the pressurizing chambers 26c and 26j corresponding to 22j are shown. The configuration of the head chip 20 will be described later.

  In the present embodiment, since the liquid holding unit has the same inner diameter as the supply port 16 and the supply port 16 and the liquid holding unit are integrally formed in a tube shape, the liquid droplet discharge head 10 is hereinafter referred to as a liquid. The holding unit and the supply port 16 are collectively expressed as “supply port 16”. Each supply port 16 communicates with an individual pressurization chamber 26 via a dedicated flow path 13. In this cross-sectional view, the supply ports 16c and 16j and the pressurization chambers 26c and 26j communicate with each other. Only the flow paths 13c and 13j are shown.

  As will be described later, when the droplet discharge head 10 is formed by stacking the substrates 30, 40, and 50 (see FIG. 3), the flow paths 13 c and 13 j are shown in a cross section taken along the line II-II in FIG. Although the pressurizing chambers 26c and 26j do not actually appear, FIG. 2 also shows these flow paths and pressurizing chambers for convenience of explanation.

  Next, an example of a method for manufacturing the droplet discharge head 10 according to this embodiment will be described.

  In the present embodiment, the droplet discharge head 10 includes three substrates 30, 40, and 50, and a tube constituting the supply port 16 is inserted into a hole provided in the substrate 50, and the head chip 20 is inserted into the substrate 30. Can be produced by adhering.

  FIG. 3A shows a plan view of the substrate 30. The substrate 30 is formed with 96 grooves 13 'for forming the flow path 13 by laminating the substrate 40 thereon. The grooves 13 ′ converge from the peripheral edge of the substrate 17 toward the center, and the ends of the grooves 13 ′ on the substrate peripheral side coincide with the pitch (formation interval) of the supply ports 16. On the other hand, a through hole connected to the pressure chamber is provided at the end of each groove 13 'on the center side of the substrate.

  FIG. 3B shows a plan view of the substrate 40 stacked on the substrate 30. The substrate 40 is formed with 96 through holes 42 in 8 rows × 12 columns. The pitch of the through holes 42 matches the pitch of the supply ports 16. The through hole 42 is a flow path that allows the flow path 13 and the supply port 16 to communicate with each other.

  FIG. 3C shows a plan view of the substrate 50. The substrate 50 has 96 through holes 52 formed therein. The pitch of the through holes 52 also matches the pitch of the supply ports 16, and the lower ends of the through holes 52 are connected to the through holes 42 of the substrate 40. As shown in FIG. 2, the through hole 52 has a large inner diameter up to a predetermined depth, and a tube constituting the supply port 16 is fitted therein.

  The substrates 30, 40 and 50 can be formed of a material such as glass or resin, and the grooves and through holes can be formed by a method suitable for the material such as etching or injection molding.

  After the substrates 30 to 50 are stacked and bonded by a method using heat welding or an adhesive, the tube-shaped supply port 16 is fitted into each hole of the substrate 50. The tube constituting the supply port 16 is preferably formed of a resin such as acrylic, vinyl chloride, polycarbonate, or polystyrene, but may be glass, metal, or the like. The inner surface of the supply port 16 is preferably treated in a lyophilic manner, so that the sample liquid can be easily sucked into the supply port 16. As a method for imparting hydrophilicity to the surface, there is a method of coating a polymer that is hydrophilic and has high affinity for biomolecules. Examples of such polymers include hydroxyethyl methacrylate, N-vinyl pyrrolidone, dimethyl acrylamide, glycerol methacrylate, polyethylene glycol methacrylate and the like. A tube whose inner side is coated with heparin can also be used.

  The inner diameter of the tube is 3 mm or less, preferably 1 mm or less. By adopting such a configuration, even when the nozzle of the inkjet head 10 is directed upward, the liquid filled inside forms a meniscus at the open end of the supply port, so that the liquid can flow without flowing out to the outside. It becomes possible to hold.

  The head chip 20 is bonded to the substrate 30 to complete the inkjet head 10. The head chip 20 is configured to be able to discharge droplets from the nozzle 22 by operating the pressurizing means of the pressurizing chamber alone by simply being electrically connected. FIG. 4 shows an enlarged cross-sectional view of an electrostatic drive type head chip as an example of the head chip 20. In FIG. 4, the substrates 40 and 50 are omitted, and only the substrate 30 is shown. The head chip 20 includes an electrode substrate 121 on which an electrode 108 is formed, a pressurizing chamber substrate 122 that forms a pressurizing chamber 26, and a nozzle substrate 123 on which a nozzle 22 is formed. The same number of pressurizing chambers 26 and nozzles 22 as the supply ports 16 are provided and correspond one-on-one. When a voltage is applied between the common electrode (not shown) and the electrode 108, the liquid flowing into the pressurizing chamber 26 is pressurized by the elastic displacement of the vibration plate 109 and is discharged from the nozzle 22. Note that a groove is formed in the electrode substrate 121 from the lower surface in the drawing, and the electrode 108 is formed on the ceiling portion thereof. Therefore, a slight gap (air gap) is formed between the electrode 108 and the diaphragm 109. ) Is formed. In the present embodiment, the electrode 108 and the diaphragm 109 correspond to the pressurizing unit. The material of the pressurizing chamber substrate 122, the nozzle substrate 123, and the electrode substrate 121 is not particularly limited, but glass, silicon, or the like is suitable when the liquid to be discharged includes a biological sample.

By bonding the head chip 20 to the substrate 30, the through holes provided in the electrode substrate 121 and the pressurizing chamber substrate 122 are connected to the through holes of the substrate 30, and the supply port 16 (see FIG. 2) is pressed. The chamber 26 is communicated to complete the ink jet head 10. In this embodiment, there is a slight step between the surface of the head chip on which the nozzles are formed and the lower surface of the substrate 30. Call.
(Microarray manufacturing equipment)
Next, the droplet discharge device according to the present invention will be described. FIG. 5 is a diagram illustrating a configuration example of a microarray manufacturing apparatus 200 as an example of a droplet discharge apparatus according to the present invention.

  The microarray manufacturing apparatus 200 is for manufacturing a microarray manufactured by arranging a plurality of liquid droplets of a sample liquid containing a biomolecule on a microarray substrate 202 such as glass, and a plurality of microarray substrates 202 can be placed thereon. A table 204 configured as above, a Y-direction drive shaft 206 for moving the inkjet head 10 freely in the Y direction, and an X-direction drive shaft 208 for moving the table 204 freely in the X direction. In addition, a fixing unit 210 for fixing the inkjet head 10, a water retention liquid holding unit 212 that can approach the nozzle when the nozzle of the inkjet head 10 is fixed upward, a fixing unit 210, and a water retention liquid And a Z-direction drive shaft 207 for freely moving the holding means 212 independently in the Z direction. The Z-direction drive shaft 207 also includes means for moving the fixing means 210 freely in the X direction.

  Further, the microarray device 200 also includes a suction device 222, and is attached to a Z-direction drive shaft 220 for moving the suction device 222 in the Z direction. The Z-direction drive shaft 220 is also attached with a table 226 on which a discharge preparation liquid plate 224 prepared with a discharge preparation liquid is placed.

  On the other hand, a 96-hole microtiter plate 203 storing sample liquid is prepared on the table 204.

Here, FIG. 6 shows a schematic view of the fixing means 210 as seen from the right direction in FIG. 6, taking the case where the inkjet head 10 is fixed as an example. The inkjet head 10 is fixed to the fixing means 210 by a rotating shaft 216 (rotating means), and only the inkjet head 10 can be rotated around the rotating shaft 216 in a plane including the vertical direction. 6A shows a state in which the inkjet head 10 is fixed with the nozzle facing downward, and FIG. 6B shows a state in the middle of rotating the nozzle to face upward. In a state where the nozzle is directed upward or downward and the substrate of the inkjet head 10 is horizontal (for example, the state shown in FIG. 6A), the inkjet head 10 can be fixed to the fixing means 210 with a fastener or the like.
(Microarray manufacturing method)
Next, a method for manufacturing a microarray according to the present invention will be described. FIG. 7 is a schematic cross-sectional view for explaining a microarray manufacturing method, and the steps will be described with reference to FIGS. For convenience of explanation, the fixing means 210 is omitted. The method for manufacturing a microarray according to the present invention is suitably performed by using the above-described droplet discharge device according to the present invention.

First, as shown in FIG. 7A, after fixing the inkjet head 10 by the fixing means 210 so that the nozzle 22 faces upward, the Y-direction drive shaft 206 is operated, and the fixing means 210 is further moved to the X direction. The inkjet head 10 is moved to above the ejection preparation liquid plate 224 by moving in the direction. A discharge preparation liquid is prepared in advance on the discharge preparation liquid plate 224. The discharge preparation liquid is preferably pure water or a buffer solution as described above. The discharge preparation liquid may be prepared in a microtiter plate similarly to the sample liquid, or may be prepared in a container in which all the supply ports 16 can be immersed at one time. In this embodiment, the latter is the latter. .

  Subsequently, the Z-direction drive shaft 207 is operated to immerse the supply port 16 in the discharge preparation liquid on the discharge preparation liquid plate 224. In this state, the Z-direction drive shaft 220 to which the suction device 222 is attached is operated to bring the suction device 222 into close contact with the first main surface 12 so as to cover the nozzle 22 of the inkjet head 10. Then, as shown in FIG. 7B, the suction device 222 is operated, and suction is performed until the discharge preparation liquid reaches the tip of the nozzle 22. When a sample liquid containing a different sample is sucked and filled to the tip of the nozzle 22, contamination may occur at the tip of the nozzle 22, but there is no fear of this being a discharge preparation liquid.

Next, the Z-direction drive shaft 220 is actuated to raise the suction device 222 to remove it from the inkjet head 10, and then the fixing means 210 is moved in the X direction to be disposed below the water-absorbing liquid holding means 212. . Even if the suction device 222 is removed, the inner diameter of the nozzle 22 is sufficiently thin, so that the discharge preparation liquid forms a meniscus at the open end of the supply port and does not flow out. Thereafter, the Y-direction drive shaft 206 and the X-direction drive shaft 208 are operated, and the inkjet head 10 and the water-absorbing liquid holding means 212 are disposed above the microtiter plate 203.

  Then, as shown in FIG. 7C, the Z-direction drive shaft 207 is operated to immerse the supply port 16 of the inkjet head 10 in the sample liquid in each well of the microtiter plate 203. Here, as the sample liquid, a buffer solution in which a biomolecule to be immobilized on the microarray substrate (for example, DNA, protein, etc.) is dissolved can be used. Next, the water-absorbing liquid holding means 212 is lowered and brought close to the nozzle 22 to a distance that the discharged liquid from the nozzle 22 reaches the water-absorbing holding means.

  Subsequently, as illustrated in FIG. 7D, the pressurizing unit of the head chip 20 is operated, and the discharge preparation liquid is discharged from the nozzle 22 into the water-absorbing liquid holding unit 212. By doing so, the sample liquid stored in the microtiter plate 203 is sucked up from the supply port 16 by the volume of the discharged liquid. When the pressurizing unit is operated repeatedly until all of the ejection preparation liquid in the inkjet head 10 is ejected, the tip of the nozzle can be filled with the sample liquid as shown in FIG.

  Since the liquid droplets are ejected instantaneously, the sample liquid can be filled to the nozzle tip in an extremely short time, and the interface between the liquid preparation liquid and the sample liquid passes through the flow path 13 in the ink jet head 10. It can also prevent air bubbles from entering. Incidentally, it is assumed that slight diffusion occurs at the interface between the discharge preparation liquid and the sample liquid. In this case, the portion where the diffusion has occurred may be discharged. Further, the discharge preparation liquid is discharged upward from the nozzle 22, but is absorbed and held by the water retention liquid holding means 212, so that the discharged liquid falls due to gravity and is around the nozzle and the first Contamination of the main surface 12 can also be suppressed.

  Next, the Z-direction drive shaft 207 is actuated to pull up the inkjet head 10 from the sample liquid and raise the water retention liquid holding means 212 to remove it from the first main surface 12 of the inkjet head 10. Then, the inkjet head 10 is rotated 180 degrees around the rotation shaft 216 of the fixing means 210 and turned upside down, and is fixed again so that the nozzle 22 faces downward.

  Subsequently, the Y-direction drive shaft 206 and the X-direction drive shaft 208 are operated to place the inkjet head 10 above the microarray substrate 202. In this state, the Z-direction drive shaft is actuated to adjust the distance between the nozzle 22 and the microarray substrate 202, and as shown in FIG. 202 Discharge onto the surface. As a result, biomolecules in the sample liquid are fixed on the surface of the microarray substrate 202, and a microarray is formed.

  According to the present invention, the liquid (sample liquid, cleaning liquid) can be quickly introduced from the supply port into the ink jet head without bubbles, so that a high performance microarray can be produced with high productivity. .

  In addition, this invention is not limited to the content of embodiment mentioned above, A various deformation | transformation implementation is possible within the range of the summary of this invention. For example, the number of nozzles, liquid holding units, and supply ports is not limited to 96, and can be freely changed according to the number of wells of a sample container such as a microtiter plate to be used. Further, the liquid to be ejected is not limited to those containing biomolecules, and any type can be used as long as it can be ejected from the ink jet head.

It is a perspective view which shows the droplet discharge head which concerns on this invention. It is an example of a sectional view of a droplet discharge head concerning the present invention. It is an example of the top view of the board | substrate which comprises the droplet discharge head which concerns on this invention. It is an example of a sectional view of a head chip of a droplet discharge head according to the present invention. 1 is an example of a droplet discharge device according to the present invention. It is explanatory drawing which shows operation | movement of the fixing means of the droplet discharge apparatus which concerns on this invention. It is explanatory drawing which shows the process of the microarray manufacturing method which concerns on this invention.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Droplet discharge head, 12 ... 1st main surface, 14 ... 2nd main surface, 16 ... Supply port, 13 ... Flow path, 13 '... Groove, 20 ... Head chip, 22 ... Nozzle, 26 ... Addition Pressure chamber, 30, 40, 50 ... Substrate, 42, 52 ... Through-hole, 200 ... Droplet ejection device, 202 ... Microarray substrate, 203 ... Microtiter plate, 204 ... Table, 206 ... Y-direction drive shaft, 207, 220 ... Z-direction drive shaft, 208 ... X-direction drive shaft, 210 ... fixing means, 212 ... water-retaining liquid holding means, 216 ... rotating shaft, 222 ... suction device, 224 ... discharge preparation liquid plate

Claims (6)

A nozzle formed on the first main surface, a pressurizing chamber provided with a pressurizing means for pressurizing the liquid discharged from the nozzle, a liquid storage unit communicating with the pressurization chamber, and the liquid storage unit And a supply port for supplying a liquid to the liquid, and the supply port is provided with a liquid droplet ejection head provided so as to protrude from the second main surface opposite to the first main surface A method of manufacturing a microarray using a droplet discharge device,
A first step of filling a discharge preparation liquid from the supply port of the droplet discharge head to the nozzle tip;
A second step of immersing each of the supply ports in a sample liquid containing a sample fixed to the microarray substrate;
A third step of bringing the liquid holding means having water retention close to the nozzle;
The pressurizing means is operated while the supply port is immersed in the sample liquid, and the sample preparation liquid is discharged to the tip of the nozzle by discharging all of the discharge preparation liquid from the nozzle into the water retention liquid holding means. A fourth step of filling;
A fifth step of operating the pressurizing means to discharge the sample liquid onto the microarray substrate. The first step includes
Immersing the supply port in the discharge preparation liquid;
The method of manufacturing a microarray according to claim 1, further comprising: sucking a gas or a liquid in the droplet discharge head from the nozzle and filling the discharge preparation liquid to a tip of the nozzle.   The microarray manufacturing method according to claim 1, wherein the discharge preparation liquid is pure water or a buffer solution contained in the sample liquid. A nozzle formed on the first main surface, a pressurizing chamber having a pressurizing means for pressurizing the liquid discharged from the nozzle, a liquid holding unit communicating with the pressurizing chamber, and the liquid holding unit A liquid supply port for supplying liquid to the liquid discharge head, and the supply port is mounted with a droplet discharge head provided so as to protrude from the second main surface opposite to the first main surface A droplet discharge device used,
Fixing means capable of fixing the droplet discharge head with the nozzle facing upward or downward;
A liquid droplet ejection apparatus comprising: a water retention liquid holding unit that can be brought close to the nozzle when the nozzle is fixed upward.   And a suction means that covers the nozzle and adheres closely to the first main surface when the nozzle is fixed upward, and is capable of sucking the gas or liquid in the droplet discharge head from the nozzle. Item 5. The droplet discharge device according to Item 4. 6. The droplet discharge device according to claim 4, wherein the fixing unit includes a rotating unit that reverses the top and bottom of the droplet discharge head.

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