JP2004020393A - Manufacturing method and manufacture equipment for probe carrier - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an excellent probe carrier manufacturing method in which a different probe material is precluded from being mixed in the respective probe materials arranged on a probe carrier substrate, and in which purity of the each arranged probe material is high. <P>SOLUTION: In this probe carrier manufacturing method wherein a plurality of kinds of probe solutions corresponding respectively to a plurality of kinds of probes is delivered on the substrate from a liquid delivery part having a liquid delivery port face of which the plurality of liquid delivery ports is opened in a two-dimensional array of m lines and n rows, so as to arrange the plurality of kinds of probes on the substrate, a process is provided to wipe out the liquid delivery port face, using a wiping-out part. In the wiping-out process, a portion of the wiping-out part passing through on the liquid delivery port conducts the wiping-out along a direction not passed through on the other liquid delivery port. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing a probe carrier on a solid phase substrate and an apparatus for producing a probe carrier exclusively used for carrying out the production method.
[0002]
[Background Art]
In the case of analyzing the base sequence of gene DNA, or simultaneously performing highly reliable gene diagnosis for multiple items, it is necessary to select DNA having the target base sequence using a plurality of types of probes. Become. As a means for providing a plurality of types of probes used for this sorting operation, a DNA microchip has been receiving attention. Also, in the case of high-throughput screening of drugs and the like or development of drugs by combinatorial chemistry, it is necessary to carry out an ordered screening of a large number of target proteins (eg, 96, 384 or 1536) of proteins or drugs. Is required. For that purpose, a method for arranging many kinds of drugs, automated screening technology in that state, dedicated equipment, software for controlling a series of screening operations and statistically processing the results are also developed. Have been.
[0003]
Basically, these parallel screening operations are performed using a so-called probe carrier (also referred to as a probe array) in which a number of known probes serving as selection means for a substance to be evaluated are arranged, and under the same conditions. This is to detect the presence or absence of an action or reaction on the probe material in step (1). Generally, what kind of action or reaction to use for a probe material is determined in advance, and therefore, a probe material mounted on one probe carrier is, for example, a group of DNA probe materials having different base sequences. It can be broadly classified as one type of substance. That is, the substances used as a group of probe materials include, for example, DNA, protein, and synthesized chemicals (drugs). In many cases, a probe carrier composed of a plurality of types of probes forming a group is often used. However, depending on the nature of the screening work, a DNA having the same base sequence, a protein having the same amino acid sequence, It is also possible to use a form in which a large number of chemical substances are arranged in an array. These are mainly used for drug screening and the like.
[0004]
In a probe carrier composed of a plurality of types of probes forming a group, specifically, a group of DNAs having different base sequences, a group of proteins having different amino acid sequences, or a group of different chemical substances, In many cases, the seeds are arranged in an array on a substrate or the like according to a predetermined arrangement order. Above all, the DNA probe carrier is used when analyzing the base sequence of gene DNA, or when performing highly reliable gene diagnosis on multiple items at the same time.
[0005]
As one method of arranging a plurality of types of probes in an array on a substrate, there is a method of sequentially discharging a plurality of types of probe solutions at a desired timing using a liquid discharge unit and arranging them on the substrate. An invention using an ink-jet method generally used in a printer is disclosed for a liquid ejection unit.
[0006]
JP-A-11-187900 discloses a method in which a liquid containing a probe material is attached as droplets to a solid phase by a thermal inkjet head, and a probe is arranged on the solid phase. In this method, DNA to be used as a probe material is synthesized and purified in advance, and in some cases, its base length is confirmed before being attached to a substrate.
[0007]
In addition, EP 0 703 825 B1 discloses that a nucleotide sequence and an activator used in solid-phase synthesis of DNA are supplied from separate piezo jet nozzles, respectively, so that a predetermined nucleotide sequence is provided. A method for solid-phase synthesis of a plurality of DNAs having the following is described. In this method, solid phase synthesis of DNA is performed on a substrate, and a solution of a substance necessary for synthesis is supplied to the substrate by an inkjet method at each elongation step.
[0008]
[Problems to be solved by the invention]
As introduced above, as a conventional method of producing a probe carrier, an ink jet method generally used for a printer is used.
[0009]
However, when fabricating a probe carrier, there is a point to be improved by simply applying the ink discharging method for a printer to the probe solution discharging method as it is. Hereinafter, this point will be described in detail using a DNA probe carrier as an example.
[0010]
As described above, different types of probe materials are disposed on the substrate of the DNA probe carrier. For this reason, it is desired to use a liquid ejection unit capable of ejecting various types of liquids, unlike a conventional ink jet head for a printer, in producing a probe carrier.
[0011]
In general ink jet heads for printers, four to seven types of ink are used.
[0012]
FIG. 1 shows an arrangement of nozzles of a conventional head. FIG. 1 shows a nozzle configuration of a head that ejects four color inks of yellow (Y), magenta (M), cyan (C), and black (BK).
[0013]
In FIG. 1, reference numeral 11 denotes a nozzle, and reference numeral 12 denotes a nozzle surface.
[0014]
In the current printer, there is a head having 256 to 512 nozzles per color, but for simplicity of description, FIG. 1 shows a head having 8 nozzles per color. In the head shown in FIG. 1, four nozzle rows composed of eight nozzles per color are arranged.
[0015]
During printing, unintended ink or dust may adhere to the nozzle surface. When such adhesion occurs, the ink ejection state is affected, and the print quality may be degraded. In order to prevent this, a general printer performs an operation called wiping at a desired timing during printing. In wiping, a wiper (blade), which is a wiping unit made of rubber or a polymer, scans and wipes a nozzle surface (liquid discharge port surface) where a nozzle (liquid discharge port) of a head is opened in a predetermined direction to thereby adhere. Removed ink and dust.
[0016]
In a general printer head as shown in FIG. 1, as shown in FIG. 2, a wiper is arranged in a direction perpendicular to a nozzle row from which the same color ink is ejected, and the wiper is arranged in the nozzle row arrangement direction (FIG. 2). (The direction indicated by a white arrow in the middle). In FIG. 2, reference numeral 13 denotes a wiper. FIG. 3 is a sectional view taken along line AA ′ in FIG.
[0017]
When wiping is performed in this manner, a part of the ink existing inside the nozzle may be drawn out when the wiper passes through the nozzle portion. Since such a phenomenon is known, in a general printer head as described above, wiping is performed so that the scanning direction of the wiper coincides with the arrangement direction of the nozzles that eject ink of the same color. The phenomenon of mixing color inks, that is, color mixing is prevented.
[0018]
By the way, as described above, in the case of producing a probe carrier, it is desired to use a liquid ejection unit capable of ejecting various kinds of liquids.
[0019]
FIG. 4 shows an arrangement of nozzles of the liquid discharge unit. FIG. 4 shows a nozzle configuration of a liquid ejection unit having a nozzle arrangement of 8 rows and 8 columns. In this liquid ejection unit, 64 different DNA solutions are ejected from each of the 64 nozzles. In FIG. 4, 21 is a nozzle, and 22 is a nozzle surface.
[0020]
In such a liquid discharge unit, if a wiping operation similar to that of the above-described printer head is performed, the nozzles that discharge different DNA solutions are arranged in each row, so that the DNA solutions are mixed. When the DNA solution is discharged in such a state, each probe of the obtained probe carrier is a mixture of unintended DNA. Therefore, it is not possible to produce a good probe carrier simply by applying the wiping method for a printer to the production of a probe carrier as it is.
[0021]
The present invention solves the above-mentioned problems, and when manufacturing a probe carrier using a liquid ejection unit, the probe carrier is arranged on the probe carrier substrate even when a scan for wiping the surface of the ejection port array is performed. Another object of the present invention is to provide a method for producing a good probe carrier having a high purity of each arranged probe material without mixing different probe materials with each other.
[0022]
[Means for Solving the Problems]
The inventor of the present invention has conducted intensive studies to solve the above-described problems. As a result, when wiping the nozzle surface of the liquid discharge unit, the direction of the scan by the wiper is appropriately set, so that unintended probe material can be used. It has been found that a probe carrier free from mixing can be produced.
[0023]
That is, the method of manufacturing the probe carrier according to the first embodiment of the present invention includes a method of manufacturing a plurality of types of liquid discharge ports from a liquid discharge section having a liquid discharge port surface opened in a two-dimensional array of m columns and n rows. By discharging a plurality of types of probe solutions corresponding to each of the probes onto a substrate, a method of manufacturing a probe carrier in which each of a plurality of types of probes is disposed on the substrate, wherein the liquid discharge port surface is The method further includes a step of wiping using a wiping unit, wherein in the wiping step, a portion of the wiping unit passing over a certain liquid ejection port is wiped in a direction not passing over another liquid ejection port.
[0024]
Here, when the column interval of the liquid ejection sections is X and the row interval of the liquid ejection ports is Y, the angle θ between the column direction of the liquid ejection ports and the wiping direction is 0 <. It is preferable that tan θ <X / Y (n−1) is satisfied. Alternatively, when the average diameter of the liquid ejection port is D, it is preferable that 3D / Y ≦ tanθ ≦ (X−3D) / Y (n−1).
[0025]
Further, the column interval of the liquid ejection ports of the liquid ejection section is X, the row interval of the liquid ejection ports is Y, and when n ≦ m, the column direction of the liquid ejection ports and the wiping direction Is preferably X (m−2) / Y (m−1) <tan θ <X / Y. Alternatively, when the average diameter of the liquid ejection port is D, it is preferable that (X (m−2) + 3D) / Y (m−1) ≦ tan θ ≦ (X−3D) / Y.
[0026]
Alternatively, the probe may be a single-stranded nucleic acid having a base sequence complementary to all or a part of the nucleic acid, and specifically hybridizing with the base sequence of the nucleic acid.
[0027]
The apparatus for manufacturing a single probe according to the second embodiment of the present invention includes a plurality of types of probes from a liquid ejection unit having a plurality of liquid ejection ports having a liquid ejection port surface opened in a two-dimensional array of m columns and n rows. An apparatus for manufacturing a probe carrier on which a plurality of types of probes are disposed on the substrate by discharging a plurality of types of probe solutions corresponding to each of the plurality of types of probe solutions onto the substrate, wherein the liquid discharge port surface A wiping portion for wiping the liquid, wherein the wiping portion wipes in a direction in which a portion of the wiping portion passing over a certain liquid discharge port does not pass over another liquid discharge port.
[0028]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the method for producing a probe carrier of the present invention will be described in more detail. Although the examples shown here are examples of the best mode of the present invention, the present invention is not limited to these examples. In the present specification, the target substance targeted by the probe carrier is a nucleic acid, and the probe has a base sequence complementary to all or a part of the nucleic acid, and is specific to the base sequence of the nucleic acid. Is a single-stranded nucleic acid that hybridizes to
[0029]
【Example】
(Example 1)
FIG. 5 shows a schematic diagram of the structure of a probe carrier manufacturing apparatus using a liquid ejection unit. In FIG. 5, reference numeral 51 denotes a liquid discharge unit (liquid discharge unit); 52, a shaft for guiding the movement of the liquid discharge unit substantially in parallel; 53, a stage (substrate holding mechanism) on which a substrate of a probe carrier is fixed; A glass substrate 55 serving as a carrier substrate is a wiping device for wiping.
[0030]
The liquid discharge unit 51 can move in the X direction in FIG. 5, and the stage 53 can move in the Y direction. Therefore, the liquid discharge unit 51 can move two-dimensionally relative to the stage 53.
[0031]
When the liquid discharge unit 51 passes over the glass substrate 54 fixed to the stage 53, the probe solution is discharged from the liquid discharge unit at a desired timing, and the probe is arranged on the glass substrate.
[0032]
FIG. 6 shows a schematic diagram of the probe carrier. The probes 56 are regularly arranged on the glass substrate 54 as shown in FIG.
[0033]
The diameter of the arranged probes is 10 μm to 150 μm, and the distance between adjacent probes is 50 μm to 1000 μm.
[0034]
When a probe material (for example, DNA) synthesized and purified in advance is arranged on a substrate, the liquid ejection unit 51 has a structure having nozzles capable of ejecting the same number of probe solutions as the probes arranged on a glass substrate. preferable.
[0035]
For example, when a probe carrier having a probe array of 8 rows and 8 columns shown in FIG. 6 is manufactured using a liquid discharge unit capable of discharging different probe materials of 8 rows and 8 columns shown in FIG. The probe carrier can be manufactured without replacement of the probe carrier.
[0036]
Further, it is preferable that the arrangement density of the probes of the probe carrier to be produced is equal to the arrangement density of the nozzles of the liquid ejection unit, since the probe carrier can be produced by one scanning of the liquid ejection unit.
[0037]
FIG. 5 shows the structure of the probe carrier manufacturing apparatus when a plurality of glass substrates 54 are fixed and the probes are arranged. However, the probes are arranged on one large glass substrate, and then the glass substrates are mounted. A plurality of probe carriers may be obtained by cutting.
[0038]
FIG. 7 is a schematic diagram of the liquid discharge unit. As a method of discharging the liquid, a bubble jet (registered trademark) (thermal jet) method in which film boiling occurs in the liquid by thermal energy generated from a heater and the liquid is discharged by the pressure of generated bubbles, and a piezo element is used. There is a piezo jet method or the like in which a liquid is ejected by deformation of an element caused by applying a voltage. FIG. 7 shows the structure of a bubble jet (registered trademark) type liquid ejection unit.
[0039]
In FIG. 7, 71 is a silicon substrate, 72 is an insulating film, 73 is a heater made of TaN, TaSiN, TaAl, or the like, 74 is a protective film, 75 is a cavitation-resistant film made of Ta or the like, 76 is a nozzle material, 77 is a nozzle ( (Liquid ejection port), 78 is a flow path, and 79 is a supply port.
[0040]
Wiring (not shown) made of aluminum or the like is connected to both ends of the heater 73, and a desired voltage pulse is applied to both ends of the heater 73 via the wiring.
[0041]
The insulating film 72 may be a thermal oxide film formed by thermally oxidizing a silicon substrate, or an oxide film or a nitride film formed by CVD.
[0042]
The protective film 74 may be any film such as an oxide film or a nitride film formed by CVD.
[0043]
The nozzle material 76 forming the nozzle 77 and the flow path 78 may be formed by attaching a nozzle material having a nozzle and a flow path to a semiconductor substrate in advance, or by using a photolithography technique and a semiconductor process. May be.
[0044]
The supply port 79 is formed by anisotropic etching of silicon using a tetramethylammonium hydroxide (TMAH) solution, and is inclined at an angle of about 54.7 ° with respect to the substrate surface as shown in FIG. Open. The supply port 79 supplies a liquid (probe solution) from the back surface of the substrate to the surface of the substrate, and also functions as a liquid reservoir for holding the liquid (probe solution).
[0045]
When the number of probe carriers manufactured is small and the amount of the probe solution discharged to one probe is small, the amount of the probe solution present in the supply port may be sufficient for manufacturing a series of probe carriers. If more probe solution needs to be discharged, a second reservoir (not shown) connected to the supply port 79 is provided.
[0046]
The liquid (probe solution) is guided from the back surface of the substrate to the surface of the substrate from the supply port 79 as shown in FIG. When a desired voltage pulse is applied to both ends of the heater 73, the liquid (probe solution) near the heater is overheated to cause film boiling, and the liquid is discharged as shown in FIG.
[0047]
In order to stably discharge a liquid (probe solution), it is essential to cause stable film boiling. In order to cause stable film boiling, it is desirable to apply a voltage pulse of 0.1 to 5 μs to the heater.
[0048]
The amount of the probe solution discharged from one nozzle at a time depends on various factors such as the viscosity of the probe solution, the affinity between the probe solution and the solid substrate, and the reactivity between the probe material and the solid substrate. Is appropriately selected according to the dot size and shape of the probe (array) to be formed. Generally, an aqueous solvent is used for the probe solution, and in the method of the present invention, the droplet of the probe solution discharged from each nozzle of the liquid discharge unit generally has a volume of 0.5 pl. It is preferable to select within the range of 100 pl, and to design the nozzle diameter and the like in accordance with the liquid amount.
[0049]
It is preferable that the probe material has a structure that can be bonded to the solid substrate, and that the probe solution is discharged and applied, and then the probe material is bonded to the solid substrate using the bondable structure. Examples of the structure that can be bonded to the solid phase substrate include an amino group, a mercapto group, a carboxyl group, a hydroxyl group, an acid halide (—COX), a halide, an aziridine, a maleimide, a succinimide, an isothiocyanate, and a sulfonyl chloride (—SO ₂ Cl), aldehyde (—CHO), hydrazine, iodoacetamide, or the like, and can be formed by performing a process of introducing an organic functional group into a probe material molecule in advance. In this case, on the other hand, it is necessary to previously perform a structure for forming a covalent bond by reacting with the above-mentioned various organic functional groups and a process for introducing an organic functional group on the substrate surface.
[0050]
Next, the wiping method which is a feature of the present invention will be described.
[0051]
As described above, the probe carrier manufacturing apparatus described with reference to FIG. 5 includes the wiping device indicated by 55 in FIG. The wiping device has wiping means (wiper) and driving means for driving the wiping means. The wiping means can use any material known for an ink jet recording head, and has a contour conforming to the nozzle surface (liquid ejection port surface). As described above, during the placement of the probe material, wiping is performed at a desired timing to remove an unintended probe solution and dust adhering to the nozzle surface.
[0052]
When performing wiping, the liquid discharge unit 51 moves to the wiping device 55 and receives a wiping operation. As described above, the conventional wiping method using a printer head is not suitable for wiping a liquid discharge unit. This will be described with reference to FIG.
[0053]
Consider a conventional wiping method, that is, a case where the wiper is moved in a direction parallel to the arrangement direction of the nozzles as indicated by arrows in FIG. As described above, in the liquid discharge unit, different solutions are discharged from the respective nozzles. Therefore, a total of 64 nozzles in 8 rows and 8 columns shown in FIG. 9 are filled with 64 different DNA solutions.
[0054]
Now, in FIG. 9, the columns are A, B, C... H in order from the left, and the rows are 1, 2, 3,.
[0055]
For example, taking row A as an example, row A has eight nozzles 1-A to 8-A, each of which is filled with eight different DNA solutions.
[0056]
Here, when performing the conventional wiping, the wiper first passes through the nozzle 1-A, but when the wiper passes through the nozzle 1-A, the DNA solution slightly filled in the nozzle is pulled out. It is.
[0057]
The wiper passes through the nozzle 2-A while moving the extracted DNA solution. At this time, a part of the DNA solution drawn from the nozzle 1-A carried by the wiper enters the nozzle 2-A. That is, the DNA solution filled in the nozzle 1-A is mixed with the DNA solution filled in the nozzle A-2.
[0058]
Similarly, with the movement of the wiper, the DNA solution is also drawn out from the nozzle 2-A and carried to the nozzle A-3. A similar phenomenon is repeated up to the nozzle 8-A. Further, the same phenomenon occurs in other rows, that is, rows B to H. As described above, the conventional wiping method is not suitable for wiping the liquid discharge unit.
[0059]
FIG. 10 shows the wiping method of the present invention. In the present invention, as shown in FIG. 10, wiping is performed by moving the wiper in a direction forming a desired angle θ with respect to the row direction of the two-dimensional array of nozzles.
[0060]
This will be described in more detail with reference to FIG. In FIG. 11, the trajectory of the DNA solution drawn from each nozzle at the time of wiping is indicated by a broken line. The trajectory of the DNA solution drawn from each nozzle reaches the outside of the area where the nozzles are arranged without crossing the nozzles other than the nozzle from which the solution was drawn. Therefore, the DNA solution drawn from each nozzle does not enter another nozzle, and the DNA solutions do not mix.
[0061]
A preferred example of the conditions under which the angle θ between the wiping direction and the nozzle array is set to enable wiping without mixing of the DNA solution as described above will be described.
[0062]
FIG. 11 shows a case where the DNA solution drawn out from the plurality of nozzles arranged in row A passes between the nozzles 8-A and 8-B and is drawn out of the nozzle arrangement region. That is, as indicated by the middle broken line in FIG. 11, the DNA solution drawn from the nozzles in an arbitrary row passes between the nozzle row and the nozzle row adjacent to the nozzle row.
[0063]
Such a state can be realized when the nozzle arrangement is m columns and n rows, the nozzle row interval is X, and the nozzle row interval is Y, when θ satisfies the following equation.
[0064]
0 <tanθ <X / Y (n-1) (1)
[0065]
Further, in order to completely prevent the mixing of the DNA solution, it is preferable to consider the spread of the DNA solution on the nozzle surface.
[0066]
Assuming that the diameter of the nozzle is D, the spread of the ink drawn from each nozzle on the nozzle surface is generally 3D or less. Therefore, when the spread of the ink is taken into consideration, the condition under which the DNA solutions drawn from the nozzles do not mix can be expressed by the following equation.
[0067]
3D / · Y ≦ tan θ ≦ (X-3D) / Y (n−1) (2)
[0068]
In this case, the diameter of the nozzle, the number of nozzles (the number of rows) n in the vertical direction, and the interval X between the nozzles in the horizontal direction must satisfy the following expressions.
3D · n ≦ X (3)
[0069]
(Example 2)
In the first embodiment, the description has been given of the case where the DNA solution drawn out from the nozzles in an arbitrary row passes between the nozzle row and the nozzle row adjacent to the nozzle row. The angle of the wiping direction for preventing the mixed DNA solution from being mixed is not limited to that shown in the first embodiment. In a second embodiment, another wiping method will be described.
[0070]
FIG. 12 shows another wiping method of the present invention. In the first embodiment, the angle θ between the nozzle row and the wiping direction is an angle close to 0 °, but in the second embodiment, θ is a relatively large angle, and the distance between adjacent nozzles is the same in rows and columns. In this case, the angle is close to 45 °.
[0071]
This will be described in more detail with reference to FIG. As shown by the middle broken line in FIG. 13, the DNA solution drawn from the nozzles in an arbitrary row is drawn from the nozzle region without mixing.
[0072]
Consider a DNA solution drawn from the first row of nozzles in FIG. In the second embodiment, the second nozzle (7-A) from the lower left is between the first and second rows, and the third nozzle (6-A) from the lower left is between the second and third rows. The eighth nozzle from the lower left, that is, the top nozzle (1-A) is between the seventh and eighth columns, and so on, the n-th nozzle from the lower left is the 1-nth column and the nth column It is drawn out of the nozzle area through the space between the eyes. In such a state, when the nozzle array has m columns and n rows and the relationship of n ≦ m is satisfied, the column interval of the nozzle array is X, and the row interval of the nozzle array is Y, This can be realized when the angle θ formed with the wiping direction satisfies the following equation.
[0073]
X (m−2) / Y (m−1) <tan θ <X / Y (4)
[0074]
As in the case of the first embodiment, in order to completely prevent the mixing of the DNA solution, it is preferable to consider the spread of the DNA solution on the nozzle surface. That is, when the spread of the ink is taken into consideration, the condition under which the DNA solutions drawn from the respective nozzles do not mix can be expressed by the following equation.
[0075]
(X (m−2) + 3D) / Y (m−1) ≦ tan θ
≦ (X-3D) / · Y (5)
[0076]
In this case, the diameter of the nozzle, the number of nozzles (the number of rows) n in the vertical direction, and the interval X between the nozzles in the horizontal direction must satisfy the following expressions.
[0077]
3D · m ≦ X (6)
[0078]
As described above, the examples in which the DNA solutions drawn out from the respective nozzles are drawn out of the nozzle region without being mixed with each other are specifically described in the first and second embodiments.
[0079]
Θ in the present invention is not limited to the above two conditions, and may be any angle as long as the DNA solutions drawn from each nozzle are drawn from the nozzle region without being mixed with each other.
[0080]
Although the description has been made using the bubble jet (registered trademark) type liquid ejection unit, the present invention is not limited to the bubble jet (registered trademark) type, and other types of liquid such as a piezo jet type may be used. It is also applicable to a discharge unit.
[0081]
【The invention's effect】
In the method of manufacturing a probe carrier of the present invention, when wiping the nozzle surface of the liquid ejection unit, the DNA solutions drawn from each nozzle are drawn out of the nozzle region without being mixed with each other. And a good product with high purity can be obtained with the probe.
[Brief description of the drawings]
FIG. 1 is a schematic diagram showing an arrangement of nozzles of a conventional inkjet recording head.
FIG. 2 is a schematic view for explaining a conventional wiping method of an ink jet recording head.
FIG. 3 is a schematic view (cross-sectional view) for explaining a conventional wiping method of an ink jet recording head.
FIG. 4 is a schematic view showing an arrangement of nozzles of a liquid discharge unit.
FIG. 5 is a schematic view of the structure of a probe carrier manufacturing apparatus.
FIG. 6 is a schematic view of a probe carrier.
FIG. 7 is a schematic diagram of a liquid discharge unit.
FIG. 8 is a schematic diagram of a liquid discharge unit.
FIG. 9 is a schematic diagram for explaining a problem when a conventional head wiping method is applied to a liquid discharge unit.
FIG. 10 is a schematic diagram for explaining an example of the present invention.
FIG. 11 is a schematic diagram for explaining an example of the present invention.
FIG. 12 is a schematic diagram for explaining another embodiment of the present invention.
FIG. 13 is a schematic diagram for explaining another embodiment of the present invention.
[Explanation of symbols]
11 nozzles
12 Nozzle surface
13 Wiper
21 nozzle
22 Nozzle surface
23 Wiper
51 Liquid discharge unit
52 shaft
53 stages
54 glass substrate
55 Wiping device
56 probes
71 Silicon substrate
72 Insulation film
73 heater
74 Protective film
75 Anti-cavitation film
76 Nozzle material
77 nozzle
78 channel
79 Supply port

Claims (7)

A plurality of types of probe solutions respectively corresponding to a plurality of types of probes are discharged onto a substrate from a liquid discharge portion having a plurality of liquid discharge ports having a liquid discharge port surface opened in a two-dimensional array of m columns and n rows. A method for producing a probe carrier in which each of a plurality of types of probes is arranged on the substrate,
Comprising a step of wiping the liquid ejection port surface using a wiping unit,
The method of manufacturing a probe carrier, wherein in the wiping step, a portion of the wiping portion passing over a certain liquid discharge port is wiped in a direction not passing over another liquid discharge port. The column interval of the liquid ejection unit is X, the row interval of the liquid ejection port is Y,
The angle θ between the row direction of the liquid ejection ports and the direction of the wiping is
0 <tanθ <X / Y (n-1)
The method for producing a probe carrier according to claim 1, wherein the following conditions are satisfied. The liquid discharge port row interval is X, the liquid discharge port row interval is Y,
The average diameter of the liquid ejection port is D,
The angle θ between the row direction of the liquid ejection ports and the direction of the wiping is
3D / Y ≦ tan θ ≦ (X-3D) / Y (n−1)
The method for producing a probe carrier according to claim 1, wherein the following conditions are satisfied. The column interval of the liquid ejection ports of the liquid ejection section is X, the row interval of the liquid ejection ports is Y, and n ≦ m,
The angle θ between the row direction of the liquid ejection ports and the wiping direction is
X (m-2) / Y (m-1) <tanθ <X / Y
The method for producing a probe carrier according to claim 1, wherein the following conditions are satisfied. The column interval of the liquid ejection ports of the liquid ejection section is X, the row interval of the liquid ejection ports is Y, and n ≦ m,
The average diameter of the liquid ejection port is D,
The angle θ between the row direction of the liquid ejection port row and the wiping direction is
(X (m−2) + 3D) / Y (m−1) ≦ tan θ
≤ (X-3D) / Y
The method for producing a probe carrier according to claim 1, wherein the following conditions are satisfied. 6. The probe according to claim 1, wherein the probe is a single-stranded nucleic acid having a base sequence complementary to all or a part of the nucleic acid, and specifically hybridizing with the base sequence of the nucleic acid. The method for producing a probe carrier according to any one of the above. A plurality of types of probe solutions respectively corresponding to a plurality of types of probes are discharged onto a substrate from a liquid discharge portion having a plurality of liquid discharge ports having a liquid discharge port surface opened in a two-dimensional array of m columns and n rows. Thus, an apparatus for manufacturing a probe carrier on which each of a plurality of types of probes are arranged on the substrate,
A wiping unit for wiping the liquid ejection port surface,
The apparatus for manufacturing a probe carrier, wherein the wiping portion wipes in a direction in which a portion of the wiping portion passing over a certain liquid ejection port does not pass over another liquid ejection port.

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