JP4522012B2 - Probe carrier manufacturing apparatus and manufacturing method - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a probe carrier manufacturing apparatus and manufacturing method, and more particularly to an apparatus for manufacturing a probe carrier by discharging a plurality of types of probe solutions from a plurality of nozzles provided in a liquid discharge device onto a carrier such as a glass substrate.
[0002]
[Prior art]
A method for selecting a DNA having a target base sequence using a plurality of types of probes capable of specifically recognizing a specific target (target) when analyzing the base sequence of gene DNA or performing genetic diagnosis Is used. There is a DNA microchip as a means for providing a plurality of types of probes used for this sorting operation. A DNA microchip has a plurality of types of probes arranged on a carrier in a two-dimensional array, and generally has several tens to several thousand different probes arranged, and is also called a probe array. .
[0003]
With respect to a method for producing a probe carrier used as a DNA microchip or the like by a liquid ejecting apparatus, a solution containing a probe is ejected from the liquid ejecting apparatus onto the carrier as disclosed in Japanese Patent Laid-Open No. 9-207837. Thus, a method of applying to spots arranged in a matrix has been proposed. About the manufacturing apparatus used for such manufacture of the probe carrier, since the configuration can be almost the same as that of a normal liquid discharge drawing apparatus or liquid discharge recording apparatus, a part thereof is customized. Generally used.
[0004]
The probe solutions spotted on each spot of the probe carrier are generally all different, and the probe solution is expensive, so that the amount of spotting is kept to the minimum necessary. For the same reason, operations that consume the discharge liquid, such as the suction recovery operation of the discharge liquid that is generally performed in a normal drawing apparatus or recording apparatus, and the preliminary discharge operation that discharges a liquid droplet that does not contribute to drawing are as much as possible. It is necessary to avoid it. However, the suction operation of the discharge liquid is performed for the purpose of refilling the discharge liquid into the nozzle or refreshing the discharge liquid in the nozzle, and the preliminary discharge is intended to improve the discharge state. Since these operations are performed for the purpose, if the frequency of these operations is reduced, the discharge state often becomes unstable, which may cause problems such as non-discharge.
[0005]
In a conventional drawing apparatus using a liquid ejecting apparatus, as a method of avoiding a defect in a drawn image caused by non-ejection of a nozzle of the liquid ejecting apparatus, JP-A-06-079956 and JP-A-11-000988 are disclosed. The method disclosed in is known. In the method disclosed in Japanese Patent Laid-Open No. 06-079956, a predetermined image pattern is drawn prior to a desired image drawing operation, and a non-ejection is detected by detecting a spot in which no image dot is formed in the drawn image pattern. Identify the nozzle. When it is detected that there is a non-ejecting nozzle, a desired image is obtained by substituting the image dot of the spot drawn by the non-ejecting nozzle with another nozzle. Further, the method disclosed in Japanese Patent Laid-Open No. 11-000988 performs a detection process for specifying a non-ejection nozzle in the same manner as described above, and is used in a normal drawing operation when it is detected that there is a non-ejection nozzle. An image dot originally drawn by a non-ejection nozzle is formed by a redundant nozzle that is not used, that is, complemented by a redundant nozzle.
[0006]
[Problems to be solved by the invention]
However, when the probe carrier is manufactured by the drawing apparatus as described above, the expensive probe solution is wasted more than necessary for the following three reasons, and the cost of the probe carrier is increased.
1. In order to specify the non-ejection nozzle, an image pattern for identifying the non-ejection nozzle must be drawn, and the probe solution is wasted for the drawing of this image pattern.
2. After a non-ejection nozzle is detected, if a new non-ejection nozzle occurs while drawing a desired image, the image obtained by the drawing operation becomes a defective image and cannot be used. The probe solution used at the time of drawing is wasted.
3. If non-ejection occurs during drawing as described above, the yield of probe carrier manufacturing will decrease. Therefore, in order to maintain a high yield, it is necessary to frequently perform preliminary ejection to always stabilize the ejection. As a result, the amount of wasted probe solution due to preliminary discharge increases.
[0007]
Accordingly, an object of the present invention is to provide a probe carrier manufacturing apparatus and a manufacturing method that can minimize the waste of the probe solution and improve the yield of the probe carrier manufacturing, and thus can manufacture the probe carrier at a low manufacturing cost. It is to provide a method.
[0008]
[Means for Solving the Problems]
In order to achieve the above-described object, the probe carrier manufacturing apparatus according to the present invention discharges a plurality of types of liquids, each containing a plurality of types of probes that can specifically bind to a target substance, to the carrier. A manufacturing apparatus for manufacturing a probe carrier,
A liquid ejection device comprising a plurality of liquid ejection ports for each type of liquid for one type of liquid;
Positioning means for determining a relative position between the liquid ejection device and the carrier;
On the carrier from the liquid ejection device based on the ejection data Whether liquid has been applied Grant information detecting means for detecting grant information;
Comparing the ejection data with the application information detected by the application information detection means, and a missing part detection means for detecting that the liquid is not applied to the part where the liquid is to be applied,
A driving means for driving the liquid ejection device and applying liquid to the missing part detected by the missing part detection means,
The drive means applies the missing portion to the missing portion from a liquid outlet different from the liquid outlet that has performed the liquid ejection operation based on the ejection data among the plurality of liquid outlets provided for each liquid type. It is characterized in that the same kind of liquid as the liquid to be applied is applied.
[0009]
According to this configuration, when there is a non-ejection nozzle that is in a state in which liquid cannot be ejected, and a missing portion where liquid is not applied to a spot to which liquid is to be applied based on the ejection data, Since the liquid can be applied and complemented, the yield of the probe carrier can be improved.
[0010]
And even if a non-ejection nozzle occurs in this way, the probe carrier can be completed, so that a suction recovery process that suppresses the occurrence of non-ejection nozzles without reducing the yield of the probe carrier, The frequency of ejection can be reduced, thereby reducing the amount of liquid consumed.
[0011]
More specifically, the positioning means can include a means for moving the liquid ejection device in the main scanning direction parallel to the liquid application surface of the carrier. Further, position detecting means for detecting the position of the liquid ejection device in the main scanning direction is further provided, and means for ejecting liquid from the liquid ejection device onto the carrier based on the ejection data while moving the liquid ejection device in the main scanning direction The liquid ejection apparatus can be driven by determining the timing at which the liquid can be applied on the carrier according to the ejection data from the position information detected by the position detection means. Further, the driving means for applying the liquid by driving the liquid ejecting apparatus to the missing portion is moved from the position information detected by the position detecting means to the missing portion while moving the liquid ejecting apparatus in the main scanning direction. The liquid ejection device can be driven by determining the timing at which the liquid can be applied. The positioning means may further comprise means for moving the carrier in the sub-scanning direction parallel to the liquid application surface and intersecting the main scanning direction.
[0012]
Moreover, you may provide the preliminary discharge means which discharges a liquid, without providing a liquid to a support | carrier from a liquid discharge apparatus. By performing the preliminary discharge, the liquid can be reliably filled in the nozzle, and the liquid can be discharged stably. As described above, in the probe carrier manufacturing apparatus of the present invention, the frequency of the preliminary discharge operation can be kept small.
[0013]
Since the application information detecting means only needs to be able to detect whether or not the liquid is applied to a predetermined location on the carrier, it can be configured from a line sensor having a relatively simple configuration.
[0014]
In the probe carrier manufacturing apparatus of the present invention, as the liquid ejection device, a device including a thermal energy generator that gives thermal energy to the liquid in order to eject the liquid can be particularly preferably used.
[0015]
The means for ejecting liquid onto the carrier from the liquid ejection device based on the ejection data, the missing portion detection means, the driving means for applying the liquid by driving the liquid ejection device to the missing location, the preliminary ejection means, for example, It can be constituted by a computer that performs predetermined processing and outputs a command signal, and an information storage medium that stores a program for causing the computer to perform predetermined processing. These means may be constituted by a circuit board configured to perform a predetermined process, or may be configured by combining it with a computer.
[0016]
The method for producing a probe carrier according to the present invention discharges a plurality of types of liquids, each containing a plurality of types of probes that can specifically bind to a target substance, to the carrier. Using a liquid ejection device A method of manufacturing a probe carrier, wherein a liquid ejection device is provided with a plurality of liquid ejection ports for each type of liquid for one type of liquid,
A step of ejecting each of a plurality of types of liquid from the liquid ejection device based on ejection data and applying the liquid to the carrier while changing the relative position between the liquid ejection device and the carrier;
Carrier Whether liquid has been applied Detecting grant information;
Comparing the ejection data with the detected application information, and detecting a missing portion where no liquid is applied to a location where liquid should be applied based on the ejection data;
A step of applying the liquid by ejecting liquid from the liquid ejection device to the detected missing portion when the missing portion is detected, and
Of the plurality of liquid discharge ports provided for each type of liquid, the same type as the liquid to be applied to the missing portion from the liquid outlet different from the liquid outlet that performed the liquid ejection operation based on the ejection data It is characterized by providing a liquid.
[0017]
In the probe carrier manufacturing method of the present invention, prior to the step of applying the liquid to the missing portion, the preliminary discharge for discharging the liquid without applying the liquid to the carrier from the liquid discharge device is applied to the missing portion, and the liquid is applied to the missing portion. You may provide further the process performed about the liquid discharge port used at the process to do. Accordingly, it is possible to improve the reliability of the liquid discharge when the preliminary discharge operation is performed with the minimum number of nozzles and the liquid is applied to the missing portion.
[0018]
In addition, before the step of applying the liquid to the carrier based on the discharge data, a step of performing preliminary discharge for all the nozzles may be further provided. Accordingly, it is possible to improve the reliability of liquid discharge by ensuring that the liquid is filled into the nozzle.
[0021]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention will be described below with reference to the drawings.
[0022]
First, the overall configuration of the drawing apparatus of this embodiment will be described with reference to FIG. FIG. 2 is a schematic perspective view of the drawing apparatus. In this drawing apparatus, a drawing head 8 (see FIGS. 8 and 9) constituted by a liquid discharge apparatus 1 (see FIGS. 4 to 7) described later is mounted on a carriage 10, and a probe solution is discharged from the drawing head 8 to carry a carrier. 16 is an apparatus for manufacturing a probe carrier 7 (see FIG. 11) as described later.
[0023]
The carriage 10 functions as a holding body for holding the drawing head 8 and is fixed to the slider portion of the CR linear motor 11 so as to be movable in the main scanning direction. Since the carriage 10 may have a load exceeding 10 kg when the mounted drawing head 8 is combined, the CR linear motor 11 supporting the carriage 10 is firmly fixed by the left and right bases 13 and 14 fixed on the surface plate 12. ing. On the other hand, on the lower side of the carriage 10, a stage 15 capable of adsorbing the carrier 16 by vacuum adsorption is disposed on the upper surface thereof. The stage 15 is supported by an LF linear motor 17 fixed on the surface plate 12 so as to be movable in the sub-scanning direction substantially orthogonal to the moving direction (main scanning direction) of the carriage 10.
[0024]
Thus, the drawing apparatus moves the carriage 10 and hence the drawing head 8 held thereon by the CR linear motor 11 and moves the stage 15 and thus the carrier 16 held thereby by the LF linear motor 17. The relative position between the carrier 16 and the drawing head 8 is arbitrarily changed, and the probe solution can be spotted at an arbitrary position on the carrier 16 by the drawing head 8. That is, the stage 15, the CR linear motor 11 and the LF linear motor 17, the surface plate 12, and the bases 13 and 14 constitute positioning means for determining the relative position between the liquid ejection device 1 and the carrier 16.
[0025]
At the right end of the carriage movement range, a preliminary discharge receiver 19 is provided for receiving the pre-discharged probe solution in preparation for the preliminary discharge of the drawing head 8. Further, an image sensor unit (applied information detection means) 18 that captures an image of the surface of the carrier is provided on the side surface of the carriage 10 so that the state of the probe solution spotted in a matrix can be observed.
[0026]
FIG. 3 shows a schematic configuration diagram of an example of the image sensor unit 18. The image sensor unit 18 illuminates a spot on the carrier 16 using an LED illumination 40 using an LED, and a line sensor that captures the reflected light of the light from the LED illumination 40 at the spot on the carrier 16 through a cylindrical lens 41. 42. The irradiation direction of the illumination light of the LED illumination 40 and the incident direction of the reflected light of the line sensor 42 are such that the illumination light reflected on the surface of the carrier 16 does not reach the line sensor 42 when the probe solution is not applied to the spot. The illumination light reflected when the probe solution is applied is adjusted to enter the line sensor 42. The image sensor unit 18 does not have a large optical system that can capture the state of the probe solution applied to the spot, but the location of the probe solution at each spot is known in advance. It has a structure sufficient to determine the presence or absence.
[0027]
Next, with reference to FIGS. 4 to 6, the configuration of the liquid ejection apparatus 1 constituting the drawing head 8 mounted on the carriage 10 will be described. FIG. 4 is a plan view of the liquid ejecting apparatus 1 as seen from the surface where the orifice 2 from which liquid is ejected is opened. 5 and 6 are enlarged views of a liquid discharge portion related to discharge of one probe solution of the liquid discharge apparatus 1, FIG. 5 is a plan view seen from the surface where the orifice 2 is opened, and FIG. FIG. 6 is a cross-sectional view taken along the line AA ′ of FIG.
[0028]
A drawing apparatus for producing a probe carrier needs to discharge various types of probe solutions arranged on the probe carrier. Therefore, the drawing apparatus must include solution reservoirs (liquid storage units) for the number of types of probes arranged on the probe carrier, and nozzles that communicate with the solution reservoirs and discharge the probe solution. The liquid ejection apparatus 1 according to the present embodiment includes a total of 16 solution reservoirs 4 that can store different types of probe solutions in a length of 4 × 4. The solution reservoirs 4 are arranged at intervals P of about 1/5 inch (5.08 mm) both vertically and horizontally. The solution reservoirs 4 are arranged in such a manner that four rows in the vertical direction are arranged in four rows in the horizontal direction. The solution reservoirs 4 in each row are arranged in the vertical direction with the solution reservoirs 4 in the adjacent rows. They are arranged with a gap of 4 intervals.
[0029]
In the present embodiment, in order to manufacture the probe carrier 7 having a total of 256 spots of 16 × 16, the drawing head 8 is configured by integrally arranging 16 liquid ejection devices 1 in a plane. Thus, 256 types of probe solutions can be discharged. Some probe carriers have 1000 or more types of probes. In that case, a drawing head in which more liquid ejection devices are arranged and integrated may be used.
[0030]
For example, as shown in FIG. 8, the planar arrangement of the liquid ejecting apparatus 1 may be an arrangement in which 16 liquid ejecting apparatuses 1 are arranged in one horizontal row. As will be described later, this configuration has the advantage that four main scans are performed to apply the probe solution to the 16 × 16 matrix spot, but the drawing head 8 becomes horizontally long. Therefore, as shown in FIG. 9, the drawing head 8 may be configured by arranging the liquid ejection devices 1 in a horizontal 8 × vertical 2 arrangement. However, in this drawing head 8, as will be described later, it is necessary to perform eight main scans in order to apply the probe solution to the 16 × 16 matrix spot.
[0031]
As shown in FIG. 5, four orifices 2 arranged in a line at a distance L from each other communicate with one solution reservoir 4 through independent liquid passages 6 as shown in FIG. That is, four independent nozzles 5 are formed. Disposed within each nozzle 5 is a discharge heater (discharge energy generating means) 3 for discharging the probe solution from the orifice 2 by foaming the probe solution at a position above the orifice 2. Accordingly, the probe solution can be individually discharged from each orifice 2.
[0032]
The orifices 2 are separated by an interval P of 1/5 inch (5.08 mm) in both the vertical and horizontal directions when looking at the orifices 2 of the four orifices 2 of the respective liquid discharge units that have the same arrangement position in each liquid discharge unit. Thus, four rows arranged in the vertical direction are arranged in four rows in the horizontal direction. The orifices 2 in each row are arranged so as to be shifted from the adjacent orifices 2 in the vertical direction by an interval of P / 4.
[0033]
The probe solution is supplied from the upper surface of the solution reservoir 4 by a tube or pipette, and fills the nozzle 5. In the present embodiment, the amount of liquid droplets ejected from the orifice 2 is about several tens of pl, and the orifice diameter is several tens of μm. Therefore, the supplied probe solution is held in the solution reservoir 4 and the nozzle 5 without leaking out of the orifice 2 due to the negative pressure generated in the orifice 2. Further, the liquid path 6 has a very short configuration. Therefore, when the probe solution is supplied, the nozzle 5 is immediately filled with the probe solution until reaching the orifice 2. For this reason, a suction operation for filling the probe solution into the orifice 2 is not necessary, and it is possible to achieve a state in which ejection can be performed normally to the extent that preliminary ejection is performed.
[0034]
In this embodiment, normally, one of the four nozzles 5 communicating with one solution reservoir 4 is selected, and the probe solution is discharged from the selected nozzle 5. FIG. 7 shows a drive circuit diagram of the discharge heater 3 for performing such discharge. In the figure, the discharge heaters 3 in the four nozzles 5 communicating with the first solution reservoir 4 are discharged heaters 3-11 and 3-12 in order from the one corresponding to the lower orifice 2 in FIG. , 3-13, 3-14. Similarly, the discharge heaters 3-21 to 3-24 indicate the discharge heaters 3 in the four nozzles 5 communicating with the second solution reservoir 4, and the discharge heaters 3-161 to 1-164 are 16. The second solution reservoir 4 is shown. In the figure, the discharge heater 3 in the nozzle 5 communicating with the 3rd to 15th solution reservoirs 4 is not shown, but is configured in the same manner as the 1st, 2nd and 16th ones.
[0035]
Among the discharge heaters 3 in the nozzles 5 communicating with the respective solution reservoirs 4, one end of each of the discharge heaters 3-11, 3-21,..., 3-161 corresponding to the lowermost orifice 2 in FIG. 35-11, 35-21,..., 35-161 are connected by common wiring. The common wiring is connected to the collector electrode of the transistor 36-1. Among the discharge heaters 3 in the nozzles 5 communicating with the respective solution reservoirs 4, the second, third, and fourth discharge heaters from the bottom of FIG. 5 are similarly connected by common wiring, and are connected to the transistors 36-2 and 36-. It is connected to 3, 36-4 collector electrodes. In this way, among the discharge heaters 3-1 to 3-164, among the ones in the nozzles 5 communicating with the respective solution reservoirs 4, the same arrangement order from the bottom of FIG. It constitutes one group and is divided into four groups.
[0036]
Wirings to which selection signals 1 to 4 are input are connected to the base electrodes of the transistors 36-1 to 36-4, respectively. Therefore, a drive voltage is applied to the common wiring connected to the transistors to which Low signals are input as the selection signals 1 to 4. As for the selection signals 1 to 4, a Low signal is normally input to only one of them, and only one group is ready for ejection.
[0037]
On the other hand, the other ends of the four discharge heaters 3 in the four nozzles 5 communicating with one solution reservoir 4 are connected by a common wire, and this common wire is connected to the collector electrodes of the transistors 37-1 to 37-16, respectively. ing. Wirings to which drive signals 1 to 16 are input are connected to the base electrodes of the transistors 37-1 to 37-16, respectively. Therefore, when a drive pulse is input as the drive signals 1 to 16, the discharge heater connected to the transistor to which the drive pulse is input is driven at that timing. At this time, since the drive voltage is applied only to the discharge heaters of the group selected by the selection signals 1 to 4, the drive voltage is selected for the discharge heaters 3 in the four nozzles 5 communicating with the individual solution reservoirs 4. Only the discharge heaters 3 belonging to the group are driven, and the probe solution is discharged from the nozzle 5 on which the discharge heaters 3 are arranged.
[0038]
In the present embodiment, the first nozzle group is normally selected and used, and as described later, any of the nozzles 5 belonging to the first nozzle group cannot discharge liquid. When a non-ejection nozzle is generated, the second nozzle group is selected, and is sequentially switched to the third and fourth groups.
[0039]
Next, the configuration of the control system of the drawing apparatus of this embodiment will be described with reference to FIG. FIG. 10 is a block diagram showing the overall configuration of the control system of the drawing apparatus. In this control system, a total of five types of boards are mounted on the expansion BOX 21 of the computer 20 for each function of the drawing apparatus, and the computer 20 controls the entire apparatus.
[0040]
When a movement command for each motor is input from the computer 20, the CR motor controller 22 and the LF motor controller 26 convert the movement command into a movement amount and a speed curve, and output them to the CR motor driver 27 and the LF motor driver 30 as pulse trains. The CR motor driver 27 and the LF motor driver 30 are respectively based on the position signals of the encoders 31 and 32 incorporated in the CR linear motor 11 and the LR linear motor 17 according to the pulse train from the controller. 17 operations are controlled. In the present embodiment, the resolution of the encoders 31 and 32 is 0.5 μm for both CR and LF, and has sufficient resolution for a spotting interval of 80 dpi (317.5 μm interval) of a general probe carrier.
[0041]
The output of the encoder 31 of the CR linear motor 11 is also sent to the drawing controller 23 via the CR motor driver 27 and is also used as an input signal of the carriage position detection circuit 33 in the drawing controller 23. The drawing controller 23 is a block having a function for driving the drawing head 8. That is, the drawing controller 23 has a function of temporarily storing image data sent from the computer 20 in the image memory 34, a function of converting image data in the image memory 34 into ejection data of the drawing head 8, and a position detection circuit 33. When it is determined that the carriage 10 has reached the drawing position, it has a function of sending ejection data and a signal for giving a timing for driving the drawing head 8 to the drawing driver 28.
[0042]
The image processing board 24 sequentially samples the one-dimensional image signal from the image sensor unit 18 according to the movement of the carriage 10, and takes the signal obtained thereby into the image memory in the image processing board 24 as a two-dimensional image signal. have. That is, the image processing substrate 24 can capture a matrix pattern image by capturing an image while the image sensor unit 18 is moving on the matrix pattern of the probe carrier 7. Then, the computer 20 can detect whether or not there is a missing spot to which the probe solution is not applied in the matrix pattern by accessing the data in the image memory and performing image processing.
[0043]
The parallel I / O 25 is connected to a vacuum pump 29 that adsorbs the carrier 16 on the adsorption stage 15, and controls the operation of the vacuum pump 29 according to a command from the computer 20.
[0044]
Next, an example of the probe carrier 7 manufactured by the drawing apparatus of this embodiment will be described with reference to FIG. FIG. 11 is an external view of the probe carrier 7. On this probe carrier 7, a total of 256 spots of 16 × 16 are arranged at 80 dpi (0.318 mm interval) in both vertical and horizontal directions. A probe solution spotted by a liquid ejection device is applied to each spot, and in general, the probe solution sprayed to each spot has a different composition. A plurality of probe carriers 7 are usually formed on one carrier 16.
[0045]
In the present specification, the probe immobilized on the carrier is capable of specifically binding to a specific target substance. Furthermore, the probes include oligonucleotides and polynucleotides that can be recognized by a specific target, or other polymers. The term “probe” refers to both a molecule having a probe function, such as an individual polynucleotide molecule, and a population of molecules having the same probe function, such as polynucleotides of the same sequence surface-immobilized in dispersed positions, often ligands Also included is a molecule called Probes and targets are also often used interchangeably, as probes can bind to or become able to bind to a target as part of a ligand-antiligand (sometimes called a receptor) pair. is there. Probes and targets in the present invention may include bases as found in nature, or analogs thereof.
[0046]
In addition, as an example of a probe supported on a carrier, a part of an oligonucleotide having a base sequence that can hybridize with a target nucleic acid has a binding part with the carrier via a linker. And a structure having a structure linked to the surface of the carrier. In addition, the position in the molecule | numerator of the oligonucleotide of a support | carrier and a coupling | bond part in the case of such a structure is not specifically limited in the range which does not impair the desired hybridization reaction.
[0047]
Probes employed in the probe array to which the method of the present invention is applied are appropriately selected according to the purpose of use. However, in order to suitably carry out the method of the present invention, DNA, RNA, cDNA (complementary DNA), PNA, oligonucleotide, polynucleotide, other nucleic acid, oligopeptide, polypeptide, protein, enzyme, substrate for enzyme, antibody, epitope for antibody, antigen, hormone, hormone receptor, It is preferably at least one selected from a ligand, a ligand receptor, an oligosaccharide and a polysaccharide.
[0048]
In the present invention, a plurality of these probes fixed on the carrier surface as independent regions, for example, dot spots, is called a probe carrier, and those arranged at a predetermined interval are called a probe array.
[0049]
On the other hand, the probe has a structure that can be bonded to the surface of the carrier, and it is desirable that the probe be fixed on the carrier via the bondable structure. At that time, the structure that can be bonded to the carrier surface of the probe includes amino group, mercapto group, carboxyl group, hydroxyl group, acid halide (haloformyl group; -COX), halide (-X), aziridine, maleimide group, succinimide Group, isothiocyanate group, sulfonyl chloride group (-SO ₂ Cl), an aldehyde group (formyl group; —CHO), a hydrazine, an iodoacetamide, and other organic functional groups are preferably introduced. Further, depending on the structure necessary for binding to the probe-side carrier, the surface of the carrier may be subjected to a necessary treatment.
[0050]
Next, a method of manufacturing the probe carrier 7 by spotting the probe solution in a matrix on the carrier 16 using the liquid ejection apparatus of this embodiment will be described with reference to the flowchart of FIG.
[0051]
First, a probe solution is injected into the solution reservoir 4 in S1. In S2, preliminary ejection is performed for all the nozzles 5 in the four nozzle groups so that the probe solution reliably fills the nozzles 5.
[0052]
When the preliminary ejection is completed, next, a nozzle group to be used is set in S3. At this time, when the liquid ejection apparatus 1 is new and has no non-ejection nozzles, the first nozzle group is set as the nozzle group to be used. However, in the case of using the liquid ejection apparatus 1 that has been used for a long time, a non-ejection nozzle history table, which will be described later, is searched to find a nozzle group having no non-ejection nozzles in order from the first nozzle group. If no nozzle group is found, that nozzle group is set as the nozzle group to be used. The setting is performed by setting the corresponding one of the selection signals 1 to 4 as a Low signal.
[0053]
At this time, the positions of the orifices 2 of the nozzles 5 belonging to each nozzle group are shifted between the nozzle groups as shown in FIG. 5 and the like, so that the probe solution is substantially at the same position regardless of which nozzle group is selected. In step S4, an offset value at the time of drawing is set. Since the first block is normally selected, for example, the offset value when the first block is selected is set to 0. Therefore, for example, when the second block is selected, the position of the orifice 2 of the nozzle 5 belonging to the second nozzle group is shifted by an interval L from that of the first group. Set to. As a result, the movement position of the stage 15 in S7 is shifted by a set offset value L from the original movement position when the first nozzle group is selected. In this way, even when the second nozzle group is selected, the probe solution can be applied to the same position as when the first nozzle group is selected.
[0054]
The carrier 16 is adsorbed and held in advance on the stage 15 by a vacuum pump 29. Next, the carrier 16 is moved by the LF linear motor 17 to the start position where the scanning path of the carriage 10 is located at the formation position of the first probe carrier 7 set on the carrier 16 in S5. At the same time, the carriage 10 is also moved by the CR linear motor 11 to the start position for performing the drawing operation.
[0055]
Next, in S6, the carriage 10 is moved in the main scanning direction, and at this time, the probe solution is ejected from each nozzle 5 at a predetermined timing, and one-scan drawing applied to the spot on the carrier 16 is performed. In S7, the stage 15 is moved in the sub-scanning direction by a predetermined amount, and then one-scan drawing is performed again. In this way, the probe solution can be applied to the matrix spots as shown in FIG. 11 by scanning and drawing a predetermined number of times. In the drawing in the present embodiment, a plurality of types of probe solutions are always applied in a fixed pattern. However, it is also possible to input discharge data that defines this pattern and perform drawing according to the discharge data.
[0056]
At this time, the discharge timing of the probe solution from each nozzle 5 detects that the carriage 10 has reached a predetermined position by the position detection circuit 33 of the drawing controller 23, and discharge data from the drawing controller 23 to the drawing head driver 28. And a drive timing signal are output. The drawing driver 28 receives these signals, converts them into drive signals for actually driving the discharge heaters 3 and outputs them to the drawing head 8, whereby the drawing head 8 discharges the probe solution onto the carrier 16. Note that which of the four nozzles 5 communicating with each solution reservoir 4 is used to discharge the probe solution is determined in S3, and the nozzles 5 belonging to the nozzle group selected by the setting of the selection signals 1 to 4 are determined. From the discharge.
[0057]
Here, a method of applying the probe solution to the matrix-like spot by performing drawing by scanning a plurality of times will be described. First, with reference to FIGS. 12 and 13, a method for applying a probe solution to 16 vertically arranged spots by the liquid ejection apparatus 1 having 16 solution reservoirs 4 will be described.
[0058]
In the drawing apparatus according to the present embodiment, one nozzle group is selected from the four nozzle groups, and in one scan drawing, the probe solution is ejected from the orifice 2 of the nozzle 5 belonging to the selected nozzle group. FIG. 12 shows the arrangement of the orifices 2 belonging to one nozzle group. As described above, these orifices 2 are arranged in such a manner that four rows arranged in the vertical direction are arranged in the horizontal direction and are separated by a distance P of 1/5 inch (5.08 mm) in both the vertical and horizontal directions. The orifices 2 in each row are arranged so as to be shifted from the orifices 2 in the adjacent row by a distance of P / 4 in the vertical direction. Therefore, when viewed in the vertical direction, the orifices 2 are arranged at intervals of P / 4, that is, at 20 dpi (interval of 1.27 mm). With respect to the nozzle pitch of 20 dpi (interval of 1.27 mm), the spot interval of the probe carrier 7 is 80 dpi (interval of 0.318 mm), so that it is not possible to apply the probe solution to the spots of this interval in one scan. Can not.
[0059]
Therefore, the probe solution is applied to 16 spots arranged vertically at 80 dpi (0.318 mm interval) by performing four one-scan drawings. FIG. 13 is a diagram for explaining this method. In FIG. 13, in order to easily show the change in the relative position between the carrier 16 and the liquid ejection apparatus 1, the liquid ejection apparatus 1 side is illustrated at a position shifted by the shift amount S. However, the drawing apparatus according to the present embodiment is illustrated. Then, it is the carrier 16 side that moves.
[0060]
First, in the drawing of the first scan, the probe solution is sequentially ejected at predetermined timing from the upper four orifices 2 indicated by the black circles in FIG. 13 while moving the liquid ejection device 1 in the main scanning direction indicated by the arrows in FIG. Then, the probe solution is applied to the four spots arranged vertically. At this time, the probe solution is applied to four spots arranged at 20 dpi (interval of 1.27 mm).
[0061]
Next, the stage 15 is moved by the shift amount S. In this case, the shift amount S is 15 times the 80 dpi interval 0.318 mm, that is, 4.76 mm. Then, when viewed in the vertical direction, the fifth to eighth orifices from the top in FIG. 13 are shifted to the lower side by an interval of 0.318 mm from the positions of the upper four orifices 2 at the time of drawing the first scan. 2 will be arranged. When the stage 15 is moved, the liquid ejecting apparatus 1 is moved to the start position, and the liquid ejecting apparatus 1 is moved from the start position even in the second scan drawing.
[0062]
Next, in the drawing of the second scan, the probe solution is ejected from the fifth to eighth orifices 2 from the top of FIG. 13 at a predetermined timing, and the probe solution is applied to the four vertically aligned spots. At this time, the probe solution is applied to four spots at positions separated by 0.318 mm from the spot to which the probe solution is applied in the first scan.
[0063]
Similarly, after moving the stage 15 by a predetermined shift amount S, the probe solution is discharged from the ninth to twelfth orifices 2 from the top of FIG. The probe solution is discharged from the four orifices 2 and the fourth scan is drawn. By doing so, the probe solution can be applied to 16 spots arranged vertically at intervals of 0.318 mm, that is, at 80 dpi.
[0064]
Therefore, as shown in FIG. 8, when the drawing head 8 in which 16 liquid ejection devices 1 are arranged side by side and formed integrally is used, each liquid ejection device 1 has a horizontal direction of 0.1 mm between the liquid ejection devices 1. The probe solution is applied to 16 spots arranged in the vertical direction at 80 dpi (0.318 mm interval) by drawing 4 scans at a position shifted by 318 mm. As a result, the probe solution can be applied to 16 × 16 matrix spots arranged at 80 dpi (0.318 mm interval) vertically and horizontally by drawing with 4 scans.
[0065]
Further, as shown in FIG. 9, when the drawing head 8 in which the liquid discharge devices 1 are integrally formed by arranging the liquid discharge devices 1 in 2 × 8 is used by the upper eight liquid discharge devices 1 in the first four scans. The probe solution is applied to the spots arranged in the width 8 × length 16 at intervals of 0.318 mm. Then, the probe solution is applied to the remaining 8 × 16 spots by the lower eight liquid ejecting apparatuses 1 in the next four scans. Thus, the probe solution can be applied to 16 × 16 matrix spots arranged at 80 dpi (0.318 mm interval) vertically and horizontally by drawing with 8 scans.
[0066]
Thus, when the probe solution is applied to the 16 × 16 matrix spot by performing a predetermined number of scans, if it is detected in S8 that the next scan is the final scan, the drawing is performed in S9. While performing the operation, the image sensor unit 18 captures a state image (drawing pattern) of each spot. In S10, the captured image is processed by the computer 20 to detect a missing spot to which no probe solution is applied.
[0067]
Accordingly, when it is determined in S11 that there is no missing spot, the carrier 16 is moved so that the scanning path of the carriage 10 is positioned on the position where the next probe carrier 7 is formed. In the same manner as the first probe carrier 7, the probe solution is applied to the matrix-like spot constituting the next probe carrier 7.
[0068]
On the other hand, when it is detected in S11 that there is a missing spot, the following recovery process is performed. First, the nozzle group used for drawing in S13 is registered in the non-ejection nozzle history table as a non-ejection nozzle. In S14, the selection signals 1 to 4 are switched to select the next nozzle group, and in S15, the drawing position offset value is set to a value corresponding to the selected nozzle group. As described above, the non-ejection nozzle history table is used to select the first nozzle group to be used when the probe carrier 7 is manufactured next time.
[0069]
Next, repair image data for drawing only the missing spot is created in S16. In S17, preliminary discharge is performed on the nozzle 5 used for discharging and applying the probe solution to the missing spot. Then, redrawing is performed according to the repair image data created in S18.
[0070]
In this redrawing, since the probe solution is discharged and applied only to the missing spot, for example, if there is only one missing spot, the redrawing is performed by a single scan. That is, of the predetermined number of scans performed when the probe solution is applied to the spot in a 16 × 16 matrix, the stage is located at a position corresponding to the position at the time of the scan in which the probe solution is discharged and applied to the missing spot. By moving 15 and performing one-scan drawing, the probe solution can be dispensed to the missing spot. Further, even when there are a plurality of missing spots, if all the missing spots are at a position where the probe solution can be dispensed by one scan, redrawing is performed by one scan. On the other hand, when missing spots are dispersed and present at positions where ejection is applied when performing a plurality of scans, redrawing is performed for all necessary scans.
[0071]
When performing redrawing on the missing spot, the state image of each spot is captured by the image sensor unit 18 while performing a drawing operation at the time of the final scan in S19. In S20, the image captured by the computer 20 is subjected to image processing, and the missing spot is detected again. As a result, when it is detected in S11 that the missing spot has disappeared, the recovery process is completed, and the process proceeds to the process of applying the probe solution to the spots constituting the next probe carrier 7.
[0072]
On the other hand, when the missing spot is detected again in S11, the nozzle group selection is switched again and redrawing is performed. In this way, redrawing is performed until there are no missing spots.
[0073]
Here, when it is detected that there is a missing spot even if the redrawing is performed a predetermined number of times or more in S12, it is determined that there is a spot to which the probe solution is not applied regardless of which nozzle group is selected. Displays a message and stops processing. This occurs when the probe solution in the solution reservoir 4 becomes empty, or when all of the four nozzles 5 communicating with the solution reservoir 4 become non-ejection nozzles.
[0074]
In this embodiment, prior to re-drawing, preliminary discharge of the nozzle for applying the probe solution to the missing spot is performed in S16. However, if the discharge is relatively stable, the preliminary discharge may be omitted. .
[0075]
In addition, when an abnormal message is displayed and the process stops, if the probe solution is empty, a re-drawing can be executed after making the probe solution dispenseable by taking measures such as injecting the solution. You may do it. By doing in this way, the recovery process can be performed on the probe carrier 7 that is not completed, the probe carrier 7 can be completed, and the production yield of the probe carrier 7 can be improved. Further, a means for detecting that the probe solution in the solution reservoir 4 has become a predetermined amount or less may be provided to display a probe solution injection request message.
[0076]
Moreover, although the detection of the missing spot is performed at the time of the final scan, the missing spot may be detected for each scan and the recovery process may be performed within the scan.
[0077]
As described above, in the present embodiment, four nozzles 5 communicating with one solution reservoir 4 are provided, and drawing is usually performed using one of these nozzles 5 and missing from the drawn spot image. When the presence or absence of a spot is detected and the presence of a missing spot is detected, recovery processing is performed using another nozzle 5. Thereby, the yield of the probe carrier 7 can be improved to the limit.
[0078]
Further, by performing the recovery process in this manner, the probe carrier 7 can be completed even when a non-ejection nozzle is generated, so that the suction that suppresses the occurrence of the non-ejection nozzle without reducing the yield of the probe carrier 7 is achieved. Recovery processing can be eliminated and the frequency of preliminary discharge can be reduced. Thereby, the consumption amount of the probe solution due to the suction recovery process and the preliminary discharge can be minimized. Further, since no special drawing is performed in order to identify the non-ejection nozzle, the probe solution is not wasted.
[0079]
In addition, since the drawing apparatus of this embodiment can minimize the consumption of the liquid to be discharged, it can be suitably used as a probe carrier manufacturing apparatus that uses an expensive probe solution as the liquid to be discharged. Alternatively, the image forming apparatus may be used as another apparatus that forms an image using a liquid ejecting apparatus, for example, a recording apparatus such as a printer. By applying the present embodiment to such a recording apparatus, it is possible to improve the quality of an image to be formed, and to obtain the effect of minimizing the consumption of recording liquid. Furthermore, the present embodiment may be applied to a recording apparatus that performs recording by a method other than liquid ejection, such as a thermal thermal head, and the effect of improving the quality of an image can be obtained.
[0080]
In addition, each component of the liquid ejection apparatus and the probe carrier manufacturing apparatus using the liquid ejection apparatus according to the present invention is used in an inkjet recording system for printing, or a head or recording apparatus using the inkjet recording system. Those appropriately selected according to the object of the invention or those having a structure changed according to the object of the present invention can be selected and used. As an example of such an ink jet recording method, a means (for example, an electrothermal converter, a laser beam, or the like) that generates thermal energy as energy used for performing ink discharge is provided, particularly among ink jet recording methods. There can be mentioned a recording head and a recording apparatus of a type in which a change in the state of ink is caused by the thermal energy, and an excellent effect is brought about by utilizing the configuration used in these. This is because such a system can achieve high recording density and high definition.
[0081]
As for the typical configuration and principle, for example, those performed using the basic principle disclosed in US Pat. Nos. 4,723,129 and 4,740,796 are preferable. This method can be applied to both the so-called on-demand type and the continuous type. In particular, in the case of the on-demand type, it is arranged corresponding to the sheet or liquid path holding the liquid (ink). By applying at least one drive signal corresponding to the recorded information and giving a rapid temperature rise exceeding nucleate boiling to the electrothermal transducer, the thermal energy is generated in the electrothermal transducer, and the recording head This is effective because film boiling occurs on the heat acting surface of the liquid and, as a result, bubbles in the liquid (ink) corresponding to the drive signal on a one-to-one basis can be formed. By the growth and contraction of the bubbles, liquid (ink) is ejected through the ejection opening to form at least one droplet. It is more preferable that the drive signal has a pulse shape, since the bubble growth and contraction is performed immediately and appropriately, and thus it is possible to achieve discharge of a liquid (ink) having particularly excellent responsiveness. As this pulse-shaped drive signal, those described in US Pat. Nos. 4,463,359 and 4,345,262 are suitable. Further excellent recording can be performed by employing the conditions described in US Pat. No. 4,313,124 of the invention relating to the temperature rise rate of the heat acting surface.
[0082]
As the configuration of the recording head, in addition to the combination configuration (straight liquid channel or right-angle liquid channel) of the discharge port, the liquid channel, and the electrothermal transducer as disclosed in each of the above-mentioned specifications, the heat acting part The configurations using US Pat. No. 4,558,333 and US Pat. No. 4,459,600, which disclose the configuration in which the lens is disposed in the bending region, are also included in the present invention. In addition, for a plurality of electrothermal transducers, Japanese Patent Application Laid-Open No. Sho 59-123670 that discloses a configuration in which a common slit is used as a discharge portion of the electrothermal transducer or an aperture that absorbs a pressure wave of thermal energy. The effect of the present invention is also effective as a configuration based on Japanese Patent Application Laid-Open No. 59-138461 which discloses a configuration corresponding to the discharge unit. That is, whatever the form of the recording head is, according to the present invention, recording can be performed reliably and efficiently.
[0083]
Furthermore, the present invention can be effectively applied to a full-line type recording head having a length corresponding to the maximum width of a recording medium that can be recorded by the recording apparatus. As such a recording head, either a configuration satisfying the length by a combination of a plurality of recording heads or a configuration as a single recording head formed integrally may be used.
[0084]
In addition, even a serial type can be replaced with a recording head that is fixed to the main body of the apparatus, or can be electrically connected to the main body of the apparatus and supplied with ink from the main body of the apparatus. The present invention is also effective when a chip type recording head or a cartridge type recording head in which an ink tank is integrally provided in the recording head itself is used.
[0085]
In addition, it is preferable to add a recording head ejection recovery means, a preliminary auxiliary means, and the like as the configuration of the recording apparatus, since the effects of the present invention can be further stabilized. Specifically, heating is performed using a capping unit, a cleaning unit, a pressurizing or suction unit, an electrothermal transducer, a heating element different from this, or a combination thereof. Examples thereof include a preliminary heating unit for performing the discharge and a preliminary discharge unit for performing discharge different from the recording.
[0086]
The most effective one for each of the inks described above is to execute the film boiling method described above.
[0087]
【The invention's effect】
As described above, according to the present invention, a plurality of nozzles that discharge one type of liquid are provided, drawing is performed using one of these nozzles, and a lack of liquid is not applied to the drawn spot When there is a missing spot by detecting whether or not there is a spot, liquid is applied to the missing spot using a nozzle that was not used for the first drawing among a plurality of nozzles that discharge one type of liquid. By performing the recovery process to be applied, the drawing yield can be improved to the limit.
[0088]
In addition, by performing the recovery process in this way, even when a non-ejection nozzle that is in a state in which liquid cannot be ejected occurs, drawing can be completed, so without reducing the yield of drawing, It is possible to reduce the frequency of suction recovery processing and preliminary ejection that suppress the occurrence of non-ejection nozzles, thereby reducing the amount of liquid consumed.
[0089]
Since the present invention can perform drawing with a high yield while minimizing the amount of liquid consumption, in particular, drawing for producing a probe carrier configured by applying an expensive probe solution to a matrix-like spot. It can be suitably used as an apparatus. That is, by using the drawing apparatus of the present invention as probe carrier production, waste of expensive probe solution can be minimized and the yield of probe carrier production can be improved, and therefore probe carrier can be produced at low production cost. Can be manufactured.
[Brief description of the drawings]
FIG. 1 is a flowchart of a drawing method according to an embodiment of the present invention.
FIG. 2 is a schematic perspective view of a drawing apparatus according to an embodiment of the present invention.
FIG. 3 is a schematic configuration diagram of an image sensor unit of the drawing apparatus in FIG. 2;
4 is a plan view of a liquid ejecting apparatus constituting a drawing head mounted on a carriage of the drawing apparatus of FIG.
5 is an enlarged plan view of a portion related to one probe solution of the liquid ejection apparatus of FIG.
6 is a cross-sectional view taken along line AA ′ of FIG.
7 is a drive circuit diagram of a discharge heater of the liquid discharge apparatus of FIG. 4;
8 is a plan view showing an example of a drawing head mounted on the drawing apparatus of FIG. 2, which is configured by integrally combining the liquid ejection devices of FIG. 4;
9 is a plan view showing a drawing head of another example of FIG. 8. FIG.
10 is a block diagram showing an overall configuration of a control system of the drawing apparatus of FIG. 2;
11 is a schematic plan view of a probe carrier manufactured by the drawing apparatus of FIG.
12 is a plan view of the liquid ejection device of FIG. 4, showing the position of the orifice used to apply the probe solution to the 16 vertically arranged spots in order to manufacture the probe carrier of FIG. Yes.
13 is a diagram for explaining a method of applying a probe solution to 16 vertically arranged spots in order to manufacture the probe carrier of FIG. 11. FIG.
[Explanation of symbols]
1 Liquid ejection device
2 Orifice
3 Discharge heater
4 Solution reservoir
5 nozzles
6 Liquid channel
7 Probe carrier
8 Drawing head
10 Carriage
11 CR linear motor
12 Surface plate
13,14 base
15 stages
16 Carrier
17 LF linear motor
18 Image sensor unit
19 Pre-discharge receiver
20 computers
21 Extended BOX
22 CR motor controller
23 Drawing controller
24 Image processing board
25 Parallel I / O
26 LF motor controller
27 CR motor driver
28 Drawing head tie bar
29 Vacuum pump
30 LF motor driver
31, 32 Encoder
33 Position detection circuit
34 Image memory
35-11 to 35-164 diode
36-1, 36-2, 36-3, 36-4, 37-1, 37-2, 37-3, 37-4 transistor

Claims (11)

A manufacturing apparatus for manufacturing a probe carrier by discharging a plurality of types of liquid containing a plurality of types of probes that can specifically bind to a target substance for each type of the probe to a carrier,
A liquid ejection apparatus comprising a plurality of liquid ejection openings for each type of the liquid for one type of the liquid;
Positioning means for determining a relative position between the liquid ejection device and the carrier;
Application information detecting means for detecting application information relating to whether or not liquid is applied to a predetermined location on the carrier from the liquid discharge device based on discharge data;
The missing part detecting means for comparing the ejection data with the application information detected by the application information detecting means and detecting that no liquid is applied to the part where the liquid is to be applied, and the missing part Drive means for driving the liquid ejection device and applying the liquid to the missing portion detected by the detection means;
The drive means, from among a plurality of liquid discharge ports provided for each type of liquid, from a liquid discharge port different from the liquid discharge port that performed the liquid discharge operation based on the discharge data, for the missing portion, An apparatus for manufacturing a probe carrier, which applies the same kind of liquid as the liquid to be applied to the missing portion. The positioning means has means for moving the liquid ejection device in a main scanning direction parallel to the liquid application surface of the carrier,
A position detecting means for detecting a position of the liquid ejection device in the main scanning direction;
At the time of ejecting the liquid onto the carrier from the liquid ejection device based on the ejection data, wherein the liquid discharge device while moving in the main scanning direction, from the position information detected by said position detecting means, the discharge data In response to determining the timing at which the liquid can be applied onto the carrier and driving the liquid ejection device,
The driving means for applying the liquid by driving the liquid ejection device with respect to the missing portion, from the position information detected by the position detection means while moving the liquid ejection device in the main scanning direction, The probe carrier manufacturing apparatus according to claim 1, wherein the liquid ejection device is driven by determining a timing at which the liquid can be applied to the missing portion.   3. The probe carrier manufacturing apparatus according to claim 2, wherein the positioning means further includes means for moving the carrier in a sub-scanning direction parallel to the liquid application surface and intersecting the main scanning direction.   The probe carrier manufacturing apparatus according to any one of claims 1 to 3, further comprising preliminary discharge means for discharging the liquid without applying the liquid to the carrier from the liquid discharge device.   The probe carrier manufacturing apparatus according to any one of claims 1 to 4, wherein the assigned information detection means is constituted by a line sensor.   The said liquid discharge apparatus is a manufacturing apparatus of the probe carrier of any one of Claims 1-5 provided with the thermal energy generator which gives a thermal energy for discharge to the said liquid. A method of manufacturing a probe carrier using a liquid ejection device that ejects a plurality of types of liquids that contain a plurality of types of probes that can specifically bind to a target substance for each type of the probe to a carrier, the liquid As a discharge device, one having a plurality of liquid discharge ports for each type of the liquid for one type of the liquid,
A step of causing each of the plurality of types of liquids to be ejected from the liquid ejection device based on ejection data while being applied to the carrier while changing the relative position between the liquid ejection device and the carrier;
Detecting application information regarding whether a liquid is applied to a predetermined portion of the carrier; and
Comparing the ejection data with the detected application information, and detecting a missing portion where the liquid is not applied to a location where the liquid is to be applied based on the ejection data;
A step of ejecting the liquid from the liquid ejection device and applying the liquid to the detected missing portion when the missing portion is detected, and
Of the plurality of liquid discharge ports provided for each type of liquid, the liquid discharge port that is different from the liquid discharge port that performed the liquid discharge operation based on the discharge data is given to the missing portion from the liquid discharge port. A method for producing a probe carrier, characterized in that a liquid of the same kind as the liquid to be obtained is applied.   The step of applying the liquid to the carrier based on the discharge data and the step of applying the liquid to the missing portion are steps of moving the liquid discharge device in a main scanning direction parallel to the liquid application surface of the carrier. And a step of detecting a position of the liquid ejection device in the main scanning direction, and in the step of applying the liquid to the carrier based on the ejection data, the liquid ejection device is moved in the main scanning direction. And determining the timing at which the liquid can be applied onto the carrier according to the ejection data from the position information detected by the position detecting means, ejecting the liquid, and applying the liquid to the missing portion Then, the liquid can be applied to the missing portion from the position information detected by the position detection means while moving the liquid ejection device in the main scanning direction. Discharging the liquid to determine the timing, according to claim 7, the manufacturing method of the probe carrier.   The step of applying the liquid to the carrier based on the ejection data and the step of applying the liquid to the missing portion include a sub-scan that is parallel to the liquid application surface of the carrier and intersects the main scanning direction. The method for producing a probe carrier according to claim 8, further comprising a step of moving in a direction. A step of applying preliminary liquid for discharging the liquid without applying the liquid from the liquid discharge device to the carrier before applying the liquid to the missing portion, and applying the liquid to the missing portion. The method for manufacturing a probe carrier according to any one of claims 7 to 9, further comprising a step of performing the liquid discharge port used in the step. Prior to the step of applying the liquid to the carrier based on the discharge data, preliminary discharge for discharging the liquid from the liquid discharge device without applying the liquid to the carrier is performed for all the liquid discharge ports. The method for producing a probe carrier according to any one of claims 7 to 10, further comprising a step of performing.

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