JP5156905B2 - Aptamer generating apparatus and aptamer generating method - Google Patents

Description

  The present invention is a DNA aptamer that binds to a target by repeatedly performing a SELEX (systematic evolution of ligands by exponential enrichment) method 淘汰 (washing) and PCR (Polymerase chain reaction) method amplification from a single-stranded DNA library. It is related with the generation method which acquires.

Conventionally, in the aptamer generation method, after pre-cleaning using a magnetic bead for immobilization to preliminarily remove DNA that prefers magnetic beads, post-cleaning is performed using the SELEX method to remove a plurality of wrinkles (washes). In this way, an aptamer generated under conditions of high soot pressure is obtained (hereinafter referred to as “prior art”). As shown in FIG. 14 , the chip holder A used for this bag is loaded with eight chips B horizontally and twelve chips B vertically. In the case of performing scissors, after picking up and gripping eight horizontal chips B necessary for a single scissor from the chip holder A and moving them to the reagent tank, the cleaning liquid is sucked by the chips B. In this method, the cleaning liquid is simultaneously injected from all the chips B by moving above the eight tubes D. For example, when wrinkles are performed four times, the horizontal eight chips B are simultaneously picked up and injected into the tube D every time the number of sprinkles is repeated. In FIG. 14 , black circles indicate a state in which the chip is loaded in the chip holder A, and white circles indicate a state in which the chip B is picked up and is empty.

As another technique for performing scissors, for example, a technique described in Patent Document 1 is known. The technique described in Patent Document 1 is such that an affinity column device (corresponding to magnetic beads), a PCR thermal cycler device, an aptamer separation / purification device, and each device are sequentially connected to collect the recovered material from each device in the next step. A candidate aptamer molecule identified from the oligonucleotide mixture via the affinity column device is amplified in the PCR thermal cycler device, and the target aptamer is selected from the PCR product by the aptamer separation and purification device and recovered. It has the composition to do. As a result, a high purity aptamer can be obtained by repeating a series of steps of affinity-selecting a mixture of oligonucleotides, amplifying the obtained aptamer obtained with a PCR apparatus, and then purifying it through a separation and purification machine. I have to.
JP 2001-61475 A

  However, in the above-described prior art, if one tube that performs four times of cleaning (cleaning) is necessary, the other seven tubes D are wasted, and as a result, the chip B is unnecessary. To consume. Further, when an aptamer having a different number of wrinkles and a required number is usually generated, not only the unnecessary consumption of the chip increases, but also the picking process of the chip B by the chip gripping part C increases accordingly. As a result, there is a problem that the work time required to generate the aptamer becomes enormous.

  For example, in order to prepare a tube that has been subjected to four times of wrinkles, a tube that has been subjected to five times of wrinkles, and a tube that has been subjected to six times of wrinkles, three aptamer generation steps are required as a whole. There is a problem that a total of 15 tasks are required for the work alone.

  Moreover, since the technique described in Patent Document 1 is provided with a separation and purification device such as a high performance liquid chromatograph, the mixture liquid containing aptamer candidate molecules amplified by a thermal cycler is purified. There are problems that the whole is complicated and large-scale, and that cumbersome operations are required, resulting in increased costs.

  The present invention has been made by paying attention to the above technical problems, and does not require complicated and troublesome operations, and it can reduce enormous labor, can be produced at low cost and can greatly reduce the time for generating aptamers. An object is to provide a generation method.

(1) To achieve the above object, the present invention provides a plurality communicating tubes as reaction vessel, met aptamer generation apparatus performs selection processing washed grip, the淘汰回 number, the dispensing machine while to be changed for each tube of said plurality with each other by supplying the number of the cleaning liquid by chips, the plurality communication tubes so as to correspond to淘汰回 number of required individual, a plurality of chips of the cleaning solution containing The chip holder is loaded in advance with holes in the plurality of holes of the chip holder, and the dispenser grips the plurality of chips together while permitting the presence or absence of the chips in the chip holder. and to Turkey and features.
(2) Further, the present invention is an aptamer generation method in which a plurality of tubes as a reaction vessel are subjected to soot by treatment washing, and the number of soots is determined by the number of times of supply of cleaning liquid by a chip held by a dispenser. The plurality of tubes each containing the cleaning liquid can be changed into the plurality of holes of the chip holder so that the plurality of tubes can be changed for each of the plurality of tubes and corresponding to the number of times required for the plurality of tubes individually. The dispensing machine grips a plurality of the chips together while allowing the state of the presence or absence of the chips in the chip holder.

  According to this, since the dispenser pulls up (holds) and holds only the chip loaded in the chip holder, the cleaning liquid is injected only into the tube corresponding to the position where the chip is gripped, and the other chips are gripped. The injection of the cleaning solution is stopped in the tube that does not. Thereby, selective selection can be performed.

  According to the present invention, the cleaning liquid is selectively injected from the dispenser according to the target number of soots required by a plurality of tubes as reaction containers held in the tube rack. For this reason, the dredging pressure (conditions) can be changed flexibly, and even dredging work with varying drooping pressure can be accomplished in a shorter time. As a result, aptamers corresponding to more targets can be achieved. The effect that can be easily created in a short time is exhibited.

  Hereinafter, the best mode for carrying out the present invention will be described in detail with reference to the drawings. FIG. 1 is an external perspective view of an aptamer generating apparatus 1 applied to the aptamer generating method of the embodiment, FIG. 2 is a plan view inside the aptamer generating apparatus 1, and FIG. 3 is a block diagram of the aptamer generating apparatus 1. The aptamer generating device 1 is provided with a touch panel 2 at the upper front portion thereof, and an electronic circuit centered on a sequencer 23 described later is incorporated, and a control signal input from the touch panel 2 is output to the sequencer 23 and the computer 24. ing. The aptamer generating apparatus 1 is fitted with a window, shuts the inside from the external atmosphere, and maintains the internal environment in a clean state by the clean unit 3 provided on the external ceiling surface. In addition, a dispenser 4 that is a part of the dispensing unit and a robot hand 5 that grips a tube containing the aptamer and the cleaning liquid are suspended from the ceiling inside the aptamer generating apparatus 1 so as to be movable. The dispenser 4 is provided with a tip gripping portion (not shown) that pulls out and holds the tip 32 inserted in a hole in the tip holder 8 described later. The robot hand 5 is composed of a pair of hand parts, and grips both side edges of a tube rack 33 and the like which will be described later by narrowing the distance between the hand parts, and releases the gripped tube rack 33 and the like. The chip rack 33 is provided with a chip detection sensor (not shown) that detects the presence or absence of a chip.

  The work table 7 in the aptamer generating apparatus 1 has a chip rack (chip holder) that holds chips arranged vertically and horizontally in a matrix as a mechanism element necessary for automatically creating an aptamer with variable repulsive pressure. 8) A tube (reaction tube) 9 as a reaction vessel for washing DNA, a mixer unit 10 that vibrates and stirs the tube 9, a magnetic lifting stage 11 that lifts and lowers the magnetic means, and a tube lid that covers the tube 9 is removed. Lid stage 12, tube lid rack place 13 for placing the removed tube lid, PCR product storage tank 14 for storing PCR products at 4 ° C., adjustment for adjusting PCR reagents under 4 ° C. Stage 15, reagent tank 16, ammonia tank 17 with automatic opening / closing door, chip disposal port 18, waste liquid tank 19, automatic opening / closing door and temperature PCR body 20 with sections reagent reservoir Area 21 and the reagent tank 22, are provided. The dispensing machine 4 and the robot hand 5 are freely moved and controlled in a three-dimensional space according to sequence control by a computer along guide rails 6 provided on the ceiling shown in FIG. Therefore, the aptamer generating apparatus 1 is operated by the dispenser 4 or the robot hand 5 moving to the predetermined stage or various mechanism elements according to the aptamer generating processing program, and performing the pre-processing cleaning and the post-processing described later. Processing cleaning can be performed. Note that a fluorescent lamp, a germicidal lamp, and the like are also provided inside the aptamer generating apparatus 1.

  The automatic control system of the aptamer generation device 1 is configured by the block diagram shown in FIG. 3 and controls appropriate mechanism elements in the aptamer generation device 1 with the sequencer 23 as a center. The sequencer 23 is provided with an input interface, an output interface, a program, and a data storage unit. The touch panel 2 and a computer 24 as a calculation unit are connected to the input interface. The touch panel 2 is provided with various switches and keys. By operating these switches, various control conditions can be input and programs can be changed. In addition, control conditions can be input from the panel 2 to the computer 24, whereby data and programs in the data storage section in the sequencer 23 can be rewritten and set. The program is executed in accordance with the control conditions input from the touch panel 2, the result of the arithmetic processing is output from the output interface, and the aptamer generation processing procedure is executed.

  In addition, a detection signal from a chip sensor installed in a chip gripping unit (not shown) of the dispenser 7 is input to the input interface. Thereby, the chip sensor detects whether the chip is held in the chip holder 8 or is not held, and the chip in which the presence of the chip is detected is gripped by the chip gripping portion of the dispenser 4. It is taken out from the chip holder 8.

  If there is a discrepancy between the detection result and a preset saddle condition, it is possible to stop the operation on the spot and display an error.

  On the other hand, the output interface includes an eight-series type dispenser 7, a robot hand 5, a PCR 20, a magnetic lifting unit 25, a capping unit 26, a cooling reagent tank 16, a 25% ammonia tank 17, a PCR product storage tank 14, and the like. Is connected. Thereby, these control objects are controlled by the control signal output from the output interface, and a predetermined aptamer generation process is performed.

  FIG. 4 is a diagram for explaining a method for varying the soot pressure. The tip holder 8 which is one component of the dispensing means has holes for holding the chips 32 arranged in a matrix of 12 rows and 8 columns, and has eight holes (hereinafter referred to as “8 series”). 12 holes are arranged in the vertical direction, and a total of 96 holes are provided. A black circle indicates the chip 32, and a white circle indicates an empty hole where the chip 32 does not exist.

  In the eight holes in each row of the chip holder 8, a dropper-shaped chip 32 is set so as to include holes according to the target number of times of scissors. Specifically, in FIG. 4, the number of cleanings (the number of sputums) of the eight tubes 34 held in the tube rack 33 described later is 4, 3, 2, 1, 4, 3, 2, 1 in order from the left. Indicates the case of setting. FIG. 4A shows the first wrinkling process in which the first row of chips 32 rows of the chip holder 8 is used, and FIG. 4B shows that the second row of chips 32 is used 2 The third wrinkle process, (c) is a third wrinkle process in which wrinkles are performed using the third row of chips 32 rows, and (d) is the fourth time in which wrinkles are carried out using the fourth row of chips 32 rows. It is a dredging process. In addition, the process of injecting the washing water in the tub is executed by the sequencer 23 described above. In order to enable an injection process with variable soot pressure (number of times of soot), the chip rack 8 has four, three, two, one in order from the leftmost vertical column to the right vertical column. Four, three, two, and one chip 32 are set in order from the top line position. Note that the number of times of washing (the number of times of washing) is arbitrarily input and set on the touch panel 2 before the apparatus is operated, so that it is possible to detect whether or not the setting condition matches the arrangement state of the chip 32.

  Thus, at the first time, the tip 32 held in all the holes in the first row is gripped by the tip gripping portion of the dispenser 4 and taken out from the tip holder 8. The taken-out tip 32 is moved to a position directly above the tube rack 33 by the dispenser 4 and then moved downward so that the tip end portion of the tip 32 enters the tube 34 to apply air pressure to the inside of the tip 32. The washing water is injected into the tube 34 (injection step). In FIG. 4, the tube into which the cleaning water has been injected is displayed in black. The washing water is preferably saline, but may be other than this. In addition, the saline concentration may be changed as appropriate, so that the types can be divided into two or more types.

  At the second time, in the same manner as described above, only the tips 32 held upright in the holes of the second row are lifted and conveyed by the dispenser, and are transferred to the corresponding tubes 34 as shown in FIG. Wash water is injected. In (c), the chips 32 in the third row and (d) in the fourth row are picked up, respectively, and finally reached the target number of soots through the implantation step, as shown in (e). A tube 34 is obtained. In this way, among the chips 32 held upright on the chip holder 4, the chips 32 are arranged in the holes of the first row corresponding to the tubes 34 that perform the first cleaning, and the second row has The tip 32 is disposed in the hole corresponding to the tube 34 that performs the second cleaning. That is, the tip 32 is not set in the hole where the second cleaning is not performed. In the third row, the tip 32 is disposed in the hole corresponding to the tube 34 that performs the third cleaning, and in the fourth row, the tip 32 is disposed in the hole corresponding to the tube 34 that performs the fourth cleaning. Is done. In other words, when the arrangement of the chips 32 on the chip holder 8 is seen for each column, the number of chips 32 corresponding to the number of times of dripping of each tube 34 is set in advance from the top row, so that within the same dredge process The scissors are executed while changing the number of times of supplying the chip 32 for each tube 34 individually.

  In this way, the injection of the cleaning liquid is stopped in the tube 34 where the chip 32 is not present, and only the tube 34 in the position where the chip is present is subjected to scissors. Thereby, even if the dispenser 4 has a structure in which injection air is simultaneously blown into all eight chips 32, the cleaning liquid can be independently injected into each tube 34 depending on the presence or absence of the chips 32. The aptamer can be generated by changing the selection pressure.

  In FIG. 5, eight tubes 34 used for post-processing cleaning, a tube rack 33 that holds these tubes, a tube lid 35 that covers each tube 34, and a tube lid rack 36 that holds these tube lids. Is shown. The interval between the eight tubes 34 arranged in the tube rack 33 and the interval between the eight tube lids 35 arranged in the tube lid rack 36 are substantially the same as the interval between the holes formed in the tip holder 8. Is set as follows. As shown in FIG. 5B, the tube lid rack 36 is overlapped with the tube rack 33, so that the tube 34 is covered with the tube lid 35 so that impurities are not mixed in from the outside and the liquid inside does not jump out. It has become. Reference numerals 37 and 38 denote positioning pins, and the two racks 33 and 36 are prevented from being displaced when the positioning pins 38 are engaged with holes formed in the tube rack 33 when they are stacked. These racks 33 and 36 are gripped by the robot hand 5 and, for example, as shown in FIGS. 2 and 6, are transported to a pair of support bases 38 provided in the vicinity of the magnetic lifting stage 11, and are in the state shown in FIG. Set by. The positioning pins 37 of the tube rack 33 are engaged with positioning holes 39 provided in the support base 38, so that the tube rack 33 and the tube lid rack 36 are positioned on the support base 38.

  The magnetic elevating stage 11 is formed so as to be movable up and down with respect to the work table 7 by an elevating mechanism (not shown), and holes 41 having magnets 40 are provided at the same interval as the holding interval of the tube 34. The work table 7 is provided with an action member 42 that travels to a position straddling the magnetic lifting stage 11 and retracts from the travel position. The action member 42 is provided with a first presser portion 43 and a second presser portion 44 that press the tube rack 33 so that the tube rack 33 does not float upward. The first pressing portion 43 is used when the tube lid 35 is removed, and the second pressing portion 44 is formed when used to press the tube rack 33 from above after the tube lid 35 is removed. As shown in FIG. 6 (b), the second presser portion 44 is formed by a skirt portion extending below the long hole portion 45, and is attached to the tube 34 that protrudes from the tube rack 33 when seated on the tube rack 33. There is no interference, and the presence of the long hole portion 45 allows the tip 32 held by the tip gripping portion to be lowered. The first and second presser portions 43 and 44 and the long hole portion 45 are formed with arc-shaped escape recesses 46 and 47 that do not interfere with the tube 34.

  Therefore, when pulling up the tube lid rack 36 in the state of FIG. 7, the first presser portion 43 of the action member 42 is caused to enter from the side between the tube rack 33 and the tube lid rack 36 so that the tube rack 33 is moved. suppress. In this state, the tube lid rack 36 is clamped from both sides by the robot hand 5 and pulled up to remove the tube lid 35 as shown in FIG. Although this lid removal processing was performed on the support base 38 of the magnetic lifting stage 11, it is of course possible to provide another support base on the work table 7 in the vicinity of the magnetic lifting stage and remove the tube lid with this support base. It is.

  When performing scissors, the action member 42 is moved to a position straddling the magnetic elevating stage 11 as a preliminary preparation. The action member 42 is lowered, and the tube rack 33 is pressed from above by the second pressing portion 44. In this state, wrinkling is performed. In the case of removing the tube lid with the other support stand in the vicinity of the support stage 11, the robot rack 5 once holds the tube rack 33 from both sides and moves it to the support stand 38 of the magnetic lifting stage 11. The second presser portion 44 may be used for pressing.

  The pressing state and the removal of the tube lid 35 are performed on the support base 38 of the magnetic elevating stage 11. However, a separate support base is provided on the work table 7 adjacent to the magnetic elevating stage 11, and pretreatment cleaning is performed here. This process may also be performed.

  In the magnetic lifting / lowering stage 11, the tube 34 is wrapped in the hole 41 when the stage is raised. Thereby, the magnetic field of the magnet 40 attached to the hole 41 is applied from the outside of the tube, and magnetic beads having magnetism are attracted to the magnet 40. It is comprised so that a soot can be performed efficiently using this function. When the adsorption of the magnetic beads is finished, the magnetic elevating stage 11 is lowered and returned to a state of almost the same height as the surface of the work table 7. The various operations (procedures) described above are executed by the sequencer 23.

  Next, the processing procedure of the aptamer generation method will be described with reference to FIGS. 2 and 8 to 13. FIG. 8 shows a cycle in which protein-bound DNA (aptamer) is collected by the SELEX method, and FIGS. 9 to 13 are protocol diagrams of aptamer production. Note that the numbers in the squares in FIGS. 9 to 13 indicate the steps of the generation process. Steps 1 to 5 are pre-processing cleaning steps, and steps after step 6 are post-processing cleaning steps. In addition, examples of conditions such as processing time, dispensing volume, processing temperature, and the like in each processing step in the present embodiment are as described in each drawing.

  Fig. 9 shows the library mixing and non-specific bead exclusion steps. At the start, single-stranded DNA (ssDNA) having various arrangement structures and magnetic beads for immobilizing DNA that prefers magnetic beads are prepared. To do. The ssDNA is amplified in the tube by the PCR device 20 (Step 0-1 to Step 0-3), and after immobilizing magnetic beads for immobilization in Step 1, the tube is vibrated by the mixer unit 10. The inside is agitated (step 2), and DNA that prefers magnetic beads is fixed to the magnet 40. In Step 3, using the magnet 40 (see FIG. 7) of the magnetic lifting / lowering stage 11, together with DNA that prefers magnetic beads, the magnetic beads are fixed to the inner wall of the tube 34, and in Step 4, only the solution is removed from the tube 34. A pretreatment washing (pre-washing) is performed by aspirating and dispensing the solution into another container (tube) and amplifying the solution by the PCR device 20. Thereby, the washing (rinsing) by non-specific adsorption is completed (step 5). This corresponds to S1 in FIG.

  In Step 6, which is the first step of the post-treatment washing step, immobilized magnetic beads with a target (protein) such as cancer cells are dispensed (corresponding to S2 in FIG. 8), amplified by a PCR device, and then mixed with a mixer (Step 7), the magnetic beads are fixed to the inner wall of the tube 34 by the magnetic lifting stage 11 (Step 8), the solution inside is sucked (Step 8), and is discarded to the waste liquid tank 19. (Step 10). Thereby, the first washing is completed (corresponding to S3 in FIG. 8), and the target protein-bound DNA can be left on the magnetic bead side.

  FIG. 10 shows mixing with a target (protein), sputum, and PCR process. In FIG. 10, binding buffer A (such as physiological saline) is dispensed into the protein-binding DNA obtained above (step 11), and then stirred. (Step 12), magnetic beads are adsorbed on the magnetic lifting stage 11 (Step 13), and the internal solution is drained (Steps 14 to 15). Thus, protein-bound DNA can be recovered by the second washing (step 15).

  In the same manner, for example, when the eighth cleaning is performed, the process returns to step 11 again. Since the selection pressure is variable in steps 12 to 15, protein-binding DNA can be obtained by the eighth washing by repeatedly executing these steps. In the present embodiment, the case where the number of times of rinsing (the number of times of rinsing) is 8 has been described, but it is needless to say that the number of times is not limited to this. Note that the variable pressure is made variable by the method already described with reference to FIG.

  In step 16-1, after the PCR solution is dispensed in the PCR reagent adjustment stage 15, it is stirred (step 17-1) and amplified in the PCR process (step 18-1).

  FIG. 11 shows the PCR product collection, storage, and bition fixing steps. In FIG. 11, the PCR product is obtained by stirring in step 19 and the magnetic beads are adsorbed by the magnetic lifting stage 11 (step 20). The solution is aspirated (step 21), the solution is dispensed into another container (step 22), a new chip is introduced and aspirated (step 23), and the resulting PCR product is dispensed into the storage tank 14. Collect and store. A new chip is put into the PCR product, and Binding Buffer B is dispensed (step 26), and the solution is drained through stirring (step 27), magnetic bead adsorption (step 28), and suction of the solution (step 29) (step 30). ). In this way, the bithion can be fixed.

  FIG. 12 shows a process for immobilization of bithione and conversion to single strand DNA. In Step 31, a new chip is introduced, Binding Buffer C is dispensed, stirring (Step 32), magnetic bead adsorption (Step 33), After passing through the solution aspiration (step 34) and the solution waste liquid (step 35), in step 36, a new chip is introduced and the Binding Buffer C is dispensed. Thereafter, stirring is performed on the lid removal stage 12 (step 37), and the solution is drained through adsorption of beads (step 38) and suction of the solution (step 39) on the magnetic lifting stage 11 (step 40). It becomes possible to make a single strand of DNA.

  FIG. 13 shows the ssDNA conversion and library readjustment process. After introducing a new chip at the lid removal stage 12, ammonia is dispensed (step 41), and after stirring (step 42), the magnetic beads are added at step 43. Adsorb and suck the internal solution (step 44), dispense it into another container, amplify (step 45), and dry (step 46). Binding Buffer A is dispensed into this and amplified by the PCR device 20 (step 47), stirred (step 48), then returned to step 6 and returned to the library readjustment step. Such single-stranded DNA can be returned to the single-stranded DNA library.

  According to the present embodiment, it is possible to change the soot pressure (condition) by changing the presence / absence of the tip in the 8-series dispenser. By adjusting the presence / absence of the chip to be loaded in the chip holder according to the number of times of loading, the wrinkles with varying pressures can be automated in a short time by sequence control without the need for complicated and complicated operations. it can. There is also an advantage that aptamers corresponding to more targets can be easily created.

  Although the present invention has been described in detail with the embodiment, the specific configuration is not limited to this embodiment, and even if there is a design change or the like without departing from the gist of the present invention, it is within the scope of the present invention. It is included.

  For example, when a mistake in the chip is found, an error display may be displayed on the display screen of the touch panel 2 or the operation of the aptamer generation device itself may be automatically stopped.

  In addition, the soot pressure (condition) setting may be set before the aptamer generating device is operated, so that the number of times of washing may be set, and it is desirable that it can be set during the operation.

  Furthermore, in the said embodiment, although illustrated only when producing | generating the aptamer by DNA, this invention is not limited to it, It can be used also when producing | generating the aptamer of RNA and a peptide.

  In the above description, the case of the eight-tube type has been described, but it is needless to say that the present invention is not limited to this.

  The present invention can be applied to an apparatus for producing aptamers made of various materials.

It is an external appearance perspective view of the aptamer production | generation apparatus 1 applied to the aptamer production | generation method in embodiment of this invention. It is a top view in the inside of this aptamer production | generation apparatus. 1 is a block diagram of the aptamer generation device 1. FIG. It is action | operation explanatory drawing which shows the method of variable soot pressure in an aptamer production | generation process. It is a front enlarged view which shows the correlation of a tube rack and a chip rack. It is an external appearance perspective view which shows the correlation of a magnetic raising / lowering stage and an action member. It is an external appearance perspective view which shows the correlation with a tube rack, a chip rack, an action member, and a magnetic raising / lowering stage. It is a conceptual diagram explaining the washing | cleaning soot process in a SELEX cycle. It is a protocol figure explaining a library and a magnetic bead non-specific exclusion process. It is a protocol figure explaining a wrinkle and a PCR process. It is a protocol figure explaining PCR product collection | recovery, preservation | save, and a bithione fixing process. It is a protocol figure explaining a bithione fixed and single stranded DNA conversion process. It is a protocol figure explaining single strand DNA conversion and a library readjustment process . It is explanatory drawing in a prior art.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Aptamer production | generation apparatus 2 Touch panel 3 Clean unit 4 Dispensing machine 5 Robot hand 6 Guide rail 7 Work table 8 Tip holder 11 Magnetic lifting stage 20 PCR main body 32 Tip 33 Tube rack 34 Tube 40 Magnet 42 Acting member 43 First presser 44 Second presser part 50 Pipette 51 Tank 53 Solenoid valve

Claims (2)

In multiple communicating tubes as reaction vessel, it met aptamer generation apparatus performs selection processing washing,
The淘汰回 number, along with the supply frequency of the cleaning liquid by the chip to be held in the dispenser so as be changed for each tube of said plurality communication,淘汰回 number of said plurality communication tubes require individually in correspondence, a plurality of chips of the cleaning solution containing, previously loaded in a state containing voids to a plurality of holes of the tip holder,
The dispensing machine, while allowing the state of the existence of the chips in the chip holder, aptamers generated and wherein the benzalkonium be gripped together a plurality of the chips.   In a plurality of tubes as a reaction vessel, an aptamer generation method for performing soot by treatment washing,
  The number of sputums can be changed for each of the plurality of tubes according to the number of times the cleaning liquid is supplied by the tip held by the dispenser, and the plurality of tubes correspond to the number of sputums individually required, A plurality of chips containing cleaning liquid are preloaded in a state including holes in a plurality of holes of the chip holder,
  The aptamer generation method characterized in that the dispenser grips a plurality of the chips together while allowing the presence or absence of the chips in the chip holder.

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