JP2007327765A - Dispensing structure in protein screening device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To selectively install disposable tips different in an inner diameter in a tip part of a nozzle, and to install a plurality of disposable tips different in the size in one nozzle. <P>SOLUTION: This dispensing structure of a protein screening device is constituted so that a plurality of tip installing parts 51B, 51C and 51D mutually different in a diameter are formed in the tip of the nozzle 51, and the disposable large, small, and medium tips 51a, 51b and 51c mutually different in the inner diameter can be installed in the respective tip installing parts 51B, 51C and 51D. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a dispensing structure in a protein screening apparatus, and in particular, can selectively attach a disposable tip having a different inner diameter to the tip of a nozzle, and can attach a plurality of disposable tips having different sizes to one nozzle. The present invention relates to a novel improvement for achieving labor saving and downsizing of the apparatus.

  Conventionally, as a dispensing structure of this kind of protein screening apparatus or the like, for example, as disclosed in Patent Documents 1 and 2, one disposable chip is detachable with respect to one nozzle. When one dispensing process is completed, the disposable tip is removed from the nozzle and discarded.

JP 2002-364526 A JP 2003-1164 A

Since the conventional dispensing structure for protein screening devices and the like has been configured as described above, the following problems existed.
That is, as shown in FIGS. 16 and 17, since disposable chips 51a and 51b having dedicated inner diameters are provided for one nozzle 51 and 51A, use of disposable chips having many different inner diameters, That is, when used in a state where the volumes of liquids to be sucked or discharged are different, a large number of nozzles 51 and 51A must be provided, and the number of dispensing robots is not enough, and two or more units are required. When this is used, the overall shape of the apparatus is to be extremely large.
In addition, as described above, when a dedicated disposable tip is provided for each nozzle, unnecessary dispensing robots may be generated among a plurality of dispensing robots, which reduces the use efficiency of the entire apparatus. It was supposed to be.

  The dispensing structure in the protein screening apparatus according to the present invention includes a tray box whose overall shape is a box shape, a stirring and purifying unit provided in a freely accessible manner in the tray box, and a horizontal and vertical direction provided on the tray box. One or a plurality of dispensing robots movable in a direction, a dispensing robot X-axis drive mechanism provided on the table box for reciprocating the dispensing robot in the horizontal direction, and on the table box A dispensing robot Z-axis lifting mechanism provided for reciprocating the dispensing robot in the vertical direction; a support plate erected on the rear side of the dispensing robot Z-axis lifting mechanism on the table box; Using an entire cover for covering the dispensing robot and a disposable tip provided on a nozzle of each dispensing robot, any or all of suction, agitation, and discharge of the liquid to be inspected using the disposable tip In the protein screening apparatus, a plurality of tip mounting portions having different diameters are formed at the tip portion of the nozzle, and disposable large, small, and medium tips having different inner diameters are mounted on the tip mounting portions. In addition, a disposable large chip having a large inner diameter is mounted on each chip mounting portion, and the inner diameter of the disposable large chip is smaller than that of the disposable large chip. A disposable small chip is mounted, and a magnet is provided at the tip of the disposable small chip, and each chip mounting portion is mounted with a disposable large chip having a large inner diameter, The inner diameter of the disposable large chip is larger than that of the disposable large chip. With mounted disposable small chip is a structure in which the filter is provided at the front end portion of the disposable large chip.

Since the dispensing structure in the protein screening apparatus according to the present invention is configured as described above, the following effects can be obtained.
That is, a tip mounting portion of one nozzle is formed with a plurality of chip mounting portions having different diameters, and each chip mounting portion is configured so that disposable chips having different inner diameters can be mounted. Accordingly, the tip can be selectively replaced with a disposable tip having an optimal capacity, and the dispensing mechanism and the entire apparatus can be reduced in size.
In addition, a double chip structure in which a disposable small chip with a smaller inner diameter is provided inside a disposable large chip with a large inner diameter provided at the tip of one nozzle is provided at the tip of the disposable small chip. A clean liquid from which magnetic particles have been removed by a magnet can be sucked through a disposable small chip. In addition, a liquid provided with impurities such as dust can be sucked by a filter provided in the disposable large chip.

  The present invention can selectively attach a disposable tip having a different inner diameter to the tip of a nozzle, and can attach a plurality of disposable tips having different sizes to one nozzle, thereby achieving labor saving and miniaturization of the apparatus. An object of the present invention is to provide a dispensing structure in the protein screening apparatus.

Hereinafter, preferred embodiments of a dispensing structure in a protein screening apparatus according to the present invention will be described with reference to the drawings.
Note that the same or equivalent parts as in the conventional example will be described using the same reference numerals.
The structure shown in FIGS. 1 to 4 shows a protein screening apparatus 100 according to the present invention. The overall shape of the apparatus is box-like and the inside of the table box 101, which is airtight, is configured to be retractable in a pull-out manner. A stirring and purifying unit 103 having 102 is incorporated.
The first and second chip disposal chutes 104 and 105 having different capacities at the respective side positions or different pitches and first and second disposable chips 51a having different capacities are used on the table 101. Second dispensing robots 106 and 107, a dispensing robot X-axis drive mechanism 110 for reciprocating each dispensing robot 106 and 107 in the horizontal direction (that is, the X-axis direction), and each dispensing robot 106 , 107 for reciprocating in the vertical direction (that is, the Z-axis direction), the first and second dispensing robot Z-axis lifting mechanisms 111, 112, and the platform 101 on the rear side of the lifting mechanisms 111, 112, respectively. A support plate 113 provided upright, an in-device cooling Peltier unit 114 and an in-device fan 115 provided on the support plate 113, and the stirring A stirring / purifying unit cover 120 for the purifying unit 103, a new disposable chip (multiple volumes) and a supernatant collecting plate which are provided between the chip discard chutes 104 and 105 and can reciprocate in the direction of arrow Y are installed. A chip rack table 121 is provided.

  An entire cover 130 for covering the above-described dispensing robots 106 and 107, the dispensing robot X-axis drive mechanism 110 and the like on the table box 101 to form a sealed chamber is provided with a mounting screw 131 and a packing (not shown). It is attached using.

  The stirring and purifying unit 103 is as shown in FIGS. 3 and 4 when pulled out from the table box 101. Although not shown in FIG. 2 below the stirring and purifying unit 103, the magnetic fine particle recovery mechanism 140 is shown. Is arranged. The base 140b having the magnet 140a of the magnetic fine particle recovery mechanism 140 is configured to be movable up and down along the direction of arrow F by the magnet lifting device 140c.

  The agitating and purifying unit 103 is configured to have a heat insulating structure as a whole by the heat insulating wall 141, and inside the heat insulating wall 141, the stirring and purifying tube mount 144 and the extraction on the pair of plate holding portions 142 and 143 are extracted. A sample collection tube mount 145 is provided, a reagent plate 150 is further provided, and a front plate 151 having the handle 102 is provided via a rail 152 so as to be freely opened and closed.

A heating / cooling Peltier unit 147 and a blower fan 148 for heating and cooling the inside of the stirring and purifying unit 103 are provided in a rear portion 146 formed by the heat insulating wall 141 of the stirring and purifying unit 103.
A plurality of ventilation holes 149a are provided in the partition plate 149 in the agitation and purification unit 103, and the air from the blower fan 148 passes through the ventilation holes 149a and the agitation and purification tube mount 144 and the extraction sample collection tube mount 145 are supplied. In addition, the temperature is adjusted by blowing air to the reagent plate 150 side.

Next, a specific configuration of the first and second dispensing robots 106 and 107 will be described. The dispensing robots 106 and 107 have the same configuration.
FIGS. 5 to 9 specifically show the dispensing robots 106 and 107. That is, what is indicated by reference numeral 1 in FIGS. 5 and 6 is a casing whose overall shape is substantially box-shaped. As shown in FIG. 6, the casing 1 has first and second rotary clutches. 2, 3 and a drive motor 4 are provided.

A first pulley 5 is provided above the first crunch 2, and a timing pulley 6 is provided below the first pulley 5.
A second pulley 7 is provided above the second crunch 3, and a third pulley 8 is provided below the second pulley 7.

  The timing pulley 6 and the third pulley 8 are connected by a first timing belt 9, and the first pulley 5 is a fourth pulley above the pitch variable drive screw 10 that is rotatably provided on the casing 1. 11 and a second timing belt 12, and the second pulley 7 has a third timing belt 15 attached to a fifth pulley 14 at the top of a dispensing piston drive screw 13 rotatably provided in the casing 1. Are connected through.

  A connecting shaft holding block 16 is fixed to the pitch changing drive screw 10 on a nut screwed with the pitch changing drive screw 10, and the connecting shaft holding block 16 extends along the vertical direction of the casing 1. The first linear track 20 is provided so as to move up and down, that is, move up and down.

  A piston holding block 21 is fixed to a nut screwed to the dispensing piston drive screw 13 at the upper part of the dispensing piston drive screw 13, and the piston holding block 21 is attached to the casing 1 in its vertical direction. Are vertically movable, that is, can be moved up and down by a second linear track 22 provided along the line.

  The lower part of the pitch-variable drive screw 10 is rotatably held by a first bearing 24 provided on a holding plate 23 extending in the horizontal direction from the lower part of the casing 1, and downward from the connecting shaft holding block 16. A groove cam body 30 having a plurality of inclined groove cams 30a is connected to the lower end of the connecting shaft 25 provided toward the end via a connecting member 26.

  As shown in FIG. 5, the groove cam body 30 is composed of a pair opposed to each other. As shown in FIG. 8, each groove cam body 30 is configured by a pair of connecting plates 31 so that the overall shape is a frame shape. The groove cam guide 32 provided on the inner side of the center of the connecting plate 31 is fixed to the casing 1 and protrudes forward and is formed at the center of the front plate 34 of the holding body 33 having an overall box shape. It is configured to engage with a groove cam guide linear track 35 formed in the vertical direction at a position so as to move up and down, that is, move up and down together with the connecting plate 31.

  The lower part of the dispensing piston drive screw 13 is rotatably supported by a second bearing 37 provided on the upper plate 36 of the holding body 33, and the dispensing piston provided on the piston holding block 21. The body 40 passes through the cylindrical guide 41 of the upper plate 36 and extends below the upper plate 36 and is connected to a horizontally long frame-shaped guide 42.

As shown in FIG. 8, the holding body 33 is provided with a rear plate 34a similarly to the front plate 34, and is similarly provided with the groove cam guiding linear track 35 shown in FIG.
Accordingly, the connecting plate 31 is also provided as shown in FIG. 8, and the pair of groove cam bodies 30 are connected by the connecting plates 31. The mold is configured to be movable up and down outside the holding body 33.

  A pair of guide rods 40a and 40b are planted and provided on both sides of the dispensing piston body 40 connected to the frame-shaped guide 42, and each guide rod 40a and 40b is provided on the upper plate 36. The frame-shaped guide 42 is positioned by projecting upwardly through a pair of guide bushes 41a and 41b.

  A plurality of horizontal bars 50, which are supported between the front plate 34 and the rear plate 34a and form a pitch variable linear track, are fixedly provided below the holding body 33. A plurality of cylinder blocks 52 each having a nozzle 51 having a disposable tip 51a at the lower portion are arranged side by side so as to be movable along the horizontal direction.

  A cam follower 52 a that engages with each of the inclined groove cams 30 a is provided at the upper part of each cylinder block 52, and a dispensing piston 53 is provided to be freely inserted. It is configured such that liquid can be sucked into the disposable chip 51d attached to or attached to each disposable chip 51d.

As shown in FIGS. 5 and 6, the frame-shaped guide 42 includes a first guide piece 42a and a second guide piece 42b, and a gap 60 having a gap D between the guide pieces 42a and 42b. In this gap 60, a roller 61 comprising a bearing rotatably provided on the upper part of each dispensing piston 53 is engaged and combined so that it can move in the horizontal direction indicated by arrow G. It has been.
The interval D is configured to be a gap 60 that does not affect the dispensing amount as much as possible with respect to the outer diameter of the roller 61.

Next, the overall operation will be described. First, the operation of the dispensing robots 106 and 107 will be described. First, the state of FIG. 5 shows a state in which the pitch of each nozzle 51 is the smallest when the groove cam body 30 is moved to the uppermost position with respect to each cylinder block 52 and the cylinder blocks 52 are joined to each other.
Next, when increasing each pitch of the nozzles 51 in the above-described state, first, based on a set pitch command set in advance by the control unit (not shown) with the second clutch 3 turned off. When the drive motor 4 is driven, the first pulley 5 rotates via the first clutch 2, and this rotation is caused by the pitch variable drive screw 10 rotating via the second timing belt 12 and the fourth pulley 11. To do.

Due to the rotation of the pitch varying drive screw 10, the connecting shaft holding block 16 is lowered, and the groove cam body 30 is simultaneously lowered via the connecting shaft 25 and the connecting member 26.
When the groove cam body 30 is lowered, each cam follower 52a of each cylinder block 52 engaged with each inclined groove cam 30a is moved outward along the groove cam shape of each inclined groove cam 30a. The drive of the drive motor 4 is stopped in a state where the 52 and the nozzle 51 are at the set pitch.

  Next, in the above-described state, when the first clutch 2 is turned off and the second clutch 3 is turned on, the drive motor 4 is driven via the first timing belt 9 to the third pulley 8, the second clutch 3, It is transmitted to the dispensing piston drive screw 13 via the second pulley 7, the third timing belt 15 and the fifth pulley 14, and the piston holding block 21 is moved up and down by the rotation of the dispensing piston drive screw 13.

Each dispensing piston 53 can move up and down with respect to each cylinder block 52 by raising and lowering the dispensing piston body 40 in conjunction with the piston holding block 21.
When the above-described dispensing pistons 53 are lifted in a state where the disposable tips 51a of the nozzles 51 of the cylinder blocks 52 are immersed in a liquid tank (not shown), the liquid is sucked and the liquid is discharged. When the dispensing piston 53 is lowered after the suction, the liquid can be discharged from the disposable tip 51a of each nozzle 51, that is, the liquid can be dispensed to another location.
Therefore, in the configuration of each of the dispensing robots 106 and 107 of the present invention, the rotation of only one drive motor 4 using the pair of clutches 2 and 3 is changed to a pitch variable drive screw 10 and a dispensing piston drive screw. 13 is selectively supplied, so that only one drive motor 4 can be used as a drive source to selectively perform two systems of dispensing and variable pitch.

The nozzle 51 is composed of only one type, and is actually configured as shown in FIG. That is, a plurality of first to third chip mounting portions 51B, 51C, and 51D having different diameters are formed on the tip portion of the nozzle 51 so as to protrude downward in a stepped manner.
The outer peripheral surfaces of the chip mounting portions 51B, 51C, 51D are formed as tapered surfaces.

  A disposable large chip 51a, a disposable middle chip 51c, and a disposable small chip 51b having different inner diameters and lengths can be selectively mounted on the first, second, and third chip mounting portions 51B, 51C, and 51D, respectively. It is configured.

As another form, the disposable large chip 51a and the disposable small chip 51b may be used by being superposed on each other to form a double chip structure as shown in FIG. 14 and FIG. it can.
That is, in the configuration shown in FIG. 14, the disposable large chip 51a is mounted on the first chip mounting portion 51B of the nozzle 51, and the disposable small chip 51b having the vent hole 51ba is mounted on the third chip mounting portion 51D. A magnet 51bb is provided at the tip of the disposable small chip 51b.

In the configuration of FIG. 15, the disposable large chip 51a is mounted on the first chip mounting portion 51B of the nozzle 51, and the disposable small chip 51b is mounted on the third chip mounting portion 51D.
A filter 51ab is provided at the tip of the disposable large chip 51a. The liquid sucked by the disposable large chip 51a is sucked from the nozzle 51 through the disposable small chip 51b after impurities such as dust are removed by the filter 51ab. It is configured to be.

Next, the basic operation of the protein screening apparatus according to the present invention will be described. Since protein screening using magnetic nanoparticles is well known, it is omitted here and the process is described.
First, an arbitrary temperature is set for the stirring and purifying unit 103 within a settable range on application software installed in a personal computer (hereinafter referred to as PC) (not shown) connected to the protein screening apparatus 100 according to the present invention. The Peltier unit 147 attached to the stirring and purifying unit 103 is heated and cooled with respect to the set temperature. At that time, temperature control is performed by a temperature sensor attached in the cabinet.

Next, an example of the screening process will be described.
The screening procedure after the temperature control of the apparatus is roughly divided into binding, washing and elution processes.
Binding Step a Disposable tip 51a suitable for the dispensing amount is attached to each dispensing robot 106, 107, and moved to the stirring purification tube of the stirring purification tube mount 144.
b Mix by pipetting (suctioning, stirring, and discharging of the liquid to be inspected) with the piston pumps of the dispensing robots 106 and 107
c. The magnetic fine particle recovery mechanism 140 is operated to perform solid-liquid separation with the magnet 140a in close contact with the tube.
d Transfer the supernatant to a supernatant collection plate (not shown).

Washing reagent e. The washing reagent is put into the tube of e using the dispensing robots 106 and 107.
f Mix by pipetting with the piston pump of the dispensing head.
g Perform solid-liquid separation.
h Transfer the supernatant to the supernatant collection plate.
Elution step i Place the elution reagent in the plate of h using a dispensing robot.
j Mix by pipetting with multiple piston pumps.
k Perform solid-liquid separation.
l Transfer the supernatant (including the target protein (or target chemical)) to the extraction sample collection tube of the extraction sample collection tube mount 145.
m Complete In addition, in the above-described screening step, each dispensing robot 106 according to the present invention is changed even when the pitch of the stirring / purifying tube mount 144, the extraction sample collecting tube mount 145 and the reagent plate 150 of the stirring / purifying unit 103 is changed. , 107 can be dealt with by changing the pitch of the nozzles 51.

  In the above-described screening process, in the present invention, for example, as shown in FIGS. 11 to 13, for each nozzle 51, the chips 51a, 51b, 51c are unified or combined. Each chip 51a, 51b, 51c can be selectively mounted according to the required application.

14 and 15, the disposable small chip 51b is mounted inside the disposable large chip 51a and used as a double chip structure.
That is, in the case of the configuration of FIG. 14, the disposable large chip 51a is mounted on the first chip mounting portion 51B of the nozzle 51, and the disposable small chip 51b is mounted on the third chip mounting portion 51D located inside thereof. A magnet 51bb is provided at the tip of the chip 51b, and a plurality of vent holes 51ba are formed on the base side.

  Therefore, in the configuration shown in FIG. 14, when the liquid to be inspected mixed with the magnetic fine particles 51bc is sucked from the tip of the disposable large chip 51a, the magnetic fine particles 51bc are magnetically attracted by the magnet 51bb, and only the liquid passes through the vent hole 51ba. Sucked from the nozzle 51.

  In the configuration shown in FIG. 15, in the same double chip structure as in FIG. 14, a filter 51ab is provided on the distal end side of the disposable large chip 51a, and this filter 51ab is connected to the distal end of the disposable small chip 51b and the disposable large chip 51a. Therefore, impurities such as dust in the liquid to be inspected sucked by the disposable large tip 51a are removed by the filter 51ab and sucked from the nozzle 51 through the disposable small tip 51b. The

It is an external view which shows the protein screening apparatus by this invention. It is a perspective view which shows the state except the whole cover of FIG. It is a disassembled perspective view which shows the stirring refinement | purification part of FIG. It is a perspective view which shows the state which pulled out a part of FIG. It is a perspective view which shows the inside of the dispensing robot of FIG. It is arrow A enlarged view of FIG. It is an arrow B enlarged view of FIG. It is sectional drawing of the principal part of FIG. It is an enlarged view of the C section of FIG. It is a block diagram which shows the nozzle of FIG. 7 concretely. It is a block diagram which shows the state which mounted | wore the disposable large chip | tip with the nozzle of FIG. It is a block diagram which shows the state which mounted | wore the disposable chip | tip with the nozzle of FIG. It is a block diagram which shows the state which mounted | wore the disposable small chip | tip with the nozzle of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the combination of the conventional nozzle and a chip | tip. It is a block diagram which shows the combination of the conventional nozzle and a chip | tip.

Explanation of symbols

51 Nozzles 51a to 51c Disposable large, small, medium chips 51B to 51D First to third chip mounting parts 51bb Magnets 51ab Filter 101 Base box 103 Stirring purification part 106, 107 Dispensing robot 110 Dispensing robot X-axis drive mechanism 111, 112 Dispensing robot Z-axis lifting mechanism 113 Support plate 130 Whole cover

Claims (3)

A box (101) having an overall shape of a box, an agitating and purifying unit (103) provided so as to be freely accessible in and out of the box (101), and horizontal and vertical provided on the box (101). One or a plurality of dispensing robots (106, 107) movable in a direction, and a dispensing robot X axis provided on the table box (101) for reciprocating the dispensing robots (106, 107) in the horizontal direction A driving mechanism (110); a dispensing robot Z-axis lifting mechanism (111, 112) provided on the table box (101) for reciprocating the dispensing robot (106, 107) in the vertical direction; and the table box ( 101) a support plate (113) erected on the rear side of the dispensing robot Z-axis elevating mechanism (111, 112) above, an overall cover (130) for covering the dispensing robot (106, 107), Disposable tips (51a to 51c) provided on the nozzle (51) of the dispensing robot (106, 107), and the liquid to be inspected using the disposable tips (51a to 51c) In a protein screening apparatus that performs any or all of body aspiration, agitation, and ejection,
A plurality of tip mounting portions (51B, 51C, 51D) having different diameters are formed at the tip of the nozzle (51), and each tip mounting portion (51B, 51C, 51D) has a large disposable size. A dispensing structure in a protein screening apparatus, characterized in that it can be mounted with small, medium chips (51a, 51b, 51c).   Each of the chip mounting portions (51B, 51C, 51D) is mounted with a disposable large chip (51a) having a large inner diameter, and the disposable large chip (51a) is disposed inside the disposable large chip (51a). The protein screening apparatus according to claim 1, wherein a disposable small chip (51b) having an inner diameter smaller than that of the disposable small chip (51b) is attached and a magnet (51bb) is provided at a tip of the disposable small chip (51b). Note structure.   Each of the chip mounting portions (51B, 51C, 51D) is mounted with a disposable large chip (51a) having a large inner diameter, and the disposable large chip (51a) is disposed inside the disposable large chip (51a). The protein according to claim 1, wherein a disposable small chip (51b) having an inner diameter smaller than that is mounted, and a filter (51ab) is provided on a tip side of the disposable large chip (51a). Dispensing structure in screening equipment.

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