JP2006007081A - Automatic solid phase extraction system - Google Patents

Abstract

An object of the present invention is to provide an automatic solid-phase extraction apparatus having a simple structure and an inexpensive structure that can perform full-automatic processing in a short time and with high accuracy even when the number of solid-phase extraction samples is greatly increased.
An automatic solid-phase extraction comprising a dispensing head for performing suction and discharge operations of liquid, a transfer means for moving the dispensing head, and a vacuum rack on which a solid-phase extraction plate is mounted. In the apparatus, the vacuum rack 8 is composed of an upper vacuum rack 81 and a lower vacuum rack 82, two vacuum containers are provided in the lower vacuum rack 82, and the upper vacuum rack 81 is supported so as to be movable in the horizontal and vertical directions. Then, the upper vacuum rack 81 is moved horizontally by the transfer means 4 in accordance with the solid phase extraction process to determine one of the two vacuum vessels of the lower vacuum rack 82, and then the upper vacuum rack The rack 81 is pressed against the lower vacuum rack 82.
[Selection] Figure 2

Description

  The present invention relates to an automatic solid-phase extraction apparatus that automatically performs a solid-phase extraction operation for concentrating and purifying a small amount of organic chemical components contained in biological samples, water, soil, foods, and the like.

  For example, in the analysis of drug components in blood and urine, in order to analyze organic chemical substances contained in sample solutions such as blood and urine, first, a small amount of organic chemical substances contained in the sample solution are concentrated and purified. It is necessary to perform preprocessing. As this pretreatment, a solid phase extraction operation is performed. In this solid phase extraction operation, a sample solution is dropped from above onto a long cylindrical solid phase extraction tube (column) packed with an adsorbent serving as a stationary phase. After the solute is adsorbed on the stationary phase, the solvent is poured to separate the solute adsorbed on the stationary phase and dissolve the target component.

  Thus, after performing the solid phase extraction operation as a pretreatment, the solution containing the target component is applied to an analyzer such as liquid chromatography or mass spectrometry to identify and quantify the component. And analysis of drug components in urine.

  Of the series of operations described above, the solid phase extraction operation for concentrating and purifying the target substance as a pretreatment takes a very long time, and the manual operation is inefficient. For this purpose, an apparatus that automatically performs these preprocessing operations has been proposed.

  For example, in Patent Document 1, after injecting a sample solution in a test tube sucked with a needle nozzle whose position can be controlled in three orthogonal directions of XYZ into a solid phase extraction tube, a solvent is put into the solid phase extraction tube. An apparatus is disclosed in which an eluate containing a desired component is extracted by dripping the liquid at a predetermined flow rate. According to this, since the injection of the sample solution into the solid phase extraction tube and the inflow of the solvent can be performed fully automatically, the pretreatment until the target component is dissolved out can be performed unattended.

JP-A-8-164302

  However, in the apparatus disclosed in Patent Document 1, it takes time to install a solid phase extraction tube in the apparatus in order to use an individual solid phase extraction tube, and every time the sample changes because a needle nozzle is used. There was also a problem that it was necessary to perform cleaning, which was laborious and mixed with other samples. In addition, since the eluate from the solid phase extraction tube is naturally dropped, there is a problem that the elution time is long.

  The present invention has been made in view of the above problems, and the target process is to perform fully automatic processing in a short time and with high accuracy even when the number of solid-phase extraction samples is significantly increased. An object of the present invention is to provide an automatic solid-phase extraction apparatus that has a simple structure and is inexpensive.

  In order to achieve the above object, the invention according to claim 1 is a vacuum rack in which a dispensing head that performs liquid suction and discharge operations, a transfer means for moving the dispensing head, and a solid phase extraction plate are mounted. The vacuum rack is composed of an upper vacuum rack and a lower vacuum rack, two vacuum vessels are provided in the lower vacuum rack, and the upper vacuum rack can be moved horizontally and vertically The upper vacuum rack is moved to the horizontal direction by the transfer means according to the solid phase extraction process to determine one of the two vacuum vessels of the lower vacuum rack, and then the upper vacuum rack is It is characterized by pressing against the lower vacuum rack.

  According to a second aspect of the present invention, in the first aspect of the invention, the upper vacuum rack is provided with a plurality of roller bearings or sliders, and the roller bearings or sliders are formed in a plurality of guide grooves formed in the lower vacuum rack. The upper vacuum rack is engaged and moved horizontally along the guide groove.

  The invention according to claim 3 is the invention according to claim 2, wherein a plurality of support plates elastically supported by springs are provided in a part of the plurality of guide grooves formed in the lower vacuum rack. To do.

  According to a fourth aspect of the present invention, in the third aspect of the invention, an uneven portion is formed on the support plate, and the roller bearing or the slider is fitted into the uneven portion, whereby the upper vacuum rack moves in the horizontal direction. It is characterized by restraining.

  The invention according to claim 5 is the invention according to claim 3, wherein the roller bearing or slider is made of a magnetic material, a magnet is provided on the support plate, and the roller bearing or slider is attracted by the magnet. It is characterized by restraining the horizontal movement of the upper vacuum rack.

  A sixth aspect of the invention is characterized in that, in the invention according to any one of the first to third aspects, an uneven portion is formed in a part of the plurality of guide grooves.

  The invention according to claim 7 is the invention according to claim 2, wherein the plurality of roller bearings or sliders are supported on the upper vacuum rack via an arm, and the arm is elastically supported on the upper vacuum rack by a spring. It is characterized by.

  The invention according to claim 8 is the invention according to any one of claims 1 to 3, wherein a magnet is provided on one of the upper vacuum rack and the lower vacuum rack, and a magnetic body part is provided on the other. It is characterized by restraining the horizontal movement of the upper vacuum rack by adsorbing the body part.

  The invention according to claim 9 is the invention according to any one of claims 1 to 8, wherein a pin is provided in one of the upper vacuum rack and the lower vacuum rack and an engagement hole is formed in the other, and the pin is engaged with the pin. The upper vacuum rack is positioned with respect to the lower vacuum rack by engaging the joint hole.

  According to a tenth aspect of the present invention, in the first aspect of the present invention, a plurality of hooks are provided on the transfer means, and the hooks are engaged with a plurality of hooks of the upper vacuum rack so that the upper vacuum rack is horizontally and It is characterized by moving in the vertical direction.

  The invention according to claim 11 is the invention according to claim 10, wherein the plurality of hooks provided in the transfer means or the plurality of hooks of the upper vacuum rack are pivotally supported, and one end thereof is supported by a spring. It is characterized by being supported.

  According to a twelfth aspect of the present invention, in the tenth aspect of the invention, a magnet is provided on one of the transfer means and the upper vacuum rack, a magnetic body portion is provided on the other, and the magnet and the magnetic body are adsorbed. The upper vacuum rack is moved horizontally and vertically.

  According to the invention of claim 1, since the upper vacuum rack can be moved horizontally and vertically by the transfer means, one transfer means serves as both the dispensing head and the upper vacuum rack moving means, There is no need to provide a separate moving means for the vacuum rack, and even when the number of solid-phase extraction samples is significantly increased, fully automatic processing can be performed in a short time and with high accuracy. And cost reduction.

  According to the invention of claim 2, since the upper vacuum rack is moved horizontally along the guide groove via the plurality of roller bearings or sliders, the upper vacuum rack is always kept at a constant height, and It can be moved smoothly with a certain interval.

  According to the invention of claim 3, since the support plate provided in a part of the plurality of guide grooves formed in the lower vacuum rack is elastically supported by the spring, the upper vacuum rack is horizontally moved manually by a person before the operation of the apparatus. The container can be moved freely in the direction, the receiving container in the vacuum container or the waste liquid container can be easily put in and out, and the contact time between the upper vacuum rack and the O-ring is shortened, so that deterioration due to deformation of the O-ring can be suppressed. The durability life of the O-ring is increased.

  According to the invention of claim 4, since the roller bearing or the slider is fitted into the uneven portion formed on the support plate to restrain the horizontal movement of the upper vacuum rack, the apparatus is placed on the inclined desk. The upper vacuum rack moves from its normal position during operation due to inadvertent contact with people, earthquakes, vibrations from other devices, etc. Etc. can be prevented.

  According to the fifth aspect of the present invention, the roller bearing or slider is made of a magnetic material, and the magnetic roller bearing or slider is attracted by the magnet provided on the support plate, so that the horizontal direction of the upper vacuum rack is increased. Since the movement is restricted, the same effect as that of the fourth aspect of the invention can be obtained.

  According to the sixth aspect of the present invention, since the uneven portion is formed in the guide groove of the lower vacuum rack, when the upper vacuum rack starts to move in the horizontal direction, a vibration that the roller bearing passes through the uneven portion is generated, and this vibration As a result, the residual liquid in the elution hole at the bottom of the solid phase extraction plate can be forcibly dropped, and occurrence of problems such as contamination of the receiving container in the vacuum container and mixing of liquid can be prevented.

  According to the invention of claim 7, since the plurality of roller bearings or sliders are supported on the upper vacuum rack via the arms, and the arms are elastically supported on the upper vacuum rack by the springs, the same as the invention of claim 3 An effect can be obtained.

  According to the eighth aspect of the present invention, a magnet is provided on one of the upper vacuum rack and the lower vacuum rack, a magnetic body portion is provided on the other, and the magnet and the magnetic body portion are attracted to each other to thereby attract the horizontal direction of the upper vacuum rack. Since the movement is restricted, the same effect as that of the fourth aspect of the invention can be obtained.

  According to the ninth aspect of the present invention, the upper vacuum rack is accurately positioned with respect to the lower vacuum rack by the engagement between the pin provided on one of the upper vacuum rack and the lower vacuum rack and the engagement hole formed on the other. Can be positioned.

  According to the invention of claim 10, since the upper vacuum rack is moved horizontally and vertically by engaging the plurality of hooks provided in the transfer means with the plurality of hooks of the upper vacuum rack, The upper vacuum rack can be moved by the transfer means for transferring the head, and the structure of the apparatus can be simplified.

  According to the eleventh aspect of the present invention, the plurality of hooks provided in the transfer means or the plurality of hooks of the upper vacuum rack are pivotally supported, and one end thereof is supported by the spring. When a phase extraction plate or a receiving container is mounted, an excessive load applied to the hook is reduced by the deformation of the spring even when the upper vacuum rack is obstructed to move horizontally and vertically. Therefore, breakage of the transfer means and the like can be prevented.

  According to the invention of claim 12, a magnet is provided on one of the transfer means and the upper vacuum rack, and a magnetic part is provided on the other, and the upper vacuum rack is horizontally and vertically moved by adsorbing these magnets and the magnetic substance. Since it is made to move, damage to the transfer means and the like can be prevented in the same manner as in the eleventh aspect.

  Embodiments of the present invention will be described below with reference to the accompanying drawings.

  First, the whole structure of the automatic solid-phase extraction apparatus according to the present invention will be described with reference to FIGS.

  1 is a perspective view of an automatic solid-phase extraction apparatus according to the present invention, FIG. 2 is a perspective view of the main part of the automatic solid-phase extraction apparatus, FIG. 3 is a perspective view of a vacuum rack, and FIG. 4 is a cross-sectional view of the vacuum rack. It is.

  An automatic solid-phase extraction apparatus 1 shown in FIG. 1 includes an apparatus main body 12, a vacuum pump 11, and a control device 15 that controls them. Here, the control device 15 is constituted by a general-purpose personal computer, for example, and is electrically connected to the device main body 12 and the vacuum pump 11 via a communication cable 16 such as a LAN (Local Area Network).

  Further, the apparatus main body 12 is provided with transfer means 4 capable of moving in the vertical space, the left and right directions, and the front and rear directions in the internal space of the apparatus main body. A dispensing head 3 is attached for collectively operating the. The dispensing head 3 is transferred and positioned by the transfer means 4 and has the same number (12 in the illustrated example) as the syringe at its tip (lower end) as shown in detail in FIG. The nozzles 31 are arranged side by side in one row, and hooks 41 made of an angle material having an L-shaped cross section are attached to both sides thereof.

  In the lower part of the automatic solid phase extraction apparatus 1, a plurality of nozzles 31 (in the present embodiment, a total of 96 columns of 12 columns × 8 columns) are mounted on the nozzle 31 provided in the dispensing head 3. The dispensing tip container 5 for accommodating the dispensing tips 2, the reagent container 6 for accommodating a plurality of reagents, and the same number (96 in the present embodiment) as the dispensing tips 2 are formed in a lattice shape. A microplate 7 for storing the sample solution in the well, a vacuum rack 8 and a waste tip container 10 for discarding the used dispensing tip 2 are arranged. If necessary, the reagent container 6 and the microplate 7 can be cooled during operation of the apparatus 1 by a cooling water circulation mechanism (not shown) or an electronic cooling device.

  As shown in FIGS. 3 and 4, the vacuum rack 8 is composed of an upper vacuum rack 81 and a lower vacuum rack 82. The lower vacuum rack 82 has a rectangular box-shaped first opening whose upper surface is open. 1 vacuum container 83 and a second vacuum container 84 are provided, and these first and second vacuum containers 83, 84 are connected to the vacuum pump 11 shown in FIG. 1 through vacuum paths 83a, 84b opened on the bottom surfaces thereof. ing.

  The waste liquid container 14 is stored in the first vacuum container 83, and the receiving container 13 is stored in the second vacuum container 84, and the first and second vacuum containers 83 on the upper surface of the lower vacuum rack 82 are stored. , 84 are fitted with a rectangular ring-shaped O-ring 98 for sealing. In addition, the inside of the receiving container 13 is divided into a lattice shape (in this embodiment, 96 pieces) like a solid phase extraction plate 9 described later.

  On the other hand, a solid-phase extraction plate 9 is detachably mounted on the upper vacuum rack 81, and its peripheral edge is in close contact with the upper vacuum rack 81 via a rectangular ring-shaped packing 99 for sealing. The solid-phase extraction plate 9 is formed with a plurality of (96) cylindrical solid-phase extraction tubes 9a in a grid of 12 vertically and 8 horizontally, and at the lower end of each solid-phase extraction tube 9a. Has a small-diameter elution hole 100 in which a filter 9b is housed and set.

  Thus, the automatic solid phase extraction apparatus 1 according to the present invention allows the upper vacuum rack 81 to freely move between the two first and second vacuum vessels 83 and 84, and this is used as the first vacuum vessel. 83 or the second vacuum vessel 84 is selectively brought into close contact, and the details of the mechanism will be described with reference to FIGS.

  FIG. 5 is a sectional view showing an engaged state between the roller bearing and the guide groove, and FIG. 6 is a front view showing the shape of the guide groove.

  As shown in FIG. 6, horizontal guide grooves 87 (only one is shown in FIG. 6) that are long in the moving direction of the upper vacuum rack 81 are formed on the left and right side surfaces of the lower vacuum rack 82, respectively. Four recesses 87a, 87b, 87c, 87d are formed in the guide groove 87, respectively.

  On the other hand, plates 20 (only one is shown in FIG. 5) are attached to both left and right sides of the upper vacuum rack 81 by screws 21, and roller bearings 85 are rotatably supported at both lower ends of each plate 20. Has been. Each roller bearing 85, as shown in FIG. 5A, is rotatably engaged with the guide groove 87 formed in the lower vacuum rack 82, and is attached to the upper vacuum rack 82. Further, the solid phase extraction plate 9 can move along the guide groove 87 of the lower vacuum rack 82 in a state of being spaced apart from the lower vacuum rack 82 through a total of four roller bearings 85 (FIG. 6). reference). Here, a hook 97 is integrally formed at the upper end of each plate 20.

  In place of the roller bearing 85, a slider 86 made of a material having a small friction coefficient such as a synthetic resin as shown in FIG. 5B is used, and this is slidably engaged with the guide groove 87. Also good.

  Thus, the driving of the transfer means 4 is controlled by a control means (not shown) according to the work process, and the transfer means 4 moves up and down, left and right and front and rear together with the dispensing head 3. When the pair of hooks 41 attached are engaged with the side portions of the hooks 97 of the pair of plates 20 attached to the upper vacuum rack 81 and the dispensing head 3 is moved in the left-right direction in FIG. The vacuum rack 82 and the solid-phase extraction plate 9 attached thereto are moved along the guide groove 87 in the same direction on the lower vacuum rack 82.

  Then, the upper vacuum rack 81 is moved on the lower vacuum rack 82, and the transfer is stopped when the upper vacuum rack 81 is positioned in the first vacuum vessel 83, for example. Then, in this state, since the four roller bearings 85 are dropped into the recesses 87a and 87b of the guide groove 87, the upper vacuum rack 81 and the solid-phase extraction plate 9 attached thereto are moved down by their own weight, and the upper vacuum rack is moved. The lower surface of 81 abuts on the upper surface of the lower vacuum rack 82. In this state, the dispensing head 3 is driven by the transfer means 4, and the lower end surface of the hook 41 attached to the dispensing head 3 is in contact with the upper end surface of the hook 97 on the lower vacuum rack 82 side, When the dispensing head 3 is moved downward, the upper vacuum rack 81 is pressed against the O-ring 98 at the periphery of the first vacuum container 83 of the lower vacuum rack, so that the first vacuum container 83 and the upper vacuum rack 81 are solid-phase extracted. If the vacuum pump 11 is driven in an airtight state by the plate 9 and the vacuum pump 11 is driven in this state, the first vacuum vessel 83 is evacuated (depressurized) by the vacuum pump 11 through the vacuum path 83a, and each of the solid phase extraction plates 9 The sample solution accommodated in the solid phase extraction tube 9 a is sucked and discharged into the waste liquid container 14. As a result, organic matter or the like is adsorbed and remains on the filter 9b.

  Next, when the transfer means 4 is driven again and the hook 41 on the dispensing head 3 side is engaged with the hook 97 on the upper vacuum rack 81 side to move the dispensing head 3 upward, the upper vacuum rack 81 is fixed. Together with the phase extraction plate 9, the roller bearing 85 is released from the recesses 87 a and 87 b of the guide groove 87. If the dispensing head 3 is moved in the right direction in FIG. 4 in this state, the roller bearing 85 is re-engaged with the guide groove 87, so that the upper vacuum rack 82 is moved into the guide groove 87 together with the solid phase extraction plate 9. Are transferred in the same direction, and the transfer is stopped when they are located in the second vacuum vessel 84.

  Then, in the above state, since the four roller bearings 85 are dropped into the recesses 87c and 87d of the guide groove 87, the upper vacuum rack 81 and the solid phase extraction plate 9 are moved down by their own weight, and the lower surface of the upper vacuum rack 81 is lower. It contacts the upper surface of the vacuum rack 82. In this state, the dispensing head 3 is driven by the transfer means 4, and the lower end surface of the hook 41 attached to the dispensing head 3 is in contact with the upper end surface of the hook 97 on the lower vacuum rack 82 side. When the dispensing head 3 is moved downward, the upper vacuum rack 81 is pressed against the O-ring 98 at the periphery of the second vacuum container 84 of the lower vacuum rack 82, so that the second vacuum container 84 is fixed to the upper vacuum rack 81. If the vacuum pump 11 is driven in an airtight state by the phase extraction plate 9 and the vacuum pump 11 is driven in this state, the second vacuum vessel 84 is evacuated by the vacuum pump 11 through the vacuum path 84a, and each solid phase extraction plate 9 is fixed. The sample solution stored in the phase extraction tube 9 a is sucked and discharged into the receiving container 13. As a result, organic matter or the like is adsorbed and remains on the filter 9b.

  As described above, in the automatic solid phase extraction apparatus 1 according to the present embodiment, the single transfer means 4 is used for both the movement of the dispensing head 3 and the movement of the upper vacuum rack 81, and the upper vacuum rack 81. Is moved horizontally to selectively position the solid-phase extraction plate 9 in the first vacuum vessel 83 or the second vacuum vessel 84, and the solution stored in the solid-phase extraction plate 9 is transferred to the waste liquid container 14 or the receiving container 13. Since the discharge is selectively performed, it is not necessary to separately provide a dedicated moving mechanism in the vacuum rack 8, and the structure can be simplified, the cost can be reduced, and the durability can be improved.

  Next, another embodiment of the moving support structure for the upper vacuum rack 81 will be described with reference to FIGS.

  7 is a front view showing the installation state of the support plate, FIG. 8 is a side view showing the engagement state of the roller bearing and the guide groove, FIG. 9 is a side view showing the engagement state of the roller bearing and the support plate, and FIG. FIG. 11 is a side view showing another embodiment of the vacuum rack, FIG. 12 is a side view showing another embodiment of the vacuum rack, and FIG. 13 is related to the pins of the vacuum rack. FIGS. 14A to 14C are enlarged perspective views of the hook portion, FIG. 15 is an enlarged perspective view showing another embodiment of the hook portion, and FIG. 16 is another view of the hook portion. It is an expansion perspective view which shows this embodiment.

  In the embodiment shown in FIG. 7, support plates 89 elastically supported by two lower springs 88 are installed at locations where the recesses 87 a and 87 b of the guide groove 87 are formed. In a state where no load is applied thereto, the upper surface of the guide groove 87 is in the same plane as the lower surface of the guide groove 87 (as shown in the figure). Although not shown in FIG. 7, the same configuration is also adopted in the portion where the other concave portions 87 c and 87 d (see FIG. 6) of the guide groove 87 are formed.

  In the above configuration, when the hook 41 of the transfer means 4 and the hook 97 of the upper vacuum rack 81 are not engaged with each other, the upper vacuum rack 81 is always kept at a proper distance from the lower vacuum rack 82 regardless of its position. Retained. When the upper vacuum rack 81 moves in the horizontal direction, the upper vacuum rack 81 is moved by moving the transfer means 4 in the front-rear direction while the hook 41 of the transfer means 4 is engaged with the hook 97 of the upper vacuum rack 81. Can be moved along the guide groove 87 in the horizontal direction.

  Thus, the movement of the upper vacuum rack 81 is stopped in a state where the upper vacuum rack 81 moves to the position of the first vacuum container 83 or the second vacuum container 84 and the roller bearing 85 is positioned on the support plate 89. When the hook 97 of the upper vacuum rack 81 is pressed downward by the hook 41 of the transfer means 4, the upper vacuum rack 81 moves downward together with the support plate 89 against the upward biasing force of the lower spring 88. If the transfer means 4 moves upward, the upper vacuum rack 81 returns to its original position by the urging force of the lower spring 88.

  By adopting such a configuration, the operator can freely move the upper vacuum rack 81 in the horizontal direction along the guide groove 87 by hand before the operation of the apparatus, and the first vacuum vessel 83 shown in FIG. The internal waste liquid container 14 or the receiving container 13 in the second vacuum container 84 can be easily taken in and out. In addition, since the time during which the upper vacuum rack 81 and the O-ring 98 are in contact with each other is shortened, deterioration due to deformation of the O-ring 98 is suppressed, and the durability life of the O-ring 98 is increased.

  In the form shown in FIG. 8, a plurality of roller bearings 85 on the upper vacuum rack 81 side support the plate 20 via the arm 101 so as to be able to rotate up and down, and the upper vacuum rack 81 is elastically supported by a spring 90. It has been adopted.

  In the above configuration, the upper vacuum rack 81 is always held in the state shown in the drawing with an appropriate space from the lower vacuum rack 82 regardless of its position, and the upper vacuum rack 81 is moved by moving the transfer means 4 in the front-rear direction. Can be moved along the guide groove 87 in the horizontal direction.

  When the upper vacuum rack 81 moves to the position of the first vacuum vessel 83 or the second vacuum vessel 84 shown in FIG. 4, the movement of the upper vacuum rack 81 is stopped, and the upper vacuum rack 81 is moved by the hook 41 of the transfer means 4. If the hook 97 of 81 is pressed downward, the upper vacuum rack 81 can move downward against the upward biasing force of the spring 90, and if the transfer means 4 moves upward, the upper vacuum rack 81 81 returns to its original position by the biasing force of the spring 90. Incidentally, the downward movement of the upper vacuum rack 81 is permitted by the rotation of the arm 101 around the shaft 102 as shown by a chain line in FIG.

  Thus, also in this configuration, the same effect as the configuration shown in FIG. 7 can be obtained.

  In the form shown in FIG. 9, the uneven portion 91 is formed on the upper end portion of the support plate 89 of the lower vacuum rack 82 shown in FIG. 7, and the roller bearing 85 of the upper vacuum rack 81 is fitted into the uneven portion 91. Thus, the horizontal movement of the upper vacuum rack 81 is slightly restrained.

  With the above configuration, the upper vacuum rack 81 is properly operated during operation when the automatic solid-phase extraction apparatus 1 is placed on a tilted desk, due to inadvertent human contact, earthquakes, vibrations from other apparatuses, or the like. Therefore, it is possible to prevent an error in dispensing to the solid-phase extraction plate 9 and a vacuum suction failure. The level difference of the concavo-convex portion 91 is set to an appropriate size that allows the upper vacuum rack 81 to be moved in the horizontal direction without difficulty by the transfer means 4 and the hand. In this embodiment, the unevenness portion 91 has a step size of 1 mm, and the upper vacuum rack 81 does not move even when the automatic solid-phase extraction apparatus 1 is placed on a desk inclined by about 10 °.

  In the form shown in FIG. 10 as well, the same configuration as shown in FIG. 7 is adopted. However, a magnet 92 is installed in the lower vacuum rack 82 and the magnetic body portion is located at a position facing the magnet 92 in the upper vacuum rack 81. When the upper vacuum rack 81 is moved to a position where the upper vacuum rack 81 can be moved in the vertical direction (a position matching the vacuum vessel), the magnetic body portion 93 is attracted to the magnet 92, so that the horizontal movement of the upper vacuum rack 81 is caused. It is restrained and the same effect as the embodiment described in FIG. 9 is obtained. The magnet 92 and the magnetic body portion 93 may be provided on either side, and the same effect can be obtained even if the magnet 92 is provided on the upper vacuum rack 81 side and the magnetic body portion 93 is provided on the lower vacuum rack 82 side. . As shown in FIG. 11, when the roller bearing 85 is made of a magnetic metal, the upper vacuum rack 81 can be moved in the vertical direction also by embedding a magnet 92 in the support plate 89. Since the roller bearing 85 is attracted to the magnet 92 when it is moved to the position, the horizontal movement of the upper vacuum rack 81 is restrained, and the same effect as that described in FIG. 9 can be obtained.

  10 and 11 is provided on both sides of the first and second vacuum vessels 83 and 84.

  In the form shown in FIG. 12, the concave and convex portion 94 is partially formed in the vicinity of the concave portions 87 a and 87 b of the guide groove 87 of the upper vacuum rack 81.

  By the way, the solid-phase extraction plate 9 moves horizontally in order to change the position from the upper part of the vacuum vessel 83 to the upper part of the vacuum vessel 84 after reagent dispensing and vacuum suction. In some cases, the liquid attached to the hole 100 (see FIG. 4) falls. In the worst case, when this liquid falls into the receiving container 13 in the vacuum container 84, problems such as contamination and mixing of other samples occur. However, with the structure shown in FIG. 12, when the upper vacuum rack 81 starts moving in the horizontal direction, the liquid remaining in the elution hole 100 due to vibration generated when the roller bearing 85 passes through the uneven portion 94. Can be forcibly dropped, and liquid mixing in the receiving container 13 in the vacuum container 84 can be prevented.

  In the form shown in FIG. 13, a plurality of pins 95 project from the lower surface of the upper vacuum rack 81, and the engagement holes 96 are formed at positions corresponding to the pins 95 on the upper surface of the lower vacuum rack 82.

  By the way, the width of the guide groove 87 is set to be slightly larger than the outer diameter of the bearing 85 or the slider 86 (see FIG. 5) so that the upper vacuum rack 81 can move smoothly along the guide groove 87. For this reason, an error occurs in the positional accuracy of the lower vacuum rack 82, and the eluate from the solid phase extraction plate 9 may not properly enter the receiving container 13 in the second vacuum container 84. However, by adopting this structure, when the upper vacuum rack 81 moves downward, the pin 95 on the upper vacuum rack 81 side engages with the engagement hole 96 on the lower vacuum rack 82 side. More accurate positioning becomes possible, and the eluate from the solid-phase extraction plate 9 can always be properly put into the receiving container 13 in the second vacuum container 84. The same effect can be obtained by providing the pin 95 on the lower vacuum rack 82 side and forming the engagement hole 96 on the upper vacuum rack 81 side. Further, if the tip of the pin 95 or the entrance of the engagement hole 96 is provided with a taper angle, the engagement between the two can be performed smoothly. Furthermore, the configuration shown in FIG. 13 is provided on both sides of the first and second vacuum vessels 83 and 84.

  On the other hand, various forms are conceivable for the hook 41 of the transfer means 4 and the hook 97 of the upper vacuum rack 81.

  For example, as shown in FIG. 14A, the hook 41 on the dispensing head 3 side is formed into a key shape, and a groove 97a for engaging the tip portion 41a of the hook 41 with the hook 97 on the upper vacuum rack 81 side. As shown in FIG. 14 (b), the hook 41 on the dispensing head 3 side is formed of a bar member bent in an L shape, and the tip of the hook 41 is connected to the hook 97 on the upper vacuum rack 81 side. By forming the circular hole 97b into which the portion 41b is fitted, the upper vacuum rack 81 can be reliably moved horizontally and vertically. In the case of a structure in which a support plate 89 supported by a spring 88 is installed in the guide groove 87 (see FIGS. 7 and 9 to 12), an upward biasing force always acts on the upper vacuum rack 81. The hook 97 does not require a groove or hole for transmitting the vertical movement, and as shown in FIG. 14 (c), the hook 41 on the transfer means 4 side is made of an angle material, and the upper vacuum rack 81 By configuring the side hook 97 with a simple convex portion 97c, the upper vacuum rack 81 can be moved horizontally and vertically.

  In the form shown in FIG. 15, the hook 41 on the transfer means 4 side is supported so as to be rotatable about a shaft 41 d, and the hook 41 is supported by a hook spring 42. When such a structure is not adopted, when the solid vacuum extraction plate 9 having an inappropriate size is mounted on the upper vacuum rack 81, or the waste liquid in the receiving container 13 or the first vacuum container 83 in the second vacuum container 84. When the container 14 has an inappropriate size, or when a foreign object is caught in the gap between the roller bearing 85 and the guide groove 87, the upper vacuum rack 81 is prevented from moving in the horizontal and vertical directions. . In this state, when the hook 41 of the transfer means 4 engages with the hook 97 on the upper vacuum rack 81 side and the upper vacuum rack 81 moves in the horizontal and vertical directions, an excessive load acts on the hooks 41 and 97, In addition to the breakage of these hooks 41 and 97, there is a concern about the breakage of the transfer means 4 and the upper vacuum rack 81.

  However, by adopting the structure shown in FIG. 15, the load acting on the hooks 41, 97 is reduced by the deformation of the hook spring 42, and the hook of the transfer means 4 is deformed by the deformation of the hook spring 42 for an excessive load. 41 and the hook 97 of the upper vacuum rack 81 are disengaged, so that each part can be prevented from being damaged. In addition, with respect to the function stop of the apparatus due to the disengagement of the hooks 41 and 97, it is possible to detect the function stop of the apparatus by providing a sensor for detecting the position of the upper vacuum rack 81.

  In the form shown in FIG. 16, magnets 43 (only one is shown in the figure) are provided on both surfaces of the hook 41 on the transfer means 4 side, and the magnetic body portion 44 provided on the upper vacuum rack 81 is attracted by the magnet 43. Thus, the upper vacuum rack 81 can be moved in the horizontal direction and the vertical direction. However, by adopting this structure, even if a state that hinders the movement of the upper vacuum rack 81 in the horizontal and vertical directions occurs, the magnet When a load equal to or greater than the attraction force 43 is applied, the magnet 43 and the magnetic body portion 44 are detached, and the apparatus can be prevented from being damaged as in the structure shown in FIG.

  Next, a specific pretreatment operation using the automatic solid phase extraction apparatus 1 according to the present invention will be described step by step.

  As a preparation stage, the worker performs the following work manually.

  The necessary number (96 in this embodiment) of dispensing tips 2 is stored and installed in the dispensing tip container 5.

  -A reagent container 6 containing a reagent and a microplate 7 containing a sample solution are installed.

  Place the solid phase extraction plate 9 on the upper vacuum rack 81 of the vacuum rack 8.

  In the present embodiment, a 96-well “Empore disk plate” manufactured by 3M is used as the solid-phase extraction plate 9, but various types of solid-phase extraction plates can be used.

  The waste liquid container 14 and the receiving container 13 are stored and installed in the first vacuum container 83 and the second vacuum container 84 of the lower vacuum rack 82, respectively.

  ・ Set the operating conditions such as reagent quantity, sample solution quantity, vacuum suction conditions, etc. using the control unit.

  ・ Turn on the power of the device 1 and start operation.

  Next, the pretreatment operation by the automatic solid phase extraction apparatus 1 will be described step by step.

Step 1) Conditioning step for activating the stationary phase (filter 9b) in the solid phase extraction plate 9:
The transfer means 4 is moved to the position of the dispensing tip container 5 and the dispensing tip 2 is mounted on the nozzle 31 of the dispensing head 3.

  The transfer means 4 is moved to the position of the reagent container 6 and the dispensing head 3 aspirates 100 μl of methanol.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses 100 μl of methanol into a predetermined solid phase extraction tube (well) of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate under predetermined vacuum suction conditions. Here, the solid phase extraction plate 9 is on the first vacuum vessel 83 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the waste liquid vessel 14 in the first vacuum vessel 83.

  In the present embodiment, the operation of the vacuum pump 11 is controlled from the output of the vacuum sensor, and the first and second vacuum vessels 83 and 84 are vacuumed at a constant vacuum of −60 kPa. If the specified vacuum degree previously memorized in the control device cannot be obtained due to changing the operation of the vacuum pump 11 during suction or clogging or breakage of the solid-phase extraction plate 9, the device 1 is turned on. It is also possible to stop. Further, by installing a distance sensor such as an ultrasonic sensor in the transfer means 4 and measuring the liquid level in each well of the solid-phase extraction plate 9 before and after vacuum suction, the solid-phase extraction plate 9 can be clogged in the same manner. It is possible to detect breakage and the like.

  The transfer means 4 moves to the position of the dispensing tip container 5 and attaches the dispensing tip 2 to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the reagent container 6 and the dispensing head 3 sucks 100 μl of pure water.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses 100 μl of pure water into a predetermined well of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate under predetermined vacuum suction conditions. Here, the solid phase extraction plate 9 is on the first vacuum container 83 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the waste liquid container 14 in the first vacuum container 83.

Step 2) Sample solution injection step:
The transfer means 4 moves to the position of the dispensing tip container 5 and attaches the dispensing tip 2 to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the microplate 7 and the dispensing head 3 aspirates 100 μl of the sample solution. In the present embodiment, a diluted sample solution is used. However, the diluted solution is dispensed from the reagent container 6 to the microplate 7, and stirring is performed by repeatedly sucking and discharging the solution at the same position in the microplate 7. It is also possible to dilute the sample in the microplate 7 by doing so.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses 100 μl of the sample solution into a predetermined well of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate under predetermined vacuum suction conditions. Here, the solid phase extraction plate 9 is on the first vacuum container 83 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the waste liquid container 14 in the first vacuum container 83.

Step 3) Cleaning of impurities:
The transfer means 4 moves to the position of the dispensing tip container 5 and attaches the dispensing tip 2 to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the reagent container 6 and the dispensing head 3 sucks 100 μl of pure water.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses 100 μl of pure water into a predetermined well of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate under predetermined vacuum suction conditions. Here, the solid phase extraction plate 9 is on the first vacuum container 83 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the waste liquid container 14 in the first vacuum container 83.

  The transfer means 4 moves to the position of the dispensing tip container 5 and attaches the dispensing tip 2 to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the reagent container 6, and the dispensing head 3 sucks 5% methanol aqueous solution.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses a 5% methanol aqueous solution into a predetermined well of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate under predetermined vacuum suction conditions. Here, the solid phase extraction plate 9 is on the first vacuum container 83 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the waste liquid container 14 in the first vacuum container 83.

Process 4) Elution process of target component:
The hook 41 of the transfer means 4 and the hook 97 of the upper vacuum rack 81 are engaged, and the upper vacuum rack 81 is moved in the horizontal direction. Then, the solid-phase extraction plate 9 moves to the second vacuum vessel 84 side of the vacuum rack 8.

  The transfer means 4 moves to the position of the dispensing tip container 5 and attaches the dispensing tip 2 to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the reagent container 6 and the dispensing head 3 aspirates 100 μl of methanol.

  The transfer means 4 moves to a position on the solid phase extraction plate 9 and dispenses 100 μl of methanol into a predetermined well of the solid phase extraction plate 9.

  The transfer means 4 moves to the position of the waste tip container 10 and removes the dispensing tip 2 attached to the nozzle 31 of the dispensing head 3.

  The transfer means 4 moves to the position of the vacuum rack 8, moves the upper vacuum rack 81 downward, and sucks the eluate containing the organic matter adhering to the filter 9b under a predetermined vacuum suction condition. Here, the solid phase extraction plate 9 is on the second vacuum vessel 84 side of the vacuum rack 8, and the eluate from the solid phase extraction plate 9 flows into the receiving vessel 13 in the second vacuum vessel 84.

  In the present embodiment, the vacuum suction is stopped when the solution in the wells of the solid-phase extraction plate 9 is exhausted. However, if the vacuum suction is continued, all the evaporated components of the solution in the receiving container 13 are gasified, and the vacuum pump 11 is discharged to the outside. Evaporation-drying treatment can also be performed in the apparatus 1, and further, the treatment time can be shortened by heating the inside of the second vacuum vessel 84.

  The hook 41 of the transfer means 4 and the hook 97 of the upper vacuum rack 81 are engaged, and the upper vacuum rack 81 is moved in the horizontal direction to finish the operation of the apparatus 1. The solid phase extraction plate 9 moves to the first vacuum vessel 83 side of the vacuum rack 8.

  -Take out the receiving container 13 by hand from the second vacuum container 83 side of the lower vacuum rack 82.

  By passing through the process demonstrated above, even if the amount of processing increased, highly accurate solid-phase extraction operation could be completed easily in a short time.

  The present invention is useful for the analysis of organic chemical components in the field of drug discovery screening, biotechnology, medicine, and the like.

1 is a perspective view of an automatic solid phase extraction apparatus according to the present invention. It is a perspective view of the principal part in the automatic solid-phase extraction apparatus which concerns on this invention. It is a perspective view of the vacuum rack of the automatic solid phase extraction apparatus concerning the present invention. It is sectional drawing of the vacuum rack of the automatic solid phase extraction apparatus which concerns on this invention. It is sectional drawing which shows the engagement state of the roller bearing and guide groove in the automatic solid-phase extraction apparatus which concerns on this invention. It is a front view which shows the shape of the guide groove in the automatic solid-phase extraction apparatus which concerns on this invention. It is a front view which shows the installation state of a support plate. It is a side view which shows the engagement state of a roller bearing and a guide groove. It is a side view which shows the engagement state of a roller bearing and a support plate. It is a side view which shows other embodiment of a vacuum rack. It is a side view which shows other embodiment of a vacuum rack. It is a side view which shows other embodiment of a vacuum rack. It is sectional drawing which shows the relationship between the pin of a vacuum rack, and an engagement hole. (A)-(c) is an expansion perspective view of a hook part. It is an expansion perspective view which shows other embodiment of a hook part. It is an expansion perspective view which shows other embodiment of a hook part.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Automatic solid-phase extraction apparatus 2 Dispensing tip 3 Dispensing head 4 Transfer means 5 Dispensing tip container 6 Reagent container 7 Microplate 8 Vacuum rack 9 Solid phase extraction plate 10 Waste tip container 11 Vacuum pump 12 Apparatus main body 13 Receptacle container 14 Waste container 15 Control device 20 Plate 31 Nozzle 41 Transfer means hook 42 Hook spring 43 Magnet 44 Magnetic body part 81 Upper vacuum rack 82 Lower vacuum rack 83 First vacuum container 84 Second vacuum container 85 Roller bearing 86 Slider 87 Guide groove 88 Lower part Spring 89 Support plate 90 Upper spring 91 Uneven portion 92 Magnet 93 Magnetic body portion 94 Uneven portion of guide groove 95 Pin 96 Engagement hole 97 Hook 98 O-ring 99 Packing 100 Elution hole 101 Arm 102 Shaft

Claims (12)

In an automatic solid phase extraction apparatus comprising a dispensing head that performs liquid suction and discharge operations, a transfer means for moving the dispensing head, and a vacuum rack on which a solid phase extraction plate is mounted,
The vacuum rack is composed of an upper vacuum rack and a lower vacuum rack, two vacuum containers are provided in the lower vacuum rack, and the upper vacuum rack is supported so as to be movable in the horizontal and vertical directions. The upper vacuum rack is moved horizontally by the transfer means to be positioned at one of the two vacuum vessels of the lower vacuum rack, and then the upper vacuum rack is pressed against the lower vacuum rack. An automatic solid-phase extraction device.   A plurality of roller bearings or sliders are provided on the upper vacuum rack, and these roller bearings or sliders are engaged with a plurality of guide grooves formed on the lower vacuum rack so that the upper vacuum rack is horizontally aligned along the guide grooves. The automatic solid phase extraction apparatus according to claim 1, wherein the apparatus is moved.   3. The automatic solid phase extraction apparatus according to claim 2, wherein a plurality of support plates elastically supported by springs are provided in a part of the plurality of guide grooves formed in the lower vacuum rack.   4. An automatic solid phase according to claim 3, wherein an uneven portion is formed on the support plate, and the horizontal movement of the upper vacuum rack is restrained by fitting the roller bearing or the slider into the uneven portion. Extraction device.   The roller bearing or slider is made of a magnetic material, a magnet is provided on the support plate, and the horizontal movement of the upper vacuum rack is restrained by attracting the roller bearing or slider with the magnet. The automatic solid phase extraction apparatus according to claim 3.   The automatic solid phase extraction apparatus according to any one of claims 1 to 3, wherein an uneven portion is formed in a part of the plurality of guide grooves.
3. The automatic solid phase extraction apparatus according to claim 2, wherein the plurality of roller bearings or sliders are supported on the upper vacuum rack via an arm, and the arm is elastically supported on the upper vacuum rack by a spring.   A magnet is provided on one of the upper vacuum rack and the lower vacuum rack, and a magnetic body portion is provided on the other, and the horizontal movement of the upper vacuum rack is restrained by attracting the magnet and the magnetic body portion. The automatic solid phase extraction apparatus according to any one of claims 1 to 3.   A pin is provided in one of the upper vacuum rack and the lower vacuum rack, an engagement hole is formed in the other, and the upper vacuum rack is positioned with respect to the lower vacuum rack by engaging the pin and the engagement hole. The automatic solid-phase extraction apparatus according to any one of claims 1 to 8,   The automatic means according to claim 1, wherein the transfer means is provided with a plurality of hooks, and the upper vacuum racks are moved horizontally and vertically by engaging the hooks with the plurality of hooks of the upper vacuum rack. Solid phase extraction device.   11. The automatic solid phase extraction according to claim 10, wherein a plurality of hooks provided in the transfer means or a plurality of hooks of the upper vacuum rack are pivotally supported and one end thereof is supported by a spring. apparatus.   A magnet is provided on one of the transfer means and the upper vacuum rack, and a magnetic body is provided on the other, and the upper vacuum rack is moved horizontally and vertically by adsorbing the magnet and the magnetic body. The automatic solid phase extraction apparatus according to claim 10.

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