JP2004239838A - Compound dissolving apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compound dissolving apparatus capable of dissolving a hardly-soluble compound in a solvent. <P>SOLUTION: In the compound dissolving apparatus for dissolving a lead compound contained in a mixed state together with a solvent in a microtiter plate 7, a leaf spring member 23 is connected between the bottom face of a placement table 6 on which the plate 7 is placed and a base part 3 and an output shaft 23a of a vibration actuator 22 is connected to an intermediate part of the spring member 23a for constituting a vibration generation part 20. For giving a vibration, the frequency of the vibration of the actuator 22 is controlled by a controller 27. The lead compound is dissolved by using one or both of a mechanical resonance mode in which the plate 7 resonates with the vibration transmitted from the vibration generation part 20 and a liquid resonance mode in which only the solvent in the plate 7 resonates with the vibration. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a compound dissolving apparatus that dissolves a compound contained in a container together with a solvent in a solvent in a test performed in drug discovery screening, biotechnology, a medical field, and the like.
[0002]
[Prior art]
In drug discovery screening for developing a new drug, various tests such as biochemical reactions are systematically performed using a lead compound as a drug candidate substance as a sample. The lead compound is stored in a container such as a microtiter plate in the form of a solution dissolved in a solvent and classified and stored.At the time of the test, the lead compound solution stored refrigerated together with the microtiter plate is taken out, and the test microtube is removed. Dispense into a titer plate.
[0003]
When a solution of such a lead compound is taken out and used, the lead compound remains in a partially precipitated state without being completely dissolved in the solvent when dispensed into a microtiter plate. There are cases. When various tests are performed on the solution in such a state, the reliability of the test results decreases because the analyte concentration in the solution is not constant. For this reason, conventionally, a lead compound has been dissolved in a solvent using a device for stirring liquid (for example, see Patent Document 1).
[0004]
[Patent Document 1]
JP-A-1-58335
[Problems to be solved by the invention]
However, the conventional liquid stirring device has the effect of merely stirring the liquid by swinging the liquid in the container. Therefore, when a poorly soluble lead compound having low solubility in a solvent is used as a sample, it is difficult to obtain a sufficient dissolving effect.
[0006]
Therefore, an object of the present invention is to provide a compound dissolving apparatus that can dissolve a hardly soluble compound in a solvent.
[0007]
[Means for Solving the Problems]
The compound dissolving apparatus according to claim 1, wherein the compound dissolving apparatus is a compound dissolving apparatus that dissolves a compound contained in a container together with a solvent in the solvent, wherein the mounting table is supported in a vibrable state and the container is placed thereon, Holding means for holding the container on the mounting table; vibrating means for vibrating the mounting table; mechanical resonance for controlling the vibration frequency of the vibrating means so that the container resonates with vibration transmitted from the vibrating means Control means for performing the dissolution in at least one of a mode and a liquid resonance mode in which the solvent in the container resonates with the vibration.
[0008]
According to a second aspect of the present invention, there is provided the compound dissolving apparatus according to the first aspect, further comprising a support for supporting the placing table from below, and a base to which the support is connected.
[0009]
The compound dissolving device according to claim 3 is the compound dissolving device according to claim 2, wherein the vibration means includes a vibration actuator mounted on the base portion, and an output end of the vibration actuator is provided on the mounting table. Are linked.
[0010]
According to a fourth aspect of the present invention, in the compound dissolving apparatus according to the third aspect, the output end is connected to the placing table via an elastic member for adjusting a resonance frequency.
[0011]
The compound dissolving apparatus according to claim 5 is the compound dissolving apparatus according to claim 4, wherein one end of the elastic member is connected to the placing table, and the other end is the base. The output end is connected to the middle of the elastic member.
[0012]
The compound dissolving device according to claim 6 is the compound dissolving device according to claim 4 or 5, wherein the elastic member is a leaf spring.
[0013]
The compound dissolving apparatus according to claim 7, wherein the compound dissolving apparatus is a compound dissolving apparatus that dissolves a compound contained in a container together with a solvent in the solvent, and a mounting table on which the container is mounted while being supported in a vibrable state, Holding means for holding the container on the mounting table; vibrating means for vibrating the mounting table; mechanical resonance for controlling the vibration frequency of the vibrating means so that the container resonates with vibration transmitted from the vibrating means Control means for performing the dissolution in a state in which one of a liquid resonance mode in which the solvent in the container resonates with the vibration can be selected.
[0014]
According to an eighth aspect of the present invention, there is provided the compound dissolving apparatus according to the seventh aspect, further comprising a support for supporting the placing table from below, and a base to which the support is coupled.
[0015]
The compound dissolving apparatus according to claim 9 is the compound dissolving apparatus according to claim 8, wherein the vibration means includes a vibration actuator mounted on the base portion, and an output end of the vibration actuator is provided on the mounting table. Are linked.
[0016]
According to a tenth aspect of the present invention, there is provided the compound dissolving apparatus according to the ninth aspect, wherein the output end is connected to the placing table via an elastic member for adjusting a resonance frequency.
[0017]
The compound dissolving apparatus according to claim 11, wherein the elastic member has one end coupled to the placing table side and the other end coupled to the base. The output end is connected to the middle of the elastic member.
[0018]
A compound dissolving apparatus according to a twelfth aspect is the compound dissolving apparatus according to the tenth or eleventh aspect, wherein the elastic member is a leaf spring.
[0019]
According to the present invention, a container in which a compound is accommodated together with a solvent is held on a mounting table supported in a vibrating state, and a mechanical resonance mode in which the container resonates with vibration transmitted from a vibration unit and a solvent in the container are provided. By controlling the vibrating means so as to dissolve in at least one of the liquid resonance modes in which the solution resonates with the vibration, the solution can be vibrated in an appropriate resonance mode according to the target compound, which makes it difficult. A soluble compound can be dissolved in a solvent.
[0020]
BEST MODE FOR CARRYING OUT THE INVENTION
Next, embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a perspective view of a compound dissolving apparatus according to one embodiment of the present invention, FIG. 2 is a side view of the compound dissolving apparatus according to one embodiment of the present invention, and FIG. 3 is a compound dissolving apparatus according to one embodiment of the present invention. FIG. 4 is a graph illustrating the relationship between vibration frequency and amplitude of a compound dissolving apparatus according to an embodiment of the present invention, and FIG. 5 is a compound dissolving process according to an embodiment of the present invention. FIG. 6 is an explanatory diagram of a liquid behavior by a conventional liquid stirring device.
[0021]
First, the structure of the compound dissolving apparatus will be described with reference to FIGS. In FIG. 1, a plate-shaped base portion 3 is held on an upper surface of a plate-shaped pedestal 1 via an insulator 2 for absorbing vibration. Four columns 4 are erected on the upper surface of the base 3, and a mounting table 6 is supported at the upper end of the columns 4 via an insulator 5 so as to be able to vibrate. The insulator 5 has a damper characteristic that does not prevent the mounting table 6 from resonating with vibration transmitted from a vibration actuator that is a vibration source described later. The columns 4 and the insulators 5 are supporting portions for supporting the mounting table 6 from below, and the supporting portions are connected to the base portion 3.
[0022]
On the upper surface of the mounting table 6, a microtiter plate 7, which is a container for accommodating a liquid sample, is mounted. The microtiter plate 7 is positioned on the mounting table 6 by a position regulating member 8 disposed around the microtiter plate. Is regulated. A plurality of wells 7a for storing a liquid are formed in the microtiter plate 7, and a liquid 9 is stored in the well 7a.
[0023]
The liquid 9 is obtained by dissolving a lead compound to be tested as a specimen in drug discovery screening in a solvent such as DMSO (dimethylsulfoxide). Here, the liquid 9 is in a state in which the lead compound stored in a refrigerated state is taken out and dispensed into the microtiter plate 7. In this state, the lead compound is not completely dissolved in the solvent but is partially precipitated. It is in. The present compound dissolution apparatus is used for completely dissolving such a precipitated lead compound in a solvent.
[0024]
At both ends of the mounting table 6, clamp mechanisms 10 for fixing the microtiter plate 7 to the mounting table 6 by holding members 11 are provided. The structure of the clamp mechanism 10 will be described. As shown in FIGS. 2 and 3, two elongated support brackets 15 are fixed to the end surface of the mounting table 6, and a pressing member 11 is mounted on the support bracket 15 by a horizontal pin 14. Pin supported. At an inner end of the holding member 11, a holding claw 11 a that abuts on the upper surface of the microtiter plate 7 and presses downward is provided. At the other end of the holding member 11, a rod 12 a of the cylinder 12 is provided. The tips are joined by a joining block 13.
[0025]
By driving the cylinder 12 to protrude the rod 12a upward, the holding member 11 rotates around the pin 14 and presses the end of the microtiter plate 7 against the mounting table 6 by the holding claw 11a. Thereby, the microtiter plate 7 is clamped to the mounting table 6. The clamp is released by retracting the rod 12a of the cylinder 12.
[0026]
The cylinder 12 is driven by a cylinder driving unit 29, and the microtiter plate 7 can be clamped and released at an arbitrary timing by controlling the cylinder driving unit 29 by the control unit 27. The position regulating member 8 and the clamp mechanism 10 are holding means for holding the microtiter plate 7 on the mounting table 6.
[0027]
As shown in FIG. 2, a vibration generator 20 is provided on the lower surface side of the mounting table 6. As shown in FIG. 3, a variable frequency vibration actuator 22 using a magnetostrictive element is mounted on an upper surface of the base section 3 via an L-shaped bracket 21. An output end 22a of the vibration actuator 22 is an elastic member. Is connected to the leaf spring member 23. The vibration actuator 22 is driven by a vibration actuator drive unit 26. The upper end and the lower end of the leaf spring member 23 are connected to the mounting table 6 and the base 3 via connecting blocks 24 and 25, respectively, and the output end 22a of the vibration actuator 22 is connected to the mounting table 6. It has a configuration.
[0028]
By driving the vibration actuator 22, vibration is transmitted to the leaf spring member 23 via the output end 22a. The vibration is transmitted to the mounting table 6 via the leaf spring member 23, so that the vibration is transmitted to the microtiter plate 7 mounted on the mounting table 6. The vibration actuator 22 and the leaf spring member 23 serve as vibration means for vibrating the mounting table 6.
[0029]
In driving the vibration actuator 22, the vibration frequency of the vibration actuator 22 can be changed by inputting a vibration command value from the operation / input unit 28 to the vibration actuator driving unit 26 via the control unit 27. By changing the frequency, resonance modes having different characteristics can be selected and used as described later.
[0030]
In the configuration of the vibration means described above, the leaf spring member 23 is a plate-like elastic body having one end coupled to the mounting table 6 and the other end coupled to the base 3. The output end 22a is connected to the middle of the leaf spring member 23. Here, the output end 22a is coupled to the leaf spring 23 at a position that internally divides the entire length of the leaf spring member 23 into L1: L2, and is transmitted to the mounting table 6 by appropriately setting this lever ratio. Vibration amplitude can be increased.
[0031]
Further, in the above configuration, the output end 22a of the vibration actuator 22 is connected to the mounting table 6 via a leaf spring member 23 which is an elastic member for adjusting a resonance frequency. The resonance frequency of the mounting table 6 can be adjusted by appropriately selecting the material, thickness and width of the leaf spring member 23 and setting the rigidity in the vibration direction to a desired value. Thereby, a resonance frequency in mechanical resonance described later can be set to a desired frequency band.
[0032]
Here, the resonance state realized in the compound dissolving apparatus will be described with reference to FIGS. When the vibration actuator 22 is driven in a state where the microtiter plate 7 containing the liquid 9 in the well 7a is clamped on the mounting table 6, vibration is transmitted to the liquid 9 in the well 7a. At this time, when a frequency sweep is performed to sequentially change the frequency of the vibration generated by the vibration actuator 22 from a low frequency to a high frequency, the microtiter plate 7 held on the mounting table 6 and the liquid 9 in the well 7a are held. Changes its vibration state.
[0033]
The graph of FIG. 4 shows the relationship between the vibration frequency of the vibration actuator 22 in this frequency sweep and the resonance frequency at which the amplitude of the liquid 9 in the microtiter plate 7 or the well 7a is maximized. When the vibration frequency is gradually increased, mechanical resonance is generated in a relatively low frequency band by the microtiter plate 7 resonating with the vibration transmitted from the vibration actuator 22 via the leaf spring member 23. I do. In the present embodiment, the resonance frequency f1 of the mechanical resonance is set to around 100 Hz.
[0034]
FIG. 3A shows this mechanical resonance state. When the microtiter plate 7 vibrates with a large amplitude, the liquid 9 contained in the well 7a vibrates together with the well 7a. Due to the vibration of the liquid 9, the liquid surface 9a locally moves up and down finely, and a triangular wave 30 is generated in the entire range of the liquid surface 9a. The vibration of the liquid 9 promotes dissolution of the lead compound precipitated in the solvent.
[0035]
When the vibration frequency is further increased, a liquid resonance occurs in which the amplitude of the vibration of the liquid 9 in the well 7a is maximized in a relatively high frequency band. FIG. 3B shows this liquid resonance state, in which the liquid 9 in the well 7 a resonates with the vibration transmitted from the vibration actuator 22 via the leaf spring member 23. In the present embodiment, the resonance frequency f2 of the liquid resonance is set to around 400 Hz.
[0036]
In this liquid resonance, fine concentric ripples 31 occur on the liquid surface 9a of the liquid 9 contained in the well 7a. The vibration of the liquid 9 promotes the dissolution of the lead compound precipitated in the solvent in the same manner as at the time of mechanical resonance. However, in this liquid resonance, the energy of vibration is large, so that the precipitated lead compound is finely crushed by vibration. And further excellent dissolution can be obtained.
[0037]
FIG. 6 shows a state where the liquid 9 stored in the microtiter plate 7 similar to the above is stirred by a conventional liquid stirring device. In this stirring operation, the microtiter plate 7 is given a swing including a displacement in a horizontal plane. As a result, a rotational flow is generated in the liquid 9 in the well 7a so as to alternately tilt the liquid surface 9a, and by continuously performing the rotational flow for a predetermined time, the liquid 9 in the well 7a is stirred. I was
[0038]
Such liquid stirring shows a sufficient effect when mixing different kinds of liquids, but does not provide a sufficient effect when dissolving a hardly soluble compound in a solvent. On the other hand, when the compound dissolving apparatus shown in the present embodiment is used, in either of the two resonance modes shown in FIG. 3, the liquid 9 in the well 7a contains the solvent for the lead compound itself in the solvent. Vibration is transmitted through. Thereby, dissolution of the lead compound in the solvent is promoted, and good solubility can be obtained even when a poorly soluble compound is targeted.
[0039]
Next, the compound dissolution treatment using the compound dissolution apparatus of the present embodiment will be described with reference to FIG. First, the microtiter plate 7 into which the liquid 9 to be treated is dispensed is set on the mounting table 6 (ST1), and then the microtiter plate 7 is clamped on the mounting table 6 (ST2).
[0040]
Then, by driving the vibration actuator 22 to gradually change the vibration frequency, the mechanical resonance frequency range R1 set to a range including the mechanical resonance frequency f1 is swept (ST3). Thereafter, the vibration frequency is increased, and the mechanical resonance frequency range R2 set to a range including the liquid resonance frequency f2 is swept (ST4). Thereafter, (ST3) and (ST4) are repeated a predetermined number of times, and the compound dissolution treatment is completed.
[0041]
The vibration actuator driving section 26 and the control section 27 control the vibration frequency of the vibration means, and the mechanical resonance mode in which the microtiter plate 7 resonates with the vibration transmitted from the vibration means, and the solvent in the well 7a of the microtiter plate 7 Only the control means dissolves the lead compound in the solvent in at least one of the liquid resonance modes that resonate with the vibration.
[0042]
Note that, in the compound dissolution processing described above, an example is shown in which the dissolution processing is performed using both the mechanical resonance mode and the liquid resonance mode, but the combination of the lead compound and the solvent in the target liquid is limited, If the dissolution characteristic is known in advance, the controller 27 selects one of the resonance modes that matches the dissolution characteristic and controls the control unit 27 to execute only one of (ST3) and (ST4). You may make it.
[0043]
In this case, the vibration actuator drive unit 26, the control unit 27, and the operation / input unit 28 control the vibration frequency of the vibration unit to cause the microtiter plate 7 to resonate with the vibration transmitted from the vibration unit. The control means performs the dissolution in a state where only one of the liquid resonance modes in which the solvent in the well 7a of the microtiter plate 7 resonates with the vibration can be selected.
[0044]
【The invention's effect】
According to the present invention, a mechanical resonance mode in which a container in which a compound is accommodated together with a solvent is held on a mounting table supported in a vibrable state, and the mounting table resonates with vibration transmitted from the vibration means together with the container Since the vibration means is controlled so as to dissolve in at least one of the liquid resonance modes in which only the solvent in the container resonates with the vibration, the solution is controlled in an appropriate resonance mode according to the target compound. Vibration can be applied, and a poorly soluble compound can be dissolved in a solvent.
[Brief description of the drawings]
FIG. 1 is a perspective view of a compound dissolving apparatus according to one embodiment of the present invention. FIG. 2 is a side view of a compound dissolving apparatus according to one embodiment of the present invention. FIG. 3 is a compound dissolving apparatus according to one embodiment of the present invention. FIG. 4 is a diagram illustrating the behavior of a liquid during operation of the apparatus. FIG. 4 is a graph showing the relationship between the vibration frequency and the amplitude of the compound dissolving apparatus according to one embodiment of the present invention. FIG. 6 is a flowchart of a process. FIG. 6 is an explanatory diagram of liquid behavior by a conventional liquid stirring device.
3 Base 6 Mounting table 7 Microtiter plate 7a Well 9 Liquid 10 Clamping mechanism 11 Pressing member 12 Cylinder 20 Vibration generator 22 Vibration actuator 23 Leaf spring member 26 Vibration actuator driver 27 Controller

Claims (12)

A compound dissolving device for dissolving a compound contained in a container together with a solvent in the solvent, wherein the mounting table is supported in a vibrating state and the container is mounted thereon, and the mounting table holds the container. Holding means, a vibration means for vibrating the mounting table, and a mechanical resonance mode in which the container resonates with the vibration transmitted from the vibration means by controlling the vibration frequency of the vibration means, and the solvent in the container has the vibration Control means for performing the dissolution in at least one of the liquid resonance modes that resonate. 2. The compound dissolving apparatus according to claim 1, further comprising: a support portion for supporting the placing table from below, and a base portion to which the support portion is connected. The compound dissolving apparatus according to claim 2, wherein the vibration means includes a vibration actuator mounted on the base portion, and an output end of the vibration actuator is connected to the placing table. The compound dissolving apparatus according to claim 3, wherein the output end is connected to the placing table via an elastic member for adjusting a resonance frequency. The elastic member is a plate-like elastic body having one end coupled to the placement table side and the other end coupled to the base unit, and the output end is a terminal of the elastic member. The compound dissolving device according to claim 4, wherein the compound dissolving device is connected to an intermediate portion. The compound dissolving device according to claim 4, wherein the elastic member is a leaf spring. A compound dissolving device for dissolving a compound contained in a container together with a solvent in the solvent, wherein the mounting table is supported in a vibrating state and the container is mounted thereon, and the mounting table holds the container. Holding means, a vibration means for vibrating the mounting table, and a mechanical resonance mode in which the container resonates with the vibration transmitted from the vibration means by controlling the vibration frequency of the vibration means, and the solvent in the container has the vibration A compound dissolving apparatus comprising: a control unit for performing the dissolution in a state in which any of the liquid resonance modes that resonate can be selected. The compound dissolving apparatus according to claim 7, further comprising: a support portion for supporting the placing table from below, and a base portion to which the support portion is connected. The compound dissolving apparatus according to claim 7, wherein the vibration means includes a vibration actuator mounted on the base portion, and an output end of the vibration actuator is connected to the placing table. The compound dissolving apparatus according to claim 7, wherein the output end is connected to the placing table via an elastic member for adjusting a resonance frequency. The elastic member is a plate-like elastic body having one end coupled to the placement table side and the other end coupled to the base unit, and the output end is a terminal of the elastic member. The compound dissolving device according to claim 7, wherein the compound dissolving device is connected to an intermediate portion. The compound dissolving apparatus according to claim 10, wherein the elastic member is a leaf spring.

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