JP3879676B2 - Compound dissolution equipment - Google Patents

Description

[0001]
BACKGROUND 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 test in drug discovery screening, biotechnology, medical field, and the like.
[0002]
[Prior art]
In drug discovery screening for developing new drugs, tests such as various biochemical reactions are systematically performed using lead compounds as drug candidates as specimens. The lead compound is stored in a container such as a microtiter plate in a solution state dissolved in a solvent and classified and stored. During the test, the lead compound solution that has been refrigerated together with the microtiter plate is taken out, and the micro compound for testing is removed. Dispense into titer plates.
[0003]
When such a lead compound solution is taken out and used, the lead compound does not completely dissolve in the solvent in a state of being dispensed to the microtiter plate, but is partially precipitated. There is a case. When various tests are performed on a solution in such a state, the concentration of the sample in the solution is not constant, so that the reliability of the test result is lowered. For this reason, conventionally, the lead compound has been dissolved in a solvent using a liquid stirring device (see, for example, Patent Document 1).
[0004]
[Patent Document 1]
JP-A-1-58335
[Problems to be solved by the invention]
However, the conventional liquid stirring apparatus has only an effect of stirring the liquid by swinging the liquid in the container. For this reason, when a poorly soluble lead compound having low solubility in a solvent is used as a specimen, it is difficult to obtain a sufficient dissolution effect.
[0006]
Therefore, an object of the present invention is to provide a compound dissolving apparatus capable of dissolving a hardly soluble compound in a solvent.
[0009]
[Means for Solving the Problems]
The compound dissolving apparatus according to claim 1 is a compound dissolving apparatus that dissolves a compound contained in a container together with a solvent in the solvent, and is mounted in a state that can be vibrated and on which the container is mounted; A holding means for holding the container on the mounting table; a vibrating means for vibrating the mounting table; a control means for controlling a vibration frequency of the vibrating means; and a support unit for supporting the mounting table from below. And a base part to which the support part is coupled, and the control means includes a mechanical resonance mode in which the container resonates with vibration transmitted from the vibration means, and a liquid resonance mode in which a solvent in the container resonates with the vibration. of are those carried out at least the dissolution in any one state, also the vibration means includes a vibration actuator mounted on the base portion, the vibration actuator An output end thereof is connected to the placing table.
[0010]
Compounds dissolution apparatus according to claim 2, wherein is a compound dissolving apparatus according to claim 1, wherein the output end is connected to the placing table through the elastic member for adjusting the resonance frequency.
[0011]
Compounds dissolved apparatus according to the third aspect, a compound dissolution apparatus according to claim 2, wherein the elastic member has one end portion side is coupled to the placing table side, wherein the base end portion of the other side It is a plate-like elastic body coupled to the part side, and the output end is connected to the middle of the elastic member.
[0012]
The compound dissolving device according to claim 4 is the compound dissolving device according to claim 2 or 3, wherein the elastic member is a leaf spring.
[0019]
According to the present invention, the container in which the compound is stored together with the solvent is held on the mounting table supported in a vibratable state, and the container resonates with the vibration transmitted from the vibration means, and the solvent in the container. By controlling the vibration means so that the solution is dissolved in at least one of the liquid resonance modes in which the liquid resonates with vibration, the solution can be vibrated in an appropriate resonance mode according to the target compound. Soluble compounds can be dissolved in a solvent.
[0020]
DETAILED DESCRIPTION OF THE INVENTION
Next, embodiments of the present invention will be described with reference to the drawings. 1 is a perspective view of a compound dissolving apparatus according to an embodiment of the present invention, FIG. 2 is a side view of a compound dissolving apparatus according to an embodiment of the present invention, and FIG. 3 is a compound dissolving apparatus according to an embodiment of the present invention. 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, and FIG. 5 is a compound dissolving process according to one embodiment of the present invention. FIG. 6 is an explanatory diagram of liquid behavior by a conventional liquid agitator.
[0021]
First, the structure of the compound dissolving apparatus will be described with reference to FIGS. In FIG. 1, a plate-like base portion 3 is held on the upper surface of a plate-like pedestal 1 via a vibration absorbing insulator 2. Four support columns 4 are erected on the upper surface of the base 3, and a mounting table 6 is supported on the upper end portion of the support column 4 via an insulator 5 so as 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 support column 4 and the insulator 5 serve as a support portion that supports the mounting table 6 from below, and this support portion is coupled to the base portion 3.
[0022]
On the upper surface of the mounting table 6, a microtiter plate 7, which is a container for storing 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 7. Is regulated. The microtiter plate 7 is formed with a plurality of wells 7a for storing a liquid, and the liquid 9 is stored in the well 7a.
[0023]
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 (dimethyl sulfoxide). Here, the liquid 9 is 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 dissolving apparatus is used to completely dissolve such a deposited lead compound in a solvent.
[0024]
Clamp mechanisms 10 for fixing the microtiter plate 7 to the mounting table 6 by the pressing members 11 are disposed at both ends of the mounting table 6. 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 attached to the upper portion of the support bracket 15 by a horizontal pin 14. Pin supported. A pressing claw 11 a that abuts against the upper surface of the microtiter plate 7 and presses downward is provided at the inner end of the pressing member 11, and the other end of the pressing member 11 has a rod 12 a of the cylinder 12. The front ends are coupled by a coupling block 13.
[0025]
By driving the cylinder 12 and projecting the rod 12a upward, the pressing member 11 rotates around the pin 14, and the end of the microtiter plate 7 is pressed against the mounting table 6 by the pressing claw 11a. Thereby, the microtiter plate 7 is clamped with respect to the mounting table 6. By immersing the rod 12a of the cylinder 12, the clamp is released.
[0026]
The cylinder 12 is driven by a cylinder drive unit 29, and the cylinder drive unit 29 is controlled by a control unit 27 so that the microtiter plate 7 can be clamped and released at an arbitrary timing. The position restricting 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 generating unit 20 is disposed 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 the upper surface of the base portion 3 via an L bracket 21, and an output end 22 a of the vibration actuator 22 is an elastic member. It is couple | bonded with the leaf | plate spring member 23 which is. The vibration actuator 22 is driven by a vibration actuator drive unit 26. The upper end portion and the lower end portion of the leaf spring member 23 are coupled to the mounting table 6 and the base portion 3 via coupling blocks 24 and 25, respectively, and the output end 22a of the vibration actuator 22 is coupled 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 through the output end 22a. This vibration is transmitted to the mounting table 6 via the leaf spring member 23, whereby 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 are 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 section 28 to the vibration actuator driving section 26 via the control section 27. By changing the frequency, resonance modes having different characteristics can be selected and used as will be described later.
[0030]
In the configuration of the vibration means described above, the leaf spring member 23 is a plate-like elastic body in which one end portion is coupled to the mounting table 6 side and the other end portion is coupled to the base portion 3 side. The output end 22 a 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 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. The amplitude of vibration can be enlarged.
[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 that is an elastic member for adjusting the 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, the resonance frequency in the mechanical resonance mentioned later can be set to a desired frequency band.
[0032]
Here, with reference to FIG. 3, FIG. 4, the resonance state implement | achieved in a compound melt | dissolution apparatus is demonstrated. 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 to the mounting table 6, vibration is transmitted to the liquid 9 in the well 7a. At this time, when a frequency sweep is performed in which the frequency of vibration generated by the vibration actuator 22 is sequentially changed from a low frequency to a high frequency, the liquid 9 in the microtiter plate 7 and the well 7a held by the mounting table 6 is held. The vibration state of changes.
[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 and the well 7a is maximized. When the vibration frequency is gradually increased, mechanical resonance realized by the microtiter plate 7 resonating with vibration transmitted from the vibration actuator 22 via the leaf spring member 23 is generated in a relatively low frequency band. To do. In the present embodiment, the resonance frequency f1 of this mechanical resonance is set near 100 Hz.
[0034]
FIG. 3A shows this mechanical resonance state. When the microtiter plate 7 vibrates with a large amplitude, the liquid 9 accommodated in the well 7a vibrates together with the well 7a. The vibration of the liquid 9 causes the liquid surface 9a to move finely up and down locally, and a triangular wave 30 is generated in the entire range of the liquid surface 9a. Then, the vibration of the liquid 9 promotes the dissolution of the lead compound precipitated in the solvent.
[0035]
When the vibration frequency is further increased, liquid resonance in which the amplitude of vibration of the liquid 9 in the well 7a is maximized occurs in a relatively high frequency band. FIG. 3B shows this liquid resonance state, and the liquid 9 itself 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 this liquid resonance is set to around 400 Hz.
[0036]
In this liquid resonance, concentric fine ripples 31 are generated on the liquid surface 9a of the liquid 9 accommodated in the well 7a. The vibration of the liquid 9 promotes dissolution of the lead compound precipitated in the solvent in the same manner as in mechanical resonance. However, since the vibration energy is large in this liquid resonance, the precipitated lead compound is finely crushed by vibration. In addition, better dissolution can be obtained.
[0037]
FIG. 6 shows a state where the liquid 9 accommodated 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 movement displacement in a horizontal plane. As a result, a rotational flow that alternately tilts the liquid surface 9a occurs in the liquid 9 in the well 7a, and the liquid 9 in the well 7a is stirred by continuously performing this rotational flow for a predetermined time. I was doing.
[0038]
Such liquid agitation exhibits a sufficient effect when different types of liquids are mixed, but a sufficient effect cannot be obtained when a poorly soluble compound is dissolved in a solvent. On the other hand, when the compound dissolving apparatus shown in the present embodiment is used, in any of the two resonance modes shown in FIG. 3, the liquid 9 in the well 7a contains a solvent in the lead compound itself in the solvent. Vibrations are 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, with reference to FIG. 5, the compound dissolution process using the compound dissolution apparatus of the present embodiment will be described. 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 in 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 in a range including the liquid resonance frequency f2 is swept (ST4). Thereafter, (ST3) and (ST4) are repeated a predetermined number of times set in advance, and the compound dissolution process is completed.
[0041]
The vibration actuator driving unit 26 and the control unit 27 control the vibration frequency of the vibration unit to resonate with the vibration transmitted from the vibration unit by the microtiter plate 7 and the solvent in the well 7a of the microtiter plate 7. Only the control means for dissolving the lead compound in the solvent in at least one of the liquid resonance modes that resonate with vibration.
[0042]
In the above-described compound dissolution treatment, an example of performing the dissolution treatment using both the mechanical resonance mode and the liquid resonance mode is shown, but the combination of the lead compound and the solvent in the target liquid is limited, When the melting characteristic is known in advance, one of the resonance modes that matches the melting characteristic is selected and controlled by the control unit 27 so that only one of (ST3) and (ST4) is executed. You may make it do.
[0043]
In this case, the vibration actuator driving unit 26, the control unit 27, and the operation / input unit 28 control the vibration frequency of the vibration unit and the mechanical resonance mode in which the microtiter plate 7 resonates with the vibration transmitted from the vibration unit. In addition, only the solvent in the well 7a of the microtiter plate 7 serves as a control means for performing the dissolution in a state in which one of the liquid resonance modes in which resonance with 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 stored together with a solvent is held on a mounting table supported in a vibrating state, and the mounting table resonates with vibration transmitted from the vibration means together with the container. Since the vibration means is controlled so that only the solvent in the container is dissolved in at least one of the liquid resonance modes in which resonance with vibration occurs, the solution can be applied in an appropriate resonance mode according to the target compound. It can be vibrated 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 an embodiment of the present invention. FIG. 2 is a side view of a compound dissolving apparatus according to an embodiment of the present invention. FIG. 4 is a graph illustrating the relationship between the vibration frequency and the amplitude of the compound dissolving apparatus according to the embodiment of the present invention. FIG. 5 is a graph illustrating the compound dissolution according to the embodiment of the present invention. Flow diagram of processing [FIG. 6] Explanatory diagram of liquid behavior by conventional liquid agitator [Explanation of symbols]
3 Base part 6 Mounting table 7 Microtiter plate 7a Well 9 Liquid 10 Clamp mechanism 11 Holding member 12 Cylinder 20 Vibration generating part 22 Vibration actuator 23 Leaf spring member 26 Vibration actuator driving part 27 Control part

Claims (4)

A compound dissolving apparatus that dissolves a compound contained in a container together with a solvent in the solvent, a mounting table that is supported in a vibrating state and on which the container is mounted, and the mounting table holds the container Holding means, vibrating means for vibrating the mounting table, control means for controlling the vibration frequency of the vibrating means, a supporting part for supporting the mounting table from below, and a base part to which the supporting part is coupled And the control means dissolves the container in at least one of a mechanical resonance mode in which the container resonates with vibration transmitted from the vibration means and a liquid resonance mode in which the solvent in the container resonates with the vibration. are those performing and said vibrating means comprises a vibrating actuator is mounted on the base portion, connecting an output end of the vibrating actuator on the placing table Compounds dissolved apparatus characterized by being. The compound dissolution apparatus according to claim 1, wherein the output end is connected to the mounting table via an elastic member for adjusting a resonance frequency. The elastic member is a plate-like elastic body in which one end portion is coupled to the mounting table side and the other end portion is coupled to the base portion side, and the output end of the elastic member 3. The compound dissolving apparatus according to claim 2, wherein the compound dissolving apparatus is connected in the middle. The compound dissolving apparatus according to claim 2, wherein the elastic member is a leaf spring.

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