JP2014054601A - Agitator and agitation method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agitator and an agitation method in which optimum agitation of liquid can be performed in short time.SOLUTION: An agitator 100 comprises: a data storage section 13 recording a reference vibration waveform of optimum vibration for agitation of liquid L; a computing section 14 which computes corrected drive voltage and corrected distance between electrodes for allowing vibration waveform of the liquid L to be close to the reference vibration waveform captured by an optical receiver 60; and an upper electrode control section 15 which applies the corrected drive voltage to control into the corrected distance between electrodes. Therefore, vibration of the liquid becomes optimum vibration in a short time comparing to a case of adjusting voltage and distance between electrodes while watching the movement of the liquid L, and the agitator 100 in which time to the end of agitation is shortened can be obtained.

Description

  The present invention relates to a stirring device and a stirring method for a small amount of liquid containing a solute.

In analysis and quantification of biological components, reactions utilizing the interaction between deoxyribonucleic acid and intercalators, antigen fixing reactions, antigen-antibody reactions, and the like are used. Although these reactions proceed by stirring, the amount of biological components is small and the antibody is expensive, so stirring with a small amount of liquid of 1 mL or less, especially μL unit is required.
As a liquid stirring device and a stirring method, a stirring device and a stirring method in which a liquid is placed in a changing electric field and the liquid is vibrated and stirred are known (for example, Patent Document 1).

JP 2010-119388 A

When the liquid is stirred in an electric field that changes between the electrodes, the drive voltage and the interelectrode distance for the liquid to vibrate optimally for stirring differ depending on the type (particularly viscosity) and amount of the liquid. For this reason, the driving voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid for each stirring. Therefore, time for adjustment is required, and it takes time until the stirring is completed.
In addition, if the amount of liquid changes due to evaporation of the liquid even if the drive voltage and the distance between the electrodes are adjusted at the start of stirring, the optimal vibration according to the amount of liquid The driving voltage and the distance between the electrodes deviate from the conditions, and even if stirring is performed for the same time, sufficient stirring cannot be obtained, and with the stirring over time, the vibration of the liquid (stirring strength) becomes weak and sufficient stirring is obtained. There may be no.
Here, the vibration optimal for stirring means a vibration in which the probability of reaction increases by stirring and the reaction proceeds faster.

  SUMMARY An advantage of some aspects of the invention is to solve at least one of the problems described above, and the invention can be implemented as the following forms or application examples.

  Application Example 1 A liquid is disposed between a first electrode and a second electrode facing the first electrode, and a driving voltage is applied between the first electrode and the second electrode. An agitating device that applies and vibrates the liquid, wherein the detection unit detects the vibration, the waveform conversion unit converts the vibration detected by the detection unit into a vibration waveform, and the detection unit and the waveform in advance. A data storage unit that records a reference vibration waveform of vibration that is optimal for stirring of the liquid obtained by using the conversion unit, and compares the vibration waveform with the reference vibration waveform, and compares the vibration waveform with the reference vibration waveform. A calculation unit that calculates a correction driving voltage between the first electrode and the second electrode to approximate a vibration waveform and a correction interelectrode distance between the first electrode and the second electrode; Based on the correction drive voltage and the distance between the correction electrodes, the first electrode An electrode control unit configured to apply the correction driving voltage to the second electrode and control the distance between the first electrode and the second electrode to the correction interelectrode distance; A stirrer characterized by.

According to this application example, the stirring device has a data storage unit that records a reference vibration waveform of vibration that is optimal for liquid stirring, and a correction drive voltage and correction that brings the vibration waveform of the liquid captured by the detection unit closer to the reference vibration waveform. A calculation unit that calculates the distance between the electrodes and an electrode control unit that applies a correction drive voltage and controls the distance between the correction electrodes are provided. Therefore, as compared with the case where the driving voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid, the liquid vibration becomes the optimum vibration in a short time, and the stirring device in which the time until the stirring is completed is shortened. can get.
In addition, even if the amount of liquid changes due to evaporation of the liquid during stirring, the detection unit captures the vibration waveform of the liquid, applies a correction driving voltage according to the amount of liquid, and controls the distance between the correction electrodes. Since the part is provided, an agitation device in which optimum vibration is maintained can be obtained.

Application Example 2 In the stirring device, the detection unit includes a light receiver that receives light reflected from the vibrating liquid.
In this application example, since the detection unit includes a light receiver that receives light reflected from the liquid, the vibration of the liquid can be detected without contact with the liquid. Therefore, the influence of the vibration detection on the stirring of the liquid is reduced, and a stirring device in which the time until the stirring is completed is shortened can be obtained.

[Application Example 3] A stirring device, characterized in that the stirring device includes a light source for irradiating the liquid with light.
In this application example, since the light source for irradiating the liquid with the light is provided, the amount of fluctuation of the light incident on the liquid is more stable and the liquid accompanying the vibration of the liquid compared to the case where the external light is incident on the liquid. The effect of fluctuations in the amount of light incident on the liquid on the amount of light reflected from the surface is suppressed. Therefore, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid becomes a more optimal vibration, and a stirring device in which the time until the end of stirring is further shortened can be obtained.

Application Example 4 In the stirring device described above, the light source is a laser light source.
In this application example, since the light applied to the liquid is a more directional laser beam, the fluctuation amount of the light incident on the liquid is more stable, and the amount of light reflected from the liquid due to the vibration of the liquid is reduced. In addition, the influence of fluctuations in the amount of light incident on the liquid is further suppressed. Therefore, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid becomes a more optimal vibration, and a stirring device in which the time until the end of stirring is further shortened can be obtained.

Application Example 5 The stirring apparatus includes a member that shields a region including an optical path from which light emitted from the light source is reflected by the liquid and incident on the light receiver from external light. Stirring device characterized.
In this application example, the amount of light reflected from the liquid accompanying the vibration of the liquid is reduced by a member that shields the region including the optical path where the light emitted from the light source is reflected by the liquid and enters the light receiver from the external light. The influence of fluctuations in external light is further suppressed. Therefore, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid becomes a more optimal vibration, and a stirring device in which the time until the end of stirring is further shortened can be obtained.

Application Example 6 In the stirring device, the detection unit detects a voltage fluctuation between the first electrode and the second electrode due to the vibrating liquid.
In this application example, the dielectric constant between the first electrode and the second electrode is changed by the vibrating liquid, and the voltage fluctuation associated therewith is detected. Therefore, the vibration of the liquid can be detected without contact with the liquid. Therefore, the influence of detection of vibration on the liquid stirring is reduced, and a stirring device in which the time until the end of stirring is shortened can be obtained.

  Application Example 7 A liquid is disposed between the first electrode and the second electrode facing the first electrode, and a driving voltage is applied between the first electrode and the second electrode. A stirring method for applying and vibrating the liquid, wherein a reference vibration waveform recording step for pre-recording a reference vibration waveform and a stirring time optimal for stirring the liquid, and the first vibration waveform is obtained. An electrode setting step of moving at least one of the first electrode and the second electrode to an inter-electrode distance between the electrode and the second electrode; and applying the driving voltage to the liquid to It is determined whether a vibration start step for starting liquid vibration, a vibration waveform detection step for detecting a vibration waveform of the liquid vibration, and a cycle of the reference vibration waveform and a cycle of the detected vibration waveform are close to each other. A period determining step for performing the reference vibration waveform A period control step of changing the inter-electrode distance and the drive voltage so that the period and the period of the vibration waveform approach each other, and whether the amplitude of the reference vibration waveform and the amplitude of the vibration waveform are close An amplitude determination step of determining, and an amplitude control step of changing the inter-electrode distance and the drive voltage so that the amplitude of the reference vibration waveform and the amplitude of the detected vibration waveform approach each other. A characteristic stirring method.

  According to this application example, the reference vibration waveform of the vibration most suitable for stirring of the liquid is recorded, the vibration waveform of the liquid is detected, and the distance between the electrodes is set so that the period and amplitude of the vibration waveform approach the reference vibration waveform. The drive voltage is changed. Therefore, compared with the case where the drive voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid, the liquid vibration becomes the optimum vibration in a short time, and the stirring method in which the time until the stirring is completed is shortened. can get.

Application Example 8 In the agitation method described above, a vibration allowable range recording step in which an allowable waveform integral value difference is recorded in advance from a reference waveform integral value corresponding to a half cycle of the reference vibration waveform; The time-dependent change monitoring step for measuring the change, the absolute value of the reference waveform integral value, and the absolute value of the waveform integral value for a half period of the vibration waveform are compared, and the difference between these waveform integral values is acceptable. A waveform integrated value difference determining step for determining whether or not the waveform integrated value difference is less than, and if the waveform integrated value difference is greater than or equal to the allowable waveform integrated value difference, the waveform integrated value difference is less than the allowable waveform integrated value difference A stirring method characterized by including a waveform integral value difference control step of changing the inter-electrode distance and the drive voltage.
In this application example, the change over time of the vibration waveform is measured, the waveform integral value is compared with the reference waveform integral value, and the inter-electrode distance and driving are performed so that the waveform integral value difference is less than the allowable waveform integral value difference. Change the voltage. Therefore, even if the amount of liquid changes due to evaporation of the liquid during stirring and the period and amplitude of the vibration waveform of the liquid change, the vibration becomes the optimal vibration and the stirring time is shortened. A method is obtained.

The perspective view which shows schematic structure of the stirring apparatus in 1st Embodiment. The block diagram showing a stirring apparatus. The figure which shows the voltage applied to a lower electrode and an upper electrode. The figure showing the mode of reflection of the light in a liquid. The figure showing the converted vibration waveform. The figure showing the converted vibration waveform at the time of a time-dependent change. The flowchart figure which shows the stirring method. The perspective view which shows schematic structure of the stirring apparatus in 2nd Embodiment. The perspective view which shows schematic structure of the stirring apparatus in 3rd Embodiment. The perspective view which shows schematic structure of the stirring apparatus in 4th Embodiment.

Hereinafter, embodiments will be described in detail with reference to the drawings.
Note that, in the embodiments described below, various limitations are made as preferred specific examples of the present invention. However, the scope of the present invention is not limited to the following description unless otherwise specified. However, the present invention is not limited to this embodiment.
In the following drawings, the scale of each member is different from the actual scale in order to make each member recognizable.

(First embodiment)
FIG. 1 is a perspective view illustrating a schematic configuration of a stirring device 100 according to the present embodiment. FIG. 2 is a block diagram showing the stirring device 100. The stirring device 100 is a device that places the liquid L in a changing electric field and vibrates the liquid L to stir.
In FIG. 1, the stirring device 100 includes a base 10, a support column 20, a flat plate lower electrode 30 as a first electrode, a flat plate upper electrode 40 as a second electrode, a light source 50, and a detection unit. And a light shielding box 70 as a member for shielding light. The light shielding box 70 is indicated by a broken line in order to make the inside covered with the light shielding box 70 easier to see.
Hereinafter, “lower” indicates a direction in which gravity is directed, and “upper” indicates a direction opposite to the direction in which gravity is directed.

The base 10 is a substantially rectangular parallelepiped casing made of metal, for example, and is installed so that the upper surface thereof is horizontal. Here, the upper surface may be slightly deviated from the horizontal within an adjustable range depending on the installation state of the base 10.
An operation display unit 11 is provided on the front surface of the base 10. In the operation display unit 11, for example, position operation and position display of the lower electrode 30 and the upper electrode 40, operation of a drive voltage applied between the lower electrode 30 and the upper electrode 40, display of the drive voltage, and the inside of the light shielding box 70 Temperature and humidity, and the temperature and humidity of the atmosphere surrounding the stirring device 100 are displayed.
In FIG. 2, the base 10 is provided with a waveform conversion unit 12, a data storage unit 13, a calculation unit 14, and an upper electrode control unit 15 as an electrode control unit.

The support | pillar 20 consists of metal, for example, and is attached to the upper surface of the base 10 perpendicularly | vertically. Here, the vertical includes a slight deviation from the vertical due to manufacturing variations.
A lower electrode 30 and an upper electrode 40 are attached to the support column 20 so that their faces are parallel to each other. The upper electrode 40 is attached above the lower electrode 30. Here, the parallel includes a slight deviation from the parallel due to manufacturing variations.
The upper electrode 40 is movably attached along the support column 20, and the vertical position of the upper electrode 40 is detected by, for example, the linear encoder 21 attached to the support column 20. The upper electrode 40 can be moved by a rack and pinion or a linear motor.
The lower electrode 30 may also be attached to be movable along the support column 20.

  The material of the lower electrode 30 and the upper electrode 40 is a transparent conductive film on transparent glass, for example, a transparent electrode formed of ITO (Indium Tin Oxide), a metal electrode, a graphite electrode, a conductive resin plate, An electrode attached with a mesh or the like can be used. An electrode in which a conductive mesh is attached to a synthetic resin plate is preferable because it is inexpensive and allows the state of the liquid L to be observed.

The upper electrode control unit 15 controls the distance between the lower electrode 30 and the upper electrode 40 by changing the position of the upper electrode 40, or controls the drive voltage applied to the lower electrode 30 and the upper electrode 40. .
Here, when the lower electrode 30 is controlled, a lower electrode control unit may be provided as the electrode control unit. When the lower electrode 30 and the upper electrode 40 are controlled, the lower electrode control unit and the upper electrode control unit are provided. 15 may be provided.

FIG. 3 shows an example of the driving voltage applied to the lower electrode 30 and the upper electrode 40.
In FIG. 3, the drive voltage is a rectangular pulse wave with a period T, and the maximum voltage applied to the lower electrode 30 and the upper electrode 40 is Vd. For example, a driving voltage having a frequency v (v = 1 / T) of several Hz to several tens Hz and Vd of several kV can be used.
The drive voltage is not limited to a drive voltage composed of a rectangular pulse wave, and may be a drive voltage composed of, for example, a sine wave or a triangular wave.

In FIG. 1, a plurality of slide glasses S on which the same type of liquid L is placed are placed on the lower electrode 30 of the stirring device 100. In FIG. 1, five glass slides S are placed, but one may be used, or five or more electrodes may be placed with a larger electrode.
Here, the same type of liquid L refers to the liquid L having the same solvent, viscosity, and the like.
The amount of the liquid L is, for example, several tens to several hundreds μL. In order to vibrate and stir a plurality of liquids L under the same conditions, the amount of each liquid L is brought as close to the same amount as possible.
As the material of the slide glass S, glass such as soda lime glass, borosilicate glass and quartz, and resin such as polystyrene can be used.

In order to vibrate and stir a plurality of liquids L under the same conditions, the shape of the liquid L needs to be close to the same shape. In order to make the shape of the liquid L placed on the slide glass S the same, the slide glass S is washed in advance under the same conditions. By cleaning, the surface state of the slide glass S is stabilized, and the contact angle of the liquid L with respect to the slide glass S is stabilized.
In addition, when the solvent of the liquid L contains water as a main component, the circumference of a circle having a predetermined diameter is repelled in order to limit the spread of the liquid L on the slide glass S and to align the height of the liquid L. Draw with a water-based material and place liquid L in a circle. The liquid L is contained in a water-repellent circle, and spread on the slide glass S is suppressed. For example, when 200 μL of the liquid L, the main component of which is water, is contained in a circle having a diameter of 12 mm, the height of the liquid L that is allowed to stand is 2 to 3 mm. Further, when 600 μL of the liquid L containing water as a main component is contained in a circle having a diameter of 20 mm, the height of the liquid L that is allowed to stand is 2 to 3 mm.
By making the amount and shape of each liquid L of the same type the same, each liquid L can be vibrated and stirred under substantially the same conditions.

  On the other hand, if the surface of the upper electrode 40 is subjected to water repellent treatment, even if the liquid L is vibrated and stirred, even if it contacts the upper electrode 40, a part of the liquid L adheres to the upper electrode 40. Separation is prevented, and a sudden change in the amount of the liquid L is suppressed.

The light source 50 is attached to the base 10 at an angle at which the emitted light illuminates the liquid L. The liquid L to be illuminated with light may be any liquid, or a dummy liquid L may be prepared to illuminate the dummy liquid L.
As the light source 50, a sodium lamp, an incandescent bulb, a fluorescent lamp, a laser light source, or the like can be used.

FIG. 4 shows a diagram illustrating how light is reflected by the liquid L. FIG. The liquid L is indicated by a broken line in a state of rising from the liquid L1 indicated by a solid line in a shape stationary on the slide glass S, for example, by a driving voltage applied between the lower electrode 30 and the upper electrode 40 (not shown). The shape changes to the liquid L2. If the drive voltage changes periodically, the liquid L vibrates and its shape vibrates in the order of liquid L1 → liquid L2 → liquid L1 → liquid L2. The liquid L is agitated with this vibration.
Here, the shape of the vibrating liquid L is not limited to the shape shown in the figure, and may vibrate between a raised shape and a raised shape from the shape placed on the slide glass S. You may vibrate between the shape where the center was dented and the shape which rose.

The direction of reflection of the light incident on the liquid L also changes due to the vibration of the liquid L.
In FIG. 4, the optical path is indicated by solid and broken arrows. For example, light incident on the liquid L at the incident angle θ from the light source 50 travels straight in the shape of the liquid L1, proceeds in the direction of the solid arrow, and does not reach the light receiver 60. On the other hand, when the shape is the liquid L2, the light is reflected, proceeds in the direction of the broken arrow, and reaches the light receiver 60. Therefore, the light intensity associated with the vibration can be detected by the light receiver 60.
When the light emitted from the light source 50 adversely affects the solute or solvent of the liquid L, for example, when the solute or solvent is decomposed or the evaporation of the solvent is promoted, the incident angle θ is reduced to reduce the light. It is better to increase the reflectance.

  In FIG. 2, the intensity of light received by the light receiver 60 is converted into an electric signal, and converted into a vibration waveform by the waveform converter 12. The converted vibration waveform is stored in the data storage unit 13. The data storage unit 13 is an element for storing data, and includes ROM, RAM, and NVRAM (nonvolatile storage element).

FIG. 5 shows a diagram showing a converted vibration waveform when the evaporation of the liquid L does not proceed with short-time stirring. The horizontal axis represents time (t), and the vertical axis represents amplitude. Both axes are arbitrary scales and are not necessarily the actual amplitude of the vibrating liquid L.
In FIG. 5, a curve indicated by a broken line indicates a vibration waveform in which a certain type of liquid L is efficiently stirred with optimal vibration. A curve indicated by a solid line shows a vibration waveform when the vibration deviates from the optimum vibration for stirring. Here, the optimal vibration for stirring is, for example, when a vibration waveform with a large amplitude is obtained, but is not limited to a vibration waveform with a large amplitude, and the interaction between deoxyribonucleic acid and the intercalator after stirring. This is a vibration waveform in which reactions such as reaction using an antigen, antigen fixing reaction, antigen-antibody reaction, etc. proceed well.

  Since the vibrations of the liquids L of different types and amounts are different depending on the same driving voltage, the data storage unit 13 stores the distance between the electrodes of the lower electrode 30 and the upper electrode 40 according to the amount of each type of liquid L. In addition, the drive voltage applied to these electrodes is changed, and a reference vibration waveform of vibration optimal for stirring is recorded in advance for each type.

  FIG. 6 shows a diagram showing the converted vibration waveform when the liquid L evaporates and changes over time. As the evaporation of the liquid L progresses, the amplitude becomes smaller and the cycle becomes shorter as the amount of the liquid L decreases.

  The calculation unit 14 compares the reference vibration waveform with the actually oscillating drive waveform, and calculates a corrected drive voltage and a corrected interelectrode distance that are close to the reference vibration waveform. The upper electrode control unit 15 controls the upper electrode 40 based on the calculated corrected driving voltage and corrected electrode plate distance.

The light shielding box 70 is made of a material that shields external light detected by the light receiver 60. For example, a metal or a material containing a substance that absorbs and reflects light detected by the light receiver 60 can be used. The shading box 70 may be manually covered, or the shading box 70 may be provided with a door that automatically opens and closes to improve workability. Further, the temperature and humidity may be adjusted inside the light shielding box 70.
A cover may be provided in place of the light shielding box 70. By providing the cover, it is possible to prevent dust and the like from the outside, and to suppress the evaporation of the liquid L. Even in the case of a cover, a door that automatically opens and closes may be provided to improve workability, and temperature and humidity adjustment may be performed inside the cover. When a material that shields light from the outside is used for the cover, the light shielding box 70 can be obtained.

FIG. 7 is a flowchart showing the stirring method in the present embodiment in which the liquid L is stirred using the stirring device 100.
In FIG. 7, the stirring method in this embodiment includes step S1 as a reference vibration waveform recording step, step S2 as a vibration allowable range recording step, step S3 as a sample setting step, and step S4 as an electrode setting step. Step S5 as a vibration start step, Step S6 as a vibration waveform detection step, Step S7 as a cycle determination step, Step S8 as a cycle control step, Step S9 as an amplitude determination step, and amplitude control Step S10 as a process, Step S11 as a temporal change monitoring process, Step S12 as a waveform integral value difference determination process, Step S13 as a waveform integral value difference control process, and Step S14 as a stirring time determination process including.

  Here, step S2 and steps S11 to S13 can be added as necessary. These steps can be added when the concentration of the solute in the solvent in the liquid L is low and long stirring is required. For example, in an antigen-antibody reaction, when an antibody is expensive and it is desired to suppress its concentration, it is necessary to advance the antigen-antibody reaction by stirring for a long time.

In the reference vibration waveform recording step (step S <b> 1), a reference vibration waveform of vibration optimal for stirring the liquid L is recorded in the data storage unit 13 in advance.
When the viscosity or the like varies depending on the type of the liquid L, a reference vibration waveform is recorded for each type of the liquid L. Also, the stirring time required when stirring is performed with the reference vibration waveform is stored.
For example, the drive waveform is obtained by adjusting the distance between the electrodes while applying the rectangular pulse wave shown in FIG. 3 to obtain the reference vibration waveform in which the amplitude of the liquid L becomes the maximum value. Alternatively, a reference vibration waveform in which the reaction proceeds well is obtained and recorded.

  In the vibration permissible range recording step (step S2), a waveform integral value difference that is permissible from a reference waveform integral value corresponding to a half cycle of the reference vibration waveform is recorded in the data storage unit 13 in advance. Also in this case, an allowable waveform integral value difference for each type of liquid L is recorded.

In the sample setting step (step S3), the slide glass S on which the liquid L is placed is set on the lower electrode 30. At this time, the operation display unit 11 may select the type and amount of the liquid L actually measured from the types of the liquid L recorded in the data storage unit 13.
The inter-electrode distance between the lower electrode 30 and the upper electrode 40 can be adjusted and adjusted so that the sample can be easily set. In this case, for example, when the movable distance of the upper electrode 40 is increased, the space between the lower electrode 30 and the upper electrode 40 can be widened, and a hand or a robot arm can be easily placed between the electrodes. The distance between the electrodes can be made easily.

In the electrode setting step (step S4), the upper electrode 40 is moved to the interelectrode distance between the lower electrode 30 and the upper electrode 40 at which the reference vibration waveform is obtained.
For example, according to the height of the liquid L of several mm, the interelectrode distance between the lower electrode 30 and the upper electrode 40 can be several to several tens of millimeters so that the liquid L and the upper electrode 40 do not contact each other. .
The upper electrode 40 may be moved manually by the operation display unit 11 or may be automatically moved to a position where a reference vibration waveform is obtained in advance by an encoder.

In the vibration start step (step S5), the drive voltage recorded in step S1 and obtained as a reference vibration waveform when applied to the liquid L is applied between the lower electrode 30 and the upper electrode 40, and the vibration of the liquid L is applied. Start.
Since the drive voltage for obtaining the reference vibration waveform for the same type of liquid L has a slightly different characteristic such as the viscosity of the liquid L for each adjustment of the liquid L, the vibration of the liquid L that is actually vibrated is the optimum vibration. It is not necessarily the drive voltage.

  In the vibration waveform detection step (step S6), the light emitted from the light source 50 enters the liquid L, the reflected light is detected by the light receiver 60, and is converted into a vibration waveform by the waveform converter 12.

In the period determining step (step S7), it is determined whether or not the period of the reference vibration waveform is close to the period of the vibration waveform.
Whether or not the period of the reference vibration waveform is close to the period of the vibration waveform is based on the difference between the period of the reference vibration waveform and the period of the vibration waveform stored in the data storage unit 13 in advance. And whether or not the difference is greater than the allowable difference between the period of the vibration waveform. If the difference between the period of the reference vibration waveform and the period of the vibration waveform is greater than or equal to the allowable difference (step S7: NO), the process proceeds to the period control step (step S8). When the difference between the period of the reference vibration waveform and the period of the vibration waveform is not greater than or equal to the allowable difference, in other words, when the difference between the period of the reference vibration waveform and the period of the vibration waveform is less than the allowable difference (step S7: (YES) proceeds to the amplitude determination step (step S9).

In the cycle control step (step S8), the inter-electrode distance and the drive voltage are calculated and changed so that the cycle of the reference vibration waveform and the cycle of the vibration waveform approach each other.
The calculation unit 14 calculates the correction drive voltage and the distance between the correction electrodes that approach the period of the reference vibration waveform and the period of the vibration waveform, and the upper electrode control unit 15 corrects the period of the reference vibration waveform and the period of the vibration waveform to approach each other. The upper electrode 40 is controlled to the driving voltage and the distance between the correction electrodes. After the control, the process proceeds to the amplitude determination step (step S9).

In the amplitude determining step (step S9), it is determined whether or not the amplitude of the reference vibration waveform is close to the amplitude of the vibration waveform.
Whether or not the amplitude of the reference vibration waveform is close to the amplitude of the vibration waveform is determined by the difference between the amplitude of the reference vibration waveform and the amplitude of the vibration waveform being the amplitude of the reference vibration waveform stored in the data storage unit 13 in advance. This is done based on whether or not the difference from the amplitude of the vibration waveform is acceptable. When the difference between the amplitude of the reference vibration waveform and the amplitude of the vibration waveform is greater than or equal to the allowable difference (step S9: NO), the process proceeds to the amplitude control step (step S10). When the difference between the period of the reference vibration waveform and the period of the vibration waveform is not greater than or equal to the allowable difference, in other words, when the difference between the amplitude of the reference vibration waveform and the amplitude of the vibration waveform is less than the allowable difference (step S9: (YES) proceeds to the temporal change monitoring step (step S11).

In the amplitude control step (step S10), the inter-electrode distance and the drive voltage are changed so that the amplitude of the reference vibration waveform and the amplitude of the detected vibration waveform approach each other.
The calculation unit 14 calculates the correction drive voltage and the distance between the correction electrodes that approach the amplitude of the reference vibration waveform and the amplitude of the vibration waveform, and the upper electrode control unit 15 corrects the amplitude of the reference vibration waveform and the amplitude of the vibration waveform to approach each other. The upper electrode 40 is controlled to the driving voltage and the distance between the correction electrodes. After the control, the process proceeds to the temporal change monitoring step (step S11).
For example, if the distance / voltage between the electrodes is adjusted after matching the periods, the periods are shifted. If the amplitude does not match the reference vibration waveform when the period is matched, it is assumed that light is absorbed by the tissue or the influence of external light, and the difference between the amplitude of the reference vibration waveform and the amplitude of the vibration waveform is calculated. The amplitude is increased (decreased) by the difference and matched with the reference vibration waveform. (Example: Reference waveform: cycle 2, amplitude 5. Vibration waveform: cycle 2, amplitude 3. In this case, amplitude 3 is regarded as amplitude 5.)

In the temporal change monitoring step (step S11), the temporal change of the vibration waveform is measured.
As with the vibration waveform detection step (step S6), the change with time is measured by the light emitted from the light source 50 entering the liquid L, the reflected light being detected by the light receiver 60, and the waveform converter 12 performing the vibration waveform. This is done by converting to

In the waveform integrated value difference determining step (step S12), the absolute value of the reference waveform integrated value for the half cycle is compared with the absolute value of the waveform integrated value for the half cycle of the vibration waveform, and these waveform integrated value differences are allowed. Judge whether or not it is less than the possible waveform integral difference.
For example, the absolute value of the reference waveform integral value corresponds to Sa shown in FIG. 5, and the absolute value of the waveform integral value for a half cycle of the vibration waveform corresponds to Sb.
If the waveform integral value difference is less than the allowable waveform integral value difference (step S12: YES), the process proceeds to the stirring time determination step (step S14). When the waveform integral value difference is not less than the allowable waveform integral value difference, in other words, when the waveform integral value difference is greater than or equal to the allowable waveform integral value difference (step S12: NO), the waveform integral value difference control step (step S13). Proceed to

In the waveform integral value difference control step (step S13), the inter-electrode distance and the drive voltage are changed so that the waveform integral value difference is less than the allowable waveform integral value difference.
The calculation unit 14 calculates the correction drive voltage and the distance between the correction electrodes that approach the absolute value of the reference waveform integral value of the reference vibration waveform and the absolute value of the waveform integration value of the vibration waveform, and the upper electrode control unit 15 calculates the reference value. The upper electrode 40 is controlled so that the absolute value of the waveform integrated value and the absolute value of the waveform integrated value of the vibration waveform approach each other and the correction drive voltage and the distance between the correction electrodes. After the control, the process proceeds to the stirring time determination step (step S14).

In the stirring time determination step (step S14), the elapsed time from the start of stirring is compared with the stirring time recorded in the reference vibration waveform recording step (step S1), and the elapsed time has passed the stirring time (step S14: YES). Ends the stirring. When the elapsed time does not pass the stirring time (step S14: NO), the process returns to the temporal change monitoring step (step S11).
The stirring method of this embodiment is completed by the flow shown above.

  In the flow shown above, either the reference vibration waveform recording step (step S1) or the vibration allowable range recording step (step S2) may be performed first. In addition, as described above, the change in the stirring intensity due to evaporation can be examined by obtaining the integral value difference, but the change in the stirring intensity can also be examined by obtaining the difference between the half cycle of the reference vibration waveform and the stirring waveform. sell. Further, a step of inputting the stirring time may be added between the steps S4 to S5, and a period difference may be used instead of the integral value in the steps S12 and S13.

  Further, in the reference vibration waveform recording step (step S1) and the vibration permissible range recording step (step S2), it is necessary to store data in the data storage unit 13 and record the reference vibration waveform of the liquid L having a new solvent in advance. When there is not, the reference vibration waveform recording step (step S1) and the vibration allowable range recording step (step S2) can be omitted and the sample setting step (step S3) can be started. The reference vibration waveform recording step (Step S1) and the vibration allowable range recording step (Step S2) are essential.

According to such an embodiment, there are the following effects.
(1) The data storage unit 13 in which the stirrer 100 records the reference vibration waveform of the vibration most suitable for stirring the liquid L, the correction drive voltage that brings the vibration waveform of the liquid L captured by the light receiver 60 close to the reference vibration waveform, and A calculation unit 14 that calculates the distance between the correction electrodes and an upper electrode control unit 15 that applies a correction drive voltage and controls the distance between the correction electrodes are provided. Therefore, compared with the case where the voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid L, the vibration of the liquid becomes the optimum vibration in a short time, and the stirring device 100 in which the time until the end of the stirring is shortened. Can be obtained.
Even if the amount of the liquid L changes due to the evaporation of the liquid L during stirring, the light receiving device 60 captures the vibration waveform of the liquid L, applies a correction driving voltage corresponding to the amount of the liquid L, and corrects the distance between the correction electrodes. Since the upper electrode control unit 15 is controlled, it is possible to obtain the stirring device 100 in which the optimum vibration is maintained.

  (2) Since the detection unit includes the light receiver 60 that receives the light reflected from the liquid L, the vibration of the liquid L can be detected without contact with the liquid L. Therefore, the influence of the vibration detection on the stirring of the liquid L can be reduced, and the stirring device 100 in which the time until the stirring is completed can be obtained.

  (3) Since the light source 50 that irradiates the liquid L with the light is provided, the amount of fluctuation incident on the liquid L is more stable than that in the case where external light is incident on the liquid L. The influence of fluctuations in the amount of light incident on the liquid L on the amount of light reflected from the liquid L can be suppressed. Accordingly, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid L becomes a more optimal vibration, and the stirring device 100 in which the time until the end of stirring is further shortened can be obtained.

  (4) The light emitted from the light source 50 is reflected by the liquid L and reflected from the liquid L accompanying the vibration of the liquid L by the light shielding box 70 that shields the region including the optical path incident on the light receiver 60 from the external light. It is possible to further suppress the influence of fluctuation of external light on the amount of light. Accordingly, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid L becomes a more optimal vibration, and the stirring device 100 in which the time until the end of stirring is further shortened can be obtained.

  (5) Record the reference vibration waveform of the vibration optimal for the stirring of the liquid L, detect the vibration waveform of the liquid L, and move the period and amplitude of the vibration waveform closer to the reference vibration waveform and the drive voltage And change. Therefore, as compared with the case where the movement of the liquid L is visually observed to adjust the driving voltage and the distance between the electrodes, the vibration of the liquid L becomes the optimum vibration in a short time, and the stirring time is shortened. A method is obtained.

  (6) The time-dependent change of the vibration waveform is measured, the waveform integral value is compared with the reference waveform integral value, and the inter-electrode distance and the drive voltage are set so that the waveform integral value difference is less than the allowable waveform integral value difference. To change. Therefore, even if the amount of the liquid L changes due to the evaporation of the liquid L during the stirring, and the period and amplitude of the vibration waveform of the liquid L change, the vibration becomes the optimal vibration and the time until the stirring is completed is shortened. The resulting stirring method is obtained.

(Second Embodiment)
In FIG. 8, the perspective view which shows schematic structure of the stirring apparatus 200 of this embodiment was shown. Although the light shielding box 70 is omitted in the figure, the light shielding box 70 may or may not be provided.
The stirring device 200 of this embodiment has the same configuration as that of the first embodiment, except that the light source 50 and the light receiver 60 of the stirring device 100 of the first embodiment are changed to a laser Doppler vibrometer 80. The laser Doppler vibrometer 80 is disposed on the upper electrode 40 so as to irradiate the laser beam toward the liquid L and receive the laser beam reflected on the surface of the liquid L.
However, at least the upper electrode 40 needs to use a transparent electrode that transmits light.
In addition, the waveform conversion unit 12 may be included in the laser Doppler vibrometer 80. For the laser Doppler vibrometer 80, a well-known device distributed in the market can be used.

According to such an embodiment, there are the following effects.
(7) Since the light applied to the liquid L is more directional laser light, the amount of light incident on the liquid L is more stable, and the amount of light reflected from the liquid L accompanying the vibration of the liquid L is increased. The influence of the fluctuation of the amount of light incident on the liquid L can be further suppressed. Therefore, the vibration waveform and the reference vibration waveform can be detected more accurately, the vibration of the liquid L becomes a more optimal vibration, and the stirring device 200 with a shorter time until the end of stirring can be obtained.

(Third embodiment)
In FIG. 9, the perspective view which shows schematic structure of the stirring apparatus 300 of this embodiment was shown. In the drawing, the light shielding box 70 is omitted, but in the present embodiment, the light shielding box 70 is preferable.
The stirring device 300 of the present embodiment has the same configuration as that of the first embodiment except that the light source 50 of the stirring device 100 of the first embodiment is not provided. The position of the light receiver 60 is not particularly limited, and may be located on the upper electrode 40 indicated by a broken line. In that case, at least the upper electrode 40 needs to use a transparent electrode that transmits light.

According to such an embodiment, there are the following effects.
(8) Similar to the effect of (1) described above, the liquid vibration becomes the optimum vibration in a short time compared with the case where the voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid L. It is possible to obtain the stirring device 300 in which the time until the end of is shortened.
Even if the amount of the liquid L changes due to the evaporation of the liquid L during stirring, the light receiving device 60 captures the vibration waveform of the liquid L, applies a correction driving voltage corresponding to the amount of the liquid L, and corrects the distance between the correction electrodes. Since the upper electrode control unit 15 is controlled, the stirring device 300 that can maintain the optimum vibration can be obtained.

(Fourth embodiment)
In FIG. 10, the perspective view which shows schematic structure of the stirring apparatus 400 of this embodiment was shown.
In the stirring device 400 of this embodiment, a lead wire 90 for detecting the voltage between the electrodes is drawn from the lower electrode 30 and the upper electrode 40 instead of the light receiver 60 of the stirring device 300 of the third embodiment, and is not shown. The base 10 is provided with a voltage monitor unit as a detection unit.
The detection of the voltage between the electrodes is performed, for example, while the constant voltage of the rectangular wave shown in FIG. 3 is applied and when the voltage is not applied in order to reduce the influence of the applied voltage fluctuation. Is preferred.

According to such an embodiment, there are the following effects.
(9) Similar to the effect of (1) above, the liquid vibration becomes the optimum vibration in a short time compared with the case where the voltage and the distance between the electrodes are adjusted by visually observing the movement of the liquid L. It is possible to obtain the stirring device 400 in which the time until the end of is shortened.
Further, even if the amount of the liquid L changes due to the evaporation of the liquid L during stirring, the vibration waveform of the liquid L is captured by the lead wire 90 that detects the voltage between the electrodes, and a correction drive voltage corresponding to the amount of the liquid L is set. Since the upper electrode control unit 15 for applying and controlling the distance between the correction electrodes is provided, it is possible to obtain the stirring device 400 in which the optimum vibration is maintained.

  (10) Since the dielectric constant between the lower electrode 30 and the upper electrode 40 is changed by the vibrating liquid L and the voltage fluctuation associated therewith is detected, the vibration of the liquid L can be detected without contact with the liquid L. Therefore, it is possible to reduce the influence of the vibration on the stirring of the liquid L and to obtain the stirring device 400 in which the time until the stirring is completed is shortened.

In addition to the above-described embodiment, various changes can be made.
For example, in the above-described embodiment, the light receiver 60 and the voltage monitor unit are described as the detection unit that detects vibration. However, the detection unit of the present invention is not limited to these, and for example, the liquid L is irradiated with ultrasonic waves. A detection unit that detects reflection from the liquid L and a detection unit that detects vibration by bringing the probe into contact with the liquid L may be used.
Further, as the detection unit, the movement of the liquid L may be detected by an image, and the vibration waveform may be obtained by an image processing unit as a waveform conversion unit.

  Furthermore, the stirring device of the present invention can be applied not only to analysis and quantification of biological components but also to stirring of a liquid micro sample. For example, the present invention can be applied to agitation of a micro sample for test research in an industrial product, chemical analysis, production and preparation of a micro sample in physical analysis, and the like.

  DESCRIPTION OF SYMBOLS 10 ... Base, 11 ... Operation display part, 12 ... Waveform conversion part, 13 ... Data storage part, 14 ... Calculation part, 15 ... Upper electrode control part, 20 ... Support | pillar, 21 ... Linear encoder, 30 ... Lower electrode, 40 ... upper electrode, 50 ... light source, 60 ... light receiver, 70 ... light shielding box, 80 ... laser Doppler vibrometer, 90 ... lead wire, 100, 200, 300, 400 ... stirrer, L ... liquid.

Claims (8)

A liquid is disposed between the first electrode and the second electrode facing the first electrode, and a driving voltage is applied between the first electrode and the second electrode to apply the liquid. A stirring device that vibrates,
A detection unit for detecting the vibration;
A waveform converter that converts the vibration detected by the detector into a vibration waveform;
A data storage unit that records a reference vibration waveform of vibration optimally used for stirring the liquid, obtained in advance using the detection unit and the waveform conversion unit,
A correction drive voltage between the first electrode and the second electrode for comparing the vibration waveform with the reference vibration waveform to bring the vibration waveform close to the reference vibration waveform, and the first A calculation unit for calculating a correction interelectrode distance between the electrode and the second electrode;
Based on the correction drive voltage and the distance between the correction electrodes, the correction drive voltage is applied between the first electrode and the second electrode, and the first electrode and the second electrode An agitation device comprising: an electrode control unit that controls the distance between the correction electrodes to the distance between the correction electrodes. The stirring device according to claim 1,
The detection unit includes a light receiver that receives light reflected from the vibrating liquid. The stirring device. The stirring device according to claim 2,
A stirring device comprising a light source for irradiating the liquid with light. The stirring device according to claim 3,
The stirrer characterized in that the light source is a laser light source. The stirring device according to claim 3 or 4, wherein
A stirrer, comprising: a member that shields an area including an optical path in which light emitted from the light source is reflected by the liquid and is incident on the light receiver from external light. The stirring device according to claim 1,
The said detection part detects the voltage fluctuation between the said 1st electrode and the said 2nd electrode by the said liquid which vibrates. The stirring apparatus characterized by the above-mentioned. A liquid is disposed between the first electrode and the second electrode facing the first electrode, and a driving voltage is applied between the first electrode and the second electrode to apply the liquid. A stirring method for vibrating
A reference vibration waveform recording step for pre-recording a reference vibration waveform and a stirring time of vibration optimal for stirring the liquid;
An electrode setting step of moving at least one of the first electrode or the second electrode to an interelectrode distance between the first electrode and the second electrode from which the reference vibration waveform is obtained;
A vibration starting step of applying the driving voltage to the liquid to start the vibration of the liquid;
A vibration waveform detection step of detecting a vibration waveform of the liquid vibration;
A period determining step for determining whether or not the period of the reference vibration waveform is close to the period of the detected vibration waveform;
A cycle control step of changing the inter-electrode distance and the drive voltage so that the cycle of the reference vibration waveform and the cycle of the vibration waveform approach each other;
An amplitude determination step for determining whether or not the amplitude of the reference vibration waveform is close to the amplitude of the vibration waveform;
An agitation method comprising: an amplitude control step of changing the distance between the electrodes and the drive voltage so that the amplitude of the reference vibration waveform and the amplitude of the detected vibration waveform approach each other. The stirring method according to claim 7,
A vibration tolerance range recording step for preliminarily recording an allowable waveform integral value difference from a reference waveform integral value corresponding to a half cycle of the reference vibration waveform;
A temporal change monitoring step of measuring the temporal change of the vibration waveform;
The absolute value of the reference waveform integral value is compared with the absolute value of the waveform integral value for a half period of the vibration waveform, and it is determined whether or not the difference between these waveform integral values is less than the allowable waveform integral value difference. Waveform integral value difference judgment step to perform,
When the waveform integral value difference is greater than or equal to the allowable waveform integral value difference, the waveform integral that changes the interelectrode distance and the drive voltage so that the waveform integral value difference is less than the allowable waveform integral value difference. A stirring method characterized by comprising a value difference control step.

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