JPWO2020050234A1 - Capillaries and pipettes - Google Patents

Abstract

The capillaries are open at both ends in the length direction, the first end and the second end. The capillary has a first hole and a second hole. The second hole is connected to the second end side of the first hole, and the water repellency of the inner surface thereof is different from the water repellency of the inner surface of the first hole.

Description

The present disclosure relates to capillaries and pipettes.

A pipette is known that drives a pumping device to generate a negative pressure inside the capillary to suck a liquid into the capillary. As such a pipette, there is also known a pipette in which a plurality of types of liquids are sucked and then the liquids inside the capillaries are reciprocated in the length direction of the capillaries to agitate and mix the liquids (for example, Patent Document 1). And Patent Document 2).

Japanese Unexamined Patent Publication No. 10-62437 Japanese Unexamined Patent Publication No. 2000-304754

In the capillary according to one aspect of the present disclosure, the first end and the second end, which are both ends in the length direction, are open. The capillary has a first hole and a second hole connected to the second end side of the first hole. The water repellency of the inner surface of the second hole is different from the water repellency of the inner surface of the first hole.

The pipette according to one aspect of the present disclosure controls the capillary, a pressure chamber leading to the inside of the capillary via the second end, a drive unit for changing the volume of the pressure chamber, and the drive unit. It has a control unit and a control unit. The capillary has a first pipe portion located on the first end side and a second pipe portion located on the second end side. The first pipe portion has the first hole penetrating in the length direction. The second pipe portion has the second hole penetrating in the length direction. The control unit repeatedly increases and decreases the volume of the pressure chamber, whereby at least a part of the liquid in the capillary repeatedly reciprocates over the boundary between the first hole and the second hole. To control.

It is sectional drawing which shows typically the specific example of the pipette of this disclosure. It is sectional drawing which shows typically the specific example of the capillary in the pipette of this disclosure. It is a partially enlarged view of FIG. It is a graph which shows typically an example of the change of voltage in the signal output by the 1st control unit. 5 (a), 5 (b), 5 (c), 5 (d), 5 (e) and 5 (f) are diagrams schematically showing the operation of the pipette of the present disclosure. .. 6 (a) and 6 (b) are schematic views for explaining a modified example of the pipette and other modified examples. It is a figure which shows the influence which the outer diameter of the tip of a capillary has on the amount of droplet adhesion. FIG. 7 is a chart showing various conditions when FIG. 7 is obtained. It is a figure which shows the influence which the inner diameter of the tip of a capillary has on the amount of liquid suction.

Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The figures used in the following description are schematic, and the dimensional ratios and the like on the drawings do not always match the actual ones. Even in a plurality of drawings showing the same member, the dimensional ratios and the like may not match each other in order to exaggerate the shape and the like.

In the present disclosure, the terms "water repellent" or "hydrophilic" may be used for both absolute and relative evaluation of properties.

For example, "having water repellency" means that the contact angle of the liquid to be sucked by the pipette is 90 ° or more (absolute evaluation). Further, for example, "having hydrophilicity" means that the contact angle of the liquid to be sucked by the pipette is less than 90 °. When the liquid to be sucked by the pipette is not specified, the presence or absence of water repellency or hydrophilicity may be determined using the contact angle of water.

On the other hand, for example, "high water repellency", "low water repellency", or "different water repellency" means that two members that come into contact with the liquid to be sucked by the pipette (which may be water as described above) are used. When the contact angles of the liquids are compared, it means that one contact angle is larger, smaller, or different (relative evaluation) than the other contact angle. Therefore, for example, when the water repellency of the first member is higher than the water repellency of the second member, both the first member and the second member, or the second member need not have the water repellency. It may have hydrophilicity.

[Overview of pipette]
FIG. 1 is a cross-sectional view schematically showing the configuration of the pipette 1 according to the embodiment of the present disclosure. In the drawings, a fixed Cartesian coordinate system xy is attached to the pipette 1 for convenience. The + x side (below the paper surface) is the side that is considered to be downward when the liquid is sucked by the pipette 1.

The pipette 1 has, for example, a capillary 10, a pipette body 20 that changes the air pressure in the capillary 10, and a first control unit 24 and a second control unit 25 that control the operation of the pipette body 20.

The inside of the capillary 10 is exhausted (decompressed) from the rear end (second end 12) of the capillary 10 by the pipette body 20 in a state where the tip (first end 11) on the + x side of the capillary 10 is in contact with the liquid. The liquid is sucked into the capillary 10. By sequentially performing this suction on a plurality of types of liquids, the plurality of types of liquids are stored in the capillary 10. After that, when the pipette body 20 repeats exhausting and supplying air (depressurizing and increasing pressure in the capillary 10) to the capillary 10 from the second end 12, a plurality of types of liquids move in the capillary 10 in the length direction thereof. It reciprocates (vibrates) along it. As a result, the plurality of types of liquids are agitated and eventually mixed.

[Capillary (overview)]
The capillary 10 has a cylindrical shape in which the first end 11 and the second end 12, which are both ends in the length direction (x direction), are open. The "cylindrical shape" means a shape that is long in one direction (the length in one direction is longer than the length in the other direction), is hollow, and has both ends open. And does not mean only a cylindrical shape.

The approximate shape of the capillary 10 may be various. For example, in the cross section of the capillary 10 (cross section orthogonal to the length direction; the same applies hereinafter), the shape of the inner edge (inner surface of the capillary 10) and / or the outer edge (outer surface of the capillary 10) is circular, elliptical, or oval. Alternatively, it may be a polygon or the like. Further, for example, the shape and / or size of the cross section (inner edge and / or outer edge) may be constant over the entire length of the capillary 10, or in at least a part of the total length of the capillary 10 in the length direction. It may be different depending on the position. Further, for example, in the cross section of the capillary 10, the inner edge and the outer edge may or may not have similar figures to each other. Further, for example, the center line of the internal space (flow path) of the capillary 10 may extend linearly from the first end 11 to the second end 12, or may be bent at least in a part.

In the description of the present embodiment, for convenience, the cross section (inner edge and outer edge) of the capillary 10 is assumed to be circular at any position in the length direction. In this case, the shape of the cross section of the hole of the capillary 10 is the same or similar (including congruence) at different positions in the length direction of the capillary 10. When the inner diameters are different from each other at different positions in the length direction of the capillary 10, the area of the cross section is different in both the aspect in which the shapes of the cross sections of the holes are similar and the aspects in which the cross sections are not similar to each other. It may be regarded as different from each other.

The dimensions of the capillary 10 may be appropriately set according to various circumstances such as the amount of liquid to be collected and / or the method of attaching to the pipette body 20. For example, the inner diameter of the capillary 10 may be 0.1 mm or more and 0.3 mm or less. Further, for example, the outer diameter of the capillary 10 may be 0.4 mm or more and 1.2 mm or less. Further, for example, the length of the capillary 10 may be 20 mm or more and 100 mm or less. Of course, dimensions outside the above range may be adopted. In the following description, values outside the above range will be illustrated for the outer diameter D1 and the inner diameter D2 (see FIG. 2) at the first end 11 of the capillary 10 (FIGS. 7 to 9). Needless to say, the outer diameter D1 and the inner diameter D2 may be within the above ranges.

The material of the capillary 10 may be various. For example, examples of the material include glass, resin, ceramics and metal. Examples of the resin include polypropylene, polyethylene and polytetrafluoroethylene. Further, for example, in the capillary 10, a part in the longitudinal direction and the other part may be made of different materials, and / or a part in the radial direction and the other part are made of different materials. You may be. Further, for example, the capillary 10 may be formed by forming a film made of another material on at least a part of the surface of a member made of one material. Further, for example, at least a part (that is, a part or all) of the capillary 10 may be made of a translucent material (for example, resin or glass).

At least a portion (ie, part or all) of the surface of the capillary 10 may be water repellent. The water-repellent region on the surface of the capillary 10 may be appropriately set. For example, the water-repellent region includes the end surface of the first end 11 (the surface facing the + x direction), a part of the inner surface of the capillary 10 on the + x side, and a part of the outer surface of the capillary 10 on the + x side. I'm out. In other words, the water repellent region includes a region in contact with the liquid. Since the region in contact with the liquid has water repellency, for example, the risk of liquid adhesion and / or unintended movement is reduced, and the accuracy of the liquid sampling amount is improved.

The capillary 10 (part or all) may have water repellency on its surface, for example, by being made of a water repellent material. Further, for example, the capillary 10 (part or all) may have water repellency on the surface by forming a water repellent film on the surface of a member made of a material having no water repellency.

As the water-repellent film, various ones may be used, and examples thereof include a water-repellent film formed by a silane coupling agent, a metal alkoxide-containing water-repellent film, a silicone-containing water-repellent film, and a fluorine-containing water-repellent film. Can be done. As a method for forming the water-repellent film on the surface of the capillary 10, various methods may be used, for example, a dry process method or a wet process method may be used. Examples of the dry process method include a physical vapor deposition method and a chemical vapor deposition method. Examples of the former include a physical vapor deposition method and a sputtering method. Examples of the latter include a chemical vapor deposition (CVD) method and an atomic layer deposition (ALD) method. Examples of the wet process method include a sol-gel method, a dip coating method, and a coating method.

The capillary 10 is, for example, disposable and can be attached to and detached from the pipette body 20. The attachment / detachment method may be an appropriate method. For example, the capillary 10 may be fixed by being press-fitted into the hole of the pipette body 20, or may be fixed by tightening or locking by a mechanism (not shown) provided in the pipette body 20. However, the capillary 10 may be used repeatedly, or may be non-detachably fixed (for example, adhered) to the pipette body 20.

[Pipette body]
The pipette body 20 has a pressure chamber 21 (cavity) leading to the inside of the capillary 10. Then, the pipette body 20 decompresses (exhausts) the inside of the capillary 10 by increasing the volume of the pressure chamber 21, and increases the pressure (air supply) in the capillary 10 by decreasing the volume of the pressure chamber 21. conduct. Thereby, for example, suction and discharge of the liquid by the capillary 10 are realized. The configuration of the pipette body 20 that realizes such an operation may be appropriate. An example is shown below.

The pipette body 20 includes, for example, a flow path member 35 constituting a flow path (including a pressure chamber 21) communicating with the inside of the capillary 10, an actuator 40 for changing the volume of the pressure chamber 21, and a flow path member. It has a valve 23 that allows and prohibits communication between the inside (flow path) of 35 and the outside.

(Flow path member)
The approximate outer shape and size of the flow path member 35 may be an appropriate shape. In the illustrated example, the approximate outer shape of the flow path member 35 is an axial shape (a shape in which the length in the x direction is longer than the length in the other direction) in series with the capillary 10. Further, the size is set to be, for example, a size that can be picked or gripped by a user (for example, a maximum outer diameter of 50 mm or less).

The internal space of the flow path member 35 connects, for example, the above-mentioned pressure chamber 21, the communication flow path 27 connecting the capillary 10 and the pressure chamber 21, and the communication flow path (pressure chamber 21 from another viewpoint) and the outside. It has an open flow path 28.

The shape, position, size, etc. of the pressure chamber 21 may be appropriately set. In the illustrated example, the pressure chamber 21 is located on the side surface of the flow path member 35. Further, for example, the approximate shape of the pressure chamber 21 is a thin shape having a substantially constant thickness, with the direction of overlapping with the actuator 40 (y direction) as the thickness direction. The thin shape here is a shape in which the length in the y direction is shorter than the maximum length in each direction orthogonal to the y direction. The planar shape (shape seen in the y direction) of the pressure chamber 21 may be an appropriate shape such as a circle, an ellipse, a rectangle, or a rhombus. The thickness (y direction) of the pressure chamber 21 is, for example, 50 μm or more and 5 mm or less. The diameter of the pressure chamber 21 (maximum length in each direction orthogonal to the y direction) is, for example, 2 mm or more and 50 mm or less.

The shapes, positions, sizes, etc. of the communication flow path 27 and the open flow path 28 may also be appropriately set. For example, the flow path member 35 extends from the capillary 10 in the length direction (x direction) of the capillary 10, and the flow path member 35 intersects the first flow path 22 from the middle of the first flow path 22. It has a second flow path 26 that extends to reach the pressure chamber 21. The communication flow path 27 is formed by the portion of the first flow path 22 on the capillary 10 side from the connection position with the second flow path 26 and the second flow path 26. With such a flow path configuration, for example, the possibility that the sucked liquid (for example, its droplets) invades the pressure chamber 21 and adheres to the actuator 40 is reduced. As a result, the possibility that the operating characteristics of the actuator 40 will change due to the adhering liquid is reduced.

Further, the first flow path 22 leads to the outside of the flow path member 35 on the opposite side of the capillary 10, for example. The open flow path 28 is formed by a portion of the first flow path 22 opposite to the capillary 10 from the connection position with the second flow path 26. Therefore, the flow path for allowing the liquid to escape so as not to enter the pressure chamber 21 is also used as the open flow path 28 for opening the pressure chamber 21 to the outside, and the space efficiency is improved.

The shapes and dimensions of the cross sections of the first flow path 22 and the second flow path 26 may be appropriately set. For example, the cross section of the first flow path 22 and the second flow path 26 is a circle having a diameter of 0.1 mm or more and 1 mm or less. Further, the inner diameters of the first flow path 22 and the second flow path 26 may be the same as each other or may be different from each other. The shape and size of the cross section of the first flow path 22 and / or the second flow path 26 may be constant or variable in the length direction.

The flow path member 35 may be formed by combining members having an appropriate shape made of an appropriate material. In the illustrated example, the flow path member 35 has a first part 30 and a second part 60 joined to each other. The first part 30 has a through hole that serves as a pressure chamber 21. The second part 60 has a first flow path 22 and a second flow path 26. The pressure chamber 21 is composed of a space surrounded by a first part 30, a second part 60, and an actuator 40. The first part 30 and the second part 60 may also be composed of a combination of a plurality of members. The materials of the first part 30 and the second part 60 may be, for example, metal, ceramic, resin, or a combination thereof.

(Actuator)
The actuator 40 constitutes, for example, one of the inner surfaces of the pressure chamber 21. Specifically, for example, the actuator 40 has a substantially plate shape, and is joined to the first part 30 so as to close the through hole of the first part 30 from the side opposite to the second part 60, and the communication flow path is formed. It constitutes an inner surface opposite to the inner surface through which 27 opens. Then, the actuator 40 reduces the volume of the pressure chamber 21 by bending toward the pressure chamber 21 (in other words, by displacing the inner surface of the pressure chamber 21 inward). Conversely, the actuator 40 increases the volume of the pressure chamber 21 by bending away from the pressure chamber 21 (in other words, by displacing the inner surface of the pressure chamber 21 outward).

The specific configuration of the actuator 40 that causes the above-mentioned bending deformation may be appropriate. For example, the actuator 40 is composed of a unimorph type piezoelectric element. More specifically, for example, the actuator 40 has two laminated piezoelectric ceramic layers 40a and 40b. Further, the actuator 40 has an internal electrode 42 and a surface electrode 44 facing each other with the piezoelectric ceramic layer 40a interposed therebetween. The piezoelectric ceramic layer 40a is polarized in the thickness direction.

Then, when a voltage is applied to the piezoelectric ceramic layer 40a by the internal electrode 42 and the surface electrode 44 in the same direction as the polarization direction, the piezoelectric ceramic layer 40a contracts in the plane direction. On the other hand, the piezoelectric ceramic layer 40b does not cause such shrinkage. As a result, the piezoelectric ceramic layer 40a bends toward the piezoelectric ceramic layer 40b. That is, the actuator 40 bends toward the pressure chamber 21 side. When a voltage opposite to the above is applied, the actuator 40 bends to the side opposite to the pressure chamber 21.

The shape, size, and the like of the actuator 40 may be appropriately set. For example, the actuator 40 has a flat plate shape having an appropriate planar shape. The planar shape may or may not be similar to the planar shape of the pressure chamber 21. The maximum length in each direction in a plan view (viewed in the y direction) is, for example, 3 mm or more and 100 mm or less. The thickness (y direction) of the actuator 40 is, for example, 20 μm or more and 2 mm or less. The materials, dimensions, shapes, conduction methods, and the like of various members constituting the actuator 40 may be appropriately set. An example is shown below.

The thickness of the piezoelectric ceramic layers 40a and 40b may be, for example, 10 μm or more and 30 μm or less. The material of the piezoelectric ceramic layers 40a and 40b may be, for example, a ceramic material having ferroelectricity. Such ceramic materials include lead zirconate titanate (PZT), NaNbO ₃ system, KNaNbO ₃ system, BaTiO ₃ system and (BiNa) NbO ₃ system, those BiNaNb ₅ O ₁₅ system. The piezoelectric ceramic layer 40b may be made of a material other than the piezoelectric material.

The internal electrode 42 is located between, for example, the piezoelectric ceramic layer 40a and the piezoelectric ceramic layer 40b, and has substantially the same size as the actuator 40. The thickness of the internal electrode 42 may be, for example, 1 μm or more and 3 μm or less. The internal electrode 42 is made conductive from the outside by, for example, a through electrode 48 penetrating the piezoelectric ceramic layer 40a and a connecting electrode 46 located on the surface of the actuator 40 and connected to the through electrode 48.

The surface electrode 44 is located, for example, on the side of the piezoelectric ceramic layer 40a opposite to the piezoelectric ceramic layer 40b (outside the pressure chamber 21), and has a surface electrode main body 44a and an extraction electrode 44b. The surface electrode body 44a has, for example, a planar shape substantially equal to that of the pressure chamber 21, and is provided so as to overlap the pressure chamber 21 in the thickness direction. The extraction electrode 44b is formed so as to be extracted from the surface electrode body 44a. The thickness of the surface electrode 44 may be, for example, 0.1 μm or more and 1 μm or less.

The material of the internal electrode 42, the surface electrode 44, the connection electrode 46, and the through electrode 48 may be, for example, a metal material. More specifically, for example, the material of the internal electrode 42 and the through electrode 48 may be Ag-Pd. The material of the surface electrode 44 and the connection electrode 46 may be, for example, Au.

The actuator 40 or a part of the actuator 40 (for example, a portion overlapping the surface electrode main body 44a) may be referred to as a drive unit 50. The actuator is not limited to the unimorph type piezoelectric element. For example, the actuator may be a bimorph type piezoelectric element or an electrostatic actuator.

(valve)
The valve 23 is provided, for example, at a position where the open flow path 28 leads to the outside. By opening and closing the valve 23, communication between the inside and the outside of the flow path member 35 is permitted or prohibited. In the state where communication is prohibited, the pressure in the capillary 10 is reduced and increased by changing the volume of the pressure chamber 21. On the other hand, in a state where communication is allowed, even if the volume of the pressure chamber 21 is changed, the depressurization and the pressure increase in the capillary 10 are not performed. An example of using the action in which the depressurization or the pressure increase is not performed will be described later.

The valve 23 opens and closes in response to a signal input from the outside, for example. As the valve 23, various valves such as an electromagnetic valve and a piezoelectric valve can be used. The valve 23 may be closed by not inputting a signal and opened by inputting a signal, or may be opened by not inputting a signal, and may be opened by inputting a signal. It may be in a closed state, or a signal for closing and a signal for opening may be input respectively.

[Control unit]
The first control unit 24 is electrically connected to the actuator 40, and changes the volume of the pressure chamber 21 by giving an electric signal to the actuator 40 to deform the actuator 40. As a result, the liquid can be sucked into the capillary 10 and the liquid can be discharged from the capillary 10. By driving the actuator 40 so that the volume of the pressure chamber 21 increases and decreases periodically, the liquid sucked into the capillary 10 can be vibrated and mixed.

The second control unit 25 is electrically connected to the valve 23, and opens and closes the valve 23 by giving an electric signal to the valve 23. When the liquid has flowed into the first flow path 22, the liquid can be discharged from the valve 23 to the outside by opening the valve 23. Further, after the actuator 40 is deformed and the liquid is sucked in, the valve 23 is opened, the deformation of the actuator 40 is restored in that state, and the actuator 40 is deformed again after the valve 23 is closed. Can inhale the liquid.

The first control unit 24 and the second control unit 25 can be configured by using various integrated circuits. The first control unit 24 and the second control unit 25 may be configured by ICs (Integrated Circuits) that are separate from each other and may be synchronized with each other, or may be partially or wholly built into the same IC. The first control unit 24 and / or the second control unit 25 may be provided fixedly to the pipette body 20, or may be provided so as to be relatively movable with respect to the pipette body 20, or a part thereof. (For example, a driver) may be fixedly provided on the pipette body 20, and another part (for example, a part for outputting a command to the driver) may be provided so as to be relatively movable with respect to the pipette body 20.

[Capillary (details)]
FIG. 2 is an enlarged cross-sectional view of the capillary 10. FIG. 3 is a partially enlarged view of FIG.
The capillary 10 has a first pipe portion 17 located on the first end 11 side and a second pipe portion 18 located on the second end 12 side. The first pipe portion 17 has a first hole 10a penetrating in the length direction, and the second pipe portion 18 has a second hole 10b penetrating in the length direction. The second hole 10b is connected to the second end 12 side of the first hole 10a. The first pipe portion 17 is a portion of the capillary 10 having a first hole 10a, and the second pipe portion 18 is a portion of the capillary 10 having a second hole 10b. The first pipe portion 17 and the second pipe portion 18 may be two parts in one integrally formed member (that is, they do not have to be separate members), or are two members fixed to each other. You may.

(Water repellency)
The water repellency of the inner surface of the first hole 10a and the water repellency of the inner surface of the second hole 10b are different from each other. That is, the capillary 10 has a first hole 10a and a second hole 10b having different water repellency on the inner surface. As a result, for example, when the liquid flows through the boundary 14 between the two, the flow of the liquid tends to be disturbed due to the difference in water repellency. As a result, for example, when the actuator 40 is driven so that the liquid repeatedly crosses the boundary 14 and reciprocates, the liquid is likely to be mixed. In the following description, the water repellency of the inner surface of the first hole 10a may be abbreviated as the water repellency of the first hole 10a. The same applies to the second hole 10b.

The water repellency of the first hole 10a and the second hole 10b may be higher than that of the other. In the present embodiment, the case where the water repellency of the first hole 10a is higher than the water repellency of the second hole 10b is taken as an example. That is, in the present embodiment, the contact angle of the first hole 10a is larger than the contact angle of the second hole 10b.

When the water repellency of the first hole 10a is higher than that of the second hole 10b, both the first hole 10a and the second hole 10b may have water repellency (contact angle is 90 ° or more). The first hole 10a may have water repellency and the second hole 10b may have hydrophilicity, and both the first hole 10a and the second hole 10b have hydrophilicity. You may be doing it. In the present embodiment, one of the two preceding embodiments (at least the embodiment in which the first hole 10a has water repellency) out of the three embodiments is taken as an example.

In each of the first hole 10a and the second hole 10b, the water repellency may be uniform or variable in the longitudinal direction and / or the axial direction of the capillary 10. In this embodiment, a uniform case is taken as an example. However, even if it is uniform, it goes without saying that there may be variations in water repellency due to processing errors. When the water repellency changes, the change may be continuous or discontinuous (gradual). However, since the boundary 14 can be conceptualized in the first hole 10a and the second hole 10b from the viewpoint of water repellency, the change in water repellency is discontinuous between the two.

The specific size of the contact angles of the first hole 10a and the second hole 10b may be appropriately set. For example, when the first hole 10a has water repellency (when the contact angle is 90 ° or more), the contact angle may be 90 ° or more and 95 ° or less (that is, a value close to 90 °). However, it may be 95 ° or more and 150 ° or less, or may be more than 150 °. In addition, more than 150 ° is a size which can be said to have so-called superhydrophobicity. Further, when the second hole 10b has water repellency, the contact angle of the second hole 10b is 90 ° or more and 95 ° or less and 95 ° or more and 150 ° as long as it is smaller than the contact angle of the first hole 10a. It may be less than or equal to or more than 150 °. Further, when the second hole 10b has hydrophilicity (when the contact angle is less than 90 °), the contact angle of the second hole 10b is 85 ° or more (that is, a value close to 90 °). It may be 10 ° or more and 85 ° or less, or it may be less than 10 °. The size of less than 10 ° is a size that can be said to have so-called superhydrophilicity.

Further, the difference between the contact angle of the first hole 10a and the contact angle of the second hole 10b may be appropriately set. For example, the difference between the two may be 5 ° or more, 10 ° or more, 30 ° or more, 90 ° or more, or 140 ° or more. Further, as long as it does not contradict this lower limit, the difference between the two may be less than 180 °, 140 ° or less, 90 ° or less, 30 ° or less, or 10 ° or less (may be combined with any of the above lower limits. ). For example, the difference between the two may be 30 ° or more and 140 ° or less, or 30 ° or more and 90 ° or less. The larger the lower limit of the range of the difference between the two, the stronger the action of causing turbulence in the flow, for example. On the other hand, the larger the upper limit of the range of the difference between the two, the more difficult it is to select the material, for example. Within the above range, for example, the selection of the material is facilitated while obtaining the action of causing turbulence in the flow.

(Hole shape, etc.)
The shapes and dimensions of the first hole 10a and the second hole 10b, the materials constituting these holes, and the like may be appropriately set. An example is shown below.

The first hole 10a extends from the first end 11 to the boundary 14, for example. The second hole 10b extends from, for example, the boundary 14 to the second end 12. In addition, unlike the illustrated example, the boundary 14 to the first end 11 is composed of another hole (for example, a hole whose water repellency is equal to or less than the water repellency of the second hole 10b), and / or the boundary 14 to the second. It is also possible to form up to the end 12 with another hole (for example, a hole whose water repellency is equal to or higher than that of the first hole 10a).

The position of the boundary 14 may be an appropriate position between the first end 11 and the second end 12. For example, the boundary 14 is located on the first end 11 side with respect to the center in the length direction of the capillary 10. For example, the length of the first hole 10a is about 5% to 30% of the total length of the capillary 10.

The shape and / or size of the cross section of the first hole 10a and the shape and / or size of the cross section of the second hole 10b may be the same as or different from each other. When both sizes are different, whichever is larger may be used. Further, in each of the first hole 10a and the second hole 10b, the shape and / or size of the cross section may or may not be constant in the length direction of the capillary 10.

In the illustrated example, the cross section (inner diameter) of the first hole 10a is larger toward the second hole 10b side. On the other hand, the cross section (inner diameter) of the second hole 10b is constant in the length direction of the capillary 10. Then, at the boundary 14, the inner diameter of the first hole 10a is larger than the inner diameter of the second hole 10b.

The specific size of the difference between the inner diameter of the first hole 10a and the inner diameter of the second hole 10b may be appropriately set. For example, at the boundary 14, the inner diameter of the first hole 10a is 1.1 times or more, 1.5 times or more or twice or more, and 5 times or less and 3 times or less with respect to the inner diameter of the second hole 10b. Or it is twice or less (the former lower limit example and the latter upper limit example may be combined as long as there is no contradiction). Further, for example, the difference between the inner diameter of the first hole 10a and the inner diameter of the second hole 10b is 2/5 or more of the thickness of the second member 16 (the length in the radial direction from the inner surface to the outer surface) described later. 2/3 or more or 1 time or more and less than 2 times, 18/10 times or less or 2/5 or less (the former lower limit example and the latter upper limit example are not inconsistent, either. May be combined.). Further, for example, the inclination angle of the inner surface of the first hole 10a with respect to the center line of the first hole 10a is 1 ° or more, 2 ° or more or 3 ° or more, and 15 ° or less, 10 ° or less or 7 ° or less ( Either the former lower limit value example and the latter upper limit value example may be combined).

The inner diameter of the first hole 10a at the first end 11 may be smaller than the inner diameter of the second hole 10b, may be the same (including the case where there is a difference due to processing error), or may be larger. good. For example, the inner diameter of the first end 11 of the first hole 10a is 1/2 or more, 2/3 or more or 4/5 or more, and 2 times or less, 1.5 times or less, or 1. It is twice or less (the former lower limit example and the latter upper limit example may be combined).

Here, assuming that the end surface of the first end 11 of the first hole 10a is the first end surface 11a, the first end surface 11a may be an annular shape having a circular opening. The outer diameter D1 of the first end surface 11a in this case may be 0.4 mm or less. The inventor has found that when the capillary 10 is pulled out of the liquid, the liquid adhering to the first end surface 11a is taken into the capillary 10. As a result, the amount of liquid taken into the capillary 10 is slightly increased with respect to the amount intentionally sucked. If the outer diameter of the first end surface 11a is large, the amount of liquid that increases also increases, which poses a problem when sucking a small amount of liquid. By setting the outer diameter of the first end surface 11a to 0.4 mm or less, it is possible to prevent a large number of droplets from adhering to the first end surface 11a, and it is possible to accurately suck a small amount of liquid.

FIG. 7 shows the results of measuring the amount of liquid (water) adhering to the first end surface 11a under various conditions in the capillary shown in FIG. Further, various conditions at that time are shown in FIG. In FIG. 7, the horizontal axis represents the outer diameter D1. The vertical axis shows the amount of liquid adhering to the first end surface 11a. The plot shows the relationship between the outer diameter D1 and the measured adhesion amount.

As shown in FIG. 8, No. 1 to No. The amount of liquid adhered to 6 types of capillaries up to 6 was measured. The six types of capillaries differ from each other in the shape and material of the first member 15, the outer diameter D1 and the inner diameter D2. In the column of the shape of the first member 15, "taper" indicates that the inner diameter D2 and the outer diameter D1 of the first member 15 are smaller toward the first end 11 side as in the example shown in FIG. ing. Further, "straight" indicates that, unlike the example of FIG. 2, the inner diameter D2 and the outer diameter D1 of the first member 15 are constant from the second end 12 to the first end 11. The meanings of the abbreviations in the material column of the first member 15 are as follows. PP: polypropylene, FEP: flexible electric pipe, ETFE: ethylene tetrafluoro dioxide, PA12: polyamide 12. In addition, No. The material of No. 5 is a capillary made of glass in which a water-repellent film is formed on a portion of the capillary that comes into contact with a liquid.

According to FIG. 7, it can be seen that by setting the outer diameter D1 of the first surface 11a to 0.4 mm or less, the amount of liquid adhering to the first end surface 11a can be reduced regardless of other conditions. Specifically, in the example of FIG. 7, the amount of adhesion can be set to 5.0 nl or less by setting the outer diameter D1 to 0.4 mm or less. Further, in the example of FIG. 7, when the outer diameter D1 exceeds 0.4 mm, the rate of change of the increase in the amount of adhesion with respect to the increase in the outer diameter D1 becomes large, and from this viewpoint as well, the upper limit value is around 0.4 mm. You can find meaning in doing so.

At this time, the inner diameter D2 of the first end surface 11a may be 0.06 mm or more. If the inner diameter D2 of the first end surface 11a is made too small, the flow path resistance increases, and the amount of liquid that can be sucked by a predetermined pressure change decreases. FIG. 9 shows a change in the amount of liquid sucked when the inner diameter D2 of the first end surface 11a is changed. In this figure, the horizontal axis represents the inner diameter D2. The vertical axis shows the amount of liquid suction due to a predetermined pressure change. The plot shows the relationship between the inner diameter D2 and the suction amount, and includes some approximate values.

According to FIG. 9, it can be seen that by setting the inner diameter D2 of the first end surface 11a to 0.06 mm or more, it is possible to prevent the amount of sucked liquid from becoming too small. Further, in the example of FIG. 9, the mode of change in the suction amount with respect to the change in the inner diameter D2 is exponential, and by setting the inner diameter D2 to 0.06 mm or more, the suction amount can be increased by increasing the inner diameter D2. It has been simplified. Contrary to the above description, an extremely small amount of suction may be realized by setting the inner diameter D2 to less than 0.06 mm.

(1st member and 2nd member)
The capillary 10 has a first member 15 forming the first hole 10a and a second member 16 forming the second hole 10b. By forming the capillary 10 from a plurality of members in this way, for example, it is easy to make the water repellency of the first hole 10a different from the water repellency of the second hole 10b.

The first member 15 and the second member 16 may be made of various materials already mentioned as materials for the capillary 10. For example, the first member 15 is integrally formed of resin as a whole. Further, for example, the second member 16 is integrally formed of glass as a whole. The water repellency of the resin constituting the first member 15 is higher than the water repellency of the glass constituting the second member 16.

Further, the material of the second member 16 may be a material having translucency, and the material of the first member 15 may be a material having or not having translucency. In other words, the translucency of the second member 16 may be higher than the translucency of the first member 15. In this case, for example, a material having high water repellency can be selected as the material of the first member 15. On the other hand, as the material of the second member 16, a material suitable for irradiating the liquid with light for analysis of the liquid can be selected.

The first member 15 and the second member 16 may be fixed by an appropriate method. Examples of the fixing method include fitting (press-fitting) one member to the other member, locking with a claw or the like, bonding with an adhesive, and welding by melting and solidifying at least one member. can. Two or more of these methods may be combined. Further, one member may be formed first, and the mold in which the one member is arranged may be filled with a material to be the other member to form both. Further, a packing made of a material having a lower rigidity than these may be arranged between the first member 15 and the second member 16.

In the illustrated example, the second member 16 is press-fitted into the first member 15 to fix both. Specifically, the first member 15 has a third hole 15a extending from the first hole 10a to the side opposite to the first end 11. The third hole 15a has a larger inner diameter than the first hole 10a. As a result, a step portion 15b is formed at the boundary between the first hole 10a and the third hole 15a. On the other hand, the outer diameter of the second member 16 is equal to or slightly larger than the inner diameter of the third hole 15a. The second member 16 is inserted into the third hole 15a from the side opposite to the first hole 10a, and the tip thereof is locked to the step portion 15b. The removal of the second member 16 from the first member 15 is prevented by the frictional force generated by the direct contact between the two members 16.

Even when the second member 16 is inserted into the first member 15 in this way, both may be joined. For example, an adhesive may be arranged between the inner surface of the third hole 15a and the outer surface of the second member 16. In this case, the outer diameter of the second member 16 may be slightly smaller, equal to, or slightly larger than the inner diameter of the third hole 15a.

Further, in the illustrated example, each of the third hole 15a and the second member 16 extends over the entire length in a constant cross section. However, one or both of these may extend in a certain cross section only in a part in the length direction and may be fitted only in the part extending in the constant cross section. Further, the portions of the third hole 15a and the second member 16 that are fitted to each other do not have to extend in a constant cross section. For example, both may be tapered so as to increase the diameter toward the second end 12 side. Further, for example, a protrusion may be provided on at least one of the inner surface of the third hole 15a and the outer surface of the second member 16, thereby increasing the contact pressure.

The stepped surface 15ba on the second member 16 side of the stepped portion 15b is inclined so as to be located toward the second member 16 side toward the inner side in the radial direction of the capillary 10, for example. On the other hand, the tip surface 16a of the second member 16 on the stepped portion 15b side is, for example, a planar shape orthogonal to the length direction of the capillary 10. Then, the radial inner corner portion 15bb of the step portion 15b (the inner edge portion of the step surface 15ba) is in contact with the tip surface 16a of the second member 16. Therefore, the contact between the step portion 15b and the second member 16 is a line contact. The contact between the step portion 15b and the second member 16 may be different from the illustrated example. For example, the stepped surface 15ba may be a surface orthogonal to the length direction of the capillary 10, and the stepped surface 15ba and the tip surface 16a may come into surface contact with each other.

The outer shapes (outer surface shapes) of the first member 15 and the second member 16 may be appropriate. In the illustrated example, the first member 15 has a first portion 15e having a first end 11 and a second portion 12 located on the second end 12 side with respect to the first portion 15e in its appearance. It has 15f.

The first portion 15e has, for example, a part (most in the illustrated example) on the first end 11 side of the first hole 10a. Further, for example, the thickness (the length from the inner surface to the outer surface) of the first portion 15e is set to be substantially constant over the entire length of the capillary 10 in the length direction. The outer shape of the first portion 15e is also tapered corresponding to the taper of the first hole 10a. The thickness of the first portion 15e is relatively thin, for example, thinner than the thickness of the second member 16.

The second portion 15f has, for example, a part of the first hole 10a on the opposite side of the first end 11 and a third hole 15a. The second portion 15f has a larger outer diameter than, for example, the first portion 15e. Further, the thickness of the second portion 15f is relatively thick, and is made thicker than, for example, the thickness of the first portion 15e and the thickness of the second member 16. The shape of the outer surface of the second portion 15f is, for example, constant in the length direction of the capillary 10.

[A series of pipette operations]
An example of the operation of the pipette 1 will be described. FIG. 4 is a graph schematically showing an example of a time-dependent change in voltage (signal level) in the drive signal SgA (Sg0 to Sg52) output by the first control unit 24. In FIG. 4, the horizontal axis t represents time, and the vertical axis V represents voltage. 5 (a) to 5 (f) are schematic views showing the state of the capillary 10 at any time shown on the horizontal axis of FIG.

As shown in FIG. 4, the drive signal SgA output from the first control unit 24 to the actuator 40 has a waveform in which the voltage changes with the passage of time. On the other hand, the actuator 40 bends by a deformation amount corresponding to the applied voltage. The correspondence referred to here is, for example, a one-to-one correspondence, in other words, a relation in which the amount of deformation is uniquely defined with respect to the voltage (excluding the state where the deformation is saturated). Therefore, the actuator 40 to which the drive signal SgA is input follows the waveform of the drive signal SgA (change with time of voltage) so that the volume of the pressure chamber 21 becomes the volume corresponding to the voltage of the drive signal SgA. The volume of the chamber 21 is changed.

The relationship between the amount of change in the voltage of the drive signal SgA and the amount of change in the volume of the pressure chamber 21 is not necessarily a proportional relationship. However, for convenience, the description will be made assuming a proportional or near-proportional relationship. Therefore, it may be considered that FIG. 4 shows not only the time-dependent change in the voltage of the drive signal SgA but also the time-dependent change in the volume of the pressure chamber 21.

A reference potential is applied to one of the internal electrode 42 and the surface electrode 44, and a drive signal SgA is input to the other. The voltage in FIG. 4 indicates the potential difference between the reference potential and the drive signal SgA. In other words, the drive signal SgA is an unbalanced signal. However, the drive signal SgA may be a balanced signal in which the potentials of both the internal electrode 42 and the surface electrode 44 are changed and the potential difference is the voltage shown in FIG. In the present embodiment, the case where the drive signal SgA is an unbalanced signal is taken as an example. Therefore, in the following, the voltage of FIG. 4 may be described as the potential of the drive signal SgA.

The increase in the voltage of the drive signal SgA (change of the potential to the positive side) may correspond to the increase in the volume of the pressure chamber 21, or may correspond to the decrease in the volume of the pressure chamber 21. In other words, the direction from the electrode to which the drive signal SgA is applied to the electrode to which the reference potential is applied among the internal electrode 42 and the surface electrode 44 and the polarization direction of the piezoelectric ceramic layer 40a are opposite to each other. It may be in the same orientation. In the following, for convenience, it is assumed that the increase in the voltage of the drive signal SgA corresponds to the increase in the volume of the pressure chamber 21 (that is, the suction of the liquid).

In the following, not only the operation of the pipette 1 itself, but also the operation performed by the user of the pipette 1 or the device using (or including) the pipette 1 will be described. Here, a mode in which the user operates the pipette 1 will be described as an example. The user's operation on the pipette 1 may be appropriately read as the operation on the pipette 1 of the device. For example, the movement of the pipette 1 by the user may be the movement of the pipette 1 by the device, and the operation of the pipette 1 by the user on a switch (not shown) may be the output of a command signal to the pipette 1 by the device. The device may perform the same operation on the pipette as the user by, for example, sequence control.

(Time t0 to t1: Wetting, etc.)
Before the time t1, the first control unit 24 outputs the initial signal Sg0 to the actuator 40 in response to the user's operation on a switch (not shown). The initial signal Sg0 is a signal having a constant potential. As a result, the volume of the pressure chamber 21 is maintained at a predetermined initial volume. The potential of the initial signal Sg0 may be a reference potential or may be different from the reference potential. The drive signal SgA does not have to include the initial signal Sg0. That is, before the time t1, the drive signal SgA may not be output instead of the initial signal Sg0 being output. The valve 23 is closed after time t0 unless otherwise specified.

The user brings the first end 11 of the capillary 10 into contact with the first liquid L1 before time t1 (performs a liquid contact step). Then, the user instructs the pipette 1 to suck the first liquid L1 by operating the switch (not shown) included in the pipette 1. The time of this instruction corresponds to the time t1 of FIG.

(Times t1 to t2: suction of the first liquid, etc.)
When the suction of the first liquid L1 is instructed, the first control unit 24 outputs the first suction signal Sg1 that drives the drive unit 50 so that the volume of the pressure chamber 21 increases. The first suction signal Sg1 is, for example, a signal that rises from the potential V0 of the initial signal Sg0 to a predetermined potential V1 and maintains the potential V1. As a result, the first liquid L1 is sucked into the capillary 10 and held in the vicinity of the first end 11 of the capillary 10. The suction amount roughly corresponds to the potential difference from the potential V0 to the potential V1. In other words, the potential difference is set according to the target value of the suction amount.

When a part of the first liquid L1 is sucked into the capillary 10, the user pulls the capillary 10 from the rest of the first liquid L1 (performs a liquid removal step). Next, the user brings the first end 11 of the capillary 10 into contact with the second liquid L2 (performs a liquid contact step). Then, the user instructs the pipette 1 to suck the second liquid L2 by operating the switch (not shown) included in the pipette 1. The time of this instruction corresponds to the time t2 of FIG.

(Time t2 to t3: Suction of second liquid, etc.)
When the suction of the second liquid L2 is instructed, the first control unit 24 outputs the second suction signal Sg2 that drives the drive unit 50 so that the volume of the pressure chamber 21 increases. The second suction signal Sg2 is, for example, a signal that rises from the potential V1 of the first suction signal Sg1 to a predetermined potential V2 and maintains the potential V2. As a result, the second liquid L2 is sucked into the capillary 10 and held near the first end 11 of the capillary 10. FIG. 5A shows the state at this time. The suction amount of the second liquid L2 roughly corresponds to the potential difference from the potential V1 to the potential V2. In other words, the potential difference is set according to the target value of the suction amount.

When a part of the second liquid L2 is sucked into the capillary 10, the user pulls the capillary 10 from the rest of the second liquid L2 (performs a liquid removal step). Then, the user instructs the pipette 1 to mix the first liquid L1 and the second liquid L2 by operating the switch (not shown) included in the pipette 1. The time of this instruction corresponds to the time t3 of FIG.

(Times t3 to t4: Air suction, etc.)
When the first control unit 24 is instructed to mix the first liquid L1 and the second liquid L2, the first control unit 24 outputs an air suction signal Sg3 that drives the drive unit 50 so that the volume of the pressure chamber 21 increases. The air suction signal Sg3 is, for example, a signal that roughly rises to a predetermined potential V3 and maintains the potential V3. As a result, the first liquid L1 and the second liquid L2 move to the second end 12 side and stop at a predetermined position in the capillary 10. FIG. 5B shows the state at this time. The amount of movement of the first liquid L1 and the second liquid L2 roughly corresponds to the potential difference from the potential V2 to the potential V3. In other words, the potential difference is set according to the target value of the movement amount.

The stop position of the first liquid L1 and the second liquid L2 may be a position where both the first liquid L1 and the second liquid L2 are located on the first end 11 side of the boundary 14, or the first liquid L1. And the second liquid L2 may both be located closer to the second end 12 than the boundary 14, or either the first liquid L1 or the second liquid L2 may be located across the boundary 14. good. In the description of the present embodiment, a case where both the first liquid L1 and the second liquid L2 are located on the first end 11 side of the boundary 14 will be taken as an example, and the subsequent operations will be described.

When both the first liquid L1 and the second liquid L2 are located on the first end 11 side or the second end 12 side of the boundary 14, the liquid and the boundary 14 may be separated or adjacent to each other. May be good. “Adjacent” means, for example, the distance between the boundary 14 and the liquid in the length direction of the capillary 10 or the distance at which the liquid overlaps (both distances may be based on the center of the liquid surface). , 1/10 or less or 1/5 or less of the length obtained by dividing the volumes of the first liquid L1 and the second liquid L2 by the area of the cross section at the boundary 14 of the first hole 10a.

The second control unit 25 controls the valve 23 so as to open the open flow path 28 when it is determined that a predetermined time has elapsed after the output of the air suction signal Sg3 is started. As already described, this control may be performed by either the output of the signal or the stop of the output of the signal. The predetermined time is set to a sufficient time for the first liquid L1 and the second liquid L2 to move to the target position by the air suction signal Sg3.

(Times t4 to t5: Restoration of pressure chamber, etc.)
When the first control unit 24 determines that a predetermined time has elapsed after starting the control to open the valve 23 (time t4), the first control unit 24 outputs a restoration signal Sg4 that drives the drive unit 50 so that the volume of the pressure chamber 21 decreases. do. The restoration signal Sg4 is, for example, a signal that roughly drops to a predetermined potential V4 and maintains the potential V4. Although the volume of the pressure chamber 21 is reduced by the restoration signal Sg4, since the valve 23 is opened, the portion of the capillary 10 on the second end 12 side of the first liquid L1 and the second liquid L2. No pressure increase is performed. As a result, the positions of the first liquid L1 and the second liquid L2 do not change.

The predetermined time from the opening of the valve 23 to the time t4 is a sufficient time for opening the valve 23. The potential V4 may be the same, higher, or lower with respect to the initial potential V0 and / or the reference potential. In the illustrated example, the potential V4 is the same as the initial potential V0. When the potential V4 is the reference potential, the restoration signal Sg4 is a falling portion (intentionally as a signal) that occurs in the process of transitioning from the state of outputting the air suction signal Sg3 to the state of stopping the output. It may be a part that is not output to.

After that, when the second control unit 25 determines that a predetermined time has elapsed from the time t4, the second control unit 25 controls the valve 23 so as to close the open flow path 28. As already described, this control may be performed by either the output of the signal or the stop of the output of the signal. The predetermined time from the time t4 is set to a sufficient time for the actuator 40 to be displaced corresponding to the potential V4 by the restoration signal Sg4.

(Time t5 to t8: Mixing, etc.)
When the first control unit 24 determines that a predetermined time has elapsed after starting the control to close the valve 23 (time t5), the mixed signal Sg5 (time t5) drives the drive unit 50 so that the volume of the pressure chamber 21 repeatedly increases and decreases. Sg51 and Sg52) are output. As a result, the movement of the liquid shown in FIGS. 5 (b) (FIG. 5 (f)), FIG. 5 (c) and FIG. 5 (d) toward the second end 12 side, and FIGS. 5 (d) and 5 (d). The movement of the liquid shown in (e) and FIG. 5 (f) toward the first end 11 side is repeated alternately. As a result, the first liquid L1 and the second liquid L2 are stirred, and both are mixed. The number of repetitions may be set as appropriate.

Then, for example, the mixed liquid is irradiated with light while being held in the capillary 10 (for example, in the second member 16), and its properties are examined. For example, fluorescence measurement, scattering measurement, absorption measurement and / or spectroscopic measurement are performed. Although not particularly shown, the liquid may be moved to a position suitable for measurement by the same operation as the operation of moving the liquid to an arbitrary position at times t3 to t4 prior to the measurement. Further, the mixed liquid may be discharged from the capillary 10 and used for various purposes instead of being held in the capillary 10 for measurement.

In FIG. 4, the waveform of the drive signal SgA is a waveform composed of a plurality of straight lines such as a rectangular wave. However, a part or all of the waveform of the drive signal SgA may be a waveform composed of a curve such as a sine wave.

[Mixing operation of pipette]
The mixed signal Sg5 alternates between a first signal Sg51 that drives the drive unit 50 so that the volume of the pressure chamber 21 increases and a second signal Sg52 that drives the drive unit 50 so that the volume of the pressure chamber 21 decreases. Is repeatedly included in. As shown in FIGS. 5 (b) (FIG. 5 (f)), FIG. 5 (c) and FIG. 5 (d), the liquid (first liquid L1 and second liquid L1 and second) due to the decrease in the volume of the pressure chamber 21. At least a part of the liquid L2) flows from the first hole 10a to the second hole 10b. Similarly, as shown in FIGS. 5 (d), 5 (e) and 5 (f), due to the increase in the volume of the pressure chamber 21, the liquid is at least partially abundant from the second hole 10b. It flows to 1 hole 10a. That is, the liquid reciprocates, at least in part, repeatedly across the boundary 14.

All of the liquids (L1 + L2) may repeatedly cross the boundary 14 as shown in the illustrated example, or unlike the illustrated example, only a part of the liquid (L1 + L2) may repeatedly cross the boundary 14. In the case where all of the liquid repeatedly crosses the boundary 14, the liquid may leave the boundary 14 after crossing the boundary 14 and then turn back, or turn back from the state of being adjacent to the boundary 14 beyond the boundary 14. May be good. “Adjacent” is as described in the air suction signal Sg3 and FIG. 5 (b). Further, whether or not all or a part of the liquid exceeds the boundary 14 and whether or not it separates from the boundary 14 differs depending on whether the liquid flows to the first hole 10a side or the second hole 10b side. It may change in the process of repeating the round trip.

In the description of the present embodiment, the liquid (L1 + L2) exceeds the boundary 14 and is adjacent to the boundary 14 both when flowing to the first hole 10a side and when flowing to the second hole 10b side. Take, for example, the case of turning back and maintaining the state even after repeated round trips. In such a case, for example, the entire liquid can be made to cross the boundary 14, and the reciprocating cycle can be shortened.

The first signal Sg51 and the second signal Sg52 may be appropriately set so as to realize the above-mentioned operation.

For example, first, in the present embodiment, immediately before mixing, the liquid (L1 + L2) is adjacent to the first end 11 side with respect to the boundary 14 by the air suction signal Sg3. In this case, the mixed signal Sg5 includes, for example, a first signal Sg51 that first moves the liquid to the second end 12 side (as a signal whose output starts at time t5). Further, the amount of change in the potential of the first signal Sg51 (the amount of increase in the volume of the pressure chamber 21) and the amount of change in the potential of the second signal Sg52 (the amount of decrease in the volume of the pressure chamber 21) are roughly liquid (amount of decrease in the volume of the pressure chamber 21). It corresponds to the volume of L1 + L2). The signal finally included in the mixed signal Sg5 may be either the first signal Sg51 or the second signal Sg52, and is, for example, the signal included in the mixed signal Sg5 second from the start (second signal Sg52 in the present embodiment).

In addition, unlike the above, the liquid may be adjacent to the second end 12 side of the boundary 14 by the air suction signal Sg3. In this case, the mixed signal Sg5 may first include, for example, a second signal Sg52 that moves the liquid to the first end 11 side. Further, the liquid may be straddled over the boundary 14 by the air suction signal Sg3. In this case, the mixed signal Sg5 may first include, for example, a signal in which the amount of change in the potential of the first signal Sg51 or the second signal Sg52 is reduced. Conversely, the air suction signal Sg3 may separate the liquid from the boundary 14. In this case, the mixed signal Sg5 may first include, for example, a signal in which the amount of change in the potential of the first signal Sg51 or the second signal Sg52 is increased.

The first signal Sg51 and the second signal Sg52 may have waveforms that match each other or different waveforms when one of them is inverted with respect to the passage of time. In other words, the waveforms of both signals may be axisymmetric or asymmetric with respect to an axis of symmetry (not shown) parallel to the vertical axis of the graph shown in FIG. In the example shown in FIG. 4, the waveforms of both signals are asymmetric.

Specifically, for example, the rate of change of the potential of the first signal Sg51 with respect to time is larger than the rate of change of the potential of the second signal Sg52 with time. In the illustrated example, the first signal Sg51 is a signal whose potential rises sharply (with a rise time of approximately 0), and the second signal Sg52 is a signal whose potential gradually drops in proportion to time. Has been done. That is, the combination of the first signal Sg51 and the subsequent second signal Sg52 is a so-called reverse saw wavy signal. Specific values of these rate of change may be set as appropriate.

Further, for example, the amount of change in the potential of the second signal Sg52 dV52 (the amount of decrease in the volume of the pressure chamber 21) is larger than the amount of change in the potential of the first signal Sg51 dV51 (the amount of increase in the volume of the pressure chamber 21). The difference may be set as appropriate, and for example, it may be set so that the action described later is exhibited. Since the change amount dV52 is larger than the change amount dV51, the potential of the mixed signal Sg5 gradually decreases. When the mixing is completed (when the output of the mixed signal Sg5 is completed), the potential of the mixed signal Sg5 may be smaller, equal to, or larger than the potential V0 and / or the reference potential of the initial signal Sg0. May be good.

As described above, in the present embodiment, the pipette 1 is inside the capillary 10 via the capillary 10 having both ends (first end 11 and second end 12) open in the length direction and the second end 12. It has a communicating pressure chamber 21, a drive unit 50 that changes the volume of the pressure chamber 21, and a control unit (first control unit 24) that controls the drive unit 50. The capillary 10 has a first pipe portion 17 located on the first end 11 side and a second pipe portion 18 located on the second end 12 side. The first pipe portion 17 has a first hole 10a penetrating in the length direction, and the second pipe portion 18 has a second hole 10b penetrating in the length direction. The second hole 10b is connected to the second end 12 side of the first hole 10a. The water repellency of the inner surface of the first hole 10a and the water repellency of the inner surface of the second hole 10b are different from each other. Then, the first control unit 24 repeatedly increases and decreases the volume of the pressure chamber 21, so that at least a part of the liquid in the capillary 10 repeatedly reciprocates beyond the boundary between the first hole 10a and the second hole 10b. Controls the drive unit 50.

Therefore, for example, when the liquid exceeds the boundary 14, the flow of the liquid is disturbed due to the difference in water repellency, and the liquid is easily agitated. Specifically, for example, when the liquid crosses the boundary 14 from the side having low water repellency to the side having high water repellency, the liquid near the inner surface of the capillary 10 becomes difficult to flow along the inner surface of the capillary 10. As a result, for example, the flow of the liquid is likely to separate from the inner surface of the capillary 10, and a vortex is likely to be generated. This vortex facilitates the agitation of the liquid. As a result, for example, mixing of the two liquids is promoted.

Further, in the present embodiment, the water repellency of the inner surface of the first hole 10a is higher than the water repellency of the inner surface of the second hole 10b.

In this case, for example, the flow from the second hole 10b to the first hole 10a side tends to have a higher resistance than the flow in the opposite direction. As a result, for example, the possibility that the liquid is discharged from the first end 11 at the time of mixing is reduced. Further, when the first hole 10a extends from the boundary 14 to the first end 11, the risk of the liquid adhering to the first end 11 is reduced when the liquid is sucked from the first end 11. NS. As a result, for example, the correspondence between the increase in the volume of the pressure chamber 21 and the suction amount of the liquid is stabilized, and the accuracy of measuring the liquid is improved.

Further, in the present embodiment, the inner diameter of the first hole 10a is larger than the inner diameter of the second hole 10b at the boundary 14 between the first hole 10a and the second hole 10b.

In this case, for example, when the liquid exceeds the boundary 14, the flow of the liquid is disturbed due to the difference in the inner diameter, and the two liquids are easily mixed. Specifically, for example, when the liquid exceeds the boundary 14 from the side having a small inner diameter to the side having a large inner diameter, the flow is likely to be separated from the inner surface of the capillary 10, and a vortex is likely to be generated. This vortex facilitates the agitation of the liquid. Further, when the water repellency of the first hole 10a is higher than that of the second hole 10b, the direction in which the water repellency increases and the direction in which the inner diameter increases coincide with each other. As a result, for example, the effect that peeling is likely to occur due to the increase in water repellency and the effect that peeling is likely to occur due to the increase in the inner diameter are superimposed. As a result, the effect of promoting stirring is improved.

Further, in the present embodiment, the inner diameter of the first hole 10a is larger toward the second hole 10b side.

In this case, for example, the liquid is more likely to be turbulent than when the inner diameter of the first hole 10a is constant. As a result, for example, stirring of the liquid is promoted. Further, for example, when the first hole 10a extends to the first end 11, the inner diameter of the first end 11 can be reduced to improve the accuracy of measuring the liquid. On the other hand, at the boundary 14, the inner diameter of the first hole 10a can be made larger than the inner diameter of the second hole 10b, and the effect of promoting mixing due to the difference in the inner diameter described above can be obtained.

Further, in the present embodiment, the capillary 10 has a first member 15 and a second member 16. The first member 15 has a hollow shape having a first hole 10a. The second member 16 has a hollow shape having a second hole 10b, and is fixed to the first member 15.

In this case, for example, it is easy to make the material forming the first hole 10a and the material forming the second hole 10b different from each other. As a result, for example, it is easy to make the water repellency of the first hole 10a and the water repellency of the second hole 10b different from each other.

Further, in the present embodiment, the first member 15 extends from the first hole 10a and the first hole 10a to the opposite side of the first end 11, and has a third hole 15a having an inner diameter larger than that of the first hole 10a. And a stepped portion 15b due to the inner diameter of the first hole 10a being smaller than the inner diameter of the third hole 15a. The second member 16 is inserted into the third hole 15a and locked to the stepped portion 15b, and has a tip surface 16a on the stepped portion 15b side. The stepped surface 15ba on the tip end surface 16a side of the stepped portion 15b is inclined so as to be located closer to the tip surface 16a side toward the inner side in the radial direction of the capillary 10. The radial inner corner portion 15bb of the step portion 15b is in contact with the tip surface 16a.

In this case, for example, both can be connected by a simple configuration in which the second member 16 is inserted into the first member 15. Further, for example, since the contact between the second member 16 and the stepped portion 15b is a line contact, it is easier to secure the contact pressure as compared with the case of the surface contact. As a result, for example, the airtightness at the boundary 14 can be improved. Further, for example, a space is formed outside the corner portion 15bb between the tip surface 16a of the second member 16 and the step portion 15b. This space can be used, for example, to allow excess adhesive to escape when an adhesive is interposed between the inner surface of the first member 15 and the outer surface of the second member 16.

Further, in the present embodiment, the first member 15 is made of resin, and the second member 16 is made of glass.

In this case, for example, it is easy to increase the water repellency of the first member 15 and decrease the water repellency of the second member 16. For example, it is easy to set the contact angle of the first member 15 to 95 ° or more and the water repellency of the second member 16 to 60 ° or less. That is, it is easy to increase the difference in water repellency between the first hole 10a and the second hole 10b. As a result, for example, it is easy to improve the effect of promoting mixing due to the difference in water repellency. Further, since a resin that can be easily molded is used as the material of the first member 15, the accuracy of the dimensions near the first end 11 can be improved, and the accuracy of measuring the liquid can be improved. On the other hand, since glass, which can easily secure translucency, is used as the material of the second member 16, the accuracy of liquid analysis using light can be improved.

Further, in the present embodiment, the first control unit 24 outputs to the drive unit 50 the drive signal SgA in which the signal level (voltage) changes with the passage of time to form a waveform. The drive unit 50 changes the volume of the pressure chamber 21 according to a change in the voltage of the drive signal SgA with time so that the volume of the pressure chamber 21 becomes a volume corresponding to the voltage of the drive signal SgA. The drive signal SgA alternately and repeatedly includes the first signal Sg51 and the second signal Sg52. The first signal Sg51 is a signal for driving the drive unit 50 so that at least a part of the liquid flows from the first hole 10a to the second hole 10b due to the increase in the volume of the pressure chamber 21. The second signal Sg52 is a signal for driving the drive unit 50 so that at least a part of the liquid flows from the second hole 10b to the first hole 10a due to the decrease in the volume of the pressure chamber 21. The waveform of the first signal Sg51 and the waveform obtained by inverting the waveform of the second signal Sg52 so that the passage of time is reversed are different from each other.

In this case, for example, when the liquid flows from the first hole 10a to the second hole 10b and when it flows in the opposite direction, a flow suitable for each can be formed. For example, the water repellency, the inner diameter and / or the position with respect to the first end 11 are different between the first hole 10a and the second hole 10b, and a flow can be formed in consideration of this difference. For example:

In the present embodiment, the absolute value of the rate of change of the signal level (voltage) of the second signal Sg52 with respect to time is smaller than the absolute value of the rate of change of the voltage of the first signal Sg51 with respect to time.

In this case, the flow from the second hole 10b to the first hole 10a becomes slower than in the case where the absolute values of the two rates of change are the same. As a result, when the liquid flows out from the second hole 10b to the first hole 10a, it is possible to reduce the phenomenon that the liquid becomes fine particles and scatters. Further, for example, the possibility that the liquid is discharged from the first end 11 is reduced.

Further, in the present embodiment, the water repellency of the inner surface of the first hole 10a is higher than the water repellency of the inner surface of the second hole 10b. The absolute value of the change amount dV52 of the signal level (voltage) of the second signal Sg52 is larger than the absolute value of the change amount dV51 of the voltage of the first signal Sg51.

In this case, it is easy to keep the liquid reciprocating over the boundary 14 within a certain range. Specifically, it is as follows. For convenience of explanation, the strictness of the principle is ignored. When the liquid is located in the capillary 10, the liquid level on the first end 11 side and the liquid level on the second end 12 side are formed. At each liquid level, surface tension that tries to shrink the liquid level acts. Due to this surface tension, a force acting on each liquid surface in the length direction (x direction) of the capillary 10 is generated with a magnitude corresponding to the magnitude of the surface tension and the magnitude of the contact angle. When the liquid straddles the boundary 14, the water repellency of the first hole 10a is higher than that of the second hole 10b, so that the contact angle on the liquid surface in the first hole 10a is the first. It is larger than the contact angle at the liquid surface in the two holes 10b. Therefore, the force in the x direction acting on the liquid surface in the first hole 10a and the force in the x direction acting on the liquid surface in the second hole 10b are not balanced. As a result, the liquid receives a force from the side having a large contact angle to the side having a small contact angle as a whole. That is, the liquid tends to flow from the first hole 10a to the second hole 10b side. Therefore, if the absolute value of the voltage change amount dV51 of the first signal Sg51 and the absolute value of the voltage change amount dV52 of the second signal Sg52 are the same, the position of the liquid gradually changes in the process of repeating the reciprocation of the liquid. There is a risk of shifting to the second hole 10b side. However, by making the absolute value of the change amount dV52 larger than the absolute value of the change amount dV51, the position of the liquid can be maintained within a certain range. As a result, for example, it becomes easy to repeat the reciprocation of the liquid so that the entire liquid crosses the boundary 14 and turns back immediately after the boundary 14. As a result, the effect of promoting stirring by utilizing the difference in water repellency can be improved.

[Modification example]
(Modification example related to the second member)
FIG. 6A is a cross-sectional view showing the configuration of the capillary 210 according to the modified example. The capillary 210 differs from the capillary 10 of the embodiment only in the material constituting the second member. Specifically, the second member 216 according to the modified example has a main body 216x and a water-repellent film 216y that covers at least a part of the inner surface of the main body 216x. The main body 216x is made of, for example, glass. The material of the water-repellent film 216y has already been described. Even in such a configuration, the same effect as that of the embodiment can be obtained by making the water repellency of the inner surface of the first hole 210a different from the water repellency of the inner surface of the second hole 210b.

(Modification example related to drive signal)
FIG. 6B is a diagram showing a drive signal SgB according to a modified example. This figure corresponds to a part of FIG. 4 (generally at times t6 to t8). In this modification, the first signal Sg51 and the second signal Sg52 included in the drive signal SgB are formed by a curved line. More specifically, in the illustrated example, each of the first signal Sg51 and the second signal Sg52 is composed of a quarter period of a sine wave. Even in such a drive signal SgB, the absolute value of the rate of change of the second signal Sg52 may be smaller than the absolute value of the rate of change of the first signal Sg51.

Here, the fact that the waveforms of the first signal Sg51 and the second signal Sg52 are each composed of curves means that the rate of change changes from the start to the end of each signal. In such a case, whether or not the absolute value of the rate of change of the second signal Sg52 is larger than the absolute value of the rate of change of the first signal Sg51 may be determined based on the average value of the rates of change of both. .. That is, in the illustrated example, since the change amount dV1 occurs in the first signal Sg51 during the time length T1, the average value of the change rate is dV1 / T1. Similarly, in the second signal Sg52, since the amount of change dV2 occurs during the time length T2, the average value of the rate of change is dV2 / T2. Then, if | dV2 / T2 |> | dV1 / T1 |, it may be determined that the absolute value of the rate of change of the second signal Sg52 is larger than the absolute value of the rate of change of the first signal Sg51.

Although not particularly shown, the signal for repeating the increase / decrease in the volume of the pressure chamber 21 may have a shape similar to a rectangular wave. In this case, for example, the rising portion of the square wave is the first signal, the falling portion of the square wave is the second signal, and the portion having a constant potential between them is a signal other than the first signal and the second signal. be.

The technique according to the present disclosure is not limited to the above embodiments and modifications, and may be implemented in various embodiments.

For example, the pipette is not limited to a mixture of two liquids sucked by the pipette itself. Specifically, for example, a capillary in which a reactant is previously deposited on the inner surface is attached to the pipette body, and then a liquid (one liquid) is sucked by the pipette, and the reactant is reciprocated by a reciprocating flow in the length direction of the capillary. May dissolve in the liquid. Further, for example, the pipette sucks a liquid (1 liquid) in which two liquids are already mixed, a solvent (1 liquid) in which a solute is already contained, or a liquid (1 liquid) in which minute substances are already dispersed. It may then be used to further promote mixing, dissolution or dispersion. Further, the pipette may be one that sucks and mixes three or more liquids.

Further, for example, in the above-described embodiment, an example in which the valve 23 is opened and closed after air suction is shown, but in some cases, the valve 23 may not be opened and closed. In this case, the restoration signal Sg4 becomes unnecessary, and the mixing signal Sg5 may be output following the air suction signal Sg3. Further, the valve 23 and the control circuit 25 may not be provided.

1 ... Pipette, 10 ... Capillary, 10a ... 1st hole, 10b ... 2nd hole, 21 ... Pressure chamber, 50 ... Drive unit, 24 ... 1st control unit (control unit), 11 ... 1st end, 12 ... 2 ends, 17 ... 1st pipe, 18 ... 2nd pipe.

Claims (13)

A capillary in which the first and second ends, which are both ends in the length direction, are open.
1st hole and
A capillary that is connected to the second end side of the first hole and has a second hole whose inner surface water repellency is different from that of the inner surface of the first hole. The capillary according to claim 1, wherein the water repellency of the inner surface of the first hole is higher than the water repellency of the inner surface of the second hole. The capillary according to claim 1 or 2, wherein the inner diameter of the first hole is larger than the inner diameter of the second hole at the boundary between the first hole and the second hole. The capillary according to any one of claims 1 to 3, wherein the first hole has an inner diameter larger toward the second hole side. A hollow first member having the first hole and
The capillary according to any one of claims 1 to 4, which is hollow and has the first member and a second member fixed to the first member. The first member is
With the first hole
A third hole extending from the first hole to the side opposite to the first end and having an inner diameter larger than that of the first hole.
It has a stepped portion due to the inner diameter of the first hole being smaller than the inner diameter of the third hole.
The second member is inserted into the third hole and locked to the step portion.
The second member has a tip surface on the stepped portion side.
The surface of the step portion on the tip surface side is inclined so as to be located closer to the tip surface side toward the inner side in the radial direction of the capillary, and the inner corner portion of the step portion in the radial direction is the tip end. The capillary according to claim 5, which is in contact with a surface. The first member is made of resin and is made of resin.
The capillary according to claim 5 or 6, wherein the second member is made of glass or is made of glass except for at least a part of the surface. Assuming that the end face of the first end is the first end face,
The first end face is an annular shape with a circular opening.
The capillary according to any one of claims 1 to 7, wherein the outer diameter of the first end surface is 0.4 mm or less. The capillary according to claim 8, wherein the inner diameter of the first end surface is 0.06 mm or more. The capillary according to any one of claims 1 to 9 and
A pressure chamber leading to the inside of the capillary via the second end,
A drive unit that changes the volume of the pressure chamber and
A control unit that controls the drive unit and
Have and
The capillary has a first pipe portion located on the first end side and a second pipe portion located on the second end side.
The first pipe portion has the first hole penetrating in the length direction.
The second pipe portion has the second hole penetrating in the length direction.
The control unit repeatedly increases and decreases the volume of the pressure chamber, whereby at least a part of the liquid in the capillary repeatedly reciprocates beyond the boundary between the first hole and the second hole. A pipette to control. The control unit outputs a drive signal in which the signal level changes with the passage of time to form a waveform to the drive unit.
The drive unit changes the volume of the pressure chamber according to the change of the signal level with time so that the volume of the pressure chamber becomes the volume corresponding to the signal level.
The drive signal is
A first signal that drives the drive unit so that at least a part of the liquid flows from the first hole to the second hole due to an increase in the volume of the pressure chamber.
A second signal that drives the drive unit so that at least a part of the liquid flows from the second hole to the first hole due to a decrease in the volume of the pressure chamber.
Is alternately and repeatedly included,
The pipette according to claim 10, wherein the waveform of the first signal and the waveform obtained by inverting the waveform of the second signal so as to reverse the passage of time are different from each other. The pipette according to claim 11, wherein the absolute value of the rate of change of the signal level of the second signal with respect to time is smaller than the absolute value of the rate of change of the signal level of the first signal with respect to time. The water repellency of the inner surface of the first hole is higher than the water repellency of the inner surface of the second hole.
The pipette according to claim 11 or 12, wherein the absolute value of the amount of change in the signal level of the second signal is larger than the absolute value of the amount of change in the signal level of the first signal.

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