JPH05184949A - Microquantitative pipette - Google Patents

Abstract

PURPOSE:To obtain an inexpensive disposable pipette capable of accurately sampling a very small amount of blood or the like by bringing a liquid sampling part provided with a liquid sample receiving part showing a capillary phenomenon of an aqueous liquid into close contact with the annular leading end part of a main body having an air compressing pore provided therein in a detachable manner. CONSTITUTION:When a constant volume of an aqueous liquid sample, especially, a physiological liquid such as blood is sampled using a microquantitative pipette 1, a liquid sampling member 11 is brought into close contact with the annular leading end part 5 of a main body 2 at first. Next, the tip of a capillary tube part 3 is dipped in a sample to raise a sample through the capillary tube part 3 by a capillary phenomenon. Continuously, the tip of the capillary tube part 13 is moved to the position above a container to receive the sample and an engaging part 9 is pressed. When the head 8 of a piston 4 passes the position of a vent hole 7, the air in the main body 2 and a bottomed cylindrical part 12 is compressed to push out the sample in the capillary part 13. When the pressing of the engaging part 9 is released, the piston 4 retreats by the recovery force of a compression coil spring 10 to return to the original position.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a microvolumetric pipette suitable for collecting a small amount of an aqueous liquid, particularly a fixed amount of a physiological liquid such as blood or body fluid.

[0002]

2. Description of the Related Art Conventionally, a micropipette has been used to accurately collect a very small amount of liquid. A general micropipette has a liquid suction tube at the tip of a plunger with an airtight structure like a syringe, and the inside of the main body is made negative pressure by the plunger to store the liquid in the cavity inside the main body. With this, the inside of the main body is made to have a positive pressure to push out a predetermined amount of liquid. This type of micropipette is extremely expensive and cannot be used as a single-use one because it is made by precision processing to make it possible to set a very small volume. On the other hand, as a simple method, there is a plastic molded article such as a syringe and a dropper with a scale, but the accuracy of constant volume is low and it is not suitable for a minute amount of 1 to 50 μl level.

In addition, there is a so-called capillary pipette or a capillary pipette using a glass capillary in order to accurately measure 1 to 100 μl of liquid. Since a thin capillary pipette is made of glass, it is dangerous to handle and difficult to see, and a thick capillary pipe having an outer diameter of about 5 to 6 mm is used or attached to another thick pipe.

Further, as a micropipette using a capillary tube, a micropipette whose cross-sectional view is shown in FIG. 10 is known. In FIG. 10, the micropipette 80
Is attached to one end of a cylindrical plastic holder 81,
Rubber cap 83 having a substantially hemispherical shell shape and provided with a hole 82
Is attached airtightly, and a rubber plug 85 penetrating a glass capillary tube 84 is airtightly inserted into the other end of the holder 81.

When collecting a certain amount of liquid sample using the micropipette 80, first, the tip 84a of the capillary tube 84 is put into the liquid sample with the hole 82 left open. The liquid sample rises in the capillary tube 84 due to the capillary phenomenon, overflows from the end 84b of the capillary tube 84, and collects in the cavity portion 86 in the holder 81. The liquid surface of the liquid sample collected in the cavity 86 is the capillary tube 8.
4, the end 84 of the capillary tube 84 is reached before reaching the end 84b.
Remove a from the liquid sample. Next, when the cap 83 is pushed while the hole 82 is closed with a fingertip or the like, the liquid sample in the capillary tube 84 is discharged, and an amount of the liquid sample corresponding to the internal volume of the capillary tube 84 can be taken out. In this way, it is possible to easily obtain an extremely small amount of liquid having a constant volume.

When collecting a fixed volume of liquid sample using the micropipette 80, the portion other than the cap 83 must be washed or discarded every time the sample changes, and the glass capillary tube 84 is handled. There is a problem in that it is dangerous. It is conceivable to replace the capillary tube 84 with a suitable plastic capillary tube, but it is technically difficult to manufacture a capillary tube with a hole diameter of about 1 mm or less from plastics, and if the hole diameter is increased, it becomes extremely small. It becomes difficult to take a sample.

[0007]

Provided is a microvolume constant-volume pipette capable of easily, quickly, reliably, and safely collecting a fixed amount of a trace amount of an aqueous liquid. In particular, it can be disposable because it is possible to prevent the risk of weighing liquids such as body fluids and blood that are highly dangerous, such as infection of the operator by pathogenic bacteria, etc., at the time of collection and weighing work. And accurate microvolumetric pipette.

[0008]

The present invention (first invention) is
At the tubular tip of the main body having a cavity provided with an air compression mechanism and having a vent hole on the outer wall, at least the inner surface has hydrophilicity, and a liquid sample accommodating portion having an inner dimension in which an aqueous liquid exhibits a capillary phenomenon is provided. , A liquid collecting part of a one-end bottomed cylinder having an inner diameter such that one end thereof does not protrude from the bottom surface and penetrates the bottom part and has an inner diameter such that the aqueous liquid does not show a capillary phenomenon, is airtightly attached and detached in the cylinder part. It is a microvolumetric pipette that is installed as possible.

Another aspect of the present invention (second aspect) has a cavity provided with an air compression mechanism, and an inner dimension at which a water-based liquid exhibits a capillary phenomenon at a tubular tip portion of a main body having a ventilation hole in an outer wall. In addition, the liquid collection part whose inner surface is hydrophilic and the inner surface of the remaining part is hydrophobic for a length corresponding to the volume of the liquid sample to be collected from one end is airtight at its hydrophobic side end. It is a microvolume constant volume pipette that is detachably attached.

According to another aspect of the present invention (third aspect), at least one end of a tube made of a hydrophobic plastic has an inner dimension in which an aqueous liquid exhibits a capillarity, and a liquid sample to be collected from the tip thereof. It is a microvolumetric pipette whose inner surface is treated to have hydrophilicity by a length corresponding to the volume.

The preferred embodiments of the present invention are as follows. (1) The main body is composed of a cylinder having a tubular tip portion at one end and a piston having a head portion that slides airtightly along the inner surface of the tube, and if necessary, the rear end of the piston and the rear end of the cylinder. The microvolumetric pipette described above, which has a shape in which a coil spring is provided between and a ventilation hole is provided in a part of a cylinder.

(2) The main body is provided with a tubular tip portion at one end, has a hollow portion inside, and has a vent hole in a part of the wall body, and is airtight except for the tubular tip portion and the vent hole. The above-mentioned microvolumetric pipette having a structure, wherein a part of the wall is deformable and is made of a self-recovering material.

(3) In the liquid collecting section, the capillary section and the cylindrical section with one end having a bottom are integrally made of plastics,
At least the inner surface of the capillary portion is subjected to hydrophilicity-imparting treatment, and the above-mentioned microvolumetric pipette.

(4) The microvolumetric pipette described above, wherein the liquid collecting portion is one in which the capillary portion and the cylindrical portion having a bottom with one end are integrally made of hydrophilic plastics.

The microvolumetric pipette of the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 is a sectional view of an embodiment of a microvolumetric pipette of the first invention. In FIG. 1, the microvolume constant volume pipette 1 is composed of a main body 2 and a liquid collecting member 11. The main body 2 includes a cylinder 3 and a piston 4 inserted in the cylinder 3. A tubular tip portion 5 is formed at the tip portion of the cylinder 3, a flange portion 6 is formed at the rear end portion of the cylinder 3, and a vent hole 7 is formed in the body portion of the cylinder 3.
Is provided. A head portion 8 that airtightly slides along the inner surface of the cylinder 3 is provided at the tip end portion of the piston 4, and a locking portion 9 is formed at the rear end portion of the piston 4. A compression coil spring 10 is mounted between the collar portion 6 and the locking portion 9 with the piston 4 passing therethrough. Liquid collecting member 11
Is composed of a one-end bottomed cylindrical part 12 and a capillary part 13 which is integrally formed by penetrating the bottom of the one-end bottomed cylindrical part 12.

The cylinder 3 and the piston 4 are generally made of hard plastic (not particularly limited, and examples thereof include polystyrene, high-density polyethylene, polypropylene, vinyl chloride, acrylate resin, polycarbonate, etc.) and tubular ends. It is preferable that the head 5 and the flange portion 6 are integrally molded, and the head portion 8 is preferably made of rubber, soft plastics (for example, soft vinyl chloride, low density polyethylene, etc.) and fixed to the piston 4. When not in use, the piston 4 is retracted by the action of the compression coil spring 10 to a position such that the tip of its head portion 8 is behind (above in FIG. 1) the vent hole 7.

The liquid collecting member 11 will be described in more detail with reference to FIG. 2 showing a sectional view thereof. In FIG. 2, the liquid collecting part 11 is configured by integrally forming a one-end bottomed cylindrical part 12 and a capillary part 13, and a hole of the capillary part 13 communicates with the inside of the one-end bottomed cylindrical part 12. ing. Inner surface 12a of one-end bottomed cylindrical portion 12 and inner surface 1 of the capillary portion 13
3a has hydrophilicity. The inner diameter d of the capillary portion 13 is
The size is such that the aqueous liquid can enter the inside of the capillary portion 13 due to the capillarity, and is generally preferably 0.1 to 3 mm, particularly preferably 0.5 to 2.5 mm, and 1 to Most preferably, it is 2 mm. The inner diameter D of the one-end bottomed cylindrical portion 12 is of a size such that the aqueous liquid does not enter the inside thereof due to a capillary phenomenon, and is a size that can be fitted into the tubular distal end portion 5 of the main body 2 in an airtight manner. It is preferably 5 to 10 mm.

The plastic for forming the liquid collecting member 11 is preferably a transparent or translucent hard plastic which is insoluble or non-swellable in an aqueous liquid and is a plastic as exemplified for the cylinder 3. It can be selected appropriately. In general, plastics are hydrophobic, and since an aqueous liquid does not enter the inside of the capillary portion 13 due to a capillary phenomenon, at least the capillary portion 13
It is necessary to make the inner surface of the hydrophilic. As a means for imparting hydrophilicity to the inner surfaces of the one-end bottomed cylindrical portion 12 and the capillary portion 13, the liquid collecting member 11 is integrally molded with plastics, and for example, a surface-active agent (nonionic surface-active agent ), Hydrophilic polymer compounds, water-soluble organic compounds (glycerin ester, ethylene glycol, amino acids, sugars, etc.), compounds having hydrophilic and hydrophobic moieties in the molecule, and immersion in an aqueous solution of a mixture thereof. After that, there is a method of making the surface hydrophilic by a method of drying. The surface other than the inside of the capillary portion 13 may be hydrophilic. The reason is that, as shown in FIG. 2, the liquid collecting member 11 has an inner diameter d at the upper end of the capillary portion 13 from which the aqueous liquid can enter due to the capillary phenomenon. This is because it has a shape that changes intermittently to D so that it does not enter, so that the aqueous liquid from the capillary tube portion 13 does not enter the one-end bottomed cylindrical portion 12.

For the above reasons, the liquid collecting member 11
May be integrally molded with hydrophilic plastic to impart hydrophilicity to the entire surface. Examples of the hydrophilic plastics include plastics having hydrophilicity themselves such as nylon and ethylene-carboxylic acid copolymers, and hydrophobic plastics such as those mentioned above, and glycerin and ethylene. Examples thereof include a plastics composition in which a hydrophilic plasticizer such as glycol, polyethylene glycol, glycerin fatty acid ester (eg, glycerin laurate, glycerin stearate, etc.) is blended.

A method for collecting a fixed volume of the aqueous liquid sample using the microvolume constant volume pipette 1 shown in FIGS. 1 and 2 will be described. First, the liquid sampling member 11 is airtightly fitted and attached to the tubular tip portion 5 of the main body 2. At this time, in the piston 4, as shown in FIG.
It is located above. When the tip of the capillary tube portion 13 is immersed in the aqueous liquid sample in this state, the aqueous liquid sample rises in the capillary tube portion 13 due to the capillary phenomenon. When the tip of the aqueous liquid sample rising in the capillary portion 13 reaches the bottom surface 12b of the one-end bottomed cylindrical portion 12, the inner diameter D of the one-end bottomed cylindrical portion 12 becomes so large that the aqueous liquid does not show a capillary phenomenon. Therefore, the rise of the aqueous liquid sample stops at that point.

Then, the tip of the capillary portion 13 is taken out from the aqueous liquid sample and moved to the upper side of a container which should receive the sample, a test piece used for analysis of the sample (not shown), and the jaw portion 6 with the fingertip. The locking portion 9 is pushed with the locking portion 9 interposed therebetween. At this time, the air inside the main body 2 and the cylindrical portion 12 with one end having a bottom at the beginning comes out from the vent hole 7, but when the head portion 8 passes the position where the vent hole 7 is provided, the inside of the main body 2 and The air in the one-end bottomed cylindrical portion 12 is compressed, and the aqueous liquid sample in the capillary portion 13 is pushed out. When all the aqueous liquid sample in the capillary tube portion 13 has been pushed out and then the finger applied to the locking portion 9 is released, the piston 4 retracts due to the restoring force of the compression coil spring 10 and returns to the initial position. In this way a fixed volume of aqueous liquid sample can be taken. By using the liquid collecting member 11 having different inner volumes of the capillary tube portion 13, a desired amount of aqueous liquid sample can be easily collected.

When an aqueous liquid sample is collected using the microvolumetric pipette of the first invention, the body 2 does not come into contact with the aqueous liquid sample, as will be apparent from the above description. When collecting a sample, the liquid collecting member 11
You only have to replace it with a new one.

FIG. 1 shows a mode in which the tubular tip portion 5 of the main body 2 is inserted into the one-end bottomed cylindrical portion 12 of the liquid collecting member 11, but conversely, the one-end bottomed cylindrical portion of the liquid collecting member 11 is shown. 12
May be inserted into the tubular tip 5 of the body 2. The tubular tip portion 5 and the one-end bottomed cylindrical portion 12 are provided with a taper at the contact portion as is generally done,
It is easy to put on and take off, and it can be fitted airtightly. Of course, it may be a screw type or any other shape as required. Further, the piston 4 may be moved by a finger without providing the compression coil spring 10, and a piston position restoring means of another type may be provided. Further, the piston 4 may be provided so as to be able to slide in the cylinder 3 in an airtight manner without fixing the head portion 8 to the piston 4.

FIG. 3 is a sectional view of another embodiment of the microvolumetric pipette of the first invention. In FIG. 3, the micro volumetric pipette 20 is composed of a main body 21 and a liquid sampling member 11. The main body 21 has a tubular tip portion 22, a cylindrical portion 23, and a spherical shell portion 24 integrally formed, and has the same structure as a so-called dropper except that a vent hole 25 is provided. The spherical shell portion 24 has a hollow inside and a substantially spherical shape, at least a part of which is deformable and self-recoverable, and a ventilation hole 25 is provided in a part of the wall body. There is. And, except for the tubular tip portion 22 and the vent hole 25, it has an airtight structure. The body 21 is preferably made of plastics or rubber. Alternatively, the spherical shell portion 24 and the cylindrical portion 23 may be separately formed and both may be airtightly attached. Further, the spherical shell portion 24 may be directly provided on the tubular tip portion 22 without providing the cylindrical portion 23. Further, the spherical shell portion 24 is not limited to a spherical shape, and may have any shape as long as it has a cavity inside.

The liquid collecting member 11 is the same as that described with reference to FIG. 2, and the liquid collecting member 11 and the tubular tip portion 2 are used.
The mutual relation with 2 is also similar to the mutual relation between the liquid collecting member 11 and the tubular tip portion 5 described with reference to FIGS. 1 and 2.

A method for collecting a fixed volume of the aqueous liquid sample using the microvolume constant volume pipette 20 shown in FIG. 3 will be described. First, the liquid collecting member 11 is airtightly fitted and attached to the tubular distal end portion 22 of the main body 21. When the tip of the capillary tube portion 13 is immersed in the aqueous liquid sample with the vent hole 25 opened, the aqueous liquid sample rises in the capillary tube portion 13 due to the capillary phenomenon. When the tip of the aqueous liquid sample rising in the capillary portion 13 reaches the bottom surface 12b of the one-end bottomed cylindrical portion 12, the inner diameter D of the one-end bottomed cylindrical portion 12 becomes so large that the aqueous liquid does not show a capillary phenomenon. Therefore, the rise of the aqueous liquid sample stops at that point.

Then, the tip of the capillary tube portion 13 is taken out from the aqueous liquid sample and moved to the upper side of a container which should receive the sample or a test piece (not shown) used for analysis of the sample, and the vent hole 25 is opened with a fingertip. Close and grip the spherical shell 24
Reduce the volume of the cavity. As a result, the air in the main body 21 and the cylindrical portion 12 with one end having a bottom is compressed, and the aqueous liquid sample in the capillary portion 13 is pushed out. After all the aqueous liquid sample in the capillary tube portion 13 has been pushed out, the vent hole 25 is released and the force applied to the spherical shell portion 24 is removed, whereby the spherical shell portion 24 naturally returns to its original shape. In this way a fixed volume of aqueous liquid sample can be taken.

When an aqueous liquid sample is collected using the microvolumetric pipette of the first invention, as is clear from the above description, the main body 21 does not come into contact with the aqueous liquid sample. When collecting a sample, the liquid collecting member 1
Only one needs to be replaced with a new one.

FIG. 4 is a cross-sectional view of an embodiment of the microvolumetric pipette of the second invention. In FIG. 4, the microvolume constant volume pipette 30 is composed of a main body 31 and a liquid collecting member 35. The main body 31 is formed by integrally forming a cylindrical portion 32 and a spherical shell portion 33, is provided with a vent hole 34, and is formed similarly to the main body 21 of the microvolumetric pipette 20 shown in FIG. The liquid collecting member 35 is composed of a capillary tube portion 36 and a collar portion 37 that is hermetically fitted to the capillary portion 36, and the collar portion 37 can be fitted and mounted in the cylindrical portion 32 in an airtight manner.

The liquid collecting member 35 will be described in detail with reference to FIG. 5 showing a sectional view thereof. In FIG. 5, the liquid collecting member 35 comprises a capillary portion 36 and a collar portion 37 hermetically fitted thereto. The capillary portion 36 is made of a hydrophobic plastic, and a part of the inner surface 36a of the capillary portion 36 which is continuous from the tip is subjected to hydrophilic treatment to form a hydrophilic surface portion 38. Means for forming the hydrophilic surface portion 38 having a predetermined length on the inner surface 36a of the capillary portion 36 include, for example, surfactants (nonionic surfactants are particularly preferable), hydrophilic polymer compounds, water-soluble organic compounds. A compound (glycerin ester, ethylene glycol, amino acid, sugar, etc.), a compound having a hydrophilic portion and a hydrophobic portion in the molecule, and an aqueous solution of a mixture thereof are used to form a capillary portion 36 formed of hydrophobic plastics. A method in which the tip is dipped for a predetermined length and then dried is exemplified. In addition, after attaching the liquid collecting member 35 to a suitable micropipette with the flange portion 37, sucking the aqueous solution of the above-mentioned surfactant or the like for a predetermined length from the tip of the capillary portion 36, and extruding the sucked aqueous solution. A method of drying can also be adopted.

A method for collecting a fixed volume of aqueous liquid sample using the microvolume constant volume pipette 30 shown in FIG. 4 will be described with reference to FIGS. 4 and 5. First, the liquid collecting member 35 is airtightly fitted and attached to the cylindrical portion 32 of the main body 31. When the tip of the capillary tube portion 36 is immersed in the aqueous liquid sample with the vent hole 34 opened, the aqueous liquid sample rises in the capillary tube portion 36 due to the capillary phenomenon. When the tip of the aqueous liquid sample rising in the capillary section 36 reaches the end of the hydrophilic surface section 38 of the capillary section 36, the surface 36a of the capillary section 36 ahead of that is hydrophobic (hydrophobic plastic Is exposed), the tip of the aqueous liquid sample does not proceed further than that, and the rise of the aqueous liquid stops.

Then, the tip of the capillary section 36 is taken out from the aqueous liquid sample and moved to the upper side of a container which should receive the sample or a test piece (not shown) used for analysis of the sample, and the vent hole 34 is formed with a fingertip. Block, grab the spherical shell 33 and hold the spherical shell 33
Reduce the volume of the cavity. As a result, the air in the main body 31 and the cylindrical portion 32 is compressed, and the aqueous liquid sample in the capillary portion 36 is pushed out. After all the aqueous liquid sample in the capillary tube portion 36 has been pushed out, the vent holes 34 are released and the force applied to the spherical shell portion 33 is removed, and the spherical shell portion 33 naturally returns to its original shape.
In this way a fixed volume of aqueous liquid sample can be taken. By changing the inner diameter of the capillary portion 36 and the length of the hydrophilic surface portion 38, it is possible to change the amount of the aqueous liquid sample that enters the capillary portion 36 by the capillarity.
By using the liquid collecting member 35 in which the inner diameter of the capillary portion 36 and the length of the hydrophilic surface portion 38 are different, a desired amount of aqueous liquid sample can be easily collected.

Even when an aqueous liquid sample is collected using the microvolumetric pipette of the second invention, as is clear from the above description, the main body 31 does not come into contact with the aqueous liquid sample. When collecting a sample, the liquid collecting member 3
You only have to replace 5 with a new one.

FIG. 6 shows an example of the liquid collecting member of the microvolumetric volume pipette of the second invention. In FIG. 6, the liquid collecting member 40 has a tapered cylindrical shape, and its rear end portion 41 is shown in FIG.
The main body 31 has an inner diameter that can be airtightly inserted into the cylindrical portion 32, and the tip portion 42 has an inner dimension that allows the aqueous liquid to exhibit a capillary phenomenon. The liquid collecting member 40 is made of hydrophobic plastics, and a part of the inner surface 42a of the tip portion 42 that is continuous from the tip is subjected to a hydrophilic treatment to form a hydrophilic surface portion 43. Tip 42
The means for forming the hydrophilic surface portion 43 having a predetermined length on the inner surface 42a of the above is similar to the method for forming the hydrophilic surface portion 38 of the liquid collecting portion 35 described with reference to FIG.

The liquid collecting member 40 can be airtightly attached to the main body 31 or the main body 2 shown in FIG. 4 or 1 to collect a liquid sample of a certain volume. The behavior of the liquid sample at that time is shown in FIGS. 5 is the same as that described with reference to FIG.

In the above description, the liquid sample storage part in the first invention and the liquid sampling part in the second invention are tubular, but the liquid sample storage part and the liquid sampling part are tubular. The shape is not limited to the above, and any shape may be used as long as the inner dimension is such that the aqueous liquid exhibits a capillary phenomenon. That is, the cross-sectional shape thereof is not limited to the circular shape, but may be various shapes such as an elliptical shape, a triangular shape, a quadrangular shape, and a polygonal shape.

FIG. 7 shows an example of a liquid sample storage section having a thin rectangular cross section as an example of a liquid sample storage section other than the tubular shape (the same applies to the liquid sampling section of the second invention). In FIG. 7, the liquid sample storage unit 50 has plate-shaped members 51 and 52, one end of which is tapered, overlapped with each other, and a space between the plate-shaped member 51 and the plate-shaped member 52 is provided on both sides. Pacers 53 and 5
4 are sandwiched and these are integrally bonded to each other, and a space 55 opened at both ends is formed between the plate-shaped member 51 and the plate-shaped member 52. The thickness of the space 55 is such that when the tapered end portions 51a and 52a are immersed in a liquid sample,
The thickness of the liquid sample is configured so as to enter the space 55 due to the capillary phenomenon. This thickness, that is, the plate member 5
In general, the gap between 1 and the plate member 52 is preferably 0.1 to 3 mm, particularly preferably 0.5 to 2.5 mm, and most preferably 1 to 2 mm.
Hydrophilic treatment is applied to the surfaces of the plate-shaped member 51 and the plate-shaped member 52 that face each other, from the entire surface or the edge portions 51a and 52a to a predetermined length. In this hydrophilic treatment, as described above, the plate-shaped member 51 and the plate-shaped member 52 may be made of a hydrophilic material, or the plate-shaped member 51 and the plate-shaped member 52 may be made of hydrophobic plastic and face each other. A hydrophilic surface portion may be formed on the surface. The liquid sample storage unit 50 can be formed by integrally molding the whole, in addition to the above-described bonding and bonding of the respective members.

The liquid sample accommodating portion 50 is attached to (or is made integrally with) a tubular member of an appropriate size, like the capillary tube portion 13 shown in FIG. 2, and the main body shown in FIG. 2 or similar to the body 21 shown in FIG. The microvolume constant volume pipette to which the liquid sample container 50 is attached can collect a fixed volume of liquid sample in the same manner as described above. Further, the liquid sampling part of the second invention similar to the liquid sample storage part 50 can be attached to the main body in the same manner as the liquid sampling member in FIG.

FIG. 8 is a sectional view of an embodiment of a microvolumetric pipette of the third invention. In FIG. 8, the micro constant volume pipette 60 is composed of a capillary tube 61 made of hydrophobic plastics, and a part of the capillary tube 61 which is continuous from the tip of the inner surface 61a is subjected to a hydrophilic treatment so as to be hydrophilic. Surface part 6
2 is formed. As means for forming the hydrophilic surface portion 62 of a predetermined length on the inner surface 61a of the capillary 61,
This is the same as the method of forming the hydrophilic surface portion 38 of the liquid collecting portion 35 described with reference to FIG.

A method for collecting a fixed volume of the aqueous liquid sample using the microvolume constant volume pipette 60 shown in FIG. 8 will be described. When the tip of the capillary 61 on the side where the hydrophilic surface portion 62 is provided is immersed in the aqueous liquid sample, the aqueous liquid sample rises in the capillary 61 due to the capillary phenomenon. The tip of the aqueous liquid sample rising in the capillary 61 has a hydrophilic surface portion 62 of the capillary 61.
When reaching the end of the sample, since the surface 61a of the capillary 61 ahead of that is hydrophobic (the hydrophobic plastics are exposed), the tip of the aqueous liquid sample does not proceed further than that, The rise of the liquid sample stops.

Then, the tip of the capillary tube 61 is taken out from the aqueous liquid sample, and the tip of the capillary tube 61 is brought into contact with a water-absorbing test piece (not shown) used for analysis of the sample that should receive the sample. The aqueous liquid sample contained in 61 is naturally absorbed by the test piece, and the entire amount is discharged from the capillary 61. In this way a fixed volume of aqueous liquid sample can be taken. By changing the inner diameter of the capillary 61 and the length of the hydrophilic surface portion 62, it is possible to change the amount of the aqueous liquid sample that enters the capillary 61 due to the capillary phenomenon, and easily collect a desired amount of the aqueous liquid sample. You can

The microvolumetric-volume pipette of the third invention may be entirely formed of a capillary as shown in FIG.
A part including a part where the hydrophilic surface part is formed is formed of a capillary tube, and the other part is formed of a tube of an appropriate size which is convenient for handling, or a spherical shell having a vent hole as shown in FIG. It may be formed into a shape.

FIG. 9 is a sectional view of another embodiment of the microvolumetric-volume pipette of the third invention. In FIG. 9, in the microvolume constant volume pipette 63, the capillary tube portion 64 and the spherical shell portion 65 are integrally formed from hydrophobic plastics.
A part of the inner surface 64a that is continuous from the tip is subjected to a hydrophilic treatment to form a hydrophilic surface portion 66, and a spherical shell portion 65 is formed with a vent hole 67. Capillary part 64
The means for forming the hydrophilic surface portion 66 having a predetermined length on the inner surface 64a is the same as the method for forming the hydrophilic surface portion 38 of the liquid sampling portion 35 described with reference to FIG.

A method of collecting a fixed volume of aqueous liquid sample using the microvolume constant volume pipette 63 shown in FIG. 9 will be described. When the tip of the capillary portion 64 on the side where the hydrophilic surface portion 66 is provided is immersed in the aqueous liquid sample, the aqueous liquid sample rises in the capillary portion 64 due to the capillary phenomenon. When the tip of the aqueous liquid sample rising in the capillary portion 64 reaches the end of the hydrophilic surface portion 66, the surface 6 of the capillary portion 64 ahead of the end of the hydrophilic surface portion 66 is reached.
Since 4a is hydrophobic (the hydrophobic plastics are exposed), the tip of the aqueous liquid sample does not proceed further than that, and the rise of the aqueous liquid sample is stopped.

Then, the tip of the capillary portion 64 is taken out from the aqueous liquid sample, and the tip of the capillary portion 64 is brought into contact with a water-absorbing test piece or the like (not shown) used for analysis of the sample that should receive the sample. , The aqueous liquid sample contained in the capillary section 64 is naturally absorbed by the test piece,
Will be totally discharged from. At this time, the vent hole 67 may be closed with a fingertip and the spherical shell portion 65 may be crushed to forcibly push out the aqueous liquid sample contained in the capillary portion 64. In this way a fixed volume of aqueous liquid sample can be taken. By changing the inner diameter of the capillary portion 64 and the length of the hydrophilic surface portion 66, the amount of the aqueous liquid sample that enters the capillary portion 64 by the capillary phenomenon can be changed, and a desired amount of the aqueous liquid sample can be easily collected. can do.

The volume of the space in which the aqueous liquid to be sampled is housed in the above-mentioned capillary section, liquid sample storage section or liquid collection section can be preset to any value within the range of generally 1 to 50 μl. ..

[0048]

EXAMPLES Examples and use examples of the microvolumetric constant volume pipette of the present invention will be shown below, but the present invention is not limited thereto.

Example 1 A liquid sampling member having a shape as shown in FIG. 2 (cylindrical portion 12: inner diameter 6 mm, length 10 mm, capillary portion 13: inner diameter 1 mm, length 7 mm) was used, and a polypropylene pipe having an inner diameter of 6 mm was used. It processed and produced 20 pieces. These liquid collecting members were immersed in an alcohol solution containing 5% polyoxyethylene nonylphenyl ether for 1 minute, then taken out and dried to impart hydrophilicity to their surfaces.

When these liquid collecting members were attached to the main body 2 of the microvolumetric pipette as shown in FIG. 1 and the tip of the capillary tube portion 13 was brought into contact with distilled water, the distilled water was converted into the capillary tube portion 1.
3, and distilled water entered the entire capillary section 13,
Distilled water did not enter the cylindrical portion 12. The piston 4 was pushed to push out the distilled water contained in the capillary portion 13, and the weight thereof was measured.

The collection and discharge of distilled water were repeated for 20 liquid collecting members (1 for each liquid collecting member).
However, the amount of distilled water discharged in one operation is 2
It was within the range of 0 μl ± 1 μl.

Example 2 A polyethylene tube having an outer diameter of 3 mm and an inner diameter of 2 mm was cut into a length of about 30 mm,
Fifty polyethylene pipes were produced. Since the surface of this polyethylene pipe is hydrophobic, water did not enter the pipe even when its tip was immersed in water.

A treatment tank having an overflow slit so that the depth to the liquid surface can be set to 1.2 mm contains 10% nonionic surfactant (Triton X-100, manufactured by Rohm and Haas). An aqueous solution was added, and the above polyethylene tubes were bundled, and the tubes were made vertical, and immersed in an aqueous solution of 1.6 mm from the end of the tube. After holding in this state for 1 minute, the bundle of polyethylene pipes was taken out and dried by blowing to prepare a polyethylene pipe whose inner and outer surfaces were hydrophilically treated to have a length of 1.6 mm. The polyethylene pipe obtained is
It can be used as the liquid collecting member 35 shown in FIGS. 4 and 5.

[Embodiment 3] A pipe having the shape of the liquid collecting member 40 shown in FIG. 6 was prepared from a polyethylene pipe, and the tip of a micropipette was airtightly attached to the rear end portion 41 of the end portion 42. 1% nonionic surfactant (Triton X-100, manufactured by Rohm and Haas)
Soaked in an aqueous solution containing
After sucking up by 1 l, discharged, and dried to impart hydrophilicity to the inner surface of the capillary portion by a surface area corresponding to a spatial volume of 20 μl, to fabricate a liquid collecting member 40 as shown in FIG. The liquid collecting member 40 was attached to the cylindrical portion 32 of the main body 31 as shown in FIG.

[Example 4] The surface of a polyethylene terephthalate film having a thickness of 180 µm was subjected to glow discharge treatment in the same manner as the hydrophilic treatment of a photographic film to give hydrophilicity, and as shown in Fig. 7. Plate member 5
1 and 52 are prepared, the hydrophilic surfaces are faced to each other, and both side portions are adhered with a double-sided adhesive tape, and a space portion has a dimension of about 20 m
m × 10 mm × 0.5 mm (length 2 m at the edge 51a)
The liquid sample storage part 50 which is m) was produced. When the tapered tip of the liquid sample storage unit 50 is brought into contact with water droplets, water instantaneously flows into the space 5 of the liquid sample storage unit 50 due to the capillary phenomenon.
Filled within 5. Next, when the tapered tip of the liquid sample storage unit 50 was brought into contact with the filter paper, all the water in the space 55 was absorbed by the filter paper.

A liquid sample container 50 having the same structure as that described above
When 0 pieces were produced, the same operation as above was repeated, the weight of the water absorbed by the filter paper was weighed, and the variation in the amount of water contained in the section 55 of the sample container 50 was examined. It was within the range of ± 4.5 mg.

[Embodiment 5] Inner diameter 1.5 mm, outer diameter 3 mm
Cut the polyethylene tube of 100mm in length,
A capillary 61 as shown in FIG. 8 was produced. Using a micropipette, use 10% nonionic surfactant (Triton
A droplet of 10 μl of an aqueous solution containing (Triton) X-100, manufactured by Rohm and Haas Co., Ltd.) was prepared on a preparation glass of a microscope, and the tip of the capillary tube 61 was brought into contact with this droplet. The total amount of droplets on the prepared glass is the capillary tube 61.
It was taken in. After leaving for 10 seconds, the tip of the capillary 61 is brought into contact with a filter paper to discharge the aqueous solution of the surfactant in the capillary 61, and left to dry to form a hydrophilic surface portion 62 on the inner surface of the capillary 61. As a result, a microvolume constant volume pipette 60 as shown in FIG. 8 was produced.

Ten minute constant volume pipettes 60 were prepared in the same manner as described above, and the accuracy of the amount of aqueous liquid collected by these pipettes was tested. Droplets of varying amounts ranging from 20 μl to 1 ml of 7% aqueous albumin solution were made on prepared glass. Micro fixed volume pipette 6
When the tip having the hydrophilic surface portion 62 of 0 was brought into contact with the droplet of the albumin aqueous solution, the albumin aqueous solution entered only in the portion where the hydrophilic surface portion 62 was formed. Next, when the tip of the microvolumetric pipette was brought into contact with the filter paper that had been weighed in advance, the entire amount of the aqueous albumin solution in the microvolumetric pipette was absorbed by the filter paper. The filter paper that absorbed the aqueous albumin solution was weighed, and the amount of the aqueous albumin solution collected in the microvolumetric pipette was determined from the difference between the weight before absorption and the weight. 1
Using 0 microvolume constant volume pipettes, the albumin aqueous solution was sampled in the same manner as above from the droplets of the albumin aqueous solution of different amounts, and the sampled amount was measured. The averaged sampled amount was 9.6 mg, The standard deviation was 0.7 mg.

[Example 1 of use] Venous blood was collected with a syringe, and one drop thereof was dropped on a plastic film. When the tip portion 42 of the liquid sampling member 40 of the microvolumetric pipette manufactured in Example 3 was brought into contact with this venous blood with the hole 34 opened, the venous blood was instantaneously introduced into the liquid sampling portion 40. Although it was taken in, it did not penetrate into the portion where the hydrophilic surface portion 43 was formed.

While the hole 34 was closed with a fingertip, the spherical shell 33 was pushed to push all the venous blood taken into the liquid collecting member 40 onto the filter paper, and the weight of the venous blood was measured. When the same operation was repeated 10 times, the variation in the weight of the venous blood taken into the liquid sampling member 40 was within ± 10%.

Using a commercially available puncture blood sampling device (Glupplic manufactured by Boehringer Mannheim) for blood sampling for blood glucose measurement of diabetic patients, from a blood drop on a fingertip punctured by puncturing the side of the tip of the finger with a needle. A minute amount of blood was collected using the minute constant volume pipette prepared in Example 3 in the same manner as above. When the blood sampling operation was repeated 10 times, the variation in the weight of the venous blood taken into the liquid sampling member 40 was within ± 10%.

[Use Example 2] Using the microvolumetric-volume pipette prepared in Example 1, venous blood was collected in the same manner as in Use Example 1, and venous blood taken into the liquid collecting member 11 was collected. When the variation of the weight of is examined, it is 27mg ± 1.5
It was within the mg range.

USE EXAMPLE 3 As in the case of Embodiment 1, the liquid collecting member 1 having an inner volume of the capillary portion of 10 μl.
A microvolumetric pipette fitted with 1 was made. When one end of the capillary portion of this microvolumetric pipette was brought into contact with one drop of plasma obtained by centrifuging venous blood, the plasma instantly entered the capillary portion. The plasma taken into the capillary part was discharged onto a Fuji Drychem glucose P slide and spotted, and the glucose concentration in the plasma was measured using a Fuji Drychem 5500 analyzer. The glucose concentration in the plasma was 92 mg / dl. there were.

Ten liquid collecting members 11 of the same size were produced, plasma was collected using different liquid collecting members 11 each time, and the measurement of glucose concentration in plasma was repeated 10 times. The coefficients of variation of the obtained glucose concentration measured values were average value = 92 mg / dl and CV = 1.7%.

For comparison, the Eppendorf 10
Glucose concentration measurements were performed 10 times on the same plasma using a micropipette for μl and a dedicated molded plastic tip. The coefficient of variation of the obtained glucose concentration measurement values was as follows: average value = 89 mg / dl, CV = 1.4%
Met.

[Use Example 4] Instead of plasma as a sample,
Hemoglobin concentration was measured in the same manner as in Use Example 3 except that heparin-collected whole blood was used and a Fuji Drychem Hb slide was used as a slide. The coefficient of variation of the obtained measurement value of the hemoglobin concentration is the average value = 14.
It was 3 g / dl and CV = 1.8%.

The coefficient of variation of the measured value of the hemoglobin concentration obtained by the measurement using the micropipette in Use Example 3 is as follows: average value = 14.7 g / dl, CV = 1.4.
%Met.

[Use Example 5] A drop of blood collected by a syringe from a vein is dropped on a microscope slide glass to form a venous blood drop, and hydrophilicity of a microvolumetric pipette prepared in the same manner as in Example 5 is obtained. The tip with a compliant surface was brought into contact with a venous blood drop. Venous blood entered only in the portion of the microvolumetric pipette where the hydrophilic surface was formed. Next, when the tip of the microvolumetric pipette was lightly contacted with the surface of the Fuji Drychem Hb slide, the venous blood in the microvolumetric pipette was discharged and spread evenly on the surface of the slide. This slide was set in Fuji Dry Chem Analyzer 2000, and the Hb concentration was measured.

One microvolume constant volume pipette of the same size as above
The same venous blood was collected and the Hb concentration was measured in the same manner as described above except that 0 pieces were prepared and the blood drop volume was different for each microvolumetric pipette. The measured value of the obtained Hb concentration is the average value = 13.8 mg / dl, the standard deviation =
It was 0.43 mg / dl and the coefficient of variation was 3.2%.

From the above, it was confirmed that high measurement accuracy can be obtained by using the microvolumetric-volume pipette of the present invention.

[0071]

INDUSTRIAL APPLICABILITY The microvolume constant-volume pipette of the present invention is capable of measuring a physiological fluid such as blood or plasma in a small amount (1 to 50).
μl) Particularly useful for harvesting. For example, by contacting the blood collected from a fingertip or an earlobe with a scalpel or a needle and bringing the liquid collecting member of the microvolumetric pipette of the present invention into contact with the blood,
A very small amount of blood can be easily collected. In the microvolumetric pipette of the present invention, only the liquid collecting member comes into contact with the aqueous liquid, and since the liquid collecting member can be manufactured at a low cost, it can be disposable, and is hygienic when handling a physiological liquid.

Since the microvolumetric pipette of the present invention has a simple structure, it hardly breaks down and can be advantageously used in combination with a dry analysis method. Therefore, it can be advantageously used for pre-examination at the time of blood donation or mass examination, and for examination of micro blood sampling of children and the like.

[Brief description of drawings]

FIG. 1 is a cross-sectional view of an embodiment of a microvolumetric pipette of the first invention.

FIG. 2 is a cross-sectional view of the liquid collecting member shown in FIG.

FIG. 3 is a cross-sectional view of another embodiment of the microvolumetric pipette of the first invention.

FIG. 4 is a cross-sectional view of one embodiment of a microvolumetric pipette of the second invention.

5 is a cross-sectional view of the liquid sampling member shown in FIG.

FIG. 6 is a cross-sectional view of an example of a liquid collecting member of the microvolumetric-volume pipette of the second invention.

FIG. 7 is a cross-sectional view of an example of a liquid container of the liquid sampling member of the microvolumetric pipette of the present invention.

FIG. 8 is a cross-sectional view of an embodiment of a microvolumetric pipette of the third invention.

FIG. 9 is a sectional view of another embodiment of the microvolumetric pipette of the third invention.

FIG. 10 is a cross-sectional view of an example of a conventional micropipette.

[Explanation of symbols]

 1 Microvolume Constant Volume Pipette 2 Main Body 3 Cylinder 4 Piston 5 Tubular Tip 6 Jaw 7 Vent 8 Head 9 Locking Part 10 Compression Coil Spring 11 Liquid Collection Member 12 One-Ended Bottom Cylindrical Part 13 Capillary Portion 20 Microvolume Constant Volume Pipette 21 Main body 22 Tubular tip 23 Cylindrical part 24 Spherical shell 25 Vent 30 Microvolume constant volume pipette 31 Main body 32 Cylindrical 33 Spherical shell 34 Vent 35 Liquid collecting member 36 Capillary 37 Collar 38 Hydrophilic surface 40 Liquid sampling Member 41 Rear end portion 42 Front end portion 43 Hydrophilic surface portion 50 Liquid sample storage portion 51 Plate member 52 Plate member 53 Spacer 54 Spacer 55 Space 60 Microvolume constant volume pipette 61 Capillary tube 62 Hydrophilic surface portion 63 Microvolume constant volume pipette 64 Capillary portion 65 Spherical shell portion 66 Hydrophilic surface portion 67 Vent hole 80 Micropipette 81 Holder 82 hole 83 cap 84 capillary 85 rubber plug 86 cavity

Claims (3)

[Claims] 1. A tubular tip portion of a main body having a cavity provided with an air compression mechanism and having a ventilation hole in an outer wall, at least an inner surface of which has hydrophilicity, and an aqueous liquid has an inner dimension which exhibits a capillary phenomenon. The liquid sample storage part is a cylindrical one-sided bottomed liquid collection part having an inner diameter such that one end of the liquid sample storage part does not protrude beyond the bottom surface and penetrates through the bottom part so that the aqueous liquid does not show a capillary phenomenon. Microvolume constant volume pipette that is airtightly and detachably attached. 2. A liquid sample to be collected from one end, which has a cavity provided with an air compression mechanism and has an inner dimension at which a water-based liquid exhibits a capillary phenomenon at a tubular tip portion of a main body having a vent hole in an outer wall. A liquid collecting part having an inner surface having hydrophilicity and a remaining part having hydrophobicity corresponding to the volume of the liquid collecting part is attached at its hydrophobic side end in an airtight and detachable manner. Micro volumetric pipette. 3. A hydrophobic plastics tube having at least one end having an inner dimension at which an aqueous liquid exhibits capillary action and having an inner surface of a length corresponding to the volume of a liquid sample to be taken from its tip. Microvolume constant-volume pipette, which is treated to have hydrophilicity.