JP3460141B2 - A test device for analyzing liquid samples with non-uniform capillaries. - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a test device for analyzing components contained in a liquid sample, particularly an aqueous solution such as blood or urine.

[0002]

2. Description of the Related Art In a simple test device for analyzing a liquid sample by a reaction with a reagent, generally, a capillary phenomenon is used for introducing or moving the sample to a reaction site of the test device with the reagent. As this type of test tool, there are a type in which a reagent applied in a capillary tube begins to dissolve in a sample, and a type in which a sample penetrates into a reagent layer provided in the capillary tube.

As an example of the former, Japanese Patent Laid-Open No. 63-27483
No. 9 discloses a test device including a lower extension member that also serves as a handle and an upper member that forms a capillary tube with the lower extension member and a spacer and that contains a reagent. As an example of the latter, Japanese Patent Laid-Open No. 4-188065 discloses a support, a reagent layer fixed on the support, a support which is fixed so as to form a capillary chamber with the support while covering the reagent layer. An analytical tool is described which comprises a cover having an exhaust port.

[0004]

However, JP-A-63-
In the test tool described in Japanese Patent No. 274839, in which the reagent dissolves in the sample, the concentration of the reaction solution must be accurately defined. Need to dispense. Also,
The test device described in JP-A-4-188065 discloses a type in which the sample penetrates into the reagent layer, so that the reagent is placed on a paper or film separate from the capillary tube in order to maintain the volume of the reagent layer. It must be included and fixed in the capillary.

Therefore, an object of the present invention is to simply measure a fixed amount of a sample and analyze it at the same time without dispensing the sample into another container or separately preparing and fixing a reagent layer. It is to provide a test tool capable of doing the above.

[0006]

In order to achieve the object, the test device of the present invention holds a reagent at a predetermined position in a capillary tube having a test solution introducing port and an exhaust port, and supplies the test solution from the introducing port. A test tool for analyzing a specific component in a test solution with a reagent by introducing and reacting with the reagent, wherein the capillary tube moves the test solution from the test solution introduction port toward the reagent. A hydrophilic region, a second hydrophilic region having a constant area for holding a reagent, a first hydrophilic region and a second hydrophilic region are separated from each other, and the first hydrophilic region and the second hydrophilic region are passed through. And a hydrophobic region that communicates with the exhaust port without being provided, and the width d of the capillary at the boundary between the second hydrophilic region and the hydrophobic region is narrower than the width D of the capillary inside the second hydrophilic region. It is characterized by

According to this test device, the test liquid introduced from the test liquid introducing port goes toward the reagent through the first hydrophilic region by the capillary phenomenon. Along with that, the air in the capillaries is pushed out and exits from the exhaust port. When the test solution reaches the hydrophobic region, the hydrophobic region temporarily stops the movement. Then, when an external force is applied to the test device, the test liquid jumps out on the extension of the first hydrophilic region and enters the hydrophobic region.

Most of the test liquid proceeds in the same direction and enters the second hydrophilic region. However, if the hydrophobic region and the second hydrophilic region are continuous in the same plane, the test liquid entering the second hydrophilic region tends to form a meniscus at the boundary with the hydrophobic region. If this meniscus is large, the test liquid cannot be quantitatively retained in the second hydrophilic region even if the second hydrophilic region is provided with excellent dimensional accuracy. On the other hand, in the present invention, the width d of the capillary at the boundary between the hydrophobic region and the second hydrophilic region is narrower than the width D of the capillary in the second hydrophilic region. Therefore, when the area of the second hydrophilic region is constant, the meniscus formed by the test device of the present invention is smaller than the meniscus formed by the test device having a uniform capillary width.

On the other hand, since the area of the second hydrophilic region is constant, when the meniscus is small enough to be ignored, the amount of the test liquid retained in the second hydrophilic region is determined by the area and the inner diameter of the capillary tube. When passing through the hydrophobic region and moving to the second hydrophilic region, the test liquid remaining on the hydrophobic region or the part that could not be retained in the second hydrophilic region is rejected by being repelled by the hydrophobic region. It Therefore, a specific component in the test liquid can be analyzed with high accuracy by the reaction between the held fixed amount of the test liquid and the reagent.

The external force applied to the test liquid to pass through the hydrophobic region is, for example, a momentary vibration caused by shaking the test tool with an operator's hand, a centrifugal force, a suction force caused by suction from an exhaust port, an inlet port. It is the pressing force from. The exhaust port is
It is preferably a through hole provided in a direction intersecting with the capillary tube. By providing the through-hole in this way, the capillary tube can be formed into a bag-like tube in which only the test solution inlet is opened except the through-hole, and the overflow of the test solution retained in the second hydrophilic region can be prevented. . The crossing angle between the through hole and the first hydrophilic region side of the capillary is preferably an acute angle. By doing so, when the test liquid is moved to the second hydrophilic region by an external force, it is possible to prevent the test liquid from jumping out from the through hole and contaminating the periphery.

The exhaust port is preferably provided at a position apart from the boundary between the second hydrophilic region and the hydrophobic region. Particularly, the distance c is preferably 0.2 mm or more. This is because even if the test liquid passes through the hydrophobic region once, it becomes slightly hydrophilic due to the action of the test liquid. For this reason, when the boundary portion and the exhaust port are close to each other, the meniscus is not blocked by the hydrophobic region and directly coupled to the exhaust port, so that the test liquid flows out through the exhaust port.

The hydrophobic region is a first hydrophobic region separating the first hydrophilic region and the second hydrophilic region, and a second hydrophobic region sandwiching the second hydrophilic region together with the first hydrophobic region. It may be separated into and. In this case, the second hydrophobic region can be communicated with the exhaust port without passing through the first hydrophilic region and the second hydrophilic region. By doing so, the air in the capillary tube can be easily removed, and the moving speed of the test solution can be increased. It is particularly preferable to provide the exhaust port on the extension of the second hydrophobic region. This is because both ends of the capillary tube can be released, and it becomes easier to eliminate air.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 shows a test device according to an embodiment of the present invention.
Is shown as a plan view. The test tool 31 is a rectangular parallelepiped main body 3
2 is provided. The main body 32 is composed of three transparent plates, an intermediate plate is processed into a frame shape, and a long and narrow cavity 33 surrounded by the frame and the upper and lower plates functions as a capillary tube.
The cavity 33 starts from one end of the main body 32 and is closed midway without reaching the other end. In this example, the starting portion becomes the inlet 34.

The inner surface of the cavity 33 is composed of a first hydrophilic region 331, a hydrophobic region 332 and a second hydrophilic region 333 in order from the inlet 34 side. The cavity 33 has a uniform width from the inlet 34 to the hydrophobic region 332.
As soon as it enters the second hydrophilic region 333, it spreads in the width direction. Then, it is closed behind the second hydrophilic region 333. Therefore, the first hydrophilic region 331 and the hydrophobic region 332 are rectangular, and only the second hydrophilic region 333 is trapezoidal.

The main body 32 has an amphiphilic region 331, 33.
A through hole 35 is provided which allows the hydrophobic region 332 to communicate with the outside without passing through 3. The through hole 35 is connected to the hydrophobic region 332 at a position away from the boundary between the hydrophobic region 332 and the second hydrophilic region 333, and the second hydrophilic region 333 is formed.
It extends to the side surface of the main body 32 so as to move away from the main body 32. This through hole 35 functions as an exhaust port. A reagent (not shown) is applied to the second hydrophilic region 333.

The manufacturing method of the test tool 31 is as follows, for example. Prepare three rectangular plates made of polystyrene PS. PS is hydrophobic in nature. The portions of the first plate region where the hydrophilic regions 331 and 333 are to be formed are irradiated with ultraviolet rays using a low pressure mercury lamp as a light source. As a result, the irradiated portion is modified to be hydrophilic. The second plate is processed into a frame shape and the through hole 35 is opened. A predetermined portion of the third plate is modified to be hydrophilic like the first plate. Second hydrophilic area 3
After applying a reagent (not shown) to 33, three plates are laminated and fixed. This is the end. Unlike conventional methods, it is not necessary to mold the reagent separately.

The procedure for analyzing a liquid sample with the test device 31 is as follows. The amount of blood that has been collected or blood that has been subjected to blood cell separation treatment should be slightly larger than the optimum amount.
Press on 4. The blood moves toward the second hydrophilic region 333 by the capillary phenomenon while wetting the first hydrophilic region 331, but is blocked by the hydrophobic region 332 in the middle. When the blood as collected is used as a sample, a pretreatment means such as a blood cell separation membrane may be provided in the middle of the first hydrophilic region 331. Therefore, the end surface (the right side surface in the drawing) of the main body 32 is tapped. The blood filled in the first hydrophilic region 331 jumps out of the first hydrophilic region 331 by the external force, passes through the hydrophobic region 332, and moves to the second hydrophilic region 333. At the same time, the air in the space surrounded by the second hydrophilic region 333 is also removed from the through hole 35. Blood begins to react with the reagents.

Since the hydrophobic region 332 is not wet with blood and the width of the boundary portion between the hydrophobic region 332 and the second hydrophilic region 333 is narrower than the width of the second hydrophilic region 333, it is formed at the boundary portion. The meniscus is small. Further, since the boundary portion is separated from the through hole 35, the test liquid retained in the second hydrophilic region does not flow out through the through hole 35 to the outside. Therefore, the amount of blood filled in the second hydrophilic region 333 is always constant, and quantitative analysis can be performed with high accuracy. Moreover, since the main body 32 is transparent, it is possible to quickly analyze by optical means.

Next, the test device of the second embodiment is shown in FIG. 4 as a plan view. In this test tool 39, (1) the through hole 35 is not provided, and (2) the cavity 37 is open on the side opposite to the inlet 378, and the opening 375 is the through hole 35.
(3) The hydrophobic regions 372 and 374 in the cavity 37 are separated in two places so as to sandwich the second hydrophilic region 373, and (4) Therefore, the second hydrophilic region is formed. Except that the width of the capillary in the boundary portion between the hydrophilic region 373 and the second hydrophobic region 374 is also narrower than the width of the capillary in the second hydrophilic region 373, except for the first embodiment. It has the same structure as the embodiment.

When the test tool 39 is used for analysis, the air in the cavity 37 is removed from the opening as the test solution progresses due to the capillary phenomenon. The hydrophobic areas 372 and 374 are not wet by the liquid. Moreover, since the width of the boundary between the two hydrophobic regions 372 and 374 and the second hydrophilic region 373 is narrow, the amount of blood filled in the second hydrophilic region 373 is always constant. Since the air is excluded from the opening 375 on the extension of the second hydrophilic region 373, the test liquid progresses quickly.

[0021]

EXAMPLE In the test device 31 having the shape shown in FIG. 1, the cavity 3 from the introduction port 34 to immediately before the second hydrophilic region 333 is shown.
The width d of 3 was 3 mm, the height was 500 μm, the depth of the second hydrophilic region 333 was 3 mm, and the maximum width D of the second hydrophilic region 333 was 5 mm. The through hole 35 was provided at a position 2 mm from the boundary portion between the hydrophobic region 332 and the second hydrophilic region 333.

Human plasma was introduced into the test device 31 as a test solution from the introduction port 34, and an external force was applied to move the test solution to the second hydrophilic region 333. For comparison, as shown in FIG. 2, a test tool 31 ′ having the same shape and quality as the test tool 31 was manufactured except that the width of the cavity 33 was uniformly 3 mm. Moved to 333 '. Separately, as shown in FIG. 3, except that a through hole was provided at the boundary between the hydrophobic region 332 and the second hydrophilic region 333, a test device 31 ″ having the same shape and quality as the test device 31 ′ was manufactured. Then, the test solution was moved to the second hydrophilic region 333 ″. The number of test devices was 20 for each of the test device 31, the test device 31 ′, and the test device 31 ″. After 3 minutes, the test liquid retained in each second hydrophilic region was extracted with a microsyringe, and the amount thereof was measured. Was measured to evaluate the holding accuracy, and the evaluation results are shown in Table 1.

[0023]

[Table 1] (N = 20) ----------------- Test tool holding accuracy (CV%) ----------------- 31 2.1 31 '3.4 31 "5.7 -----------------

As can be seen from Table 1, according to the test device of this example, when the test liquid is moved to the portion where the reagent is held, the test liquid is quantitatively held without forming a meniscus. On the other hand, in the case of the test tools 31 'and 31 ", the holding accuracy was poor. In the case of the test tools 31',
It is considered that the retained amount varied due to the size of the meniscus. The second hydrophilic region 33 when using the test device 31 "
It is considered that by the time the test liquid was drawn out from 3 ", a small amount of the test liquid leaked from the through hole 35", which caused the retained amount to vary.

[0025]

EFFECTS OF THE INVENTION Since the present invention has the above-mentioned features, the reagent can be fixed only by applying the reagent to a predetermined position, so that the test tool can be manufactured with a small number of steps. Further, since the test liquid can be spotted and analyzed without weighing it with a measuring instrument, the test liquid can be analyzed quickly and easily.

[Brief description of drawings]

FIG. 1 is a plan view showing a test device of a first embodiment.

FIG. 2 is a plan view showing a test device of a comparative example.

FIG. 3 is a plan view showing a test device of another comparative example.

FIG. 4 is a plan view showing a test device of a second embodiment.

[Explanation of symbols]

31,39 Test tool 32 body 33,37 cavities 34,378 inlet 35,375 exhaust port 331,371 first hydrophilic region 332, 372, 374 hydrophobic region 333, 373 second hydrophilic region

─────────────────────────────────────────────────── ─── Continuation of the front page (58) Fields surveyed (Int.Cl. ⁷ , DB name) G01N 33/52 G01N 31/22

Claims (5)

(57) [Claims] 1. A reagent is held at a predetermined position in a capillary having a test solution inlet and an exhaust port, and the test solution is introduced from the inlet and reacted with the reagent, whereby a specific component in the test solution is converted into a reagent. A test device for analysis, wherein the capillary comprises a first hydrophilic region for moving a test solution from a test solution inlet to a reagent, and a second hydrophilic region having a certain area for holding the reagent. And a second hydrophilic region, which separates the first hydrophilic region and the second hydrophilic region and communicates with the exhaust port without passing through the first hydrophilic region and the second hydrophilic region. The width d of the capillary at the boundary between the hydrophilic region and the hydrophobic region is narrower than the width D of the capillary in the second hydrophilic region. 2. The test device according to claim 1, wherein the exhaust port is provided at a position apart from a boundary portion between the second hydrophilic region and the hydrophobic region. 3. The test tool according to claim 2, wherein a distance c between the exhaust port and the boundary portion is 0.2 mm or more. 4. The first hydrophilic region sandwiching the second hydrophilic region together with the first hydrophobic region, wherein the hydrophobic region separates the first hydrophilic region and the second hydrophilic region from each other. The test device according to claim 1, wherein the test device is separated into a hydrophilic region and a second hydrophobic region communicating with the exhaust port without passing through the second hydrophilic region. 5. The test device of claim 4, wherein the vent is on an extension of the second hydrophobic surface.