KR100350694B1 - Test paper and analyte measuring tip - Google Patents

Abstract

The component measuring tip 5 includes a cap 51, a capillary 52 protruding from the bottom 511 of the cap 51, and a test paper 53 provided on the bottom inner side. The test paper 53 is obtained by laminating the first layer 53a and the second layer 53b. The first layer 53a is composed of a porous membrane that carries a reagent that reacts with a specific component in the blood (for example, glucose) to color, and the second layer 53b is a colored medium. It is composed of a porous membrane having a function of separating red blood cells and the like in the blood through the filtrate while reaching the deep side. Here, red blood cells are examined with an automatic test device. Test guidance is also creative.

Description

TEST PAPER AND ANALYTE MEASURING TIP}

The present invention relates to a test paper and a component measuring tip for measuring the amount of a target component in a sample, such as, for example, a blood glucose value of a blood sample.

BACKGROUND A blood glucose measurement apparatus for measuring a blood sugar value is known. This blood glucose measurement device quantifies the blood glucose value by optically measuring the degree of coloration of the test paper (color) that is colored according to the amount of glucose or other components in the blood.

In such a conventional blood glucose measurement apparatus, color measurement of a test paper is performed by irradiating light on a test paper and measuring the intensity of the reflected light in a light metering portion including a light emitting element and a light receiving element.

In this blood glucose measuring device, a blood sample is supplied and developed on a test paper, and then the test paper is inserted into a space where a shading state is secured, and a blood glucose value measurement is started. There is a problem in that the time from the supply to the colorimetry is not constant and a measurement error occurs accordingly.

Therefore, there is a demand for the development of an automatic blood glucose measurement apparatus capable of continuously and automatically performing a series of operations from supplying and deploying a specimen to measurement.

Moreover, the conventional test paper is a structure which settled the reagent to one sheet base material which consists of the porous material which can absorb a sample. In this test paper, since the pore diameter of the pores of the sheet base material is as small as 0.5 µm, the water permeability, that is, the delay property is low, and thus there is a problem that the development of the specimen takes time. Such a long time required for the development of the sample is particularly disadvantageous in the automatic blood glucose measurement apparatus.

An object of the present invention is to provide a test paper and a component measuring tip which can shorten the time required for the development of a specimen and have high measurement accuracy.

According to the present invention, a porous first layer having a reagent that reacts with a specific component in a sample and colored, and a porous second layer having a function of separating a filtrate from a sample emanating from the first layer Test paper for colorimetric evaluation of an in-plane component is provided, said test surface being the face of the second layer distant from the first layer.

Also provided is a component measuring method using a measuring tip on a component measuring device, wherein the tip has a tubule protruding from the tip to form a flow path for introducing the sample into the tip, and the present invention disposed inside the tip. A test paper according to the present invention is provided, and the method carries a sample supplied to the inlet of the tubule to the outlet by capillary action of the tubule, and supplies the sample to the first layer of the test paper, and filters the sample from the second layer. And colorizing the sample on the test surface side of the second layer.

In addition, a tip is provided at one end having a mounting portion for mounting to the component measuring device, the device having a tubule protruding at both ends forming a sample flow path to collect a sample, and the sample is capillary phenomenon along the flow path to the test paper. The test strip according to the present invention for delivery is characterized in that it is arranged to communicate with the sample outlet of the customs.

Test strips and constituent tips according to the invention are now described below in connection with the preferred embodiment shown in the accompanying figures.

Figure 1 is a side cross-sectional view showing the internal structure of the device for measuring blood components used by mounting a component measuring tip embodying the present invention.

2 is a cross-sectional view of a component measuring device.

3 is a block diagram showing a circuit configuration of a component measuring device.

4 is an elevation view showing a typical structure of a component measuring tip.

5 and 6 are schematic diagrams showing the respective structures of the sample inflow side end and the sample outflow side end of the transport tubing in the component measuring tip of the present invention.

7 and 8 are diagrams showing the dimensions of each part of the various parts;

Fig. 9 is an elevation view showing the tip in a state where it is mounted on the component measuring device.

10 and 11 are schematic and plan views showing a typical structure of the test paper of the present invention.

12 is a cross-sectional view taken along the line A-A of FIG.

Fig. 13 is a side view showing a state when collecting a sample using a component measuring tip.

14-17 are graphs showing experimental data.

<Explanation of symbols for main parts of drawing>

1: blood component measuring device 2: casing

3: printed board 31: operation buttons

32, 33, 34: operation member 4: light metering portion

41: light emitting element 42: light receiving element

43: holder 44: A / D converter

5: tip 51: cap

511: bottom 512: pedestal

513: body part 514: flange

52: customs 520: sample introduction euro

521: sample inlet side end 522: groove

523: sample inlet 525: sample outlet side end

526: home 527: sample outlet

53: test sheet 53a: first layer

53b: second layer 531: convex portion

532: annular convex portion 533: fixed portion

534: fixed point 54: spacing

55: sample storage section 56: spacer

6: power supply 61: battery

7: power supply voltage detector 8: switch circuit

9: liquid crystal display device 10: control means

11: control oscillator 12: clock oscillator

13: Data storage unit 14: Buzzer output unit

15: External output unit 16: Temperature measuring unit

18: blood

As shown in these figures, the blood component measuring apparatus 1 has a casing 2, and a printed circuit board 3 is disposed in the casing 2. As shown in FIG. In addition, a light metering portion 4 is provided at one end of the casing 2. A liquid crystal display (LCD) 9 is provided in the window portion of the casing 2.

On the printed board 3, a microcomputer 10 is installed as a control means that operates to control various functions of the blood component measuring device. The control means 10 has a built-in calculation unit for calculating a target blood component (for example, glucose) based on the signal from the photometric unit 4. This calculating section also performs correction processing such as hematocrit value correction calculation and temperature correction calculation as necessary.

The light metering portion 4 has a light emitting element (light emitting diode) 41 and a light receiving element (photodiode) 42, which are stored and held in a holder 43. The light emitting element 41 is electrically connected to the control means 10, and the light receiving element 42 is electrically connected to the control means 20 through an amplifier (not shown) and the A / D converter 44.

The light emitting element 41 is operated by the signal from the control means 10 and emits pulsed light at predetermined time intervals. For example, the pulsed light has a period of about 0.5-3.0 msec, and a light emission time of about 1 pulse is about 0.05-0.3 msec. Moreover, the wavelength of this pulsed light becomes about 500-720 nm, for example.

The holder 43 is detachably mounted with a component measuring tip (hereinafter simply referred to as a "tip") 5 having a test paper 53 therein therein. In addition, here, the general structure of the tip 5 is demonstrated briefly, and the preferable structure of the tip 5 and the test paper 53 is demonstrated in detail later.

The tip 5 consists of a cylindrical transparent or translucent cap 51 with a pointed end. The tip 5 is colored transparent, for example blue transparent. The test paper 53 is provided inside the bottom part of the cap 51 (refer FIG. 1). The test paper 53 is obtained by laminating a first layer 53a and an opaque second layer 53b.

The tubules 52 protrude from the bottom outer surface of the cap 51. When a sample (blood) is brought into contact with the tip of the tubule 52, the sample is sucked into the tubule 52 by capillary action, transported to reach the test paper 53, and supplied. The sample supplied near the center of the test paper 53 is colored by reacting with a reagent which is radially developed and carried on the test paper 53.

When the light emitting element 41 is turned on while the tip 5 is attached to the holder 43, the light emitted from the light emitting element 41 is irradiated to the second layer 53b side of the test paper 53, and the reflected light Get The intensity of the reflected light corresponds to the color intensity of the second layer 53b, that is, the amount (concentration) of the target component in the sample. This reflected light is received by the light receiving element 42 and photoelectrically converted. From the light receiving element 42, an analog signal according to the amount of received light is output and amplified as desired, and then converted into a digital signal by the A / D converter 44 and input to the control means 10, and again the data storage unit 13 Is stored in the first memory.

In addition, the blood component measuring apparatus 1 includes a power supply unit 6, a power supply voltage detection unit 7, a switch circuit 8, a control oscillation unit 11, a clock oscillation unit 12, a data storage unit 13, and a buzzer output unit ( 14), the external output unit 15 and the temperature measuring unit 16.

The battery 61 is loaded in the power supply unit 6. The power supply voltage detection unit 7 detects the voltage of the battery 61 and outputs the detected value to the control means 10. Thereby, the remaining amount of the battery 61 can be checked.

The switch circuit 8 detects inputs of various switches as follows and inputs the signal to the control means 10. Examples of the switch include a power switch, a memory data read switch, a time setting / change switch, a reset switch, a buzzer operation / non-operation selection switch, and a 50 Hz / 60 Hz commercial power frequency selection switch.

The power switch can be turned ON / OFF by pushing down the operation button 31.

The other switches can be operated by operating one or two or more of the operation button 31, the operation members 32, 33, 34, and the like in combination.

The control oscillator 11 is a timer. This oscillates a clock pulse at a predetermined time interval and supplies a reference signal for operation of the microcomputer (microprocessing unit: MPU) of the control means 10.

The clock oscillation unit 12 is a clock for specifying an absolute time (date and time). This oscillates clock pulses of a predetermined time interval to supply the reference signal for operation of the clock control circuit built in the control means 10.

The data storage unit 13 includes a first memory (RAM), a second memory (ROM), and a third memory (nonvolatile RAM). The magnitude of the metering value input from the metering section 4 is stored in the first memory in accordance with a predetermined format.

In the second memory, a relationship (measurement curve) between the absorbance obtained from the photometric value and the target blood component amount (hereinafter, referred to as "blood glucose value") is stored in a table in advance.

In the third memory, unique calibration values are stored in advance for each device. Intrinsic " correction values " herein include prescribed values of the reflected light amount, correction coefficients of final absorbance calculation, and the like.

The blood sugar value is obtained based on the data stored in the first to third memories as described above. In this case, it is preferable to obtain a blood glucose value based on the relative ratio of the half-light intensity at the time of color development to the reflected light intensity of the test paper 53 at the time of uncolored development.

The buzzer output unit 14 emits sound by operating the buzzer based on the signal from the control means 10.

The external output unit 15 is for outputting data such as the obtained blood sugar value to an external device such as a personal computer. In this case, the external output unit 15 has a built-in communication driver such as RS232C. In the case of performing infrared communication, the external output unit 15 incorporates an infrared light emitting element and its driving circuit.

The temperature measuring unit 16 includes a temperature sensor such as a thermistor capable of measuring the ambient temperature. In the temperature measuring section 16, a temperature measurement is sometimes made, and the temperature information is stored in the first memory of the data storage section 13. The temperature information read from the first memory is input to the control means 10 and used for the temperature correction calculation of the blood sugar value.

Next, the preferable example of the test paper of this invention and the component measuring tip provided with this is demonstrated.

The lower side of the diagram of FIG. 4 is described as "base" and the upper side as "tip".

As shown in FIG. 4, the tip 5 has a bottomed conventional cap 51, tubules 52 protruding from the bottom 511 of the cap 51, and test paper 53 installed in the cap 51. Consists of

The cap 51 supports the test paper 53 and constitutes a mounting portion for mounting the tip 5 to the photometric portion 4 of the blood component measuring device 1.

The used cap can be removed from the measuring device by the release button 35 without hand contact as shown in Figs. 1 and 9, thus reducing the possibility of blood contamination. If the tip continues to be surrounded by the cap 19 while the cap 19 is removed from or placed on the measuring device, contamination from the handler becomes very rare.

The cap 51 consists of the bottom part 511, the trunk | drum 513, and the flange 514 formed in the base end outer periphery of the trunk | drum 513. As shown in FIG. In addition, a pedestal part 512 for fixing the test paper 53 is formed inside the bottom part 511. In the outer peripheral portion 533, the test paper 53 is fixed to the pedestal portion 512 by a method such as fusion or adhesion with an adhesive, for example.

As shown in FIG. 9, the holder 43 of the light metering portion 4 is fitted inside the fuselage 513 of the cap 51, and the tip 5 is attached to the light metering portion 4 of the blood component measuring device 1. )).

As shown in Figs. 4 and 9, the body portion 513 preferably has a tapered shape in which the inner diameter thereof gradually decreases toward the tip direction. As a result, even if the inner diameter of the body portion is slightly different from the outer diameter of the holder 43, it can be reliably fitted and mounted.

The flange 514 has a function as a gripping portion which engages a finger or the like when the tip 5 is attached to or detached from the light metering portion 4 of the blood component measuring apparatus 1. Thereby, the detachable operation of the tip 5 can be performed easily and reliably.

As described above, in the present embodiment, the bottom part 511, the fuselage part 513, the flange 514, and the capillary 52 are all formed integrally, but they may be formed by joining separate members.

Customs 52 is for collecting a sample of blood, the sample introduction passage 520 is formed therein. The sample introduction passage 520 extends in a direction substantially orthogonal to the test paper 53, and a sample inlet 523 is formed at the tip thereof, and a sample outlet 527 is formed at the proximal end thereof, respectively.

Since blood is supplied to the test paper 53 through the sample introduction passage 520 by capillary action, the internal diameter or the average diameter of the sample introduction passage 520 is preferably about 0.2 to 2.0 mm, and about 0.3 to 1.0 mm. It is more preferable that is. If the internal diameter of the sample introduction passage 520 is too large, it is difficult to transfer blood by capillary phenomenon. If the internal diameter is too small, the blood supply speed is slow, and a long time is required for supplying a sufficient amount of blood to the test paper 53.

The internal diameter (lateral cross-sectional area) of the sample introduction passage 520 may be constant or change along the longitudinal direction of the sample introduction passage 520.

The total length of the sample introduction passage 520 is preferably about 1 to 10 mm, more preferably about 2 to 5 mm. If the length of the sample introduction passage 520 is too long, it takes a long time to transfer the blood by the capillary phenomenon. If this conduit is too short, the blood 18 may adhere to the bottom outer surface of the cap 51 in the state shown in FIG.

As shown in Figs. 4 to 6, the front end and the proximal end of the customs pipe 52 constitute a sample inflow side end 521 and a sample outflow side end 525, respectively.

In the cross section of the sample inlet side end portion 521, a groove 522 communicating with the sample introduction passage 520 is formed. In the illustrated example, the groove 522 is a one-letter groove extending in the radial direction of the customs pipe 52. Both ends of the groove 522 are open to the outer circumferential surface of the capillary 52, respectively.

When the groove 522 is provided, when the end surface of the sample inlet side end portion 521 is brought into contact with the surface of the finger or the like, the sample introduction passage 520 is not blocked and the blood inflow path is secured. Therefore, the blood supply to the test paper 53 can be smoothly and reliably performed.

In FIG. 7, the sum of the perimeter of the joint boundary portion between the groove 522 and the sample introduction passage 520 is L ₁ , and the inside diameter of the sample introduction passage 520 (the inside diameter near the sample inlet 523). When it is set to d ₁ , it is preferable to satisfy the following relationship.

L ₁ ≦ πd ₁ × 50%. (Ⅰ)

Accordingly, the inhalation of blood by the sample introduction passage 520 can be started more quickly and smoothly.

Moreover, the depth P ₁ of the groove 522 has the most suitable range according to the state of skin, etc., Although it does not specifically limit, Usually, 0.01 mm or more is preferable and 0.2-1. About 8 mm is more preferable. If the depth P ₁ is too shallow, the passage of blood in the grooves 522 may be insufficient, particularly in the case where the adhesion to the skin is large.

Further, the purpose of the groove 522 is that a part of the cross section does not contact the skin when the cross section of the sample inlet side end portion 521 is brought into contact with the skin. For example, the plurality of grooves 522 may be formed radially (for example, in the form of dozens of characters) or contact the sample introduction passage 520 in various ways with respect to the sample inlet 523 of the sample introduction passage 520. It is formed in parallel so that.

The sample outflow side end 525 (FIG. 6) of the tubule 52 (on the test paper 53 side) forms a protruding part which protrudes slightly inside the tip (base end) of the bottom part 511, and this sample outflow side A second groove 526 is formed in the cross section of the end portion 525 to communicate with the sample introduction passage 520. In the illustrated example, the groove 526 is a one-letter groove extending in the radial direction of the customs pipe 52. Both ends of the groove 526 are open to the outer circumferential surface of the protrusion of the capillary 52, respectively.

By installing the groove 526, blood passing through the sample introduction passage 520 is spread from the sample outlet 527 through the groove 526 in the circumferential direction of the end portion 525, and is supplied onto the test paper 53. As it develops, the development is rapid and uniform, thus obtaining more accurate measured values.

In FIG. 8, the sum of the perimeter of the junction boundary between the groove 526 and the sample introduction passage 520 is L ₂ , and the inside diameter of the sample introduction passage 520 (internal diameter near the sample outlet 527) is determined. when a d _2, it is preferred to satisfy the relation of the following formula (ⅱ).

L ₂ ≦ πd ₂ × 50%. (Ⅱ)

As a result, the blood flowing out from the sample outlet 527 of the sample introduction passage 520 can be spread more rapidly and smoothly in the outer circumferential direction of the test paper.

The depth P ₂ of the groove 526 is not particularly limited, but is preferably 0.01 mm or more, and is preferably from 0.05 to 0.0. About 5 mm is more preferable. If the depth P ₂ is too shallow, the groove 526 may not be able to fully exhibit its function.

Like the groove 522, the plurality of grooves 526 are formed radially (for example, in the form of dozens of characters) around the sample outlet 527 of the sample introduction channel 520 or in contact with the sample introduction channel 520. Parallel to form.

Moreover, as shown in FIG. 4, the space | interval 54 is formed between the part of the tubule 52 side of the test paper 53, ie, between the test paper 53 and the inner surface of the bottom part 511 of the cap 51. As shown in FIG. The gap 54 has a function of assisting the development of blood on the test paper 53. That is, since the blood flowing out from the sample outlet 527 of the sample introduction channel 520 is radially widened past the interval 54 by capillary phenomenon, on the test paper 53 (especially on the first layer 53a) Development of blood can be performed quickly and uniformly.

Although the width (depth) of the space | interval 54 is not specifically limited, 0.02 mm or more (average value) is preferable, and is 0.04 mm-0.04 mm. 4 mm is more preferable. In such a dimension, the above function of the gap 54 can be more effectively exhibited. In addition, although the width | variety (depth) of the space | interval 54 is constant, you may change (for example, gradually decrease) toward the outer peripheral side from the center part of the test paper 53. As shown in FIG.

In addition, a sample storage portion 55 is formed on the outer circumference of the gap 54, which is formed in an annular recess formed in communication with the gap 54 and formed deeper than the gap 54. As a result, the blood widened radially past the gap 54 is stored in the sample storage unit 55, and therefore, movement of the blood to the fixed attachment site by adhesion or fusion of the test paper 53 is prevented. In addition, excess blood leakage is prevented even when excess blood is supplied. Therefore, contamination by blood adhesion of the photometric part 4 of the blood component measuring apparatus 1 is prevented.

Non-contact between the test paper 53 and the holder 43 when the tip 5 is attached to the light metering portion 4 of the blood component measuring device 1 at a position on the outer circumferential side of the base 512 on the inner surface of the bottom 511. Spacer 56 is formed as a separating means for securing the gap.

As shown in FIG. 9, the spacer 56 is composed of a plurality of convex portions arranged at the inner surface of the bottom portion 511 along the circumferential direction, and here, at intervals of 90 °, and the photometric portion of the tip 5 ( At the time of attachment to 4), the tip of the holder 43 is prevented from contacting the test paper 53 by abutting against the tip of the holder 43 of the photometric portion 4.

In addition, the spacer 56 maintains a fixed distance between the test paper 53 and the light emitting element 41 and the light receiving element 42 of the light metering portion 4 when the tip 5 is attached to the light emitting portion 4. It also has the ability to: As a result, the measurement error due to variation in the distance and generation of nonuniformity in optical characteristics can be reduced, thereby contributing to the improvement of measurement accuracy.

The cap 51 and the capillary 52 as described above are made of a rigid material having a predetermined rigidity. Examples of such rigid materials include alkali resins, polystyrene, polyethylene, polypropylene, hard polyvinyl chloride, polycarbonate, polymethyl methacrylate, ABS resins, polyesters, polyphenylene sulfides (PPS), polyamides, Various resin materials, such as a polymer alloy containing a polyimide, a polyacetal, or at least 1 or more of these, a polymer blend, etc. are mentioned. Among them, particularly suitable for rapidly introducing and developing a specimen, a material having high hydrophilicity such as acrylic resin or hydrophilized treatment is preferable.

As the hydrophilization treatment, for example, plasma treatment, glow discharge, corona discharge, ultraviolet irradiation, or other physical activation treatment may be performed by applying or applying a surfactant, water-soluble silicone, hydroxypropyl cellulose, polyethylene glycol, polypropylene glycol, or the like. Can be.

Next, the shape and structure of the test paper 53 will be described with reference to FIGS. 9 to 12.

The overall shape of the test paper 53 is preferably a circle as shown in the figure, but is not limited thereto. For example, a rectangular, triangular, hexagonal or octagonal shape such as an oval, square, rectangle or rhombus may be selected and used as necessary. Can be.

In the case of the circular test paper 53, the outer diameter of the test paper 53 is preferably about 2 to 10 mm, more preferably about 3 to 6 mm.

In addition, the thickness of the test paper 53 is 0.0 to 1-2. About 0 mm is preferable and it is 0.05-0. 4 mm is more preferable.

The test paper 53 has a convex portion 531 protruding toward the sample introduction passage 520 side at the center thereof, that is, at the position facing the sample introduction passage 520. The height of the convex portion 531 is not particularly limited, but at least the tip of the convex portion 531 is preferably inserted into the sample outlet 527 in the sample introduction passage 520.

Therefore, the shape of the convex portion 531 is preferably equal to or smaller than the inner diameter of the sample outlet 527 of the sample introduction passage 520 and is circular. Moreover, the height of the convex part 531 is 0.2-2. About 0 mm is preferable and it is 0.05-0. 4 mm is more preferable. In addition, the shape, dimension, etc. of the convex part 531 are not limited to what was mentioned above, According to the cross-sectional shape of the sample introduction flow path 520, etc., it can select suitably.

By providing such a convex portion 531, the blood passing through the sample introduction passage 520 can be supplied to the test paper 53 more quickly.

In addition, the test paper 53 has a radially convex convex portion 532 projecting in the same direction as the convex portion 531 at a position innermost than the outer circumference. The annular convex portion 532 forms an annular shape centering on the convex portion 531, and the tip portion thereof is inserted into the sample storage portion 55.

This annular convex portion 532 has a function of regulating the development of blood on the test paper 53. This prevents excess blood from flowing out radially beyond the periphery of the test paper 53.

Although the diameter of the annular convex part 532 is not specifically limited, About 70 to 95% of the outer diameter (diameter of the 2nd layer 53b) of the test paper 53 is preferable, and about 85 to 95% is more preferable.

Moreover, the width | variety of the annular convex part 532 is 0.03-1. About 0 mm is preferable and it is 0.05-0. About 5 mm is more preferable. The height of the annular convex part 532 is 0.2-2. About 0 mm is preferable and it is 0.05-0. 4 mm is more preferable.

In addition, the shape and dimension (diameter, width, height, etc.) of the annular convex part 532 can be suitably selected according to the shape of the cap 51, etc.

The convex portion 531 and the annular convex portion 532 as described above are formed by, for example, a method of pressing by pressing (cutting down the proximal end surface of the test paper 53 by a punch or the like) or a method of cutting out. can do.

Such test paper 53 is comprised from the laminated body of the 1st layer 53a and the 2nd layer 53b.

The first layer 53a is a precipitated reagent such as a color developing reagent in a carrier capable of absorbing a sample. The carrier is preferably composed of a porous membrane or other sheet-like porous substrate.

In the case of a reagent system in which a reagent impregnated by using a carrier by a porous membrane includes a process of reacting with oxygen in the atmosphere as a substrate, in particular, such as an oxidase reaction, the specimen is developed and then atmosphere on the first layer 53a. Since a sufficient supply of oxygen is ensured, the reaction can be rapidly developed, and thus, a color development state can be detected without removing the sample or its filtration components (such as red blood cells).

Examples of the porous membrane of the first layer 53a include a nonwoven fabric, a woven fabric, a stretched sheet, a membrane filter, a filter paper, and the like.

Examples of the constituent material of the porous membrane of the first layer 53a include polyesters, polyamides, polyolefins, polysulfones, celluloses, silicates, fluorine resins, and the like. More specifically, polyethylene terephthalate, polybutylene terephthalate, polyether sulfone, nitrocellulose, cellulose, glass, polytetrafluoroethylene (teflon), nitrated polyether sulfone, etc. are mentioned, for example.

It is preferable that the material of such a porous membrane is prepared by impregnating an aqueous solution in which a reagent is dissolved, or a material having a hydrophilicity or hydrophilized in order to promptly absorb and develop a specimen. Examples of the hydrophilization treatment include those similar to those described above.

Examples of reagents impregnated into the porous membrane of the first layer 53a include a glucose oxidizer (GOD), a peloxy oxidizer (POD), and 4-aminoantiphylline, N-ethyl-N And a coloring agent such as-(2-hydroxy-3-sulfopropyl) -m-truidine. In addition, depending on the measurement component, for example, blood such as ascorbic acid oxidant, alcohol oxidant, cholesterol oxidant The same coloring agent as the above which reacts with a component is mentioned. A buffer such as phosphate buffer may also be included. In addition, it is needless to say that the types and components of the reagents are not limited to those provided with a color signal to the observed surface of the second layer 53b.

The porous membrane of the first layer 53a preferably has a pore diameter that can penetrate blood cells, particularly red blood cells (hereinafter, represented by red blood cells) contained in the blood. Specifically, the pore diameter of the pores in the first layer 53a is preferably about 8 to 50 µm, and more preferably about 10 to 30 µm. If the pore diameter is too small, the permeation amount of red blood cells decreases, and the development of blood decreases. If the pore diameter is too large, the reagent becomes difficult to precipitate and the color becomes difficult to color, thereby lowering the sensitivity of coloration.

This first layer 53a has an outer diameter smaller than the outer diameter of the second layer 53b and is radially located inside the annular convex portion 532. As described above, since the outflow of blood to the outer circumferential side is prevented by the annular convex portion 532, the first layer 53a, which is responsible for the development of blood, is radially inward from the annular convex portion 532. It is enough if placed. Unlike the illustration, the first layer 53a and the second layer 53b may have the same outer diameter.

Although the thickness of the 1st layer 53a is not specifically limited, About 10-1000 micrometers is preferable, and about 50-200 micrometers is more preferable.

On the other hand, the second layer 53b is composed of the same porous membrane (sheet-like porous substrate) as described above.

Examples of the porous membrane include nonwoven fabrics, woven fabrics, stretched sheets, membrane filters, filter papers, and the like, and the constituent materials thereof are the same as those described above such as polyesters, polyamides, polyolefins, polysulfones, or celluloses. It can be mentioned. In this case, the second layer 53b is preferably a material having hydrophilicity or hydrophilized. Examples of the hydrophilization treatment method include the same ones as those described above.

This second layer 53b has a function of separating red blood cells in a sample as a filtrate. In other words, it is preferable that the porous membrane constituting the second layer 53b has a pore diameter that can at least filter the red blood cells contained in the blood. Specifically, the pore diameter of the pores in the second layer 53b is preferably 5 µm or less, and is preferably 0.2 to 3. It is more preferable that it is about 5 micrometers. The second layer is an isotropic film or anisotropic film. This is because if the pore diameter is too large, red blood cells penetrate the second layer 53b and move to the base end surface (measurement surface) side of the test paper 53, thereby reducing the measurement accuracy of the developed color intensity.

Moreover, the 1st layer 53a and the 2nd layer 53b may be in which the whole surface or a part is couple | bonded, or may just overlap without having a bonding force.

Although the thickness of the 2nd layer 53b is not specifically limited, About 10-1000 micrometers is preferable, About 50-200 micrometers is preferable. It should be opaque enough so that filtrates, such as red blood cells on the rear face, will not affect the reading of the test face.

The fixing part 533 is formed in the outer peripheral part of the test paper 53.

In this case, as shown in FIG. 11, the some fixing point 534 is formed intermittently (preferably at equal intervals) along the outer peripheral part of the test paper 53. As shown in FIG. As a result, air is allowed to flow between adjacent fixing points 534, and air in the gap 54 and the sample storage part 55 when the blood flowing out from the sample outlet 527 is deployed on the test paper 53. Is effectively discharged, and therefore blood can be developed more quickly.

In addition, the test paper 53 may be fixed to the end surface of the sample outflow side end portion 525 by a method such as fusion or adhesion with an adhesive. As a result, the test paper 53 can be more stably supported and fixed to the cap 51, and gaps are generated due to deformation (curvature, distortion, undulation, etc.) of the test paper 53, thereby preventing blood development. It is also prevented.

FIG. 13 is a side view showing a state when collecting blood using the tip 5. FIG. As shown in the same drawing, the blood is first collected by puncturing a fingertip (or ear ball) with a needle, a scalpel, or the like, and a small amount (for example, about 2 to 6 μl) of blood 18 on the skin from the puncture portion. Spill.

On the other hand, the tip 5 is attached to the photometric part 4 of the blood component measuring apparatus 1, and the end surface of the sample inlet side end 521 of the tubule 52 is brought into contact with the skin. The blood 18 at the fingertip reaches the sample inlet 523 through the groove 522 and is sucked by the capillary phenomenon to flow in the sample introduction passage 520 in the proximal direction to reach the sample outlet 527. At this time, the blood 18 of the fingertip is effectively sucked from the side opening of the groove 522 (the part opened to the outer circumferential surface of the tubule 52), so that it is not excessively dispersed on the skin and thus there is little loss.

The blood reaching the sample outlet 527 is absorbed in contact with the convex portion 531 of the test paper 53 and a part of the blood reaches the gap 54 beyond the groove 526. The blood flowing in the gap 54 is radially spread toward the outer circumferential direction while being absorbed and developed by the first layer 53a of the adjacent test paper 53. As a result of the absorption and development of the blood by the first layer 53a, particularly the absorption in the vicinity of the convex portion 531, a new suction force is generated in the sample introduction channel 520, and the blood is continuously flowed into the first layer. It can supply to 53a.

Therefore, even when the amount of blood 18 at the fingertip is relatively small, it can be supplied to the first layer 53a (test paper 53) without waste. On the contrary, even when the amount of blood 18 at the fingertips is excessively supplied to the first layer 53a, the extra blood is stored in the sample storage unit 55, and the annular convex portion 532 is used to store excess blood. Since the outflow to the outer circumferential side is prevented, blood leaks out of the test paper 53 and adheres to the inner surface of the fuselage part 51, the light metering part 4, or a peripheral part thereof, and the like, thereby preventing contamination. For this reason, there is no adverse effect on the next measurement, and there is no fear of infection or the like at the disposal of the used tip 5, and the safety thereof is increased.

Accompanying the supply and development of blood onto the first layer 53a, the target component (for example, glucose) in the blood and the reagent precipitated in the first layer 53a react to color according to the amount of the target component. The pigment by this color moves with the blood component (except red blood cells) to the 2nd layer 53b, and colorizes the 2nd layer 53b with the same color tone and color intensity. At this time, red blood cells in the blood penetrate near the boundary between the first layer 53a and the second layer 53b because the first layer 53a penetrates but the second layer 53b does not.

By measuring the color intensity of the second layer 53b with the blood component measuring apparatus 1 as described above, the target component (blood sugar value) in the blood is obtained. Here, red blood cells contained in the blood are filtered by the second layer 53b and stored near the boundary between the first layer 53a and the second layer 53b, and move toward the proximal end surface of the second layer 53b. Since this does not adversely affect the color measurement of the test paper 53, high measurement accuracy can be maintained.

In the first layer 53a, since red color cells are also transmitted, the color development develops rapidly, and the development speed is high and uniformly developed. In addition, blood components excluding red blood cells and other filtrates colored in the first layer 53a are Since the second layer 53b is moved to color the second layer 53b and the color intensity is measured, more accurate measurement is possible by excluding the effect of red blood cells and the like. In such a case, the time required for measurement can be shortened.

In the case where the tip 5 is used, the blood can be supplied and expanded to the test paper 53 quickly and reliably with a simple operation despite the amount of blood 18 spilled on the fingertip. Therefore, there are very few measurement errors, which contributes to the improvement of measurement accuracy.

Hereinafter, specific examples of the present invention will be described.

Example 1

Test paper for blood glucose value measurement of the shape and structure (two-layer laminated body) shown to FIGS. 10-12 was produced. The conditions of each part of the test paper are as follows.

[First layer 53a]

Material: Nitrocellulose (hydrophilic) (Milliporesa)

Outer diameter: 4. 2mm

Thickness: 135㎛

Pore diameter of pore: 12㎛

Precipitated reagents: GOD, POD and 4-aminoantipyrine, N-ethyl-N- (2-hydroxy-3-sulfopropyl) -m-toluidine (TOOS)

Settling amount of reagent: GOD / 250μg / cm ² test paper

: POD / 125μg / cm ² test paper

: 4-aminoantipyrine / 60 μg / cm ² test paper

: TOOS / 90μg / cm ² test paper

[2nd layer 53b]

Material: polyethersulfone (hydrophilic) (manufactured by Paul Gelmann)

Outer Diameter: 5. 4mm

Thickness: 135㎛

Pore diameter of pores: 0.45㎛

[etc]

Diameter of the convex portion 531: 0.4 mm

Height of the convex portion 531: 0.3 mm

Inner diameter of annular convex portion 532: 0.3 mm

Width of the annular convex portion 532: 0.3 mm

Height of the annular convex portion 532: 0.3 mm

This test paper was attached to the tip of the structure shown in FIGS. The conditions of each part are as follows.

Tip material: Acrylic resin (hydrophilic)

Outer diameter of tip: 9. 5 to 11. 0 mm

Inside diameter of tip: 9. 0 to 10. 0 mm

Internal diameter of the sample introduction path (d ₁ ): 0.7 mm

Internal diameter of the sample introduction path (d ₂ ): 0.7 mm

Sample introduction length: 4. 2mm

Perimeter Length (L ₁ ): 0.7mm (= πd ₁ × 32%)

Depth of the groove 522 (P ₁ ): 0.5mm

Perimeter Length (L ₂ ): 0.7mm (= πd ₂ × 32%)

Depth of the groove 526 (P ₂ ): 0.3 mm

Width (depth) of the gap 54: 0.1 mm

Depth of the specimen storage part 55: 0.3mm

Height of spacer 56: 0.5 mm

Test fixation method: fusion fixation at the fixed point of the arrangement shown in FIG.

Comparative example

A test paper for measuring blood glucose value composed of one layer of porous membrane was produced. The conditions of each part of the test paper are as follows.

Porous Membrane

Material: polyethersulfone (hydrophilic) (manufactured by Paul Gelmann)

Outer Diameter: 5. 4mm

Thickness: 135㎛

Pore diameter of pores: 0.45㎛

Precipitated Reagent and Precipitated Amount: As in Example

[etc]

Diameter of the convex portion 531: same as in the above embodiment

Height of the convex portion 531: same as in the above embodiment

Inner diameter of annular convex portion 532: same as in the above embodiment

Width of the annular convex portion 532: same as in the above embodiment

Height of the annular convex portion 532: same as in the above embodiment

This test paper was attached to the tip of the same conditions as the above Example.

<Experiment 1>

The following experiment was performed using the tip of the said Example and a comparative example.

As a sample, blood adjusted to a blood sugar value of 186 mg / dl was prepared, and 4 µl of this blood was brought into contact with the tip of the capillary tube and aspirated into the sample introduction passage. The blood is supplied to the convex portion 531 at the center of the test paper, and the time point at which the diffusion starts radially there is measured at 0 (second), and on the opposite side from the blood supply side of the test paper every 1 second from 1 second to 18 seconds. Transmittance and light reception were performed on the surface of and the absorbance of the reflected light was measured. The results are shown in the graph of FIG. In addition, the absorbance in a graph is computed by following formula (III).

[Formula 1]

<Experiment 2>

The same experiment as in Experiment 1 was conducted except that blood was adjusted to a blood glucose value of 292 mg / dl as a sample. The results are shown in the graph of FIG. The absorbance in the graph is calculated by the above formula (III).

As shown in the graphs of FIG. 14 and FIG. 15, it was confirmed that the Example of the present invention had a faster development rate of the specimen than the Comparative Example, and therefore the color intensity (absorbance of the reflected light) was stabilized in a shorter time. By using the time when the graph actually reached the equilibrium state, such as the end point of the measurement, high-precision blood glucose values can be measured.

Example 2

Using a first layer of polyester (nonwoven) having a pore diameter of 16 μm (manufactured by Tonen K. K.) and a second layer of polyether sulfone (manufactured by Fuji Photo Film Co., Ltd.) having a pore diameter of 0.45 μm A test paper was produced by following the same procedure as in Example 1, which was attached to the tip shown in FIGS. 4 to 8.

Example 3

Except for using the first layer of nitrided polyethersulfone (manufactured by Paul Gelman Co., Ltd.) and the second layer of anisotropic polyethersulfone (manufactured by Fuji Photo Film Co., Ltd.) having a pore diameter of 0.45 占 퐉, Test papers were produced following the procedure, which was mounted to the tips shown in FIGS. 4-8.

<Experiment 3>

The same experiment as in Experiment 1 was carried out at the tip of Example 2, except that blood adjusted to a blood glucose value of 122 mg / dl was used as the specimen. The results are shown in the graph of FIG.

<Experiment 4>

The same experiment as in Experiment 3 was carried out at the tip of Example 3. The results are shown in the graph of FIG.

As mentioned above, although the test paper and the tip for component measurement of this invention were demonstrated based on the Example which showed, this invention is not limited to this.

In addition, the test paper of the present invention is not limited to the one attached to the tip 5 as described above. For example, only the test paper, the test paper is superimposed on a plate or sheet-shaped base (substrate), and the test paper is Any form may be sufficient as it is hold | maintained by the holder (especially nip).

In the above embodiment, blood has been described as a sample. However, the sample is not limited thereto, and may be, for example, body fluids such as urine, lymph, sap, or saliva, or a diluted solution thereof, or a concentrated solution.

The component to be measured is not limited to glucose (blood sugar value), but may be, for example, inorganic ions such as protein, cholesterol, uric acid, creatine, alcohol, sodium, hemoglobin (latency), and the like.

In addition, the component measuring device equipped with the test paper or the component measuring tip of the present invention optically measures the color intensity of the test paper colored by the reaction of the components and reagents in the sample as described above, and converts and displays the measured value. In addition, the potential change generated according to the amount of the component in the sample may be measured electrically and converted into a measured value.

As described above, according to the test paper and the component measuring tip of the present invention, the development speed of the specimen on the test paper is high, so that the time required for development can be shortened. Moreover, the time until the coloration state is stabilized is also short. Therefore, faster measurement is possible. In addition, the measurement of red blood cells and the like can be eliminated at the time of coloration, and the measurement can be performed with higher accuracy.

According to the component measuring tip of the present invention, the sample can be collected simply, quickly and reliably and deployed on the test ground regardless of the conditions, such as the shape and quantity of the sample, the collection site, and the harvesting technology. Accurate measurements can be obtained.

It is also easy to handle the component measuring tip, and in particular, the detachable operation of the component measuring device is simple. In particular, an appropriate mounting state can be easily and reliably obtained, and measurement errors and measurement errors caused by inappropriate mounting conditions can be prevented.

In addition, contamination by sample adhesion is prevented, and safety at the time of disposal of the used component measuring tip is also high.

From the above, it is advantageous to automate the measurement by the component measuring device.

Claims (21)

Laminating a porous first layer having a reagent that reacts with a specific component in a sample and coloring a second porous layer having a function of separating a filtrate in a sample emitted from the first layer. And the test surface is a second layer surface far from the first layer surface. The method of claim 1, The test paper for component colorimetric evaluation, wherein the first layer and the second layer each have hydrophilicity. The method according to claim 1 or 2, The hole diameter of the pore in the said 1st layer is 8-50 micrometers, The test paper for component side color evaluation characterized by the above-mentioned. The method of claim 1, The hole diameter of the pores in the said 2nd layer is 5 micrometers or less, The test paper for component side color evaluation characterized by the above-mentioned. The method of claim 1, The sample is blood, and the test paper is a component paper evaluation test sheet, characterized in that it is adjusted to separate the filtrate, which is a blood cell mainly containing red blood cells. In the component measuring method using the measuring tip (5) of the component measuring device (1), The measuring tip 5 is disposed inside the tip with the tubule 52 protruding from the tip to form a sample introduction passage for introducing the sample into the tip, and reacts with a specific component in the sample. A first porous layer having a colorant reagent and a second porous layer having a function of separating a filtrate in a sample emanating from the first layer are laminated. And a test paper 53 for component side color evaluation, characterized in that the second layer is far from the layer . The method transfers the sample supplied to the sample inlet 523 of the tubule 52 to the sample outlet 527 by capillary action of the tubule, and supplies the sample to the first layer 53a of the test paper, It develops, a sample is filtered in a 2nd layer (53b), and a component is measured by the said test surface side of a 2nd layer (53b). And a tubule 52 protruding at both ends forming a sample introduction passage 520 for collecting a sample, and for transferring the sample to the test paper 53 along the sample introduction passage 520 by capillary action. In order to communicate with the sample outlet 527 of the customs , a porous first layer having a reagent which reacts with a specific component in the sample and coloration is separated from the filtrate in the sample emitted from the first layer. A component is characterized by arranging a test paper for component side color evaluation (53), which is made by laminating a porous second layer having a function to make a test surface, and the test surface is a second layer surface far from the first layer surface. A component measuring tip (5) having a mounting portion at one end for mounting to the measuring device (1). The method of claim 7, wherein The tubule (52) is a tip for measuring the component, characterized in that the sample inlet 523 has a structure having a first groove (522) in communication with the sample introduction passage (520). The method of claim 8, The first groove (522) extends in the radial direction of the tubule (52), the tip for component measurement, characterized in that open to the outer peripheral surface of the tubule (52). The method according to any one of claims 7 to 9, The tubule 52 is a component measuring tip having a structure having a second groove 526 in communication with the sample introduction passage 520 in the sample outlet (527). The method of claim 10, It has a protrusion 525 protruding inward adjacent to the sample outlet 527, the second groove 526 is formed in the protrusion extending in the radial direction of the tubules, and the outer peripheral surface of the protrusion 525 Component measuring tip, characterized in that open to. The method of claim 7, wherein And a convex portion 531 protruding toward the specimen introduction channel at a position facing the specimen introduction channel 520 of the test paper. The method of claim 12, At least the tip of the convex portion 531 is inserted into the sample introduction passage 520, characterized in that the tip for component measurement. The method of claim 7, wherein The test paper has a tip for component measurement, characterized in that it has an annular convex portion (532) on the outer circumference. The method of claim 14, And a first layer (53a) of the test paper is disposed radially inward from the annular convex portion (532). The method of claim 7, wherein And the test paper has a fixing portion (533) fixed to an outer circumference thereof with respect to the inner surface (512) of the tip. The method of claim 16, The fixing part (533) is a component measuring tip, characterized in that fixed to the tip by intermittent fusion or adhesion (接着). The method of claim 7, wherein It is mounted on the test strip mounting portion 43 of the component measuring device 1, and secures non-contact between the test strip 53 and the test paper mounting portion 43 when the test strip mounting portion 43 of the component measuring device 1 is mounted. Tip for measuring the component, characterized in that it has a separation means (56) for. The method of claim 18, The separating means (56) is a tip for component measurement, characterized in that protruding from the inner surface of the tip, the spacer 56 is in contact with the test paper mounting portion (43). The method of claim 7, wherein Tip for measuring the component, characterized in that the internal diameter of the sample introduction channel is 0.3 ~ 1.0mm. The method of claim 7, wherein Tip for measuring the component, characterized in that the length of the sample introduction passage is 2 ~ 5mm.