JPH06229970A - Humor constituent measuring device - Google Patents

Abstract

PURPOSE:To prevent an inspector from being infected by human immunity partial syndrome virus, hepatitis virus, etc., by allowing a member constituting a measuring device to carry an antibacterial agent or antivirus agent. CONSTITUTION:Silver paste is printed on an insulation substrate 21 by screen printing to form leads 22 and 23. Then, conductive carbon paste is printed, heated, and then dried, thus forming a measuring electrode 24 and a counter electrode 25. Further, insulation paste is printed and heated, thus forming an insulation layer 26. Then, a spacer 28 and a cover 29 are adhered and formed in one piece. The spacer 28 is provided with an introduction port 30 of a sample liquid and a space part 31 is formed at a center part. Also, a hole 32 of a cover 29 becomes the delivery port of air. A paint where antibacterial and antivirus silver silica gel antibacterial agent particles are kneaded applied to the surface excluding the electrode lead parts 22 and 23 of a biosensor thus produced, thus preventing propagation of contamination due to sampling of humor and preventing the danger of infection in inspection work.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improvement of a body fluid component measuring device for rapidly, accurately and simply measuring a specific component in various biological samples in clinical tests.

[0002]

2. Description of the Related Art In recent years, various biosensors utilizing the specific catalytic action of enzymes have been developed, and their application to the clinical field has been attempted. There is a demand for a biosensor that can accurately measure.

Taking a glucose sensor as an example, in the present day when the increase of diabetes is remarkable, it is very time-consuming to measure and control blood glucose level in blood by centrifuging blood and measuring plasma. Therefore, a sensor that can measure whole blood is required. As a simple type, similar to the test paper used at the time of urinalysis, an enzyme that reacts only with sugar (glucose) on a stick-shaped support and a dye that changes during the enzymatic reaction or by the product of the enzymatic reaction. There is one in which a carrier containing is installed. Drop blood on this carrier,
This is a method of visually or optically measuring the change in the dye after a certain period of time, but the accuracy is low due to the large interference of colored substances in the blood.

Therefore, a multi-layer type analytical carrier as shown in FIG. 1 has been proposed (Japanese Utility Model Publication No. 54-178495).
This has a structure in which a reagent layer 2, a spreading layer 3, a waterproof layer 4, and a filtration layer 5 are sequentially laminated on a transparent support 1. When a blood sample is dropped from the top, first, solid components such as red blood cells and platelets in the blood are removed by the filtration layer 5, and the solid components such as red blood cells and platelets permeate uniformly into the spreading layer 3 through the small holes 6 in the waterproof layer 4 and react in the reagent layer 2. Progresses. After completion of the reaction, light is irradiated from the direction of the arrow through the transparent support 1 and the substrate concentration is measured by colorimetric analysis. The structure is more complicated than the conventional simple stick-shaped carrier, but the accuracy is improved by removing blood cells. However, since it takes a long time for blood to penetrate and react, a waterproof layer 4 for preventing the sample from drying is required, and incubation at high temperature is required to accelerate the reaction, which complicates the device and the carrier. is there.

On the other hand, a biosensor as shown in FIG. 2 has been proposed as a method for quantifying a specific component in a biological sample such as blood with high accuracy without performing operations such as dilution and stirring of the sample solution. (For example, JP-A-59-1
66852). This biosensor has an insulating substrate 9
Measuring electrode 1 made of platinum, etc., each having leads 7 and 8
0 and the counter electrode 11 are embedded, and the exposed parts of these electrode systems carry a redox enzyme and an electron acceptor to form a porous body 12.
It is covered with. When the sample solution is dropped on the porous body,
The oxidoreductase and the electron acceptor are dissolved in the sample solution, the enzymatic reaction proceeds with the substrate in the sample solution, and the electron acceptor is reduced. After the reaction is completed, the reduced electron acceptor is electrochemically oxidized, and the concentration of the substrate in the sample is determined from the oxidation current value obtained at this time.

However, in such a structure, the porous body can be easily subjected to the measurement by exchanging it for each measurement, but the electrode requires an operation such as cleaning. On the other hand, if it is possible to dispose of each measurement including the electrode system, it will be extremely simple in terms of measurement operation, but it will have to be very expensive in terms of the electrode material and configuration such as platinum. Absent. Moreover, although a sputtering method or a vapor deposition method can be used as a method of forming the platinum electrode, it is expensive in manufacturing.

Further, as a method of making it disposable including the electrode system, a biosensor disclosed in Japanese Patent Application Laid-Open No. 61-294351 has been proposed. This biosensor is shown in FIG.
An electrode system 14 (14 ') made of carbon or the like on the insulating substrate 13 by a method such as screen printing as shown in FIG.
15 (15 ′) and 16 (16 ′) are formed, and the insulating layer 17 is formed.
After the above, the electrode system is covered with a porous body 19 carrying an oxidoreductase and an electron acceptor, and the holding frame 18 and a cover 20 are integrated as a whole. When the sample solution is dropped on the porous body, the redox enzyme and the electron acceptor supported on the porous body are dissolved in the sample solution, and the enzyme reaction proceeds with the substrate in the sample solution to reduce the electron acceptor. To be done. After the reaction is completed, the reduced electron acceptor is electrochemically oxidized, and the concentration of the substrate in the sample solution is determined from the oxidation current value obtained at this time.

[0008]

In recent years, when human immunodeficiency syndrome virus (HIV), hepatitis virus, etc. have been regarded as problems, in the treatment of body fluids, the inspection of the inspector, the work of discarding the specimen, and the disposal of the specimen are also performed. It is required to improve the inspection environment such as handling during the period.

On the other hand, since specific components in various biological samples can be measured quickly, accurately and simply by using a body fluid component measuring device, it is increasingly used for personal use.

If the subject is a body fluid-borne infectious virus-infected subject, an appropriate method for treating the sample is essential.

[0011]

The present invention provides a body fluid component measuring apparatus utilizing at least a body fluid and an enzymatic reaction, wherein an antibacterial agent or an antiviral agent is carried on at least a part of members constituting the measuring apparatus. It is a body fluid component measuring device characterized by the above. Further, the present invention is a body fluid component measuring device having a measuring device, wherein the measuring device, which is the main body of the device, has a biosensor mounting part in a part of the housing, and an antibacterial part in the measuring device. A body fluid component measuring device, characterized in that it carries an agent or an antiviral agent. Furthermore, the present invention has a body fluid collecting device, wherein the body fluid collecting device has a replaceable needle part in the housing, and an antibacterial agent or an antibacterial agent is provided on at least a part of the body fluid collecting device such as the housing or the needle part. It is characterized by carrying an antiviral agent. Further, the present invention is characterized in that the biosensor part is packed in a packaging member, and an antibacterial agent or an antiviral agent is carried on at least a part of the packaging member. The present invention further provides silver as an antibacterial or antiviral material,
It is characterized by using silver ions and silver complex salts.

[0012]

[Function] An antibacterial agent is applied to a portion which is easily touched when handling the body fluid component measuring device, that is, the surface of not only the biosensor but also the measuring device and the body fluid collecting instrument which is the body of the body fluid component measuring device, and the packaging member of the biosensor. By carrying the agent or the antiviral agent, the virus in the body fluid attached to the instrument such as the measuring instrument can be killed, and the propagation of the contamination can be prevented. In addition, the secondary contamination caused by the body fluid that directly adheres to the finger when collecting body fluid adheres to the body fluid component measuring device,
It can be prevented by an antibacterial or antiviral agent carried on a measuring instrument or the like.

[0013]

【Example】

(Embodiment 1) In the drawings for explaining the following embodiments, common elements are designated by the same reference numerals, and the description thereof will be partially omitted.

A glucose sensor will be described as an example of a biosensor. FIG. 4 is an exploded perspective view of a glucose sensor manufactured as an example of the biosensor of the present invention, FIG. 5 is an external view thereof, and FIG. 6 is a sectional view of the biosensor shown in FIG. It is sectional drawing at the time of doing. The reaction layer 274 shown in FIG. 6 is not shown in FIG.

The method of manufacturing the sensor will be described below. A silver paste is printed on the insulating substrate 21 made of polyethylene terephthalate by screen printing and then reprinted.
To form the cords 22 and 23 (23 '). Next, a conductive carbon paste containing a resin binder is printed and heated and dried to form an electrode system including the measurement electrode 24 and the counter electrode 25 (25 '). Further, an insulating paste is printed so as to partially cover the electrode system, keep the area of the exposed portion of the electrode constant, and cover unnecessary portions of the lead, and heat treatment is performed to form the insulating layer 26.

Next, the exposed portions of the electrode systems 24, 25 (25 ') were polished and then heat-treated in air at 100 ° C. for 4 hours. After forming the electrode portion in this way, carboxymethyl cellulose (hereinafter referred to as CMC) is used as a hydrophilic polymer.
Abbreviated to 0.5 wt% aqueous solution is spread on the electrode, dried and
Form the MC layer. And to cover this CMC layer,
Glucose oxidase (GOD) as an enzyme dissolved in a phosphate buffer was developed, dried, and then CMC-G.
A reaction layer 27 composed of an OD layer was formed. In this case, CM
C and GOD are in a partially mixed state in the form of a thin film having a thickness of several microns.

Next, as shown in FIG. 4, the three members of the substrate 21, the spacer 28 made of a resin plate and the cover 29 are bonded so that the respective members have a positional relationship shown by a broken line. , As shown in the external view of FIG. here,
The spacer has a thickness of about 300 μm, and has a shape in which the central portion is cut into a U shape with a width of 2 mm in the longitudinal direction, and the end portion of the cut portion is the sample solution when integrated. And the central portion forms a space portion 31. Also,
The cover 29 has a hole with a diameter of 2 mm, and becomes a discharge port 32 for air in the space when integrated.

A coating prepared by kneading antibacterial and antiviral silver silica gel type antibacterial agent particles is applied to the surface of the biosensor thus manufactured excluding the electrode lead portions.

The above-mentioned paint is a urethane paint in which 5 wt% silver silica gel antibacterial and antiviral particles of a paint resin component are dispersed and kneaded, and appropriately diluted with a solvent.

Next, the above-mentioned silver-silica gel type antibacterial and antiviral agent particles will be described together with their manufacturing method.

100 parts by weight of a water-soluble silver salt such as silver acetate was added to and dissolved in water containing no chlorine, and 450 parts by weight of a mixture of sodium sulfite and sodium bisulfite, and 300 parts by weight of a water-soluble salt of sodium thiosulfate were added. Sequentially
The mixture was thoroughly stirred and dissolved to obtain a silver complex salt aqueous solution. The weight of sodium thiosulfate is the hydrate N
It is shown as the weight of _{a 2 S 2 O 3 · 5H} 2 O.

The carrier used for the silver silica gel antibacterial and antiviral agent particles in this example is B-type silica gel powder described in "JIS Z 0701 Silica gel desiccant for packaging". This B-type silica gel powder is a silica gel powder having a low moisture absorption rate at low humidity, a high moisture absorption rate at high humidity, and a high total moisture absorption amount at high humidity, and its average particle size is about 8 μm.

The silica gel powder was dried at 180 ° C. for 2 hours or more. The thiosulfato silver complex salt aqueous solution was mixed with 100 parts by weight of the obtained silica gel so that the silver component was 2 parts by weight. Then, the water absorbed in the solvent and the carrier was promptly removed. Then, this was crushed to a predetermined particle size to obtain a silica gel carrying a silver complex salt.

As a coating material, 100 parts by weight of silica gel was dispersed in a solution prepared by diluting 100 parts by weight of tetraethoxysilane with 100 parts by weight of ethyl alcohol, and then 20 parts by weight of pure water was added thereto to add tetraethoxysilane. Was hydrolyzed and at least part of the surface of the silica gel was coated. Then, this was dried to obtain silver silica gel antibacterial and antiviral agent particles.

(Embodiment 2) A 5 cm × 1 unit having an arithmetic circuit inside and a display unit for displaying a blood glucose level, a GOT value, a GPT value, a uric acid level, a cholesterol level, a lactic acid level, etc. in the center of the surface.
The casing of the measuring instrument, which is the main body of the body fluid component measuring device having a thickness of 0 cm × 1 cm, is made of ABS resin. Further, this measuring instrument has a biosensor mounting portion for detecting the body fluid component.

The raw material resin for molding this ABS resin is 1.
5 wt% of the silver silica gel-based antibacterial and antiviral agent particles described in Example 1 are kneaded to obtain colored pellets. The colored pellets are injection-molded to obtain the above housing.

(Embodiment 3) An embodiment of a body fluid component measuring device having a body fluid collecting device will be described.

The body fluid collecting device has a replaceable needle part in the housing, and an antibacterial agent or an antiviral agent is carried on at least part of the body fluid collecting device including the housing and the needle part. be able to.

2% of the above silver-silica gel type antibacterial agent particles are kneaded with polypropylene resin to obtain colored pellets. The colored pellets are used to hold a puncture needle used in a body fluid collecting device in a molding die and injection-molded to obtain a puncture needle portion with a holder. As in Example 2, 1.5w for ABS raw material resin
A body fluid sampling tool housing is obtained by injection molding with colored pellets in which t% of the above-mentioned silver silica gel antibacterial agent particles are kneaded.

(Embodiment 4) The biosensor of Embodiment 1 is housed in a packaging member in order to maintain a sterilized state until just before use. The packaging member is, for example, an aluminum foil laminated with a resin film, and the silver silica gel antibacterial and antiviral agent particles are arranged inside the packaging member in a form that does not directly touch the inlet of the biosensor. is doing. That is, the silver silica gel agent is applied by coating the surface of the resin film or by laminating the kneaded resin film on the innermost side. Furthermore, it is packaged with a desiccant or the like contained in the packaging member.

The following anti-virus tests were conducted on the members subjected to the anti-bacterial and anti-virus treatments of Examples 1 to 4 above. The results are shown in (Table 1). From Table 1, it can be seen that the antibacterial and antiviral material of this example has a practical antiviral performance.

Antivirus test: Various viruses including poliovirus, measles virus, HIV were used, and each virus was mixed with a sample at a ratio of 1: 1. After 1 hour, African green monkey kidney-derived vero cells 10 ⁶ cells / m
The evaluation was carried out based on the life and death and morphological change of cells infected with 1 for 1 week. Samples were prepared by adding 1 ml of culture solution to 1 mg of silver-silica gel antibacterial and antiviral agent particles and extracting for 30 minutes to obtain 1, 10, 100 nM, 1, 1
Used at each concentration of 0,100 μM.

Although silver silica gel type antibacterial agent particles are used as the antibacterial and antiviral material in the above examples, it is also possible to use a mixture of thiosulfato silver complex salt and at least one antibacterial and antiviral material of silver and silver ion. it can.

(Comparative Example 1) In Example 2, only the ABS resin was molded to obtain a resin casing having the same shape as in Example 2, and this resin casing was subjected to the antivirus test in the same manner as in Example 2. went. The results are shown in (Table 1).

[0035]

[Table 1]

[0036]

EFFECTS OF THE INVENTION An antibacterial or antiviral agent is applied to the part which is easily touched when handling a body fluid component measuring device, that is, the surface of not only the biosensor but also the measuring device or the body fluid collecting device which is the body of the body fluid component measuring device. By arranging them, it is possible to prevent the propagation of contamination associated with the collection of body fluid. In addition, it is possible to prevent the risk of infection in the body fluid collection inspection work of the body fluid collector.

Furthermore, the anti-virus property against the sample after collecting the body fluid reduces the environmental pollution due to the used sample,
It can be expected that the inspection can be easily performed even at home without sterilization equipment.

[Brief description of drawings]

FIG. 1 is an explanatory view of a conventional multi-layer type analytical carrier.

FIG. 2 is an explanatory view of a conventional biosensor.

FIG. 3 is an explanatory diagram of a conventional biosensor.

FIG. 4 is an exploded perspective view of a glucose sensor that is a biosensor according to an embodiment of the present invention.

FIG. 5 is an external view of the biosensor of the same example.

FIG. 6 is a cross-sectional view of the biosensor of the same example taken along the longitudinal direction at the central portion.

[Explanation of symbols]

 1 Support 2 Reagent Layer 3 Development Layer 4 Waterproof Layer 5 Filtration Layer 5 Small Hole 7 Lead 8 Lead 9 Insulating Substrate 10 Measuring Electrode 11 Counter Electrode 12 Porous Body 13 Insulating Substrate 14 Electrode System 15 Electrode System 16 Electrode System 17 Insulation Layer 18 Holding Frame 19 Porous Body 20 Cover 21 Insulating Substrate 22 Lead 23 (23 ') Lead 24 Measuring Electrode 25 (25') Counter Electrode 26 Insulating Layer 27 Reaction Layer 28 Spacer 29 Cover 30 Sample Liquid Inlet 31 Space 32 outlet

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Internal reference number FI Technical indication location G01N 1/10 V 7519-2J 27/327 (72) Inventor Kenji Hoshino 1006 Kadoma, Kadoma, Osaka Prefecture Address Matsushita Electric Industrial Co., Ltd. (72) Inventor Atsushi Nishino 1006 Kadoma, Kadoma City, Osaka Prefecture Matsushita Electric Industrial Co., Ltd. (72) Inventor Shiro Nankai 1006 Kadoma, Kadoma City, Osaka Pref. 72) Inventor Toshihiko Yoshioka 1006 Kadoma, Kadoma City, Osaka Prefecture Matsushita Electric Industrial Co., Ltd. (72) Kinichi Adachi, 1006 Kadoma, Kadoma City, Osaka Prefecture Matsushita Electric Industrial Co., Ltd.

Claims (7)

[Claims] 1. A body fluid component measuring apparatus utilizing an enzymatic reaction with a body fluid, characterized in that an antibacterial agent or an antiviral agent is carried on at least a part of members constituting the measuring apparatus. apparatus. 2. A biosensor mounting portion is provided in a part of the housing, and electrochemical changes due to a reaction layer and body fluid in the biosensor are measured and calculated, and converted into specific component amounts in various biological samples and displayed. The body fluid component measuring device according to claim 1, wherein in the measuring device, an antibacterial agent or an antiviral agent is carried on at least a part of members constituting the measuring device. 3. A biosensor, wherein a space portion including the reaction layer is formed on a substrate having an electrode system and a reaction layer, and an inlet for introducing a test liquid into the space portion and a gas in the space portion are provided. The test solution has an outlet for discharging the test solution, the electrode system has at least a measuring electrode and a counter electrode, and the reaction layer carries at least an enzyme, and the reaction of the enzyme with the test solution is carried out. The substance concentration change is input to the measuring device main body through the electrode system to measure the substrate concentration in the test liquid, and an antibacterial agent or antiviral agent is provided on at least a part of the surface of the member constituting the biosensor. The body fluid component measuring device according to claim 1, which carries a sexual agent. 4. A body fluid component measuring apparatus having a body fluid collecting device, wherein the body fluid collecting device has a replaceable needle part in a housing, and an antibacterial agent or an antiviral agent is provided on at least a part of the body fluid collecting device. The body fluid component measuring device according to claim 1, wherein 5. The body fluid component measuring device according to claim 1, wherein the biosensor part is packed with a packaging member, and at least a part of the packaging member has an antibacterial agent or an antiviral agent. 6. The body fluid component measuring device according to claim 1, wherein at least one of silver, silver ion, and silver complex salt is used as the antibacterial agent or antiviral agent. 7. The antibacterial agent or antiviral agent is characterized in that after silica thiosulfato silver complex salt is supported on silica gel, at least a part of the surface thereof is coated by hydrolysis of tetraalkoxysilane. The body fluid component measuring device described.