JP2007205989A - Biosensor and its manufacturing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biosensor capable of being manufactured without requiring many processes and many materials required in the manufacture of a conventional sensor and free from a shape change, and its manufacturing method. <P>SOLUTION: In the biosensor obtained by successively forming an electrode, a spacer and a cover on an electrically insulating substrate, the electrically insulating substrate and the cover are connected by a soft sheet. This biosensor is manufactured by forming the spacer on the surface of the electrically insulating substrate having the electrode formed thereto and the surface of the cover and folding the electrically insulating substrate and the cover at the soft sheet part connecting them so as to house the electrode in the biosensor. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a biosensor and a method for producing the same. More specifically, the present invention relates to a biosensor having a spacer layer on an electrode and a method for producing a biosensor having a folding step.

Conventionally, disposable sensors (Patent Document 1 and Patent Document 3) have a three-dimensional structure in order to ensure quantification, and further, a sample solution is automatically obtained by utilizing a capillary phenomenon (Patent Documents 5 and 6). In particular, a mechanism for introducing the sensor inside the sensor is known (Patent Document 7). The sensor having such a structure is assembled by stacking a spacer and a cover on an electrically insulating substrate. An electrode pattern is formed on the substrate, and air holes necessary for air necessary for capillary action to escape are formed on the cover. Each of these components must be punched into a predetermined shape in advance, and positioning for accurate overlaying of each component in 3D processing is also required. Becomes complicated. Furthermore, when these sensors require application of reagents such as molecular identification elements and mediators (Patent Documents 2 and 4) and formation of films (Patent Document 8) to avoid the influence of interfering substances Has a problem that it becomes a more complicated process.
JP 47-500 A JP-A-48-37187 JP-A-52-142585 JP-A-54-50396 JP 56-79242 A JP-T 61-502419 Japanese Patent Laid-Open No. 1-291153 Japanese Patent Laid-Open No. 3-202864 JP-A-5-199898 JP-A-9-222414 JP 2001-204494 A WO 01/33216 US 4225410 US 5563864 US 6071391 A. Ahmadian et al., Biotechniques, 32, 748 (2002)

  The conventional sensor described above requires many processes and materials for manufacturing, and has to take a complicated structure. As a result, a large capital investment was required for the production line, the product yield was not sufficient, and the cost was high. Naturally, the environmental load at the time of material procurement and manufacturing was also large. Furthermore, due to complicated processes, especially alignment during substrate lamination, the coefficient of variation (CV), which is an indicator of variations in sensor characteristics produced, was not sufficient. In addition, since the change in shape of the biosensor causes a decrease in measurement accuracy and reproducibility, it has been required to ensure long-term shape stability in the biosensor without causing warping of a cover or the like after manufacturing. .

In order to solve the above problems, the inventors have previously proposed a biosensor manufactured by folding, bending, or bending a single electrically insulating flat substrate. In this biosensor, an electrode is formed on a single electrically and electrically insulating substrate, and a flat substrate is three-dimensionally processed so that the electrode is arranged inside the substrate, so that the electrode arrangement is planar or three-dimensional. As described above, it enables quantitative measurement in a narrow region, and is characterized in that the main structure of the sensor is formed from a single flat substrate. Accordingly, in order to prevent the folded portion from being warped, it is necessary to attach a fixing tool to the folded portion, thermocompression bonding, cutting, or the like, and to make an empty space for the spacer formed between the substrate and the cover. Since the sample inlet is formed by using the sample solution, the sample liquid permeates into the groove formed at the boundary between the substrate near the sample inlet, the spacer, and the constituent materials of the cover, and there is a problem that the sample volume fluctuates. .
Japanese Patent Laying-Open No. 2005-233917

  The problem of the biosensor will be described in detail with reference to FIG. a) and b) differ only in the shape of the substrate 1, and show an assembly example of a conventional biosensor. i) shows a single substrate 1 having conductors 7 and 7 formed on the surface and provided with perforations 16 to be folded portions, and a resist layer 6 coated thereon. The resist layer 6 also functions as the spacer 2. ii) shows a substrate 1 having a resist layer formed on the surface and an adhesive layer 5 to be coated in the next assembly step. Here, the adhesive layer 5 also functions as the spacer 2 in the same manner as the resist layer 6. In iii), the substrate on which the adhesive layer 5 is formed is folded along the perforations 16 and shows a state before being overlapped. In iv), the biosensor 3 which is the folded molded body 14 formed by the substrate 1 is shown. In this case, since the folded portion formed along the perforation 16 may be warped depending on the thickness of the spacer such as the resist layer 6 and the adhesive layer 5, a fixing tool is attached to this portion or the warping stress is caused by thermocompression bonding. Some kind of treatment such as removing was necessary.

  As described above, such a folding sensor has succeeded in greatly improving the conventional sensor manufacturing method by greatly simplifying the manufacturing process, reducing the material, and extremely simple structure. The formed sensor needs to be fitted with a fixing tool, thermocompression-bonded, cut, or the like in the folded portion in order to prevent the folded portion from being warped, and improvement is desired.

  An object of the present invention is to provide a biosensor that can be manufactured without requiring many processes and materials as in the conventional sensor, and has no shape change, and a method for manufacturing the biosensor. .

  The object of the present invention is achieved by a biosensor in which electrodes, spacers and a cover are sequentially formed on an electrically insulating substrate, wherein the electrically insulating substrate and the cover are connected by a soft sheet. In such a biosensor, a spacer is formed on the surface of the electrically insulating substrate and the cover on which the electrode is formed, and then folded at the soft sheet portion connecting the electrically insulating substrate and the cover so that the electrode is accommodated inside the biosensor. Manufactured by folding.

  In the biosensor according to the present invention, since the electrically insulating substrate and the cover are connected by the soft sheet made of a soft material, the folding portion does not warp, and the fixture to the folding portion to prevent this is not necessary. Excellent effects such as no need for mounting, thermocompression bonding and cutting.

  Furthermore, the needle-integrated biosensor according to the present invention has a puncture needle that breaks through a soft sheet portion that connects the electrically insulating substrate and the cover when blood is collected when the puncture needle is contained and fixed in the biosensor having a folding structure. Thereafter, the puncture needle returns to the original position by the restoring force of the soft sheet material, and blood collection is introduced from the newly formed sample introduction port at that time, so that the blood collection component can be measured electrochemically. .

  As the substrate and the cover, it is sufficient if they are electrically insulating, for example, plastic, biodegradable material, paper or the like is used, and preferably polyethylene terephthalate is used. Further, an oxygen permeable material can be used, and in this case, since the reagent can be prevented from being reduced, there is an effect of suppressing variation in the measured value depending on the state of reduction.

  The electrode is formed on the substrate by a screen printing method, a vapor deposition method, a sputtering method, a foil pasting method, a plating method, etc., and the materials include carbon, silver, silver / silver chloride, platinum, gold, nickel, copper, Examples include palladium, titanium, iridium, lead, tin oxide, and platinum black. Here, as the carbon, carbon nanotubes, carbon microcoils, carbon nanohorns, fullerenes, dendrimers, or derivatives thereof can be used.

  The electrode may be a two-pole method formed by a working electrode and a counter electrode or a three-pole method formed by a working electrode and a counter electrode, a reference electrode, or an electrode method having more poles. Here, when the three-pole method is adopted, in addition to the electrochemical measurement of the measurement target substance, it is possible to measure the moving speed of the blood sample introduced into the conveyance path, thereby measuring the hematocrit value. Moreover, you may be comprised by 2 or more sets of electrode systems.

  A reagent layer (electrode reaction part) can be formed on the substrate on which the electrode is formed. The reagent layer is formed by a screen printing method or a dispenser method, and the reagent layer can be immobilized on the electrode surface or the substrate surface by an adsorption method involving drying or a covalent bonding method. Examples of the reagent arranged in the electrode reaction part of the biosensor include those containing glucose oxidase as an oxidase and potassium ferricyanide as a mediator when configured for blood glucose measurement. When the reagent is dissolved by the blood, the enzyme reaction is started. As a result, potassium ferricyanide coexisting in the reaction layer is reduced and potassium ferrocyanide, which is a reduced electron carrier, is accumulated. The amount is proportional to the substrate concentration, ie the glucose concentration in the blood. The reduced electron carrier accumulated for a certain time is oxidized by an electrochemical reaction. An electronic circuit in the main body of the measuring apparatus, which will be described later, calculates and determines the glucose concentration (blood glucose level) from the anode current measured at this time, and displays it on the display unit arranged on the main body surface.

  In addition, a surfactant and lipid can be applied around the blood collection port and on the surface of the electrode or reagent layer (electrode reaction part). By applying a surfactant or lipid, the sample can be moved smoothly.

  In the biosensor in which the reagent layer is provided on the electrode filled with the above blood collection, the blood collection and the reagent react when the blood collected from the blood collection port contacts the reagent layer on the electrode. This reaction is monitored as an electrical change at the electrode.

  Further, in the biosensor, the electrode may be defined by a resist layer, and this resist layer can be easily formed by screen printing or the like. The resist is not particularly limited as long as it does not react or dissolve with the substrate. For example, the resist is made of an ultraviolet curable vinyl / acrylic resin, a urethane acrylate resin, a polyester acrylate resin, and the like. One having a thickness of about 500 μm, preferably about 10 to 100 μm is used. The purpose of using the resist is mainly to clarify the electrode pattern and to clarify the above-mentioned definition of the electrode area, and to insulate the sample transport path where no reagent layer is present. Therefore, the resist layer may or may not be formed with the same pattern as the adhesive layer described later.

  The substrate on which the electrodes (and the resist layer) are formed and the cover are bonded via an adhesive such as an acrylic resin adhesive to constitute a biosensor. Such an adhesive layer can also be formed by a screen printing method, and is formed with a thickness of about 5 to 500 μm, preferably about 10 to 100 μm. Such an adhesive layer is the same as when a resist layer is formed. Also acts as a spacer. In addition, the said reagent can also be contained in an adhesive bond layer.

The soft sheet is made of a soft material that does not react or dissolve with the substrate and does not cause bending of the folded portion when folded, such as ultraviolet or visible light curable vinyl / acrylic resin, urethane acrylate resin, polyester. It consists of acrylate resin, polyvinyl chloride, polyethylene, polyester, polyolefin, polyvinyl fluoride, cellophane, etc., and these are (1) screen printing method, (2) thermocompression laminating method, (3) method using adhesive tape or ( 4) It can be formed preferably by a method using an adhesive tape, such as a method of fixing the material formed into a sheet shape to a substrate and a cover using an adhesive. The specific method is as follows.
(1) After disposing a release plate between the electrically insulating substrate and the cover, a soft sheet is formed by a screen printing method. Examples of the material of the release plate include silicone, tetrafluoroethylene, polyethylene, and the like. A material obtained by coating these release materials on the surface of an arbitrary plate material can also be used. The release plate is removed by peeling when the flexible sheet portion between the electrically insulating substrate and the cover is folded.
(2) Use adhesive tape such as cellophane tape as a flexible sheet to connect the substrate and cover. However, since the adhesive portion is exposed between the substrate and the cover, it is preferable to cut the exposed portion after forming the sensor.
(3) After forming an adhesive layer on the substrate and the cover, a soft sheet is laminated and fixed.
(4) The pressure-bonding surface of the polypropylene sheet that can be thermocompression-bonded is stacked on the electrode forming substrate, and thermocompression bonded under the conditions of 100 ° C. and 250 kg / cm ² . At this time, it is sufficient to add the thermocompression bonding for the portion that needs to maintain the flexibility of the sheet. As such a thermocompression-bondable sheet, a commercially available laminate material such as polyvinyl chloride, polyethylene, polyester, polyolefin, and polyvinyl fluoride can be used as it is.
Japanese Patent Laid-Open No. 56-42652

  In connecting the substrate and the cover using such a soft sheet, the substrate and the cover are connected without any interval, or the distance between the substrate and the cover, that is, the length of the soft sheet connecting the substrate and the cover is 10 mm. In the following, it can be connected after preferably 0.5 to 10 mm, more preferably 1.0 to 5.0 mm. In the former case, placing the flexible sheet inside the biosensor has the effect that it is not necessary to consider the thickness of the spacer during manufacturing, while in the latter case, the connection between the substrate and the cover is achieved. A sample introduction port for introducing a sample to be measured can be provided in the portion, and when a puncture needle is disposed inside the biosensor and a vacuum is applied, a desired vacuum atmosphere space can be set.

  In addition, the biosensor having the above configuration is provided with a soft sheet so as to connect a long substrate having a large number of electrodes and a long cover, and then folded along a portion connecting the substrate and cover of the soft sheet. By punching into a sensor shape, a large number of biosensors can be manufactured at once. The needle-integrated biosensor manufactured by such a manufacturing method has very good reproducibility and has features that cannot be achieved by a conventional lamination method.

  A puncture needle for collecting body fluid from the skin of the subject can also be disposed on the adhesive layer. As the puncture needle, it is necessary to puncture the subject, and it is desirable that the puncture needle is strong and sharp enough to withstand this, and a thin puncture needle is preferable in order to suppress pain during puncture. Specifically, a 21-33 gauge thing by Terumo company is used. The puncture needle may be a hollow needle or a rod-like needle as long as it can penetrate the subject's skin. Furthermore, since the puncture needle needs to be hygienicly stored in the biosensor until it is used, a photocatalytic function effective for antibacterial and antiviral effects may be imparted to the needle tip surface. In that case, a film of titanium oxide or titanium dioxide is desirable.

  Here, there is a possibility that the puncture needle contained in the inside of the sample conveyance path is contaminated by the application of the reagent layer, surfactant or lipid into the sample transport path. In order to prevent such contamination, it is preferable not to apply these reagents around the tip of the puncture needle, or to isolate them from the reagent layer in the sample transport path by a resist layer or an adhesive layer.

  The needle-integrated biosensor having the above-described configuration, in which the inside of the biosensor is sealed, is manufactured under a negative pressure condition, preferably a vacuum condition, than the outside air, so that the sensor is in a negative pressure state. In addition to the capillary phenomenon, the suction means utilizing the difference from the external pressure can be used in combination for the movement of blood collection into the sample conveyance path after puncturing. By adopting such a configuration, blood can be collected smoothly. Here, a blood collection introduction guide can be provided in the vicinity of the puncture blood collection port. Examples of the material for the blood collection introduction guide include gels, elastic materials, and foamable materials, and the same material as the resist can be used. A blood collection introduction guide made of such a material maintains the negative pressure and also has the effect of improving the adhesion between the skin of the subject and the puncture blood collection port.

  In the needle-integrated biosensor of the present invention, it is desirable that a series of operations of puncture, blood collection, and measurement be performed by a measurement device having a puncture drive. In this case, for example, it is desirable that the puncture drive has a mechanism in which the needle penetrates the soft material of the biosensor and breaks through the skin of the subject, and a mechanism that quickly returns to the original position immediately after the puncture.

  An example of structural features of the measuring device will be described. In this measurement apparatus, the puncture needle drive unit and the measurement apparatus unit are integrated, and the puncture needle drive unit includes a trigger unit, a puncture start button unit, and a drive unit using an elastic body such as a spring. On the other hand, for the measuring device section, the sensor introduction section, the connector, the electrochemical measurement circuit, the memory section, the operation panel, the measurement section that measures the electrical values at the electrodes of the biosensor, and the display that displays the measurement values at the measurement section Further, a radio wave, for example, Bluetooth (registered trademark) can be mounted as a wireless means. With such a slide structure, since the puncture drive is received while the needle-integrated biosensor is securely held, the strength of the entire measuring apparatus can be increased. The measurement device can further include a mechanism that can recognize the left-right asymmetric structure with the puncture needle of the needle-integrated biosensor as the center line by the protruding portion of the measurement terminal.

  The puncturing drive of the measuring device is preferably a mechanism that returns quickly after tapping the upper part of the needle-integrated biosensor in the vertical direction, and preferably has a mechanism that can adjust the depth of puncturing the skin of the subject.

  The measuring device must have voice guidance and voice recognition functions for visual impairment caused by diabetes, measurement data management functions using the built-in radio clock, communication functions for medical data such as measurement data, and charging functions. Can do.

  A measurement method in the measurement unit of the measurement apparatus is not particularly limited, and potential step chronoamperometry, coulometry, cyclic voltammetry, or the like can be used.

  As described above, the needle-integrated biosensor of the present invention does not limit the user, that is, can handle a universal project.

  The needle-integrated biosensor according to the embodiment of the present invention will be described in detail with reference to the drawings. However, the present invention is not limited to the following examples unless it exceeds the gist.

  FIG. 1 is a view showing an assembly example of a biosensor according to the present invention. In (a), an electrically insulating substrate 1 and a resist layer 6 are shown. A conductor 7 is provided on the surface of the substrate 1. (b) shows the adhesive layer 5 disposed on the substrate 1 provided with the resist layer 6. The resist layer 6 and the adhesive layer 5 shown here also function as a spacer 2 for forming the sample transport path and the electrode reaction part. (c) shows a flexible sheet 41 having an electrically insulating cover 15 member and an adhesive layer 5 on the surface in addition to the substrate 1. The soft sheet 41 connects the substrate 1 and the cover 15 to the outside corresponding to the production of the biosensor by the adhesive layer 5 as shown in (d). By making the soft sheet 41 function as a connection for folding and overlapping the cover 15 member and the substrate 1 in this state, the biosensor 3 which is the folded molded body 14 as shown in (e) can be manufactured. The A-A ′ cross section shown here is shown in (f). The substrate 1 and the cover 15 can be made into a folded molded body by using a soft sheet having an adhesive layer 5 exemplified by an adhesive tape as a tie, and the spacer 2 provided on the substrate 1 is free at this time. The part forms the biosensor 3 by forming a space for forming the sample transport path 8 and the electrode reaction part 13 where the electrode 10 is exposed. Here, the soft sheet 41 provided with the adhesive layer 5 in advance is used. However, the adhesive layer 5 is provided on the substrate 1 and the cover 15 where the soft sheet 41 is arranged, and the adhesive layer 5 is provided there. A biosensor may be manufactured by bonding a non-soft sheet 41, or a biosensor may be manufactured by forming a soft sheet by another method described above. In this way, by attaching a soft sheet with an adhesive layer on the surface to the outside of the biosensor, the substrate and the cover are bonded to each other so that the electrode and the spacer layer are arranged inside, and the biosensor is a folded molded body Is produced. Unlike the case where a soft sheet as shown in FIG. 3 to be described later is disposed inside the biosensor because the soft sheet is provided on the side corresponding to the outside when the biosensor is manufactured, the resist layer is formed. In this case, there is an advantage that it is not necessary to consider the presence of the soft sheet.

  FIG. 2 is a diagram showing a manufacturing example of the biosensor according to the present invention shown in FIG. This figure shows a process of manufacturing a plurality (five) of biosensors 3 together. (a) includes five sets of two conductors 7, a substrate 1 on which a resist layer 6 and an adhesive layer 5 are arranged as spacers 2, a cover 15 member covering the substrate 1, and an adhesive A soft sheet provided with layer 5 is shown. The substrate 1 and the cover 15 can also be formed by cutting out from a single long substrate. A state in which the adhesive layer 5 of the soft sheet 41 is pasted so as to connect the substrate 1 and the cover 15 is shown in FIG. Here, (b) and (i) show the side that constitutes the inside of the biosensor of the substrate 1, and (b) and (ii) show the side that constitutes the outside of the biosensor of the substrate 1. In this state, the folded molded body 14 shown in (c) is manufactured by folding the electrode 1 and the like on the substrate 1 with the soft sheet as a boundary so that the cover 15 member is covered. As shown in (c), since the folding accuracy of the substrate 1 and the cover 15 is increased by forming a plurality of biosensors 3 together in the production of the folded molded body 14, it is compared with the existing lamination method. This eliminates the need for a special positioning mechanism and makes it possible to produce a biosensor with excellent economic efficiency. (d) has shown the state cut out to each sensor 3 along the cutting line shown by the dotted line in (c). The configuration of the biosensor thus manufactured is shown in (e) and (f).

  FIG. 3 is a view showing another assembly example of the biosensor according to the present invention. The difference from FIG. 1 is that the flexible sheet 41 connects the substrate 1 and the cover 15 to the inside corresponding to the biosensor production as shown in FIG. Therefore, in (b), there is a portion where the arrangement of the adhesive layer 5 does not coincide with the resist 6, and a mode in which the soft sheet 41 shown in (c) is attached to this portion is shown in (d).

  FIG. 4 shows an example of manufacturing the biosensor shown in FIG. In the present embodiment in which the flexible sheet 41 connects the substrate 1 and the cover 15 inside the biosensor, after the conductor 7 or the like is formed on the substrate 1, the substrate 1 and the cover 15 are connected without moving them. Since the flexible sheet 41 can be arranged in the manner described above, unlike the embodiment of FIG. 2 in which the flexible sheet 41 connects the substrate 1 and the cover 15 outside the biosensor, the biosensor can be manufactured more easily and accurately. There is an effect.

  FIG. 5 is a view showing an assembly example of the suction blood collection type needle integrated biosensor according to the present invention. (a) to (d) are examples of manufacturing a needle-integrated biosensor, i) is a constituent material required for manufacturing the needle-integrated biosensor, and ii) is a molded body thereof. (a) (i) shows a substrate 1 having a conductor 7 on its surface and a resist 6. The resist 6 has a through hole 37 for defining the electrode area. In (b) (i), a resist 6 is provided on the surface of the substrate 1, and the adhesive layer 5 and the surface of the cover-side adhesive layer 5 are formed on the surface of the resist 6 formed in (a) (ii). The puncture needle portion 33 to be placed on the substrate and the ventilation filter 25 to be placed on the empty portion of the substrate side adhesive layer 5 are shown, and the state in which they are placed on the surface of the resist 6 is shown in (b) (ii). . (c) (i) shows a state in which the adhesive layer 5 is further disposed on the surface of the puncture needle portion 33. Here, the cover-side adhesive layer 5 sandwiching the puncture needle portion 33 is provided with a concave recess for causing the puncture needle 20 to protrude from the adhesive layer 5. This depression serves as a sample transport path when the needle-integrated biosensor is formed ((c) (ii)). Further, here, a state is shown in which a soft sheet 41 provided with an adhesive layer 5 on one side connects the substrate 1 and the cover 15 corresponding to the outside of the biosensor. Although the adhesive layer 5 is not provided in the center of the soft sheet 41, this portion serves as a puncture film during puncture. (d) (i) shows the molded body shown in (c) (ii) from the back, and a blood collection introduction guide 36 made of a soft material is attached to the bent portion of the soft sheet 41. A needle-integrated biosensor 29 formed by folding the substrate 1 and the cover 15 inside is shown in (d) (ii).

  (e) and (f) show the A-A ′ and B-B ′ cross sections shown in (d) and (ii), respectively. In (e), the electrode 10 formed in the empty portion formed by the through hole provided in the resist layer 6 on the substrate 1, the surrounding electrode reaction portion 13, and the sample transport path 8 are within the bending space of the soft sheet 41. The space 26 is also widely provided in the center of the substrate 1 in accordance with the pattern of the adhesive layer 5. This space 26 can make the internal pressure of the needle-integrated biosensor unit 40 in a vacuum (negative pressure) state by evacuating the atmosphere during the folding process, and is a needle-integrated biosensor for suction blood collection. be able to. The puncture needle 20 is protected by the adhesive layer 5 except for the puncture tip, and direct contact with the reagent provided in the electrode reaction unit 13 is prevented. Further, there is a soft sheet 41 in the puncture direction, and this portion functions as a puncture blood collection port 32 and functions as a puncture membrane in which a through hole is formed by puncture. At that time, the blood collection introduction guide 36 provided in the vicinity of the puncture membrane is used to smoothly guide the blood collection from the through hole provided in the puncture membrane to the inside of the sensor 29, and may be any one having high adhesion to the skin. . (f) is a cross-sectional view at a part different from (e), and there is no vacuum space including the sample transport path 8 shown in (e), but a vacuum space 26 is wide in the center of the substrate. Is provided. By adopting such a structure, the sample volume can be reduced, while blood can be collected more smoothly by taking a wide vacuum volume.

  FIG. 6 is a diagram showing an example of use of the suction blood collection type needle integrated biosensor shown in FIG. In this suction blood collection type needle integrated biosensor 29, as shown in (a), the puncture blood collection port 32 is brought close to the skin 27 of the subject, the blood collection introduction guide 36 is brought into close contact, and the sensor 29 is pressed against the skin 27. As shown in (b), the puncture needle 20 breaks through the portion of the soft sheet 41 where the adhesive layer is not provided, and punctures the skin. At this time, the space 26 formed by bending the soft sheet 41 is temporarily contracted due to the flexibility of the soft sheet 41. Next, after the skin 27 is punctured, when the elasticity of the soft sheet 41 works and the needle 20 quickly returns to a fixed position, the blood collection 24 passes through the through-hole 32 formed at the time of puncture and the sample transport path 8 and the electrode reaction unit 13 Led to. At this time, since the internal negative pressure works, the blood collection 24 can be introduced more smoothly. Here, a ventilation filter 25 is provided between the electrode reaction part 13 and the wide vacuum space 26 provided in the center part, so that the blood collection 24 cannot reach the inside from the electrode reaction part 13. As described above, blood sampling is introduced into the sensor, and blood components are measured.

  The biosensor according to the present invention is a home-use self-diagnosis blood glucose meter, urine sugar meter, glycated hemoglobin meter, lactic acid meter, cholesterol meter that electrochemically measures the component concentration of various liquids using an enzyme or the like. It is effectively used as a biosensor for use in uric acid meters, protein meters, single nucleotide polymorphism sensors, DNA chips used for genetic diagnosis, as well as alcohol meters, glutamic acid meters, pyruvic acid meters, pH meters and the like.

It is a figure which shows one assembly example of the biosensor which concerns on this invention. It is a figure which shows one manufacture example of the biosensor which concerns on this invention. It is a figure which shows the other assembly example of the biosensor which concerns on this invention. It is a figure which shows the other manufacture example of the biosensor which concerns on this invention. It is a figure which shows one assembly example of the suction blood collection type | mold needle integrated biosensor which concerns on this invention. It is a figure which shows one manufacture example of the suction blood collection type | mold needle | hook integrated biosensor which concerns on this invention. It is a figure which shows one assembly example of the conventional biosensor.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Board | substrate 2 Spacer 3 Biosensor 5 Adhesive layer 6 Resist layer 7 Conductor 8 Sample conveyance path 9 Sample inlet 10 Electrode 11 Terminal 12 Air outlet 13 Electrode reaction part (reagent layer)
14 Folding molding 15 Cover 16 Perforation 17 Sample liquid 19 Puncture needle support 20 Puncture needle 25 Ventilation filter 26 Vacuum space 27 Finger 29 Needle integrated biosensor 32 Puncture blood collection port 33 Puncture needle portion 36 Blood collection introduction guide 37 Through hole 40 Biosensor unit 41 Soft sheet

Claims (13)

In a biosensor in which electrodes, spacers, and a cover are sequentially formed on an electrically insulating substrate,
A biosensor characterized in that an electrically insulating substrate and a cover are connected by a soft sheet.   The biosensor according to claim 1, wherein the soft sheet connecting the electrically insulating substrate and the cover is provided on at least one of the inside and the outside of the biosensor.   The biosensor according to claim 1, wherein the length of the flexible sheet connecting the electrically insulating substrate and the cover is 10 mm or less.   The biosensor according to claim 3, wherein a sample introduction port for introducing a sample to be measured is provided in the soft sheet portion connecting the electrically insulating substrate and the cover.   The biosensor according to claim 1, wherein the soft material forming the soft sheet is made of vinyl / acrylic resin, urethane acrylate resin, polyester acrylate resin, polyvinyl chloride, polyethylene, polyester, polyolefin, polyvinyl fluoride, or cellophane.   The biosensor according to claim 1, wherein the soft sheet is an adhesive tape having an adhesive layer on one side or both sides.   The biosensor according to claim 1, wherein at least one reagent layer of an enzyme, a mediator or a surfactant is formed on the electrode.   A biosensor according to claim 1, further comprising a puncture needle fixed perpendicularly to a soft sheet portion connecting an electrically insulating substrate and a cover.   At the time of puncturing the subject, the puncture needle breaks through the soft sheet part connecting the electrically insulating substrate and the cover, pierces the subject's skin, and then the puncture needle is pulled back from the subject's skin by the restoring force of the soft sheet material. 9. The needle-integrated biosensor according to claim 8, wherein the body fluid is introduced into the sample transport path of the biosensor through the through hole of the soft sheet portion generated at that time.   The needle-integrated biosensor according to claim 8, wherein a blood collection introduction guide is provided on a soft sheet connecting the electrically insulating substrate and the cover.   The needle-integrated biosensor according to claim 8, wherein the inside of the biosensor is maintained at a negative pressure or a vacuum, and blood is collected using a suction force based on a difference from the external pressure at the time of puncture blood collection.   The biosensor according to any one of claims 1 to 7, wherein after the spacer is formed on the surface of the electrically insulating substrate and the cover on which the electrode is formed, and the electrode, the electrically insulating substrate and A method of manufacturing a biosensor manufactured by folding at a soft sheet part connecting covers. The biosensor manufacturing method according to claim 12, further comprising a puncture needle fixedly disposed inside the biosensor.

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