JP2006239062A - Biosensor integral with needle - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biosensor integral with a needle which is easy to assemble because of a simple structure, while having enough strength, can certainly execute the collection of the sample body fluids, has a puncture needle which does not contaminate a reagent layer, is easy to carry because of a simple packaging, and is hygienic even after use. <P>SOLUTION: The biosensor integral with the needle is constituted by integrating the puncture needle to puncture the skin of a subject for the collection of the body fluids and a main body of the biosensor for executing analysis of the body fluids, wherein the puncture needle is constituted to drive and penetrate the main body of the biosensor in a vertical direction and to puncture the skin by an external driving means. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a needle-integrated biosensor. More specifically, a needle integrated type having a configuration in which a puncture needle for piercing the skin to obtain a body fluid (blood etc.) and a biosensor for collecting and analyzing the body fluid taken out on the surface of the skin are integrated. It relates to biosensors.

Conventionally, a diabetic patient himself collects blood and measures a blood glucose level which is a glucose level in blood. In this case, the patient uses a blood collection device called a lancet that attaches and detaches a blood collection needle, collects blood by inserting a blood collection needle into his fingertip or arm, and moves the collected blood to a blood glucose analyzer to measure the blood glucose level. is doing. In such a measurement method, the patient must carry a set of measuring instruments consisting of several points, such as a blood glucose analyzer, a lancet, a blood collection needle and an analytical element, and combine them when necessary to perform the measurement. However, it takes a lot of training and it takes a considerable amount of time before the patient can make reliable measurements. Actually, measurements at sites other than the fingertips and forearms (abdominal wall, earlobe, etc.) are difficult even for an expert. In recent years, biosensors that can be measured with a sample volume of 1 μl or less have been developed due to the need for less invasive specimen supply with less pain. The work of supplying accurately becomes very difficult. As a result, the measurement failed, and the patient as the measurement subject had to puncture again and replace the biosensor, and the measurement had to be performed again.
JP-A-9-266898 Japanese Patent Publication No. 8-20412

Thus, several needle-integrated biosensors have been devised. First, in the needle-integrated biosensor disclosed in Patent Document 3, the puncture needle and the biosensor are set at different positions inside a pen-type (two-color ballpoint pen-like) measuring device equipped with a puncture needle drive unit. The tip of a pen-like measuring device is applied to the skin of the subject and punctured, and then the biosensor is exposed to the tip and blood is collected to measure blood glucose. However, this method does not eliminate the troublesomeness of setting the needle and the biosensor in the measuring device.
JP 2000-217804 A

Further, in the needle integrated biosensor disclosed in Patent Document 4, the puncture needle is entrusted to external drive, and the puncture needle moves in parallel along the longitudinal direction of the elongated piece-like biosensor. Have taken. However, in this type, since the puncture needle is exposed from the biosensor, a cover for protecting the tip of the puncture needle is necessary, and the puncture needle moves through the blood collection conveyance path and the reagent layer of the biosensor, so that the puncture needle is covered. There is a risk that the surface of the puncture needle is contaminated with the reagent before the skin of the specimen is pierced.
Republished 2002-056769

  Furthermore, the conventional needle-integrated biosensor has a large amount of blood necessary as a sample solution and has an influence such as entering a useless space. This also has problems such as adhesion between the puncture blood collection port and the skin of the subject. In addition, the packaging for preventing infection and reagent deterioration is costly, and after disposal, there is insufficient consideration for infectious diseases, etc., and a puncture drive is provided on the measuring device side. Many problems remain, such as the structure of a needle-integrated biosensor unit that cannot withstand the impact of driving during puncture.

  The object of the present invention is that the structure is simple and easy to assemble while having strength, the sample body fluid can be collected reliably without waste, the puncture needle is not contaminated by the reagent layer, and easy to carry by simple packaging. Another object is to provide a needle-integrated biosensor that is hygienic after use.

  An object of the present invention is that a puncture needle for puncturing the skin of a subject and collecting a body fluid and a biosensor body for analyzing body fluid are configured integrally, and the puncture needle is externally connected. This is achieved by a needle-integrated biosensor configured to drive the biosensor body vertically by driving means to penetrate and penetrate the skin.

  The needle-integrated biosensor according to the present invention has a simple structure and is easy to assemble while having strength, and can reliably collect a sample body fluid without waste, and the puncture needle is not contaminated by the reagent layer, and simple packaging It is easy to carry and has the characteristics of being hygienic after use, it can be used as a cartridge. In addition, the function to reflect data such as the temperature of the measurement environment and blood hematocrit value in accurate blood sugar level calculation (temperature correction and hematocrit value correction), calibration function to compensate for the lot difference, automatic display and puncture part in the dark In addition to lighting function, voice guidance function and voice recognition function corresponding to visual impairment due to diabetes disease, measurement data management function by built-in radio clock, communication function to medical institutions such as measurement data, charging function, etc. It is possible to provide a measuring device for a needle-integrated biosensor that is easy to carry and supports universal projects.

  The needle-integrated biosensor according to the present invention includes a biosensor that can be easily manufactured, and can be printed on an insulating substrate such as a plastic by electrode printing and an adhesive layer as a spacer by screen printing. This biosensor will be described in more detail.

Including a biosensor insulating substrate, an insulating cover that is bonded to the substrate via an adhesive layer that also serves as a spacer layer, and an electrode on the substrate formed in a space between the substrate and the cover. In the sandwiched space, a blood collection conveyance path extending from the puncture blood collection port to the air discharge port through the electrode is provided, and the puncture needle penetrating membrane (hereinafter referred to as puncture membrane), substrate, spacer, and cover are arranged in this order. The cover is provided with a through hole for collecting body fluid from below as a puncture blood collection port, a substrate through hole is also provided at a position overlapping the through hole, and a puncture membrane is provided thereon, from the cover A puncture needle penetration path is provided over the membrane.

  In the biosensor in which the reagent layer is provided on the electrode through which the sample transport path passes, the sample and the reagent react when the sample sent from the sample transport path comes into contact with the reagent layer on the electrode. This reaction is monitored as an electrical change in the electrode.

  In the above configuration, a surfactant and a lipid can be applied to the periphery of the puncture blood collection port on the cover member and the blood collection conveyance path surface. By applying a surfactant or lipid, the sample can be moved smoothly.

  In addition, in the blood collection conveyance path near the puncture blood collection port, the adhesive layer pattern can have a tapered structure in order to facilitate the introduction of blood collection. Similarly, in order to suppress introduction of blood more than necessary, the air outlet may be narrowed or a breathable film may be provided at the air outlet.

  Furthermore, for efficient introduction of blood collection into the biosensor, the material of the puncture blood collection port can be replaced with a soft material for the purpose of improving the adhesion between the puncture blood collection port and the skin of the subject. As the soft material, a gel, an elastic material, a foamable material, or the like can be used. As another method for efficiently introducing blood into the biosensor, a convex structure can be provided around or outside the puncture blood collection port. In this case, a gel, an elastic material, a foamable material, or the like can be used as a material having a convex structure. For example, if the outer contour of the puncture blood collection port has a convex structure, the skin of the subject can be raised by pressing the puncture portion against the needle-integrated biosensor before puncturing, and the apex can be punctured. The modification to the puncture blood collection port described above is useful as a puncture blood collection port guide for the user to sensuously grasp the puncture position, and can also show an effect as a non-slip.

  Furthermore, in order to visually grasp the puncture position, illumination means from the sample introduction port can be used. Illumination is irradiation of light in the visible light region, and preferably a light emitter such as a laser beam or an organic EL by a light emitting diode or the like. When the light emitter is a light emitting diode, the puncture site can be illuminated by forming the puncture needle housing, the plate member of the biosensor, the puncture membrane, and the like with a transparent material and incorporating the light emitting diode therein. If only the bottom plate of the puncture needle housing and the biosensor cover among the puncture needle housing and biosensor formed of a transparent material as described above are members that absorb the color, the sample can be removed from the sample introduction port. Since only light is irradiated, it can be a spotlight at the puncture site. When using organic EL, at least part or all of the bottom plate of the puncture needle housing and the biosensor cover may be surface-treated with organic EL. As a power supply source in the case of adopting the irradiation means described above, there is a battery of a measuring device. In this case, it is desirable to supply power through the terminals of the biosensor.

  As the plate member of the biosensor, plastic, biodegradable material, paper, or the like can be selected as long as it is electrically insulating. A suitable example of plastic is polyethylene terephthalate.

  The electrode can be composed of carbon, silver, silver / silver chloride, platinum, gold, nickel, copper, palladium, titanium, iridium, lead, tin oxide, platinum black, and the like. As carbon, carbon nanotubes, carbon microcoils, carbon nanohorns, fullerenes, dendrimers, or derivatives thereof can be used. Such an electrode can be formed on a plate member by a screen printing method, a vapor deposition method, a sputtering method, a foil bonding method, a plating method, or the like.

  The electrode may be a two-pole method formed with a working electrode and a counter electrode or a three-pole method formed with a working electrode and a counter electrode, a reference electrode, or an electrode method with more poles. Here, when the tripolar 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 transport path, thereby measuring the hematocrit value. Moreover, you may be comprised by 2 or more sets of electrode systems.

  The adhesive layer can also be formed by a screen printing method. As the adhesive, for example, an acrylic resin adhesive is used, and the adhesive layer formed with a thickness of about 5 to 500 mm, preferably about 10 to 100 mm also functions as a spacer. Moreover, you may contain a reagent in an adhesive bond layer.

  Further, in the biosensor, the electrode may be defined by a resist layer, and the resist layer can be easily formed by screen printing or the like.

  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 plate member surface by an adsorption method involving drying or a covalent bonding method.

  When the needle-integrated biosensor of the present invention is configured for blood glucose measurement, the reaction reagent disposed in the reaction part of the biosensor includes, for example, glucose oxidase that is an oxidase and potassium ferricyanide as a mediator. Adopted.

  When the reaction part 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. The electronic circuit in the measuring apparatus main body 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 as described above.

  The needle-integrated biosensor device of the present invention includes any one of the biosensors as described above, a measurement unit that measures an electrical value at an electrode of the biosensor, and a display unit that displays a measurement value at the measurement unit. As a measuring method in this measuring unit, a potential step chronoamperometry method, a coulometry method, a cyclic voltammetry method, or the like is used. Furthermore, radio waves such as Bluetooth (registered trademark) can be mounted on the apparatus as wireless means.

Needle-integrated biosensor A needle-integrated biosensor penetrates the biosensor through a site different from the reagent layer, and a puncture needle for collecting body fluid from the skin of the subject is placed in the same container together with the biosensor. It is integrally formed by being divided into upper and lower parts with the substrate as a boundary.

  In the puncture needle housing of the needle-integrated biosensor, an elastic body for returning to the original position immediately after the puncture needle protrudes to the outside by external driving and a guide for driving the puncture needle as prescribed are provided. . Since the needle-integrated biosensor can be easily packaged, it is hygienic all the time before and after use, and since it is a cartridge type, it can be stored in a dedicated container that is convenient to carry, and anyone can easily and easily It can also be securely attached to the measuring device. By adopting this cartridge type aspect, the convenience of the needle-integrated biosensor can be dramatically improved as compared with the conventional method. More specifically, the structure inside the puncture needle housing will be described.

  The puncture needle is housed in a housing that is driven in the vertical direction, and the puncture needle driven by an external drive means penetrates the biosensor in the puncture needle housing and punctures the skin of the subject. It is necessary to provide a mechanism for returning to the position. As an example of a method that satisfies this condition, in addition to the puncture needle housing, a guide for minimizing orbital deviation may be provided inside. For example, the guide protects the periphery of the puncture needle provided below the puncture needle fixing substrate that is driven from the outside by a cylindrical guide, and also on the puncture needle folder substrate of the puncture needle housing. By providing a cylindrical guide with a small radius, the guide on the puncture needle folder board enters the inside of the guide on the puncture needle fixing board with a slight gap during puncturing, ensuring the trajectory of the puncture needle as specified. it can.

  In addition, an elastic body for returning the puncture needle protruding outside the biosensor to the original position by external driving is required. As this elastic body, for example, a winding spring can be considered. The winding spring can be provided outside a cylindrical guide provided below the puncture needle fixing substrate in the puncture needle housing. In this case, the movement of the winding spring can be defined only in the vertical direction by the presence of the guide that defines the trajectory of the puncture needle. In addition to the winding spring, the use of a stretchable film can be considered. In this case, by fixing the stretchable film to both the puncture needle fixing substrate and the upper part of the puncture needle housing, the same effect as the winding spring can be obtained. That is, when the puncture needle fixing substrate moves from the upper side to the lower side by external driving, the stretchable film is extended with the distance between both the puncture needle fixing substrate and the upper portion of the puncture needle housing being opened. Then, this recoil occurs with the retreat of the external drive, and the puncture needle can return to the original position.

  When the stretchable film is used for the above purpose, the inside of the puncture needle housing can easily ensure airtightness. Accordingly, by providing the puncture needle housing with a mechanism for adjusting the internal air pressure, it becomes possible to take in the body fluid after puncture into the biosensor with suction force. As a tool for realizing this mechanism, there is a backflow prevention valve. That is, the inside of the puncture needle housing temporarily becomes high pressure due to the external drive. After this pressure is lowered by the backflow prevention valve, a force to return to the original state acts on the stretchable film. As a result, the air pressure inside the housing is lower than the external air pressure, which can be a suction force for collecting body fluid. Further, since the suction force of blood collection can be changed by changing the stretchability of the stretchable film, it is possible to reflect the difference in the user's constitution (blood viscosity).

  Next, the puncture membrane will be described. The puncture membrane on the biosensor substrate portion needs not to prevent introduction of blood collection into the sensor by capillary action after puncture. In addition, if the puncture membrane is a material that does not change the volume in the transport path with the introduction of blood collection, the puncture membrane can be made to serve as a substrate by omitting the plate member of the substrate. In this case, if the puncture film is in close contact with the puncture needle folder substrate, the puncture film does not need to be hard, and therefore, a soft material through which the puncture needle easily penetrates can be selected. The puncture membrane satisfying such conditions is desirably formed of natural materials, plastics, biodegradable materials, shape memory materials, etc., and more preferably, natural materials include paper, collagen, cellulose, cotton, etc. In plastics, foamable materials, especially artificial skin, elastic materials, film forming materials, etc., in film forming materials cellophane, polyvinylidene chloride, polyvinyl chloride, polyvinyl acetate, polyimide, polyethylene, polyethylene terephthalate, polyvinyl alcohol, polylactic acid , Polyester, polyamide, ethylene-vinyl alcohol copolymer, fluorine resin, and the like.

  Further, the structure of the puncture membrane may have a multilayer structure of two or more layers made of different materials. For example, in the case of a two-layer film, the lower film may be a thin film with no holes, and the upper film may be a bulky film for filling holes punctured by puncture. The puncture membrane is desirably a thin film having a thickness of 100 μm or less in order to improve the passage of the puncture needle. Further, instead of the puncture membrane, a shutter that opens and closes in conjunction with the movement of the puncture needle may be provided on the cover portion of the biosensor.

  Since the puncture membrane is arranged independently of the reagent layer, it is possible to prevent the reagent from adhering to the needle tip due to puncture, so that it is safe and hygienic.

  The puncture needle used for the needle-integrated biosensor needs to penetrate the puncture membrane and puncture the subject. Therefore, it is desirable that the puncture needle has some strength and is sharp. Further, a thin puncture needle is preferable in order to suppress pain during puncture. Furthermore, since the puncture needle needs to be stored hygienically in the housing until it is used, a photocatalytic function effective for antibacterial and antiviral effects may be imparted to the surface of the needle. In that case, a film of titanium oxide or titanium dioxide is desirable.

  As a method for hygienically storing the needle-integrated biosensor of the present invention until use, there is a simple packaging method using an adhesive protective film (hereinafter referred to as a protective film). The needle-integrated biosensor needs to be packaged in a puncture blood collection port and / or an air discharge port of the biosensor that comes into contact with the outside air, and in the upper portion of the puncture needle housing. The above wrapping means can prevent exposure of the puncture needle, so that it is important not only for hygiene but also for safety.

  In the case of packaging in the biosensor of the present invention, packaging in a puncture blood sampling port that is in direct contact with outside air is effective. A protective film that can be bonded and peeled is most suitable as a simple package used in this case. Furthermore, the protective film can be used as a knob for adhering and peeling the protective film by providing a non-adhesive portion in addition to at least an adhesive layer that can be bonded and peeled. Furthermore, repackaging with the protective film after peeling becomes possible by fixing at least a part of the protective film to the biosensor substrate with a strong adhesive layer.

  Moreover, there is a cutting line at the boundary between the part of the biosensor that does not include the electrode of the insulating substrate and the part of the biosensor that includes the electrode of the insulating substrate, and this cutting line also matches the cutting line on the substrate in the cover member. The biosensor with the air discharge port opened can be used by separating the portion of the insulating substrate that does not include the electrode along the cutting line. In this case, at least a part of the opening cap portion has a portion that strongly adheres to the protective film, and the protective film is further provided with an adhesive portion that can be attached to and detached from the adhesive portion with the biosensor body. By separating the cap from the biosensor body during use, it is possible to adopt a structure in which the protective film can be peeled off at the same time. If it is this structure, it will become possible to re-apply the packaging body which consists of a cap and a protective film in the original state after use of a biosensor.

Similarly, considering the packaging form of the needle-integrated biosensor, it is necessary to protect the terminals of the biosensor. In this case, the terminal on the insulating substrate can be covered with the cover.
The cover that covers the terminal may be provided with a foldable return line without providing an adhesive layer, and the external terminal may be exposed along the return line. In this case, the fold line may be a perforation or a cut line.

  Next, the example of the simple packaging method to the upper part of a puncture needle housing is given. First, as a first means, an example of using a cap will be given. The cap can be packaged most simply by simply fitting it into the top of the puncture needle housing. In addition, by connecting the cap to the housing with a scissors, the cap is kept open during use of the needle-integrated biosensor, and the cap is re-covered with the cap after use, so that the needle-integrated biosensor after use is used. The sensor can be discarded without being affected by infection.

  As a second means, an example of using a protective film is given. The protective film can be bonded and peeled off similar to the one used in the biosensor, and a non-adhesive part may be provided as a knob, and at least a part of the protective film may be fixed to the puncture needle housing with a strong adhesive layer. . By providing a strong adhesive layer, the protective film remains peeled off during use of the needle-integrated biosensor, and after use, the needle-integrated biosensor is affected by infection, etc. Can be discarded without receiving.

  Furthermore, as a third means, the case where the elastic film described above is provided on the upper portion of the puncture needle housing can be applied as it is. That is, in this embodiment, since the inside of the puncture needle housing is kept airtight, this makes the needle-integrated biosensor cartridge including the puncture needle housing an unnecessary form of packaging. If it is this aspect, since simple packaging of the puncture needle housing part is unnecessary, it is possible to omit both the operation of unpacking before use (labor) and the operation of repackaging. It is the most convenient packaging means.

  A box capable of storing a plurality of cartridges together can be used as a means for improving the portability of the needle-integrated biosensor cartridge together with the measuring device. Even if the storage box is a type that can store, for example, 10 cartridges, the storage box can be kept as small as a ballpoint pen. The cartridge of the present invention can be carried in such a form because it has a safe shape that is difficult for the user to be injured, including elements that are normally difficult to wrap, such as terminals of biosensors.

Measuring device for needle-integrated biosensor An example of the measuring device for needle-integrated biosensor of the present invention ensures operability and durability for repeated and reliable measurement using a cartridge-type needle-integrated biosensor. It is characterized by being easy to carry with the same size and shape as a ballpoint pen. For example, a hook for hanging on an inner pocket such as a breast pocket or a suit may be provided on the upper part of the measuring device.

  Furthermore, this measuring apparatus is approximately the same size as a commercially available lancet, and is provided with a mechanism for generating power for driving a normal puncture needle. The measuring device is in a state in which measurement is possible by sliding a cartridge-type needle-integrated biosensor to the introduction portion at the lower side and connecting the terminal of the biosensor to the connector of the measuring device. Next, the preparation for measurement is completed by pulling the trigger for puncture at the top, and then the puncture / blood sampling / measurement sequence is automatically activated by pressing the puncture start button switch. The measurement results are guided.

  An example of structural features will be described in more detail. 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, the measuring device unit has a basic configuration including a cartridge introduction unit, a connector, an electrochemical measurement circuit, a memory unit, an operation panel, and a display unit.

  Since the slide structure receives the puncture drive while keeping the cartridge securely held, the strength of the measuring apparatus as a whole can be increased.

  The puncturing drive of the measuring device is preferably a mechanism that returns quickly after tapping the upper part of the cartridge in the vertical direction, and preferably has a mechanism that can adjust the depth of puncturing the skin of the subject. Further, in order to reliably puncture the subject's skin, an anti-slip tool may be attached to the bottom of the measuring apparatus, for example, near the bottom of the connector that is a contact point with the cartridge. In that case, a rubber anti-slip device is preferred. Similarly, the puncture start button may be modified with such an anti-slip tool. In addition, the illumination function may automatically operate in conjunction with triggering the puncture drive of the measurement device, and the function of illuminating the puncture portion of the subject with the light emitted from the blood collection introducing portion may be provided. . As a result, a series of operations for puncture, blood collection, and measurement including the visually impaired can be performed more reliably.

  As another illuminating means in the measuring apparatus of the present invention, a light detection element such as a photodiode incorporated in the measuring apparatus automatically measures illuminance, and may be provided with a mechanism for illuminating the puncture portion and the display unit as necessary. good. As a result, even in a dark place such as a dark place or a toilet, measurement can be performed without bothering to switch on the illumination. In addition, the convenience of the measurement apparatus of the present invention is further improved by this mechanism only working during certain specific operations such as data call and display operation. However, incorporating such a convenient mechanism may increase power consumption. As a countermeasure, the measurement apparatus may be a system that can be charged, and further, a solar cell may be provided for charging. An auxiliary battery may be provided inside.

  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.

  Various correction mechanisms can also be provided. Important corrections in blood glucose measurement include temperature correction and hematocrit values. Temperature correction is often important especially when shortening the measurement time because the activity of the enzyme used for blood glucose measurement is easily affected by temperature. The hematocrit value is also a factor that affects blood glucose measurement. The measurement of the hematocrit value can be estimated from, for example, the moving speed of blood collection in the biosensor. As the means, for example, using three electrodes, the time when the blood collection has passed through the first two and the time when the third blood collection has been obtained are obtained, and the moving speed of the blood collection is calculated from the time difference and the distance between the electrodes. You can also.

  In addition, it is necessary to suppress fluctuations in measured values due to differences in biosensor lots. In that case, it is only necessary to provide a function capable of performing calibration automatically for each lot.

  In order to manage the blood glucose level data accurately obtained by the above means, it is necessary to also manage the exact time. In that case, an element of a radio-controlled timepiece that has recently become inexpensive and easily available may be incorporated into the measuring apparatus. This makes it possible to store past data under accurate time management.

  Another means for managing the measurement data is to move the data to another medium. As an example, in addition to a method of sending data from a measuring apparatus to a PC or the like via a data transmission cable, use of communication means using radio waves or the like can be considered. By applying such communication means to the measuring apparatus, troublesomeness such as cord connection is eliminated.

  Furthermore, by installing a voice guide and a voice recognition function in the measurement device, many users, including users with physical disabilities, can recognize the ease of use. For example, for voice guidance, when actually measuring blood glucose using a measuring device, the operating procedure and related precautions are guided to the user in real time, thereby reducing the frequency of operational failures. It can be kept low. In addition, measurement results can be reported and past data can be called by voice.

  Similarly, the voice recognition function leads to improved operability. For example, it is possible to call the past data, illuminate the puncture site, etc. by simply speaking to the measuring device without pressing the operation button. In addition, when the display unit is placed in a state where the measuring device is placed, that is, when the display unit is placed vertically or horizontally, it is desirable that the display unit can be automatically switched to portrait or landscape according to the placement method. Alternatively, it is desirable that the display is continuously switched according to the angle at which the measuring device is placed, so that the characters on the screen are always displayed in parallel. With such a function, the user does not have to perform an operation of adjusting the line of sight according to the way the characters on the display unit are placed.

  As described above, the needle-integrated biosensor, the cartridge, and the needle-integrated biosensor measuring device of the present invention do not limit the user, that is, can support universal planning.

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

  FIG. 1 shows an example of a configuration diagram of the biosensor of the present invention. FIG. 1A shows the outer surface side of the substrate 1, and a puncture film 5 is stuck on the substrate 1. FIG. 1 (b) shows the inner surface side of the substrate 1. Two conductors 3 and 3 are arranged on the substrate 1, and the through hole 4 is at the center in the width direction of the substrate. FIG. 1 (c) shows the outer surface side of the cover 2, and a through hole is provided in the center of the cover 2. FIG. 1 (d) shows the inner surface side of the cover 2. An adhesive layer 8 is provided on the cover 2 for the spacer, and a through hole 4 and a non-spacer part 6 are provided in a portion where the adhesive layer 8 is not provided. Is provided. FIG.1 (e) has shown the board | substrate 1 side of the biosensor 42 after an assembly. Similarly, FIG. 1 (f) shows the cover 2 side of the biosensor 42 after assembly. Here, the through hole 4 shown in FIG. 1 (c) becomes the puncture blood collection port 10, and the two conductors 9, 9 not covered by the cover 2 become terminals. The left and right substrates 1 protruding from the cover 2 are hooked on a sensor cover folder 33 (not shown) at the bottom of the puncture needle housing 61, which will be described later, and the biosensor main body 42 drops from the puncture needle housing 61 due to an impact at the time of puncture. It is provided to prevent this. FIG.1 (g) shows the AA 'cross section in (f). A puncture film 5 is provided on the upper surface of the substrate 1, and the conductor 3, the adhesive layer 8 as a spacer, and the cover 2 are divided into two from the substrate 1 with the puncture needle penetration path 12 as a boundary. In (g), the puncture needle penetrates the puncture membrane 5 from above the puncture membrane 5, passes through the puncture needle penetration path 12, protrudes from the puncture blood collection port 10, and then returns to the original position. In the process, the through-hole of the puncture membrane 5 once opened is blocked or reduced, so that blood flowing from the puncture blood collection port 10 is introduced to the electrode reaction section 13 on the blood collection conveyance path 7 without disturbing the capillary phenomenon. it can. FIG. 1 (h) also shows a cross-sectional view of BB ′. Blood collected by the puncture needle penetrating the puncture membrane 5 is taken from the puncture blood collection port and sent to the electrode reaction unit 13. In the biosensor of FIG. 1, an air outlet 11 is provided at the top of the biosensor as shown in (h).

FIG. 2 is a device for efficiently introducing blood collection in the biosensor shown in FIG. 1 to make it difficult to take in more body fluid than necessary. The features appear in the following three parts.
(1) The diameter of the through hole 4 of the cover part 2 is made larger than that of the substrate 1 (compare (b) and (c)). Thereby, the blood sample that has entered the blood sampling port 10 of the cover unit 2 can easily reach the substrate unit 1 due to its surface tension.
(2) In order to quickly move the blood collected from the puncture blood collection port 10 to the electrode reaction unit 13, the width of the blood collection conveyance path 7 on the electrode reaction unit 13 side is partially increased (see (d)). As a result, the blood collected through the puncture blood collection port is easily directed to the electrode reaction unit 13 by the taper structure in which the blood collection conveyance path 7 narrows from the puncture blood collection port 10 toward the electrode reaction unit 13.
(3) By narrowing the width of the air discharge port 11, it becomes difficult to take in more body fluid than necessary (see (d)).

  FIG. 3 is an example in which a blood collection introduction guide 14 is attached to the outline of the puncture blood collection port of the biosensor shown in FIG. 1 (see (c), (f), (g), (h)). The blood collection introduction guide 14 is not particularly concerned with the material, but is preferably made of a material that is elastic and difficult to slide if possible. By attaching such a guide, the puncture part can be sensed and the anti-slip effect works at the time of puncture, and the skin of the subject can be pressed, thereby raising the puncture part and collecting blood by puncture. Can be easily.

  FIG. 4 is an example in which a blood collection introduction guide 14 is attached around the puncture blood collection port 10 of the biosensor shown in FIG. 1 (see (c), (f), (g), (h)). The blood collection introduction guide 14 is not particularly concerned with the material, but is preferably in the form of a gel if possible. By attaching such a guide, like the biosensor shown in FIG. 3, the puncture portion can be sensed and the anti-slip effect and adhesion to the skin can be enhanced during puncture. Accordingly, it is possible to eliminate the waste of blood collection that allows the body fluid collected at the puncture site to penetrate into the cover 2 member. Furthermore, with the biosensor shown in this figure, as described above, since it is possible to improve the adhesion to the skin, blood collection is performed using the negative pressure generated in the puncture needle housing 61 (not shown). And blood collected to the electrode reaction unit 13 can be quickly transferred. In the biosensor shown in this figure, in order to enable blood collection by suction, the puncture film 5 is put in close contact between the front side of the substrate 1 and the puncture needle housing 61, and the air discharge port 11 is placed in the puncture film 5. A through-hole is provided (see (a), (e), (g), and (h)), and a structure is adopted in which exhaust air sucked by negative pressure can be sent into the puncture needle housing 61. Therefore, the puncture membrane in this case may be one having high adhesion to the substrate, such as artificial skin.

  FIG. 5 is a simple packaging example of the biosensor shown in FIG. FIG. 5A shows the surface side of the cover 2 in which a blood collection introduction guide 14 is provided around the puncture blood collection port 10. FIG. 5B shows a state in which the protective film 17 is covered from the surface side of the cover 2 of the biosensor shown in FIG. 4F to the terminal 9 on the substrate 1. FIG. 5C shows a cross section taken along the line AA ′ shown in FIG. The protective film 17 is fixed with a strong adhesive layer 18 in a range from the upper surface side of the cover 2 to the fold 15 of the protective film 17. The other portions of the protective film 17 are not particularly provided with an adhesive layer (non-adhesive portion 20), but can be easily combined with the gel-like blood collection introduction guide 14 which is one of the features of the biosensor shown in FIG. By bonding, the puncture blood collection port 10 is covered. FIG. 5 (d) shows an example of using a biosensor that is simply packaged with a protective film 17. By turning the protective film 17 to the crease 15, the biosensor can be used for measurement. Furthermore, since repackaging can be performed by reattaching the protective film 17 after use, the risk of infection can be avoided.

  FIG. 6 shows an example in which a breathable film 60 is provided in the air outlet 11 of the biosensor shown in FIG. In addition to the puncture membrane 5, a breathable film 60 is attached to the back side of the substrate 1 in FIG. The air permeable film 60 covers the through hole 4 shown in FIG. The through hole 4 becomes an air discharge port 11 as shown in FIG. The biosensor shown in this figure is characterized in that, like the biosensor shown in FIG. 4, blood is sucked by negative pressure generated after puncturing with the puncture needle housing 61 and sent into the biosensor. This is to keep inflow of body fluid more than necessary due to excessive suction that may sometimes occur up to the air permeable film provided at the air outlet 11.

  FIG. 7 and FIG. 8 show examples of modifications to the structure of the most basic biosensor of the present invention shown in FIG. The biosensor has been devised to keep the inside of the biosensor sealed until it is used, and to keep the state of the reagent inside for a long time. FIG. 7A shows the substrate 1 shown in FIG. 1A in which a plate member is extended in the upper direction with the groove 15 as a boundary. In FIG. 7B, the groove 15 on the substrate 1 is provided without straddling the conductor 3. The cover 2 shown in FIG. 7 (c) is the same as the cover 2 shown in FIG. 1 (c). A plate member is extended in the upper direction with the groove 15 as a boundary. In FIG. 7D, the groove 15 on the cover 2 is provided across the non-spacer portion 6. FIGS. 7E and 7F show the substrate 1 side or the cover 2 side of the biosensor body 42, respectively. Further, FIGS. 7G and 7H show an AA ′ section and a BB ′ section. As shown in FIG. 7 (h), the groove 15 is provided so as to divide the blood collection conveyance path 7.

  FIG. 8 shows an example of a state in which a package is formed by the protective film of the biosensor shown in FIG. FIG. 8A shows an example in which the outer side of the cover portion 2 of the biosensor 42 is wrapped with the protective film 17. FIG. 8B shows an AA ′ cross section of FIG. In this figure, a removable layer 19 is newly provided on the protective film 17 to be used. Here, the detachable layer 19 is different from the adhesive used in the strong adhesive layer 18 and means an adhesive layer having a weak adhesive force that can be repeatedly bonded and peeled. FIG. 8 (c) shows an example of use of a biosensor simply packaged with a protective film 17, based on the AA ′ cross section of FIG. 8 (b). Thus, by dividing the biosensor along the V-shaped groove provided in the substrate 1 and the cover 2 part, the sealing cap portion 16 not including the electrode pattern is detached, and the air discharge port 11 is newly opened. The puncture blood collection port 10 is also opened when the removable layer 19 of the protective film 17 is peeled off. At this time, the protective film 17 fixed by the strong adhesive layer 18 is also attached to the sealing cap portion 16 and removed from the biosensor body 42 as the sensor separation portion 57. This sensor separation portion 57 can be used for re-packaging and repackaging as before after using the biosensor body 42 for measurement.

  FIG. 9 shows an example of a configuration diagram of a cartridge-type needle-integrated biosensor. Incidentally, the biosensor shown here is the one shown in FIG. FIG. 9A shows an exploded view of the needle-integrated biosensor 21. The needle-integrated biosensor 21 is configured such that the upper part is a puncture needle and the lower part is a biosensor. The puncture needle 26 is fixed to the puncture needle fixing substrate 24, and a winding spring guide 25 for avoiding contact with the winding spring 27 and defining the movement direction of the winding spring is provided on its outer frame. A puncture needle folder substrate 30 is provided below the puncture needle 26, and a puncture needle guide 28 for protecting the through hole 4 of the puncture needle and the trajectory of the puncture needle from the inside is provided on this substrate. In the space between the puncture needle folder 22 and the puncture needle folder substrate 30, parts necessary for puncture are stored, and a puncture needle housing 61 is formed.

  Two folders are provided in a portion below the puncture needle housing 61 in order to prevent the biosensor 42 from falling off due to an impact during puncture. FIGS. 9B and 9C show the state in which the sensor substrate 1 (32) is fitted into the sensor substrate folder 31 when viewed from above or below, and FIGS. 9D and 9E show the sensor cover 2 ( 34) shows a case where the sensor cover folder 33 is fitted into the sensor cover folder 33 as viewed from above or below. As shown in FIGS. 9B to 9E, these folders can fit the sensor substrate 32 and the sensor cover 34 having different shapes in accordance with the shape in order to prevent the biosensor from falling off due to puncture. It has a structure. By providing the sensor cover folder 33 under the sensor substrate folder 31 that fixes the sensor substrate 32 having a size larger than the cover 34, the substrate portion protruding from the cover 34 is supported by the sensor cover folder 33. In addition to helping to prevent the biosensor 42 from falling off due to an impact during puncturing, this support is convenient for sliding the biosensor 42 into these folders when assembling a needle-integrated biosensor. . Further, as shown in FIGS. 9B and 9C, the sensor substrate fixing tool 35 is attached to the sensor substrate folder 31 in order to securely fix the sensor substrate 32 so that it does not come off. 31 is provided. FIGS. 10A to 10B show an assembly example of the needle-integrated biosensor 21 shown in FIG.

  FIG. 11 shows a case where the biosensor 42 shown in FIGS. 7 and 8 is incorporated as a needle-integrated biosensor. FIGS. 11 (a) and 11 (b) show the state in which the sensor substrate 32 is fitted into the sensor substrate folder 31 when viewed from above or below, and FIGS. 9 (c) and 9 (d) show the sensor cover 34 as the sensor cover folder. 33 shows a case where the state fitted in 33 is viewed from above or below. As shown in FIGS. 11 (a) and 11 (b), in order to house and fix the biosensor of this shape in the needle-integrated biosensor cartridge, it is necessary to fix four places with the fixture 35 for the sensor substrate 32. is there. FIG. 11 (e) shows a case where the biosensor 42 in the packaged state is stored in the cartridge as viewed from below. Here, a broken line 40 indicates an outer frame portion of the sensor substrate 32 when seen through. From the broken line 40, it can be seen that the biosensor is slid in the folder and can sufficiently withstand the impact during puncture. FIG. 11 (f) shows a case where the biosensor is unpacked from the state shown in FIG. 11 (e), and FIG. 11 (g) shows the sensor separation portion 57 removed at that time. If it is such an aspect, it turns out that repackaging by reattaching is easy after using a biosensor.

  FIG. 12 is a diagram three-dimensionally showing the positional relationship between the needle-integrated biosensor 21 and the external drive 41. As shown in this figure, the external drive 41 is structured to enter the external drive introduction part 23 opened in the head of the puncture needle folder 22, and the external drive 41 is in the puncture needle fixing substrate 24 in the puncture needle housing 61. It has a structure that is transmitted to the top.

  FIG. 13 shows a case where the needle-integrated biosensor 21 shown in FIG. 9 is viewed from the side. FIG. 13A shows a state where the biosensor body of the needle-integrated biosensor 21 has the head portion facing the front, and FIG. 13B shows a cross-sectional view at that time. FIG. 13C shows a state where the biosensor body of the needle-integrated biosensor 21 is viewed from the side, and FIG. 13D shows a cross-sectional view at that time.

  FIG. 14 shows the needle-integrated biosensor 21 shown in FIG. 13 together with the puncture driving behavior. From these cross-sectional views, in FIG. 14B, the puncture needle 26 is located in the center of the puncture needle housing 61, and the puncture passage of the puncture needle is provided below the puncture membrane 5 below it. I understand. FIG. 14 (d) shows a state in which the tip of the puncture needle moves downward by receiving the puncture drive and protrudes outside the cartridge for a short time after penetrating the biosensor.

  FIG. 15 shows an example in which the stretchable film is applied to the needle-integrated biosensor 21. In FIG. 15A, the difference in configuration from the needle integrated biosensor 21 shown in FIG. 9A is that the stretchable film 58 is fixed to the upper part of the puncture needle housing 61 with an adhesive, and the puncture needle housing 61 A backflow prevention valve for adjusting the internal air pressure is provided in the inside, and a puncture needle folder substrate 30 is provided with a through hole for blood collection and suction. As shown in FIGS. And the ability to suck blood by negative pressure generated in the puncture needle housing.

  FIG. 16 shows the internal behavior of the sealed cartridge shown in FIG. 15 due to the puncture drive. FIG. 16A shows the inside of a sealed cartridge before use. FIG. 16B shows a scene where the biosensor packaging 17 is unwound and the puncture drive is working. As shown in this figure, the puncture needle 26 penetrates the puncture membrane 5 and the biosensor main body 42 and protrudes to the outside. At this time, in the puncture needle housing 61, the internal air is exhausted by the backflow prevention valve as the air pressure rapidly increases.

  FIG. 17 shows an example in which the sealed cartridge using the stretchable film shown in FIG. 15 (a) is improved. In FIG. 15 (a), a winding spring is used as the elastic body, but in FIG. 17, instead of using the winding spring, only the stretchable film 58 is used. In other words, the elastic film 58 is fixed to the puncture needle fixing substrate 30 in addition to the upper part of the puncture needle housing 61, thereby eliminating the need for a winding spring. This is because when the puncture needle protrudes to the outside by the puncture drive, the stretchable film 58 is in the most extended state, and this reaction becomes power for returning the puncture needle. 17A shows a case in which one elastic film 58 is fixed to the puncture needle fixing substrate 30, and FIG. 17B shows an example in which two elastic films 58 are fixed on the upper and lower sides of the puncture needle fixing substrate 30, respectively. Shows when to do.

  18 (a) is a cross-sectional view of the sealed cartridge shown in FIG. 17 (a), FIG. 18 (a) shows the state before use, and FIG. 18 (b) shows the biosensor packaging 17 unwrapped. It shows the scene where the drive is working.

  19 (b) is a cross-sectional view of the sealed cartridge shown in FIG. 17 (b), FIG. 19 (a) shows the state before use, and FIG. 19 (b) shows the biosensor packaging 17 unwrapped. It shows the scene where the drive is working.

FIG. 20 shows an example of a measuring apparatus with a puncture drive for measuring using the needle-integrated biosensor cartridge of the present invention. FIG. 20A shows a state before the cartridge 21 is introduced into the measuring device 43. The measurement apparatus will be described with reference to this figure. The measuring device 43 includes:
The needle-integrated biosensor cartridge 21 includes an introduction part 44, a trigger part 45 for puncture driving, an operation panel 46, a connector part 49 of a biosensor terminal, and a puncture start button 50. A display unit 47 and operation buttons 48 are provided on the operation panel 46, and an anti-slip tool 51 is provided on the puncture start button 50. FIG. 20B shows a state in which the sensor cartridge 21 is introduced into the measuring device 43 and the trigger 45 at the top is pulled to turn on the measuring device and enter the measurement mode. The characters displayed at this time are in an easy-to-read orientation by the automatic switching mode operation for equalizing the orientation of the measuring device. FIG. 20C shows the state after the sensor cartridge 21 is introduced into the measuring device 43 from the side. As shown in the figure, a hook 63 is provided on the back side of the display unit, so that the measuring device main body can be easily stored in a breast pocket, an inner pocket or the like. FIG. 20D shows a state when the sensor cartridge 21 and the measuring device 43 are viewed from below. The biosensor 42 provided in the sensor cartridge 21 is obtained by attaching the blood collection introduction guide 14 to the outline of the puncture blood collection port 10 shown in FIG. Further, an anti-slip tool 51 is provided at the bottom of the measuring device, that is, at the bottom of the sensor cartridge introducing portion 44 so as not to cause a positional shift between the measuring device and the skin during puncturing.

  FIG. 21 shows a usage example of the sensor cartridge 21 with simple packaging. In FIG. 21 (a), the sensor cartridge 21 is covered with a cap 52 that can be removed, and the biosensor 42 is covered with a protective film. The sealed biosensor shown in FIGS. 7 and 8 is set in the sensor cartridge 21. FIG. 21 (b) shows a state before the cap 52 and the separation part 57 with the protective film of the biosensor 42 are removed from the sensor cartridge 21 and introduced into the measuring device 43. FIG. 21 (c) shows that the sensor cartridge 21 is set in the measuring device 43, the display unit is switched on, and measurement is possible. FIG. 21 (d) shows a state where the sensor cartridge 21 used for measurement is taken out from the measuring device 43, repackaged, and disposed.

  FIG. 22 shows another example of use of the sensor cartridge 21 with the simple packaging shown in FIG. As shown in FIG. 22 (a), a cap 53 similar to that shown in FIG. 22 is attached to the upper part of the sensor cartridge 21 and attached to the upper part of the puncture needle housing 61 with a scissors. FIG. 22 (b) shows a state before the cap 53 is opened and fitted into the measuring device. FIG. 22 (d) shows a state where the sensor cartridge 21 used for measurement is taken out of the measuring device 43, repackaged, and can be discarded. In this case, since the cap 53 is structured not to be detached from the puncture needle housing 61 by scissors, the cap is not lost after use.

  FIG. 23 and FIG. 24 show another example of use of the sensor cartridge 21 which is simply packaged with the protective film 17. The protective film 17 shown in FIG. 23 is a type that is detachable from the cartridge, and the protective film 17 shown in FIG. 24 is a type that is partly strongly bonded to the cartridge. The biosensor 42 used is the same as that shown in FIG.

  FIG. 25 shows a usage example of the sensor cartridge 21 in which the stretchable film 58 is applied to the upper part of the puncture needle housing 61. With this sensor cartridge 21, measurement can be started most simply by simply removing the protective film 17 of the biosensor 42 before use.

  FIG. 26 shows a state in which the needle-integrated biosensor of the present invention is attached to the measurement device, the measurement device is applied to the fingertip that is the subject, and the puncture start button 50 is pressed to enter the measurement mode after puncture. Show. As shown in this figure, the screen of the measuring device is displayed horizontally, and the characters in the display are easily recognized.

  FIG. 27 shows a cross section along the longitudinal direction of the biosensor 42 in the sensor cartridge 21 during the measurement operation by the measurement apparatus shown in FIG. The puncture unit used here is as shown in FIG. 9, and for the biosensor 42, the air discharge port 11 is provided as an extension of the blood collection conveyance path 7, and blood collection is introduced into the outline of the puncture blood collection port 10. A guide 14 is attached. This figure shows a state where the skin of the puncture scheduled portion is raised by the blood collection introduction guide 14 by pressing the finger 54 against the measuring device 43. When the puncture drive unit 41 of the measuring device is driven in this state, the puncture needle 26 is driven downward, penetrates the puncture membrane 5 and the biosensor body 42, and protrudes toward the finger. Thereafter, the puncture needle 26 returns to the original position, and the puncture membrane 5 becomes smaller in size due to the characteristics of the material, and simultaneously, body fluid (blood) from the finger flows into the puncture blood collection port.

  FIG. 28 shows an example of use of the sensor cartridge 21 shown in FIG. 15 in a cross-sectional view along the longitudinal direction of the biosensor 42. The sensor cartridge 21 incorporates a puncture needle housing 61 covered with an elastic film 58 and a biosensor capable of collecting blood by suction. The puncture needle housing shown here is provided with a backflow prevention valve 59, and the biosensor 42 has a structure capable of collecting blood by suction. Furthermore, the gel-like blood collection introduction guide 14 attached to the puncture blood collection port 10 of the biosensor provides a mechanism that improves the adhesion with the skin and enables efficient blood collection.

  FIG. 29 shows an example in which a biosensor 42 in which a breathable film 60 is provided in the air outlet 11 is incorporated in the sensor cartridge 21 shown in FIG. This is such that blood drawn into the sensor by suction stays on the breathable film 60. By this mechanism, it is possible to prevent the intake of blood collection more than necessary.

  FIG. 30 shows a measurement example in a dark place. As shown in this figure, in a dark place, the measurement device automatically turns on the backlight of the display unit, and the puncture blood collection port 10 emits light that illuminates the puncture unit.

  31 and 32 show the storage box 56 of the sensor cartridge 21 incorporating the biosensors 42 having different shapes. For example, about ten sensor cartridges 21 can be accommodated in the box, and the sensor cartridge can be taken out by opening and closing the lid 53.

It is a figure which shows one embodiment of the biosensor of this invention. It is a figure which shows the other embodiment of the biosensor of this invention. It is a figure which shows the other embodiment of the biosensor of this invention. It is a figure which shows one embodiment of the suction type biosensor of this invention. It is a figure which shows one embodiment of the suction type biosensor which has the packaging form of this invention. It is a figure which shows the other embodiment of the suction type biosensor of this invention. It is a figure which shows the other embodiment of the biosensor of this invention. It is a figure which shows the other embodiment of the biosensor which has the packaging form of this invention. It is a figure which shows the example of 1 structure of the needle | hook integrated biosensor of this invention. It is a figure which shows the example of 1 structure of the needle | hook integrated biosensor formed by inserting a biosensor in the folder in the bottom part of the puncture needle housing of this invention. It is a figure which shows one structural example of the sensor folder of the needle | hook integrated biosensor which has a packaging form of this invention, and one usage example of this sensor. It is a figure which shows one example of operation | movement of the needle | hook integrated biosensor of this invention. It is a figure which shows an example of the side surface and its cross section of the needle | hook integrated biosensor of this invention. It is a figure which shows the other operation example of the needle | hook integrated biosensor of this invention in the side surface and its cross section. It is a figure which shows the example of 1 structure of the aspiration type | mold needle | hook integrated biosensor which has the packaging form of this invention. It is a figure which shows the operation example of the suction type needle | hook integrated biosensor which has the packaging form of this invention in the cross section of a side surface. It is a figure which shows the other structural example of the suction type needle | hook integrated biosensor which has the packaging form of this invention. It is a figure which shows the other operation example of the suction-type needle | hook integrated biosensor which has the packaging form of this invention in the cross section of the side surface side. It is a figure which shows the other operation example of the suction-type needle | hook integrated biosensor which has the packaging form of this invention in the cross section of the side surface side. It is a figure which shows an example of the lancet built-in type measuring apparatus attached to the needle | hook integrated biosensor of this invention. It is a figure which shows an example which attaches and uses the needle-integrated biosensor which has a packaging form of this invention to a lancet built-in type measuring device. It is a figure which shows the other example which attaches and uses the needle-integrated biosensor which has the packaging form of this invention to a lancet built-in type measuring device. It is a figure which shows the other example which attaches and uses the needle-integrated biosensor which has the packaging form of this invention to a lancet built-in type measuring device. It is a figure which shows the other example which attaches and uses the needle-integrated biosensor which has the packaging form of this invention to a lancet built-in type measuring device. It is a figure which shows an example which attaches and uses the aspiration type | mold needle | hook integrated biosensor which has the packaging form of this invention to a lancet built-in type | mold measuring apparatus. It is a figure which shows an example which attaches the needle | hook integrated biosensor of this invention to a lancet built-in type measuring apparatus, and implements a measurement. It is a figure which shows an example when the operation | movement at the time of blood collection of the needle | hook integrated sensor of this invention is seen in the cross section of the side surface side. It is a figure which shows an example when the operation | movement at the time of blood collection of the attraction | suction type | mold needle | hook integrated biosensor which has a packaging form of this invention is seen in the cross section of the side surface side. It is a figure which shows the other example when the operation | movement at the time of blood collection of the aspiration type | mold needle integrated biosensor which has a packaging form of this invention is seen in the cross section of the side surface side. It is a figure which shows an example which attaches the needle | hook integrated biosensor of this invention to a lancet built-in type measuring apparatus in a dark place, and performs a measurement. It is a figure which shows an example of the container which accommodates the needle | hook integrated biosensor which has the packaging form of this invention. It is a figure which shows an example of the container which accommodates the suction-type needle | hook integrated biosensor which has the packaging form of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Board | substrate 2 Cover 3 Conductor 4 Through-hole 5 Puncture membrane 6 Non-spacer part 7 Blood collection conveyance path 8 Adhesive layer (spacer)
9 Terminal 10 Puncture blood collection port 11 Air exhaust port 12 Puncture needle passage 13 Electrode reaction part (reagent layer)
14 Blood Collection Introduction Guide 15 Groove 16 Seal Cap Part 17 Protective Film 18 Strong Adhesive Part 19 Detachable Part 20 Non-adhesive Part 21 Needle Integrated Biosensor (Sensor Cartridge)
DESCRIPTION OF SYMBOLS 22 Puncture needle folder 23 External drive introducing | transducing part 24 Puncture needle fixed board | substrate 25 Winding spring guide 26 Puncture needle 27 Winding spring 28 Puncture needle guide 29 Puncture needle moving part 30 Puncture needle folder board 31 Sensor board folder 32 Sensor board 33 Sensor cover folder 34 Sensor Cover 35 Sensor board fixture 36 Sensor board outer surface side 37 Sensor board inner surface side 38 Sensor cover inner surface side 39 Sensor cover outer surface side 40 Dashed line for fluoroscopy 41 External drive 42 Biosensor body 43 Puncture needle driver 44 Needle integrated biosensor Cartridge introduction (needle integrated biosensor cartridge folder)
45 Trigger part 46 Operation panel 47 Display part 48 Operation button 49 Connector part 50 Puncture start button 51 Non-slip tool 52 Cap 53 Stick cap 54 Finger 55 Blood sampling 56 Sensor integrated box with sensor integrated sensor 57 (Sealing cap and protective film) )
58 Stretchable film 59 Backflow prevention valve 60 Breathable film 61 Puncture needle housing 62 Taper 63 Hook 64 Crease

Claims (58)

  A puncture needle for puncturing the skin of a subject and collecting a body fluid and a biosensor main body for analyzing the body fluid are integrally configured, and the puncture needle is vertically moved by an external driving means. A needle-integrated biosensor configured to pierce through the skin by driving in the direction.   Puncture blood collection port and puncture blood collection port for injecting blood into the cover through the spacer, electrode, blood collection conveyance path, electrode reaction part, puncture needle installed in the space between the electrically insulating substrate and the cover It consists of a substrate with a through-hole and a membrane through which the needle can penetrate (puncture membrane) or a substrate made of only the puncture membrane, and has a puncture needle penetration part through which the puncture needle can penetrate the substrate and the cover. Then, blood that flows out by puncturing the skin of the subject with the puncture needle is guided by capillary action from the puncture blood collection port to the blood collection conveyance path and the electrode reaction section, and the measurement target substance in the blood reacts with the reagent in the electrode reaction section. The needle-integrated biosensor according to claim 1, further comprising an electrode reaction part for electrochemically measuring the result, and a folder for integrating the biosensor body with the puncture needle.   The biosensor according to claim 2, wherein the puncture needle moving through the puncture needle penetrating portion is installed so as not to contact the reagent in the electrode reaction portion.   The biosensor according to claim 2, wherein the electrode is defined by a resist layer.   The needle-integrated biosensor according to claim 2, wherein a pattern of the spacer between the substrate and the cover at the sample inlet and the air outlet is tapered.   The puncture membrane used for the substrate portion does not interfere with the capillary phenomenon after the puncture needle has penetrated in order to smoothly introduce the blood collection introduced from the puncture blood collection port after puncture into the blood collection conveyance path by capillary action. 2. The needle-integrated biosensor according to 2.   The needle-integrated biosensor according to claim 2, wherein the puncture membrane is formed of any one of natural materials, plastics, biodegradable materials, and shape memory materials.   The needle-integrated biosensor according to claim 7, wherein the natural material is paper, collagen, cellulose, or cotton.   The needle-integrated biosensor according to claim 7, wherein the plastic is any one of a foamable material, an elastic material, and a film-forming material.   The needle-integrated biosensor according to claim 7, wherein the foamable material is artificial skin.   The film forming material is any of cellophane, polyvinylidene chloride, polyvinyl chloride, polyvinyl acetate, polyimide, polyethylene, polyethylene terephthalate, polyvinyl alcohol, polylactic acid, polyester, polyamide, ethylene-vinyl alcohol copolymer, fluorine resin The needle-integrated biosensor according to claim 9.   The needle-integrated biosensor according to claim 2, wherein the puncture membrane has a multilayer structure of two or more layers made of different materials.   The needle-integrated biosensor according to claim 2, wherein the puncture membrane is a thin film having a thickness of 100 µm or less.   The needle-integrated biosensor according to claim 2, wherein a shutter that opens and closes in conjunction with the movement of the puncture needle is provided on a substrate portion of the biosensor.   The needle-integrated biosensor according to claim 2, wherein the puncture blood collection port is formed of a soft material.   The needle-integrated biosensor according to claim 15, wherein the soft material is a gel, an elastic material, or a foamable material.   The needle-integrated biosensor according to claim 2, wherein a step is formed around or outside the puncture blood collection port on the cover plane, and the step is used as a sample introduction port guide.   18. The needle-integrated biosensor according to claim 17, wherein a material forming the sample inlet guide is one of gel, elastic material, and foamable material.   The needle-integrated biosensor according to claim 2, wherein light in the visible light region is irradiated from the puncture blood collection port toward the puncture position before puncturing.   The needle-integrated biosensor according to claim 19, wherein the light in the visible light region is an organic EL or a laser beam.   21. The needle-integrated biosensor according to claim 20, wherein the laser beam is irradiated by a light emitting diode.   The needle-integrated biosensor according to claim 2, wherein a terminal on the insulating substrate is covered with a cover, and the cover has a foldable line so that the external terminal is exposed.   The needle-integrated biosensor according to claim 2, wherein a protective film capable of adhesion and peeling is provided on the outer surface of the insulating substrate.   The needle-integrated biosensor according to claim 23, wherein the protective film has a portion that strongly adheres to at least a part of the outer surface of the insulating substrate.   There is a cutting line at the boundary between the portion of the insulating substrate that does not include the electrode and the portion of the insulating substrate that includes the electrode, and the air outlet is opened by separating the portion of the insulating substrate that does not include the electrode from the boundary. The needle-integrated biosensor according to claim 2, further comprising a cap for opening.   26. The needle-integrated biosensor according to claim 25, wherein at least a part of the cap portion has a portion that strongly adheres to the protective film, and the protective film can be peeled off simultaneously by separating the cap from the biosensor body when the biosensor is used. .   27. The needle-integrated biosensor according to claim 2 or 26, wherein the package comprising the cap and the protective film can be reattached to the original state after the biosensor is used.   The puncture needle is housed in a housing that is driven in the vertical direction, and the puncture needle driven by an external driving means penetrates through the biosensor in the puncture needle housing and returns to its original position after puncturing the skin of the subject. The needle-integrated biosensor according to claim 1, further comprising a mechanism for returning.   The needle-integrated biosensor according to claim 1 or 2, wherein a guide for making the operation of the puncture needle coincide with a driving direction received from the outside is provided in the puncture needle housing.   The needle-integrated biosensor according to claim 1 or 2, wherein the mechanism for returning the puncture needle in the puncture needle housing to the original position is either a spring or an elastic film.   The needle-integrated biosensor according to claim 30, wherein the spring in the housing is a spiral spring.   32. The needle-integrated biosensor according to claim 31, wherein a guide for allowing the movement of the winding spring to coincide with the moving direction of the puncture needle is provided in the housing.   The needle-integrated biosensor according to claim 1 or 2, wherein the stretchable film is adhesively fixed to at least a part or all of the upper flat surface of the puncture needle housing.   34. The needle-integrated biosensor according to claim 33, wherein the elastic film is adhered and fixed to the entire upper surface of the puncture needle housing, whereby the inside of the puncture needle housing is in a sealed state.   The needle-integrated biosensor according to claim 1 or 2, further comprising an internal pressure adjustment mechanism that softens the pressure that is suddenly applied to the sealed puncture needle housing when driven externally.   36. The needle integrated biosensor according to claim 35, wherein the mechanism for relieving pressure is a backflow prevention valve.   37. The needle-integrated biosensor according to claim 36, wherein the backflow prevention valve is provided in a direction to exhaust the air in the puncture needle housing to the outside.   The needle-integrated biosensor according to claim 1 or 2, wherein the inside of the puncture needle housing which is in an airtight state after puncturing by an external drive becomes a negative pressure, which becomes a suction force for introducing blood into the conveyance path.   The needle-integrated biosensor according to claim 33, wherein the stretchable film is bonded and fixed to the puncture needle fixing substrate.   The needle-integrated biosensor according to claim 1 or 2, wherein a breathable film is provided at an air discharge port necessary for introducing blood into the biosensor.   The needle-integrated biosensor according to claim 1 or 2, wherein the puncture needle has a photocatalytic action.   The needle-integrated biosensor according to claim 1 or 2, further comprising a cap for simple packaging on an upper portion of the puncture needle housing.   43. The needle integrated biosensor according to claim 42, wherein the simple packaging cap is connected to the puncture needle housing with a scissors.   The needle-integrated biosensor according to claim 1 or 2, which is a cartridge type.   45. The needle-integrated biosensor cartridge according to claim 44, which is a disposable type.   45. The needle-integrated biosensor cartridge according to claim 44, which is a simple packaging type.   45. The needle-integrated biosensor cartridge according to claim 44, wherein the needle-integrated biosensor cartridge is a simple packaging type that can be repackaged when discarded.   45. The needle-integrated biosensor cartridge according to claim 44, which can be applied to infectious disease patients and pets.   49. A needle-integrated biosensor cartridge package containing a plurality of needle-integrated biosensor cartridges according to any one of claims 44 to 48.   49. The needle-integrated biosensor cartridge according to any one of claims 44 to 48, the needle-integrated biosensor cartridge introduction portion that slides and sets the needle-integrated biosensor cartridge, and the electricity in the electrode of the needle-integrated biosensor cartridge Connector unit that captures a typical signal, a measurement unit that measures electrical values via the connector unit, an operation panel unit for measurement, a display unit that displays measurement values in the measurement unit, a memory unit that stores measurement values, A measuring device for a needle-integrated biosensor, comprising a puncture needle drive section, a drive section trigger section, and a puncture start button for starting puncture with a puncture needle.   51. The measuring device for a needle-integrated biosensor according to claim 50, wherein the measuring method in the measuring unit is a potential step chronoamperometry method, a coulometry method or a cyclic voltammetry method.   52. The measuring device for a needle integrated biosensor according to claim 50 or 51, wherein the driving means outside the puncture needle includes a mechanism for returning the original position after driving the puncture needle.   53. The measuring device for a needle-integrated biosensor according to claim 50, having a mechanism capable of adjusting a depth of puncturing the skin of the subject.   54. The measurement device for a needle-integrated biosensor according to any one of claims 50 to 53, wherein a component measurement result during blood collection is recorded based on an accurate time carved by a radio clock.   At least one of temperature correction, automatic blood glucose level correction related to hematocrit value, biosensor calibration, manual or automatic illumination of the display and puncture unit in the dark, voice guidance, voice recognition, automatic display orientation switching, wireless communication, and charging 55. The measuring device for a needle-integrated biosensor according to any one of claims 50 to 54, having one function.   56. The needle integrated type according to any one of claims 50 to 55, wherein an illumination function is activated in conjunction with triggering of the puncture drive of the measuring device, and the light irradiated from the blood collection introducing portion illuminates the puncture portion of the subject. Measuring device for biosensor.   57. The measuring device for a needle-integrated biosensor according to claim 50, wherein the hematocrit value is measured by measuring a moving speed in the biosensor. Place the needle-integrated biosensor cartridge in a measuring device equipped with a means for driving the puncture needle, and pull the trigger to enable measurement. Place the tip of the measuring device on the subject and press the puncture start switch. The needle-integrated biosensor according to any one of claims 50 to 57, wherein a series of operations of puncture, blood collection, and measurement are automatically performed, and the result is displayed on a display unit of the measurement device. How to use the measuring device.

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