JP4873536B2 - Non-conductive needle - Google Patents

Description

  The present invention relates to a needle-integrated biosensor. More particularly, the present invention relates to a needle-integrated biosensor having a configuration in which a puncture needle for piercing the skin to obtain blood and a biosensor for collecting and analyzing body fluid taken on the surface of the skin are integrated.

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. 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 fails, and the patient who is the subject has the inconvenience of having to puncture again and replacing the biosensor and restart the measurement.
Japanese Patent No. 3,621,502 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 placed in different positions in a pen-type (two-color ballpoint pen-like) measuring device equipped with a puncture needle drive unit. The blood glucose is measured by placing the tip of the pen-like measuring device against the skin of the subject and puncturing it, exposing the biosensor to the tip, and collecting blood. However, in this method, the troublesomeness of setting the needle and the biosensor in the measuring device has not been solved.
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 blood collection is sent to the entire space sharing the sample conveyance path and the puncture needle passage, more blood collection than necessary is required. In addition, since the shape of the entire needle-integrated biosensor is bilaterally symmetric, there is a possibility that the user may make a mistake in insertion into a measuring apparatus equipped with a puncture drive.
Republished 2002-056769

  Thus, in the conventional needle-integrated biosensor, since the electrode system is formed on the flat substrate, the structure is flat, and it is necessary to fill the flat surface with the sample liquid, resulting in a large sample volume. There was a problem of becoming.

  In response to such a problem, the inventors pierce the biosensor provided with electrodes and spacers in the space between the two electrically insulating substrates, and the skin of the subject placed in the biosensor. In a biosensor in which a puncture needle for collecting body fluid is integrated with a puncture needle support, the puncture needle is perpendicular to the major axis direction of the electrode formed on one substrate. A biosensor with an integrated needle has been proposed (Japanese Patent Application 2005-185989).

  According to this biosensor, although it has an excellent effect of reducing the amount of blood collected after puncturing, since a metallic puncture needle is used, the puncture needle orthogonal to the electrode is used as the electrode. There was a restriction that contact with the surface must be avoided.

  Further, as a puncture needle used in a needle-integrated biosensor that is required to be further reduced in size and weight, it is conceivable to use a puncture needle having a smaller diameter, that is, a thin puncture needle. There was a problem.

  An object of the present invention is to reduce the weight of a needle-integrated biosensor comprising a puncture needle for piercing the skin of a subject and collecting a body fluid and a biosensor for analyzing the body fluid. In addition, it is possible to provide a puncture needle that is not particularly limited in the biosensor.

The purpose of such invention is a puncture needle for collecting body fluid pierce the skin of a subject, and biosensors for the analysis of body fluids in the needle-integrated biosensor constructed together, medium This is achieved by a needle-integrated biosensor using a real rod-shaped non-conductive needle as a puncture needle .

  The needle-integrated biosensor using a non-conductive material such as a resin as a puncture needle has a diameter of the needle only for the purpose of reducing the weight, for example, compared to a conventional one that uses a metal puncture needle. Since it is not necessary to reduce the size of the biosensor body, it is possible to reduce the weight of the biosensor body with the needle integrated while maintaining the strength of the needle. In addition, even in a needle-integrated biosensor in which puncture needles are arranged in a manner orthogonal to each electrode, no special restriction is required for the placement of the puncture needle in the biosensor, that is, the puncture needle contacts the electrode surface. In this manner, it is possible to arrange in such a manner, and there is an excellent effect of enabling efficient measurement without collecting blood more than necessary after puncturing.

As the puncture needle for puncturing the subject's skin and collecting the body fluid, non-conductive, for example, a resin-made one is used. Needle-integrated biosensors that use non-conductive puncture needles need to have a smaller needle diameter for the purpose of reducing weight only compared to conventional ones that use metal puncture needles, for example. Therefore, it is possible to reduce the weight of the needle-integrated biosensor body while maintaining the strength of the needle. In addition, as the puncture needle , a solid bar-shaped one that does not have a cavity at the center of the needle is used from the viewpoint of reducing the measurement sample solution.

  As the puncture needle made of resin, cyclic olefin resin, polyphenylene sulfide, polyether ether ketone, polybutylene terephthalate, polycarbonate, polyamide, polyacetal, modified polyphenylene ether, polyester resin, polytetrafluoroethylene, fluorine resin, polysulfone, Polyetherimide, polyethersulfone, polyetherketone, polyetherlactone, liquid crystal polyester, polyamideimide, polyimide, polyethernitrile, polypropylene, polyethylene and other thermoplastic resins, epoxy resin, unsaturated polyester resin, phenol resin, urea resin , Melamine resin, polyurethane resin thermosetting resin, polycarbonate, cyclic olefin resin, polybutylene terephthalate, poly Chromatography ether ether ketone, polyetherimide, polyphenylene sulfide, wholly aromatic polyester resin, a puncture needle made of a biodegradable resin such as polylactic acid is used.

  Such a puncture needle is integrated with a biosensor to constitute a needle-integrated biosensor. The puncture needle can be arranged at any position regardless of inside or outside of the biosensor, and can also be arranged in such a manner as to contact the electrode surface. In addition, the puncture needle can be arranged in any manner such as a movable state where the puncture needle moves in the biosensor during blood collection or a fixed state where the biosensor is adhered using an adhesive or the like. When the electrode is fixed and arranged in contact with the electrode surface, contact between the puncture needle and the electrode surface is possible even when the puncture needle is arranged along the sample transport path for introducing the measurement sample into the sensor. Therefore, there is an effect that the measurement can be performed by collecting the minimum necessary measurement sample for the measurement. In this case, by arranging the puncture needle and each electrode in a state of being orthogonal to each other, it is possible to further reduce the amount of blood collected compared to the case where the puncture needle is arranged in parallel with the major axis direction of the electrode.

  The biosensor is not particularly limited as long as it can detect and quantify a measurement substance in a measurement sample solution. For example, a biosensor in which an electrode and a spacer are provided in a space between two electrically insulating substrates. Examples include sensors.

  As the substrate, it is sufficient if it is electrically insulating, for example, plastic, biodegradable material, paper or the like is used, and preferably polyethylene terephthalate is used.

  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 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 arrangement of these electrodes is not particularly limited as long as the electrodes do not contact each other. For example, the electrodes are collectively formed on one substrate or individually formed on two substrates.

  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 disposed 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 measurement apparatus main body, which will be described later, calculates and determines a glucose concentration (blood glucose level) from the anode current measured at this time, and displays it on a display unit arranged on the surface of the main body.

  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.

  Here, if the tip of the puncture needle fits inside the biosensor due to the application of the reagent layer, surfactant or lipid into the sample transport path, the tip of the puncture needle may be contaminated. is there. In order to prevent such contamination, it is preferable not to apply these reagents around the tip of the puncture needle.

  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, and examples thereof include ultraviolet curable vinyl / acrylic resins, urethane acrylate resins, and polyester acrylate resins. 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. In the latter case, the resist layer is preferably formed on the electrode substrate for insulation. Further, the resist layer is provided thicker than the electrode in the sample transport path in which the puncture needle of the needle-integrated biosensor of the present invention is accommodated, so that the puncture needle movable within the biosensor and the electrode on which the reagent layer is formed Can be suppressed. Such a resist layer can also be formed by a screen printing method. For example, the resist layer formed with a thickness of about 5 to 500 μm, preferably about 10 to 100 μm, using any of the above-mentioned materials also acts as a spacer. To do.

  The two substrates 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, and such an adhesive layer acts as a spacer as well as a resist layer. In addition, the said reagent can also be contained in an adhesive bond layer.

  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 that case, for example, for puncture driving, it is desirable to have a mechanism in which the needle breaks through the skin of the subject and a mechanism to quickly return to the original position immediately after puncturing.

  As a measuring device for a needle-integrated biosensor, a measuring device that uses operability and durability to ensure repeatable and reliable measurement using a needle-integrated biosensor and is easy to carry is used. Inserts a biosensor with a needle into the introduction part at the bottom so that the puncture needle faces downward and the terminal of the biosensor is connected to the connector of the measuring device so that measurement is possible. The preparation for the measurement is completed by pulling the trigger to give the drive to the needle integrated biosensor, and then the puncture, blood collection, and measurement are automatically activated by pressing the puncture start button switch. The system with a mechanism that leads to the measurement results is used.

  An example of the structural features of the measuring device 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, 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 puncture 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 at which the skin of the subject is punctured.

  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 shows an assembly example of the needle-integrated biosensor of the present invention. FIGS. 1a) to c) are examples of manufacturing a needle-integrated biosensor, i) is a constituent material required for manufacturing the needle-integrated biosensor, and ii) and iii) indicate the molded body. FIG. 1a) shows a resist layer 6 in which conductors 7, 7 are formed on one surface of a substrate 1, 1 of a biosensor. The resist layer 6 serves not only as a spacer 2 but also to define the electrode area, and when a reagent layer is provided on the electrode surface, it is provided to prevent contact between this and the movable puncture needle. It is done. Accordingly, the through-hole 4 is provided in the resist 6 layer. Here, the board | substrate 1 can be safely used by rounding a corner | angular. FIG. 1b) shows how the adhesive layer 5 is formed on the resist layer. Here, since the adhesive layer 5 is also provided between the plate members of the substrates 1 and 1, like the resist layer 6, it plays the role of the spacer 2. Further, FIG. 1b) ii) shows an electrode 10 and its electrode reaction part 13 whose area is defined by the resist layer 6 and the adhesive layer 5. FIG. 1c) i) shows the configuration of the puncture needle section 14. The puncture needle section 14 is composed of a puncture needle 20, a support body 19 that supports the puncture needle 20, and an external drive connection section 17, and an external drive connection section 17 is shown. Is connected to a measuring device equipped with a puncture drive so that the puncture drive from the measurement device can be obtained. Further, FIG. 1c) shows that the puncture needle portion 14 is disposed along the sample transport path 8 and perpendicular to the electrodes. As shown in this figure, the movable puncture needle portion 14 has a structure in which contact with the electrode surface 10 can be avoided by forming the resist layer 6. Therefore, even if the reagent layer 13 is formed on the surface of the electrode 10, contact between the reagent layer 13 and the puncture needle portion 14 can be prevented, and as a result, contamination of the movable puncture needle 20 with the reagent is prevented. be able to. FIG. 1c) iii) shows the needle-integrated biosensor 3 formed in this way.

  FIG. 2 shows a cross-sectional view of the needle-integrated biosensor 3 shown in FIG. FIG. 2b) shows a cross-sectional view taken along the line AA 'shown in FIG. 2a). As shown in this figure, a puncture needle 14 is arranged on the pattern surface provided on the substrate 1 of the biosensor. FIG. 2c) shows a cross-sectional view along BB 'shown in FIG. 2a). A puncture needle 14 is disposed at the center of the two substrates 1 and 1. As shown in these figures, the needle-integrated biosensor 3 of the present invention has a puncture needle 14 disposed perpendicular to the major axis direction of electrodes 10 and 10 formed inside one substrate 1. Thus, the terminal 11 can be removed from the trajectory of the puncture needle 14. Further, since the terminal 11 is disposed at a position off the trajectory of the puncture needle 14, the shape of the needle-integrated biosensor 3 is asymmetrical with the puncture needle as the center line, which is a mark for the user. The insertion into the measuring device can be performed without mistake, and the measuring device can also be provided with a mechanism for specifying the position of the terminal 11 of the needle-integrated biosensor 3 of the present invention. Further, by reducing the width of the electrode and the distance between the electrodes, the width of the substrate at that portion is also reduced, so that the amount of the sample solution can be reduced.

  FIG. 3 shows an example of use of the needle-integrated biosensor 3 shown in FIGS. In FIG. 3, steps a) to d) are shown. In i) and ii), the state of the needle-integrated biosensor 3 at that time is shown in i) as a configuration diagram, and in ii) as shown in FIG. 'Shown in cross section. FIG. 3a) shows a state before use of the needle-integrated biosensor 3 connected to a measuring device with a puncture drive. At this time, the skin as the subject is in close contact with the puncture blood collection port 12 of the needle-integrated biosensor 3. FIG. 3b) shows the state of puncture, and although not shown, the puncture needle 20 protrudes from the sensor and pierces the skin. FIG. 3c) shows a state where the puncture needle portion 14 has returned to its original position after puncturing. FIG. 3d) shows a state in which the blood collection 24 from the punctured skin is subsequently sucked by capillary action.

  FIG. 4 shows another assembly example of the needle-integrated biosensor of the present invention. Unlike FIG. 1, a resist layer is not provided on the electrode, and the puncture needle 20 is fixed by an adhesive layer 5 in the biosensor. Therefore, the adhesive layer defines the electrode area and plays a role as the spacer 2. Thus, in the biosensor in which the puncture needle is fixed inside the biosensor except for the tip portion, even if a reagent layer is formed on the electrode, the tip of the puncture needle is not contaminated by the reagent layer. Since the puncture needle is non-conductive without special consideration for its arrangement, it can be fixed inside the biosensor in such a manner that it contacts the electrode on which the reagent layer is formed. In this figure, the puncture needle 20 is fixed after the puncture needle support 14 is mounted, but the puncture needle 20 can be fixed as it is without mounting the puncture needle support 14. Then, as shown in the cross-sectional views of FIGS. 5b) and c), the puncture needle is placed in contact with the electrode surface, so that the volume of the electrode reaction part is suppressed to the minimum volume necessary for measurement. It becomes possible.

It is a figure which shows one assembly example of the needle-integrated biosensor according to the present invention. It is a figure which shows one structural example of the needle-integrated biosensor according to the present invention. It is a figure which shows the usage example of the needle | hook integrated biosensor which concerns on this invention. It is a figure which shows the other assembly example of the needle | hook integrated biosensor which concerns on this invention. It is a figure which shows the other structural example of the needle | hook integrated biosensor which concerns on this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Substrate 2 Spacer 3 Needle-integrated biosensor 4 Through-hole 5 Adhesive layer 6 Resist layer 7 Conductor 8 Sample transport path / puncture needle path 10 Electrode 11 Terminal 12 Puncture blood sampling port 13 Electrode reaction part (reagent layer)
14 Puncture needle part 17 External drive connection part 19 Puncture needle support body 20 Puncture needle 24 Blood collection

Claims (8)

  Solid needle-shaped non-conductive needle in a needle-integrated biosensor in which a puncture needle for puncturing the skin of a subject and collecting a body fluid and a biosensor for analyzing the body fluid are integrated A needle-integrated biosensor characterized by using as a puncture needle.   The needle-integrated biosensor according to claim 1, wherein the non-conductive needle is made of resin.   The needle-integrated biosensor according to claim 1, wherein at least a part of the puncture needle is disposed in contact with an electrode formed inside the biosensor.   The needle integrated biosensor according to claim 1, wherein the puncture needle other than the puncture tip is fixed in the needle integrated biosensor.   The biosensor according to claim 4, wherein the puncture needle is fixed orthogonally to each electrode formed inside the biosensor.   The needle-integrated biosensor according to claim 4, wherein the puncture needle is fixed by at least one of an adhesive and a resist.   The needle-integrated biosensor according to claim 4, wherein a reagent layer is provided on and / or around the electrode.   The needle-integrated biosensor according to claim 4, wherein a cap for protecting the tip of the puncture needle is provided.

Images