JP4682360B2 - Needle integrated biosensor - Google Patents

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. 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.
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. In this case, 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 sampling is performed. 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 moves in the blood collection conveyance path and the reagent layer of the biosensor, there is a risk that the surface of the puncture needle is contaminated with the reagent before the puncture needle pierces the skin of the subject.
Republished 2002-056769

  In addition, the disposal after use is not enough to consider infectious diseases, etc., or the puncture drive is provided on the measurement device side, and the needle-integrated biosensor unit cannot withstand the impact of the drive during puncture Many problems remain, such as structure.

The object of the present invention is that the puncture driving unit as seen in a lancet is not required, so that the configuration is very simple, so that the assembly is easy, and the sample body fluid can be collected reliably in a small amount without waste. It is to provide a needle-integrated biosensor.

The purpose of such invention, the puncture needle consists of a hollow columnar structures is fixed is embedded with respect to the substrate, the substrate of the second plate electrode of at least a working electrode and a counter electrode inside the columnar structure This is achieved by a needle-integrated biosensor in which a puncture needle including an electrode is formed by penetrating vertically.

  The needle-integrated biosensor according to the present invention does not require a puncture driving unit such as that found in a lancet for collecting a sample body fluid, and thus has a very simple configuration, and therefore is easy to assemble, and also has capillary action or By providing a blood collection means by any one of the suction blood collection method and the vacuum blood collection method, the sample body fluid is reliably collected in a small amount without waste. Since such a biosensor can be used as a cartridge, it can be easily carried by simple packaging and has an effect of being hygienic after use.

  The needle-integrated biosensor according to the present invention is composed of a combination of a puncture needle composed of a hollow columnar structure vertically disposed on an electrically insulating substrate such as plastic and an electrode system composed of at least two. . This biosensor will be described in more detail.

As a puncture needle composed of a hollow columnar structure integrated with a needle, a hollow prismatic or columnar needle is used, and the shape of the tip of the puncture needle is cut in a right angle with respect to the long axis direction. Alternatively, an obliquely cut state, preferably an obliquely cut state is used. The material of the puncture needle is preferably the same as that of a commercially available injection needle, and stainless steel or the like is used. Furthermore, you may process and use a commercially available injection needle.

  As the electrode system composed of at least two electrodes, plate electrodes having two or more planes or curved surfaces are used. A part of the plate member may be an electrode, and the part other than the electrode (electrode forming substrate) is made of an insulating material such as an inorganic material such as plastic or ceramic, a biodegradable material, paper, etc. Preferably, polyethylene terephthalate is used. Each of these two types of electrodes will be described.

  The electrode forming a part of the plate member is formed by depositing a conductive material on the surface of the electrode forming substrate or by bonding the electrode member and the electrode forming substrate.

  Film formation of the conductive material on the electrode forming substrate surface is performed by a screen printing method, a vapor deposition method, a sputtering method, a foil bonding method, a plating method, etc., and the bonding between the electrode member and the electrode forming substrate is This is done with an adhesive.

  Examples of the conductive material include carbon, silver, silver / silver chloride, platinum, gold, nickel, copper, palladium, titanium, iridium, lead, tin oxide, and platinum black. As carbon, carbon nanotubes, carbon microcoils, carbon nanohorns, fullerenes, dendrimers, or derivatives thereof can be used.

  The electrode may be a two-pole method formed by a working electrode and a counter electrode or a three-pole method formed by a working electrode and a counter electrode, a reference electrode, or a number of poles larger than that. Two or more electrodes can be formed.

  A substrate is used to form a needle-integrated biosensor composed of a puncture needle including at least two electrodes. It is sufficient that the substrate is made of an electrically insulating material. The puncture needle is embedded perpendicularly to the substrate, and the electrode (formation substrate) is included in the puncture needle. A terminal that is arranged by penetrating vertically and that sends an electrical signal from the biosensor to the measuring device is provided on the opposite side of the electrode from the substrate. At this time, a spacer may be provided between the electrodes (forming substrate) to fix the electrode interval.

  A reagent layer is formed on the electrode (forming substrate) as necessary. The reagent layer is preferably immobilized on the electrode surface or the plate member surface. In this case, the reagent layer is formed by a screen printing method or a dispenser method, and is immobilized on the surface of the electrode (forming substrate) by an adsorption method with drying or a covalent bonding method. The reagent varies depending on the detection target. For example, when a needle-integrated biosensor is configured for blood glucose measurement, a reagent containing glucose oxidase that is an oxidase and potassium ferricyanide as a mediator is employed. When these reagents are dissolved by blood, the enzyme reaction is started. As a result, potassium ferricyanide coexisting in the reagent 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 glucose concentration (blood glucose level) is calculated from the anode current measured at this time.

The needle-integrated biosensor having the above configuration is configured such that blood that has bleeds through puncture follows the inner wall of the hollow needle by capillary action to reach the electrode plate member, and the inner wall (electrode reaction part) of the electrode plate member is filled, Reaction between the reagent arranged in the reaction part and the measurement target substance in the blood occurs, and the measurement target substance is measured by measuring the result electrochemically. At this time, depending on the blood, the electrode may not be sufficiently covered, for example, when the hematocrit value is high. Therefore, the electrode (formation substrate) portion away from the blood collection introducing portion is preferably covered with a resist. Thereby, even when the hematocrit value is high, the electrode can be filled at a minimum, so that the sample liquid can be transferred without being influenced by the state. On the other hand, when the hematocrit value is low and blood transfer is performed smoothly, it is necessary to stop capillary action in order to prevent excessive blood collection. As this means, an air outlet is provided in the substrate or the hollow needle.

  As a blood collection method, in addition to the method using the capillary phenomenon, a method using a vacuum blood collection method, for example, a method in which the puncture blood collection part at the tip of the hollow puncture needle is covered with a diaphragm and the inside is evacuated. Can be mentioned. In such a biosensor, the diaphragm is broken at the time of puncture, and the negative pressure inside the needle-integrated biosensor is applied to the skin after puncture, and blood can be collected using this negative pressure.

  Further, in order to enhance the adhesion to the skin, a blood collection introduction guide is preferably provided so as to border the outside of the diaphragm, that is, the hollow puncture needle. Examples of the material for the blood collection introduction guide include gels, elastic materials, and foamable materials. The blood collection introduction guide also has an effect of maintaining the internal airtightness. In addition, since the hematocrit value also affects the vacuum blood sampling method, the electrode area is defined within a range where the minimum blood collection is possible even in the case of a high hematocrit value, that is, the electrode portion of the electrode plate member is in the vicinity of the puncture blood sampling port. It is preferable to use the resist described above as a method for defining the electrode area.

  The puncture needle preferably has a photocatalytic function effective for antibacterial and antiviral effects on its surface, and a titanium oxide or titanium dioxide film is formed by vapor deposition or sputtering.

  Since such a needle-integrated biosensor is of a cartridge type, it can be stored in a dedicated container that is convenient to carry, and anyone can easily and reliably attach it 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. Moreover, simple packaging is possible, and it can be kept hygienic from start to finish before and after use. In more detail, a packaging form is described.

Packaging Form As a packaging form of the needle-integrated biosensor, first, packaging of individual needle-integrated biosensors, particularly one that protects the puncture blood collection part at the tip of the needle-integrated biosensor. As such a package, a cap-shaped simple package that protects the tip is preferable. Thereby, the puncture blood collection part can be protected hygienically and safely until use. Furthermore, by having such a form, repackaging after use is possible, and it is possible to prevent infectious diseases that are a concern after disposal, and as another method of use, body fluid after puncture collection is stored. It is also possible.

As a second packaging form, there is a container in which a plurality of simply packaged cartridge-type needle integrated biosensors can be carried together. The cartridge-type needle-integrated biosensor of the present invention is extremely small even if it includes the bulk of the simple packaging, so even if a plurality of packages are stored together in a container, the overall size of the packaging container is small. . Specifically, it is desirable that the pocket size is easy to carry.

As a third packaging form, a packaging container itself is capable of individually packaging and storing cartridge-type needle integrated biosensors . In this case, for example, a cartridge-type needle-integrated biosensor is individually stored in a well-shaped tray and individually packaged with a packaging film or the like in order to maintain airtightness.

Measuring device The measuring device for the needle-integrated biosensor is easy to carry and secures operability and durability for repeated and reliable measurement using a cartridge-type needle-integrating biosensor. preferable.

  Specifically, a form in which a cartridge-type needle-integrated biosensor is slid laterally or inserted in a vertical direction into the introduction part at the lower part of the measuring apparatus is preferable. At this time, the terminal of the biosensor is connected to the connector of the measuring device so that measurement is possible. After that, when the user decides the puncture portion and starts puncturing, puncturing, blood sampling and measurement are automatically performed, and finally the measurement result is derived.

An example of structural features will be described in more detail. This measuring device displays the measured value in the measuring unit and the measuring unit that measures the electrical values in the introduction part of the biosensor with integrated needle , the connector, the electrochemical measurement circuit, the memory unit, the operation panel, and the electrode of the biosensor The display unit is configured as a basic component, and radio waves such as Bluetooth (registered trademark) can be mounted on the apparatus as wireless means.

In addition, an illumination function can be provided in consideration of use by a dark place or a low vision person. In this case, it is preferable that the user can improve the operability when attaching and puncturing the cartridge-type needle-integrated biosensor . For example, the introduction of the needle-integrated biosensor of the measuring apparatus is preferable. By irradiating light for illumination from the head, the user can easily introduce the cartridge- type needle-integrated biosensor into the measuring device, and even after the cartridge- type needle-integrated biosensor is attached, A form in which the puncture portion is illuminated by illumination is preferable. Therefore, a material such as a spacer or a diaphragm that fixes the electrode plate member of the cartridge-type needle-integrated biosensor having an illumination function is preferably a transparent material.

  In addition to the automatic illumination function of the display unit and puncture unit in the dark place, the measurement device includes a voice guide function and a voice recognition function corresponding to visual impairment due to diabetes, a measurement data management function using a built-in radio clock, measurement data A communication function for a medical institution, a charging function, and the like can be provided.

  The measuring method in the measuring unit of the measuring device is not particularly limited, and potential step chronoamperometry, coulometry, cyclic voltammetry, or the like can be used.

As described above, the needle-integrated biosensor, the needle-integrated biosensor cartridge, and the package thereof according to the present invention do not limit the user, that is, can support universal standards .

The needle-integrated biosensor and the cartridge-type 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 limited to the following examples as long as the gist thereof is not exceeded. It is not something.

  FIG. 1 shows an example of a needle-integrated biosensor in which a hollow puncture needle is disposed outside a cylindrical electrode plate member. 1a is a block diagram, FIG. 1b is a longitudinal sectional view of the center line in FIG. 1a, FIG. 1c is a transverse sectional view of the center line in FIG. 1a, FIG. These show rear views when the substrate 5 is viewed from the terminals 3. In the case of this needle-integrated biosensor, the puncture needle 6 is hollow, the puncture portion 19 has an acute angle, and an electrode system is provided therein. The puncture needle 6 and the cylindrical electrode plate member 18 are disposed on the substrate 5, and the hollow puncture needle 6 is provided with a through hole 8 for a capillary phenomenon stop portion 22. Thereby, after puncturing the skin with the needle-integrated biosensor in use, blood is naturally fed into the biosensor by capillary action, and measurement is performed by reacting with the reagent. Again, the electrode area in the vicinity of the puncture blood collection port 9 is defined by the resist so as not to be affected by fluctuations in the incorporation into the biosensor due to individual differences in blood collection.

  FIG. 2 shows an example of a vacuum blood collection type needle-integrated biosensor in which a hollow puncture needle is disposed outside a cylindrical electrode plate member. 2a is a configuration diagram, FIG. 2b is a longitudinal cross-sectional view of the center line in FIG. 2a, FIG. 2c is a cross-sectional view taken along the line BB 'in FIG. 2a when the substrate 5 is viewed from the puncture blood sampling port 9, and FIG. The rear view when 5 is seen is shown, respectively. In the case of this needle-integrated biosensor, the puncture blood collection port 9 is provided with a diaphragm 12 for keeping the inside vacuum and a blood collection introduction guide 7 on the surface thereof. At the time of use, the needle-integrated biosensor is punctured into the skin, the diaphragm 12 is broken, and blood is fed by the negative pressure inside the biosensor, and the measurement is performed by reacting with the reagent.

  FIG. 3 shows an example of a vacuum blood collection type needle-integrated biosensor in which a hollow puncture needle is disposed outside a prismatic electrode plate member. 3a is a configuration diagram, FIG. 3b is a cross-sectional view taken along line AA ′ in FIG. 3a, FIG. 3c is a cross-sectional view taken along line BB ′ in FIG. 3a, and FIG. . In the case of this needle-integrated biosensor, three electrode plate members are provided in a cylindrical hollow puncture needle so as to form a triangular prism. The puncture blood collection port 9 is provided with a diaphragm 12 for keeping the inside vacuum and a blood collection introduction guide 7 on the surface thereof. In use, the needle-integrated biosensor is punctured into the skin, so that the diaphragm 12 is broken, and blood is fed by the negative pressure inside the biosensor, and the measurement is performed by reacting with the reagent.

  FIG. 4 shows a state during puncturing operation (immediately after puncturing) of the vacuum blood collection type needle integrated biosensor shown in FIG. The diaphragm 12 is broken by puncturing, and the outside air enters the vacuum needle-integrated biosensor.

  FIG. 5 is a sectional view showing an example of use of the vacuum blood collection type needle integrated biosensor shown in FIG. 3 and FIG. By inserting the puncture portion of the vacuum blood collection type needle integrated biosensor obliquely into the skin of the subject (FIG. 5a), the diaphragm is broken (FIG. 5b), and the blood collection 17 is transferred into the sensor through the gap. (Figure 5c).

FIG. 6 shows a packaging example of the cartridge-type needle-integrated biosensor of the present invention and one usage example with a measuring device. FIG. 6a shows a packaging container 23 that can accommodate a plurality of cartridge- type needle-integrated biosensors , and FIG. 6b shows the inside thereof. In the form of this packaging container, since the cartridge- type needle integrated biosensor itself is small, the overall size becomes a small pocket size. Furthermore, in this case, each cartridge- type needle-integrated biosensor is housed in a well-shaped space and packaged by the simple packaging film 26. At the time of use, this simple packaging film 26 can be used by peeling it along the perforation 30 from the knob portion 28 which is a non-adhesive layer. At this time, the simple packaging film 26 is prevented from peeling off (generating dust) by preventing only the weak adhesive layer 27 from being peeled off and the strong adhesive layer 29 from being peeled off. Furthermore, if the weak adhesive layer 27 can be re-adhered, the used cartridge- type needle integrated biosensor can be restored. In this case, it is convenient to use a cartridge-type needle-integrated biosensor as a sampling container for blood collection or the like as in a normal syringe.

FIG. 6c shows a simple packaging example of the cartridge-type needle-integrated biosensor 15 and is housed in the packaging container 23 in this state. This simple package 24 is in the form of a cap and can be easily removed and reattached after use, and can be applied to a method of use for collecting and storing body fluids. The spacer 25 of the cartridge-type needle-integrated biosensor is made of a transparent material, so that when it is attached to a measuring device with an illumination function, illumination is performed through the spacer even in a dark place. Can be easily.

FIG. 6d shows a cartridge type needle-integrated biosensor measuring device. The measuring device 31 includes an operation panel 32, a display unit 33, a button 34, a hook 35, a non-slip 36, and a needle-integrated biosensor introduction unit 37. The cartridge- type needle-integrated biosensor 15 has a cap 24 removed. After that, it is attached to the needle-integrated biosensor introduction part 37 under the measuring device 31. If it is the shape of this measuring device 31, it is easy to carry and operability is also excellent.

FIG. 7 shows an example of operation when a cartridge-type needle integrated biosensor is used for measurement in a dark place. FIG. 7 a shows a state where one cartridge- type needle integrated biosensor 15 packaging portion in the packaging container 23 is illuminated by the illumination 14 from the needle integrated biosensor introduction part 37 of the measuring device 31. FIG. 7 b shows a state where the illumination 14 illuminates the planned puncture portion of the subject through the transparent spacer of the cartridge- type needle-integrated biosensor 15 attached to the measuring device 31. FIG. 7c shows a state where a portion specified by the illumination 14 is punctured, and blood is collected and measured. In this case, the visibility of the display unit can also be enhanced by a backlight or the like.

It is a figure which shows one structural example of the needle-integrated biosensor in which the hollow puncture needle is disposed outside the cylindrical electrode plate member. It is a figure which shows the example of 1 structure of the vacuum blood collection type | mold needle integrated biosensor by which the hollow puncture needle is arrange | positioned on the outer side of a cylindrical electrode plate member. It is a figure which shows the example of 1 structure of the needle-integrated biosensor in which the hollow puncture needle is disposed outside the prismatic electrode plate member. It is a figure which shows one usage example of a vacuum blood-collecting type needle-integrated biosensor. It is a figure which shows the other usage example of a vacuum blood-collecting type needle-integrated biosensor. It is a figure which shows the usage example with the packaging example of a cartridge type needle-integrated biosensor, and a measuring device. It is a figure which shows one usage example in the dark place of a cartridge type needle | hook integrated biosensor and a measuring apparatus.

Explanation of symbols

1 Flat electrode (electrode plate member)
3 Terminal 5 Substrate 6 Puncture needle 7 Blood sampling introduction guide 8 Air outlet 9 Puncture blood sampling port 10 Electrode reaction part (reagent layer)
12 Diaphragm 14 Illumination 15 Needle-integrated biosensor 16 Subject 18 Cylindrical electrode (electrode plate member)
19 Puncture part 22 Capillary phenomenon stop part 23 Packaging container 24 Cap for packaging 25 Transparent spacer 26 Packaging film 27 Weak adhesive layer 28 Non-adhesive layer (pick)
29 Strong adhesive layer 30 Perforation 31 Measuring device 32 Operation panel 33 Display unit 34 Button 35 Hook 36 Non-slip 37 Needle-integrated biosensor introduction unit

Claims (18)

  A puncture needle composed of a hollow columnar structure is embedded and fixed to the substrate, and at least two working electrodes and a counter electrode are passed through the columnar structure perpendicularly to the substrate. A needle-integrated biosensor formed by forming a puncture needle containing   The needle-integrated biosensor according to claim 1, wherein the hollow columnar structure has a hollow prismatic shape or a cylindrical shape.   The needle-integrated biosensor according to claim 1, wherein a terminal for sending an electrical signal to the measuring device is provided on the opposite side of the substrate from the substrate.   The needle-integrated biosensor according to claim 1, wherein the electrode is formed on a substrate for electrode formation by film formation or bonding to the electrode formation substrate.   The needle-integrated biosensor according to claim 1, wherein an electrode area is defined by a resist.   The needle-integrated biosensor according to claim 1, wherein a reagent layer is formed on the electrode.   The needle-integrated biosensor according to claim 1, wherein a puncture hollow needle provided with a photocatalytic function is used.   The needle-integrated biosensor according to claim 1, further comprising a bodily fluid collection stop unit by capillary action by providing a through-hole in the substrate or the puncture needle.   The needle-integrated biosensor according to claim 1, wherein the substrate is transparent.   The needle-integrated biosensor according to any one of claims 1 to 9, which is of a cartridge type. The cartridge-type needle integrated biosensor according to claim 10, which is a disposable type. The cartridge-type needle-integrated biosensor according to claim 10, which is in a packaged state. 13. The cartridge-type needle integrated biosensor according to claim 12, wherein the biosensor is packaged in a repackable state. A needle-integrated biosensor package containing a plurality of cartridge-type needle-integrated biosensors according to any one of claims 10 to 13. A needle-integrated biosensor cartridge according to any one of claims 10 to 13, the needle-integrated biosensor introducing part set by inserting the needle-integrated biosensors, in the needle-integrated biosensor electrode Connector unit for capturing electrical signals, measurement unit for measuring electrical values via the connector unit, operation panel unit for measurement, display unit for displaying measurement values in the measurement unit, memory unit for storing 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.   The measuring device for a needle-integrated biosensor according to claim 15, wherein a potential step chronoamperometry method, a coulometry method, or a cyclic voltammetry method is applied as a measurement method in the measurement unit. The measuring device for a needle-integrated biosensor according to claim 15 or 16, wherein the insertion port of the cartridge-type needle-integrated biosensor can be illuminated.   The needle according to any one of claims 15 to 17, comprising at least one of a voice guide function and a voice recognition function, a measurement data management function using a built-in radio clock, a communication function of measurement data to a medical institution, and a charging function. Integrated biosensor measuring device.

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