JP4576672B2 - Biosensor - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a biosensor that electrochemically measures a specific component in a sample solution.
[0002]
[Prior art]
A biosensor is a sensor that utilizes the molecular recognition ability of biological materials such as microorganisms, enzymes, and antibodies, and applies biological materials as molecular identification elements. That is, the immobilized biological material utilizes a reaction that occurs when a target substrate is recognized, an enzyme consumption due to respiration of microorganisms, an enzyme reaction, luminescence, and the like.
[0003]
Among biosensors, enzyme sensors are being put to practical use. For example, enzyme sensors for glucose, lactic acid, cholesterol, lactose, urea, and amino acids are used in the medical measurement and food industries. The enzyme sensor reduces the electron acceptor by electrons generated by the reaction between the substrate and the enzyme contained in the sample liquid that is the specimen, and the measurement device electrochemically measures the reduction amount of the electron acceptor, Perform quantitative analysis of specimens.
[0004]
Hereinafter, a conventional biosensor will be described with reference to the drawings. FIG. 5 is a diagram showing a state in which the biosensor is inserted into the measuring instrument. FIG. 6 is a diagram showing perspective views of a conventional biosensor in the order of manufacturing steps. FIG. 7 is a diagram showing the relationship between electrode terminals and connector pins of a conventional biosensor.
[0005]
In FIG. 6, reference numeral 101 denotes an insulating substrate made of polyethylene terephthalate or the like. Reference numeral 102 denotes an electrically conductive layer made of carbon, a metal material, or the like, which is formed on the entire surface of the substrate 101. Reference numerals 103 a, 103 b, 103 c, and 103 d are slits formed in the electrically conductive layer 102.
[0006]
Reference numerals 104, 105, and 106 denote electrodes formed by dividing the electrically conductive layer 102 by slits 103a, 103b, 103c, and 103d, which are measurement electrodes, counter electrodes, and detection electrodes. Reference numeral 107 denotes a spacer that covers the measurement electrode 104, the counter electrode 105, and the detection electrode 106. Reference numeral 108 denotes a rectangular notch that is provided in the center of the front edge of the spacer 107 and forms a sample supply path. Reference numeral 10 denotes an inlet of the sample supply path.
[0007]
Reference numeral 111 denotes a reagent layer formed by applying a reagent containing an enzyme to the measurement electrode 104, the counter electrode 105, and the detection electrode 106 by dropping. An upper cover 112 covers the spacer 107. Reference numeral 113 denotes an air hole provided in the central portion of the upper cover 112.
[0008]
In FIG. 7, reference numerals 114, 115, and 116 denote electrode terminals of the measurement electrode 104, the counter electrode 105, and the detection electrode 106. In FIG. 5, 17 is a biosensor. Reference numeral 18 denotes a measuring instrument to which the biosensor 17 is attached. Reference numeral 19 denotes an insertion port of the measuring instrument 18 for inserting the biosensor 17. Reference numeral 20 denotes a display unit of the measuring instrument 18 that displays the measurement result. Reference numerals 121a, 121b, and 121c are connector pins built in the measuring instrument 18 and connected to the electrode terminals 114, 115, and 116, respectively.
[0009]
As shown in FIG. 6A, an electrically conductive layer 102 is formed on the entire surface of the substrate 101 by a sputtering method or the like. Next, as shown in FIG. 6 (b), slits 103a, 103b, 103c, and 103d are formed in the electrically conductive layer 102 using a laser or the like, and the measurement electrode 104, the counter electrode 105, and the detection electrode 106 are electrically conductive. Divide layer 102.
[0010]
Next, as shown in FIG. 6 (c), in the case of a blood glucose level sensor, a reagent comprising glucose oxidase as an enzyme and potassium ferricyanide as an electron acceptor is applied to the measurement electrode 104, the counter electrode 105, and the detection electrode 106. The reagent layer 111 is formed by applying by dropping. Next, a spacer 107 having a notch 108 for forming a specimen supply path is placed on the measurement electrode 104, counter electrode 105, and detection electrode 106. Further, an upper cover 112 is installed thereon. Here, one end of the notch 108 of the spacer 107 communicates with an air hole 113 provided in the upper cover 112.
[0011]
In order to measure the specimen, the electrode terminals 114, 115, and 116 of the biosensor 17 are inserted into the insertion port 19 of the measuring device 18 and connected to the connector pins 121a, 121b, and 121c as shown in FIG. Next, when a sample solution such as blood is supplied to the inlet 10 of the sample supply path, a certain amount of sample is sucked into the sample supply path by capillary action through the air holes 113, and the counter electrode 105, the measurement electrode 104, It reaches the specimen electrode 106. The reagent layer 111 formed on the electrode is dissolved by blood, for example, an oxidation-reduction reaction occurs between the reagent and the specimen, and an electrical change occurs between the measurement electrode 104 and the counter electrode 105.
[0012]
At the same time, if the sample is correctly filled in the sample supply path, an electrical change occurs between the measurement electrode 104 and the detection electrode 106. When this is sensed through 121a, 121b, 121c and a voltage is applied to the measurement electrode 104 and the counter electrode 105 after a certain period of time, for example, in the case of a blood glucose level sensor, a current proportional to the glucose concentration is generated. 18 measures the blood glucose level and displays the blood glucose level on the display unit 20.
[0013]
The biosensor 17 has a difference in output characteristics of electrical change for each production lot. It is necessary to correct the difference in the output characteristics in the measuring device 18. The measuring device 18 includes correction data corresponding to the output characteristics of each manufacturing lot, and corrects the output of the biosensor 17 for each manufacturing lot to obtain a correct blood glucose level.
[0014]
Therefore, it is necessary to specify necessary correction data to the measuring device 18 by inserting the correction chip specified for each production lot into the insertion port 19 of the measuring device 18 before the measurement. The correction chip has information on which correction data is used, and the measuring instrument 18 prepares necessary correction data by inserting the correction chip into the insertion slot 19. The correction chip is removed from the insertion port 19, the biosensor 17 is inserted into the insertion port 19 of the measuring device 18, and the specimen is measured as described above. The measuring device 18 obtains a correct blood glucose level from the measured current value and the correction data, and displays the blood glucose level on the display unit 20.
[0015]
[Problems to be solved by the invention]
However, in the conventional biosensor, the electrode terminal portion is in a stripped state, and particularly in the case of a thin film conductive electrode using a sputtering method or the like, due to external factors, for example, in the biosensor production process or In addition, there is a problem that an accurate measurement result cannot be obtained due to scratches or dirt on the surface of the electrode terminal due to scratching or rubbing, which may occur when the user operates the product.
[0016]
In addition, when forgetting to insert the correction chip every time measurement is performed, or when measuring a blood glucose level, for example, when a correction chip for measuring cholesterol is mistakenly inserted, or for blood glucose level measurement. However, when a correction chip having different output characteristics is inserted, there is a problem that an error occurs in the measurement result.
[0017]
The present invention has been made in view of the above-mentioned problems, and prevents scratches and dirt from being caused by external factors on the electrode terminal surface, and only inserts a biosensor without inserting a correction chip. Thus, an object of the measuring device is to provide a biosensor capable of discriminating correction data for each production lot.
[0018]
[Means for Solving the Problems]
In order to achieve the above object, the biosensor of the present invention provides a reagent for a specific component in a sample solution by disposing a cover so as to partially cover an insulating substrate on which an electrically conductive layer is formed. In the biosensor formed with an electrode for detecting by a reaction with the electrode and an electrode terminal for reading a current value generated by the reaction at the electrode by connecting to an external measuring device, the electrode terminal is the biosensor The cover is formed with an opening so that only a region necessary for connection with the connection terminal of the measurement device is exposed in a state where the attachment to the measurement device is completed. Yes, thereby preventing the electrode terminals from being damaged.
[0019]
Also, the position of the opening is changed according to the type of sensor, and this can be detected by a measuring instrument, thereby eliminating the operation of inserting a correction chip.
[0020]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, a biosensor according to an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a diagram illustrating perspective views of a biosensor according to one embodiment in the order of manufacturing steps, and FIG. 2 is a diagram illustrating a configuration example of electrode terminals of the biosensor. FIG. 3 is a diagram showing the positional relationship between the electrode terminals and the connector pins. FIG. 4 is a view showing an example of forming an opening (through hole). FIG. 5 is a diagram showing a state where the biosensor is inserted into the measuring instrument.
[0021]
In the figure, reference numeral 1 denotes an insulating substrate made of polyethylene terephthalate or the like. Reference numeral 2 denotes an electrically conductive layer formed on the entire surface of the substrate 1 and made of an electrically conductive material such as a noble metal such as gold or palladium or carbon. Reference numerals 3 a, 3 b, 3 c, and 3 d are slits provided in the electrically conductive layer 2. Reference numerals 4, 5, and 6 denote electrodes formed by dividing the electrically conductive layer 2 by slits 3a, 3b, 3c, and 3d. The measurement electrode, the counter electrode, and the specimen are reliably sucked into the specimen supply path. This is a detection electrode for confirming whether or not.
[0022]
A spacer 7 covers the measurement electrode 4, the counter electrode 5, and the detection electrode 6. Reference numeral 8 denotes a rectangular notch that forms a sample supply path provided in the center of the front edge of the spacer 7. Reference numeral 9 denotes an opening that exposes the electrode terminal, and includes through holes 9 a, 9 b, and 9 c formed in the spacer 7.
[0023]
Reference numeral 10 denotes an inlet of the sample supply path. Reference numeral 11 denotes a reagent layer formed by applying a reagent containing an enzyme to the measurement electrode 4, the counter electrode 5, and the detection electrode 6 by dropping. Reference numeral 12 denotes an upper cover that covers the spacer 7. Reference numeral 13 denotes an air hole provided in the central portion of the upper cover 12. Reference numerals 14, 15 and 16 denote electrode terminals of the measurement electrode 4, the counter electrode 5 and the detection electrode 6. Reference numeral 17 denotes a biosensor. Reference numeral 18 denotes a measuring instrument to which a biosensor is attached. Reference numeral 19 denotes an insertion port of the measuring instrument 18 for inserting the biosensor 17. Reference numeral 20 denotes a display unit of the measuring instrument 18 that displays the measurement result. Reference numerals 21 a, 21 b, 21 c, 21 d, 21 e, and 21 f are connector pins built in the measuring instrument 18 and connected to the electrode terminals 14, 15, and 16.
[0024]
As shown in FIG. 1A, an electrically conductive layer 2 of a noble metal thin film such as gold or palladium is formed by sputtering, which is a method for forming a thin film on the entire surface of the substrate 1.
The electrically conductive layer 2 may be formed not only on the entire surface of the substrate 1 but only on a portion necessary for forming the electrode.
[0025]
Next, as shown in FIG. 1B, slits 3a, 3b, 3c, and 3d are formed in the electrically conductive layer 2 using a laser, and the electrically conductive layer 2 is measured with the measurement electrode 4, the counter electrode 5, and the detection. Divide into electrodes 6.
[0026]
The substrate 1 is formed by a screen printing method or a sputtering method using a printing plate or a masking plate on which a pattern necessary for forming the electrically conductive layer 2 having the slits 3a, 3b, 3c, and 3d is previously arranged. Electrodes and slits 3a, 3b, 3c, and 3d may be formed thereon. In addition, as a method of providing the slits 3a, 3b, 3c, and 3d in the electrically conductive layer 2, a part of the electrically conductive layer 2 may be shaved with a jig having a sharp tip.
[0027]
Next, as shown in FIG. 1 (c), the measurement electrode 4, the counter electrode 5 and the detection electrode 6 are made of, for example, glucose oxidase which is an enzyme and ferricyanium potassium or the like as an electron acceptor. Reagent is applied dropwise.
[0028]
Next, a notch 8 for forming a sample supply path on the electrodes of the measurement electrode 4, the counter electrode 5, and the detection electrode 6 and terminals 14, 15, 16 of each electrode are built in the measuring instrument. A spacer 7 having through holes 9a, 9b, 9c for connecting to the connector pins 21a or 21d, 21b or 21e, 21c or 21f is provided.
[0029]
Here, the through holes 9a, 9b, 9c are built in the measuring device 18 on the electrode terminals 14, 15, 16 of the measuring electrode 4, the counter electrode 5, and the detecting electrode 6, as shown in FIG. The connector pins 21a or 21d, 21b or 21e, 21c or 21f are provided so as to leave only the portions necessary for connection. That is, only when the biosensor 17 completes the mounting on the measuring instrument 18, each of the electrode terminals is exposed so that the connector pin and the electrode terminal come into contact with each other, and an area unnecessary for this connection is covered with the spacer 7. In this way, the surface of the electrode terminal is prevented from being scratched or soiled due to scratching or rubbing that may occur during the biosensor production process or when the user operates the product.
[0030]
As shown in FIG. 2B, the opening 9 is integrally provided without providing the through holes 9a, 9b, 9c corresponding to the respective electrode terminals, and the electrode terminals 14, 15, 16 and the measuring device 18 are provided. A portion necessary for connection with a built-in connector pin may be provided in a concave shape.
[0031]
As the positions where the through holes 9a, 9b, 9c are provided, for example, eight combinations as shown in FIGS. 4A to 4H are conceivable. By combining the positions where these through holes 9a, 9b, 9c are provided, the measuring device 18 can determine the information of correction data for correcting the difference in output characteristics for each production lot.
[0032]
For example, when three through holes 9a, 9b, 9c are provided in parallel in front of the biosensor of FIG. 4A (positions connected to the connector pins 21a, 21b, 22c), the production lot number 1 When the biosensor having output characteristics is provided in parallel with three through holes 9a, 9b, 9c behind the biosensor in FIG. 4B (positions connected to the connector pins 21d, 21e, 21f) A biosensor having the output characteristics of production lot number 2 is assumed.
[0033]
Next, the upper cover 12 is installed on the spacer 7. Here, one end of the notch 8 of the spacer 7 communicates with an air hole 13 provided in the upper cover 12. In addition, after forming the spacer 7 on the electrodes of the measurement electrode 4, the counter electrode 5, and the detection electrode 6, the reagent is applied to the portions exposed from the notches 8 of the measurement electrode 4, the counter electrode 5, and the detection electrode 6. The reagent layer 11 may be formed by dripping.
[0034]
Further, after the spacer 7 having the notch 8 formed thereon and the cover 12 are bonded and integrated, the through holes 9a, 9b, 9c are formed as the electrodes of the measurement electrode 4, the counter electrode 5, and the detection electrode 6. You may install on top of. (In this case, the cover 12 also has through holes 9a, 9b, 9c at the same position.)
When measuring a specimen with a biosensor, first, the electrode terminals 14, 15 and 16 of the biosensor 17 are inserted into the insertion port 19 of the measuring device 18. Since the electrode terminals 14, 15 and 16 are opened by through holes 9a, 9b and 9c provided in the spacer, they are connected to the connector pins 21a or 21d, 21b or 21e, 21c or 21f built in the measuring instrument 18. The
[0035]
According to this configuration, when blood as a specimen is supplied to the inlet 10 of the specimen supply path, a certain amount of specimen is sucked into the specimen supply path by capillary action through the air holes 13, and the counter electrode 5, the measurement electrode 4, and the detection are detected. It reaches on the electrode 6. The reagent layer 11 formed on the electrode is dissolved in blood as a sample, and an oxidation-reduction reaction occurs between the reagent and a specific component in the sample. Here, if the sample is correctly supplied into the sample supply path, an electrical change occurs between the counter electrode 5 and the detection electrode 6. Thereby, it is confirmed that the specimen is sucked up to the detection electrode 6. In addition, since an electrical change also occurs between the measurement electrode 4 and the detection electrode 6, it may be confirmed that the specimen is aspirated to the detection electrode 6.
[0036]
After the specimen is aspirated to the detection electrode 6, the reaction between the specimen and the reagent is promoted for a certain period of time, and then a constant voltage is applied to the measurement electrode 4 and the counter electrode 5 or both the counter electrode 5 and the detection electrode 6. To do. Since it is a blood glucose level sensor, a current proportional to the glucose concentration is generated, and the measuring device 18 measures the value.
[0037]
The measuring device 18 measures the electrical change in each electrode of the measurement electrode 4, the counter electrode 5, and the detection electrode 6. The electrode terminal 14 is exposed from the through holes 9 a, 9 b, 9 c provided on the spacer 7. , 15, and 16 through connector pins 21a or 21d, 21b or 21e, 21c or 21f.
[0038]
In addition, the measuring instrument 18 has the electrode terminals 14, 15, and 16 exposed from the through holes 9 a, 9 b, and 9 c of the electrodes of the measurement electrode 4, the counter electrode 5, and the detection electrode 6 of the biosensor 17. Find out if there is.
[0039]
If there is no through hole at a position connected to the connector pin, electrical conduction cannot be obtained, and if there is a through hole, electrical conduction can be obtained. For example, when electrical continuity is confirmed in connector pins 21a, 21b, and 21c, and electrical continuity is not confirmed in 21d, 21e, and 21f, the biosensor of production lot number 1 is shown in FIG. In this state, the measuring device 18 obtains the blood glucose level from the correction data corresponding to the output characteristic of the production lot number 1 stored in advance and the measured current value, and displays the blood glucose level on the display unit 20. .
[0040]
Similarly, when electrical continuity is not confirmed in connector pins 21a, 21b, and 21c, and electrical continuity is confirmed in 21d, 21e, and 21f, correction data corresponding to the output characteristics of production lot number 2 is corrected. The blood glucose level is obtained from the measured current value and the blood glucose level is displayed on the display unit 20.
[0041]
In addition, it cannot be overemphasized that even in the structure which formed the opening part 9 of FIG.2 (b) integrally, it can comprise so that a manufacturing lot number can be discriminate | determined by changing the formation position.
[0042]
As described above, although the blood glucose level sensor has been described in the present embodiment, it can be used as a biosensor other than the blood glucose level sensor, for example, a lactate sensor or a cholesterol sensor by changing the components and the specimen of the reagent layer 11. Even in such a case, if the measuring device can determine the information of the correction data corresponding to the output characteristics of the lactate sensor or the cholesterol sensor depending on the position of the opening 9, the measuring device 18 stores the lactate stored in advance. The measured value is obtained from the correction data corresponding to the output characteristics of the sensor or cholesterol sensor and the current value, and displayed on the display unit 20.
[0043]
In the present embodiment, a biosensor having three electrodes has been described. However, the number of electrodes may be other than that.
[0044]
In addition, the number of combinations that can be discriminated can be easily increased by arbitrarily changing the number of connector pins as necessary.
[0045]
【The invention's effect】
As described above, according to the biosensor of the present invention, the electrode terminal surface is not damaged or contaminated by an external factor or the like, and the effect of being able to perform accurate measurement without variation when measuring a specimen. Have Furthermore, since the contact position with the connector pin on the electrode terminal can be regulated with high accuracy, a highly accurate biosensor with a stable electrode resistance value can be provided.
[0046]
Further, by detecting the type of biosensor based on each production lot or the type of reagent at the position of the opening, it is not necessary for the operator to input correction data using a correction chip or the like. Operation mistakes can be prevented and correct results can be obtained.
[Brief description of the drawings]
FIG. 1 is a perspective view showing a biosensor according to an embodiment of the present invention in the order of manufacturing steps. FIG. 2 is a perspective view showing the shape of an opening of the biosensor. FIG. Fig. 4 is a plan view showing the positional relationship between the electrode terminals and connector pins of the biosensor. Fig. 5 is a perspective view showing a state in which the biosensor is inserted into a measuring instrument. FIG. 7 is a perspective view and a plan view showing electrode terminals and connector pins of a conventional biosensor.
DESCRIPTION OF SYMBOLS 1 Insulating board | substrate 2 Electrically conductive layer 3a, 3b, 3c, 3d Slit 4 Measuring electrode 5 Counter electrode 6 Detection electrode 7 Spacer 8 Notch part 9 Opening part 9a, 9b, 9c Through-hole 10 Entrance of specimen supply path 11 Reagent layer 12 Cover 13 Air hole 14, 15, 16 Electrode terminal 17 Biosensor 18 Measuring device 19 Biosensor insertion port 20 Display part 21a, 21b, 21c, 21d, 21e, 21f Connector

Claims (10)

An electrode for detecting a specific component in a sample solution by reaction with a reagent by arranging a cover so as to partially cover an insulating substrate having an electrically conductive layer formed on the surface; In the biosensor formed with the electrode terminal for reading the current value generated by the reaction connected to an external measuring instrument,
The electrode terminal has an opening formed in the cover so that only a region necessary for connection with the connection terminal of the measuring device is exposed in a state where the mounting of the biosensor to the measuring device is completed. In addition, the biosensor is characterized in that the openings are formed at different positions according to the type of the biosensor.   The biosensor according to claim 1, wherein the type of sensor varies depending on the production lot or the type of reagent.   By splitting the electrically conductive layer formed over the entire surface of the insulating substrate with slits, an electrode composed of at least a measurement electrode and a counter electrode is formed, and electrode terminals are also divided and formed corresponding to these electrodes. The biosensor according to claim 1 or 2, wherein:   The biosensor is an elongated piece, and the opening is provided in the cover so that the electrode terminal is formed at a position away from one end of the biosensor. Biosensor.   The biosensor according to any one of claims 1 to 4, wherein the opening is a through hole provided in the cover.   The biosensor according to claim 5, wherein the opening is a through hole provided in the cover, and the through hole is formed for each electrode terminal corresponding to at least the measurement electrode and the counter electrode.   The cover has a spacer formed with a notch for guiding the sample solution on the electrode and an opening for forming the electrode terminal, and a space for covering the upper part of the notch to hold the sample solution. The biosensor according to claim 1, comprising an upper cover.   The biosensor according to claim 1, wherein the electrically conductive layer is formed by sputtering.   9. The biosensor according to claim 1, wherein openings provided corresponding to the plurality of electrode terminals are formed integrally with each other.   The biosensor according to claim 7, wherein an opening is also formed in the upper cover.

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