JP4184573B2 - Biosensor - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a biosensor for quantifying a substrate contained 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, oxygen consumption due to respiration of microorganisms, an enzymatic reaction, luminescence, and the like.
[0003]
Among biosensors, enzyme sensors have been put to practical use. For example, enzyme sensors for glucose, lactose, urea, and amino acids are used in medical measurement and the food industry. 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. 3 is a diagram showing a state in which the biosensor is inserted into the measuring instrument. FIG. 4 is a diagram showing a perspective view of a conventional biosensor in the order of creation steps. Reference numeral 101 denotes an insulating substrate made of polyethylene terephthalate or the like. Reference numeral 102 denotes an electrically conductive layer formed on the surface of the substrate 101 and made of carbon, a metal material, or the like. Reference numerals 103 a, 103 b, 103 c, and 103 d are slits formed in the electrically conductive layer 102. Reference numerals 105, 106, and 107 denote electrodes formed by dividing the electrically conductive layer 102 by slits 103a, 103b, 103c, and 103d, which are a measurement electrode, a counter electrode, and a detection electrode. Reference numeral 108 denotes a spacer that covers the measurement electrode 105, the counter electrode 106, and the detection electrode 107. Reference numeral 109 denotes a rectangular notch that is provided in the center of the front edge of the spacer 108 and forms a specimen supply path. Reference numeral 10 denotes an inlet of the sample supply path. Reference numeral 111 denotes a reagent layer formed by applying a reagent containing an enzyme to the measurement electrode 105, the counter electrode 106, and the detection electrode 107 by dropping. A cover 112 covers the spacer 108. Reference numeral 113 denotes an air hole provided at the center of the cover 112. 14 is a biosensor. Reference numeral 15 denotes a measuring instrument to which the biosensor 14 is attached. Reference numeral 16 denotes an insertion port of the measuring instrument 15 for inserting the biosensor 14. Reference numeral 17 denotes a display unit of the measuring instrument 15 that displays the measurement result.
[0005]
As shown in FIG. 4A, an electrically conductive layer 102 is formed on the entire surface of the substrate 101 by a screen printing method or the like. Next, as shown in FIG. 4B, slits 103a, 103b, 103c, and 103d are formed in the electrically conductive layer 102 using a laser, and the electrically conductive layer is formed on the measurement electrode 105, the counter electrode 106, and the detection electrode 107. 102 is divided. Next, as shown in FIG. 4C, in the case of a blood glucose level sensor, a reagent composed of glucose oxidase as an enzyme and potassium ferricyanide as an electron acceptor is dropped onto the measurement electrode 105, the counter electrode 106, and the detection electrode 107. The reagent layer 111 is formed by coating. Next, a spacer 108 having a notch 109 for forming a specimen supply path is placed on the measurement electrode 105, the counter electrode 106, and the detection electrode 107. Further, a cover 112 is installed thereon. Here, one end of the notch 109 of the spacer 108 communicates with an air hole 113 provided in the cover 112.
[0006]
In order to measure the specimen, the biosensor 14 is inserted into the insertion port 16 of the measuring instrument 15 as shown in FIG. Next, when a sample liquid 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 106, the measurement electrode 105, It reaches on the detection electrode 107. 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 105 and the counter electrode 106. At the same time, if the sample is correctly filled in the sample supply path, an electrical change occurs between the measurement electrode 105 and the detection electrode 107. When this is sensed and a voltage is applied to the measurement electrode 105 and the counter electrode 106, for example, in the case of a blood glucose level sensor, a current proportional to the glucose concentration is generated, and the measuring device 15 measures the blood glucose level from that value. The blood glucose level is displayed on the display unit 17.
[0007]
The biosensor 14 produces a difference in output characteristics for each production lot. It is necessary to correct the difference in the output characteristics in the measuring instrument 15. The measuring device 15 includes correction data corresponding to the output characteristics of each manufacturing lot, and corrects the output of the biosensor 14 for each manufacturing lot to obtain a correct blood glucose level. Therefore, it is necessary to specify necessary correction data to the measuring instrument 15 by inserting the correcting chip specified for each production lot into the insertion port 16 of the measuring instrument 15 before the measurement. The correction chip has information on which correction data is used, and the measuring instrument 15 prepares necessary correction data by inserting the correction chip into the insertion slot 16. The correction chip is removed from the insertion port 16, the biosensor 14 is inserted into the insertion port 16 of the measuring instrument 15, and the specimen is measured as described above. The measuring device 15 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 17.
[0008]
[Problems to be solved by the invention]
However, it is cumbersome to insert the correction chip for each measurement, forgetting to insert the correction chip, or by mistake, for example, inserting a correction chip for urea measurement, or for blood glucose level measurement. Even when a correction chip having different output characteristics is inserted, there is a problem that an error occurs in the measurement result.
[0009]
The present invention has been made in view of the above problems, and a measuring instrument provides a biosensor that can determine correction data for each production lot by inserting a biosensor without inserting a correction chip. For the purpose.
[0010]
[Means for Solving the Problems]
In order to achieve the above object, the biosensor according to claim 1, a plurality of electrodes formed by dividing an electrically conductive layer formed on the whole surface or a part of an insulating substrate by a first slit, A biosensor having a reagent layer made of a reagent to be reacted with a sample solution and outputting an electrical change caused by a reaction between the sample solution and the reagent layer, wherein each electrode outputs the electrical change And a correction unit having correction data information corresponding to the output characteristics of the biosensor, and in each of the electrodes, a second slit that divides between the measurement unit and the correction unit. The measuring device can determine the information of the correction data depending on the presence or absence .
[0012]
The biosensor according to claim 2 is the biosensor according to claim 1 , wherein the biosensor according to claim 1 is disposed on the spacer having a notch that forms a specimen supply path for supplying the sample solution to the electrode. And a cover having an air hole communicating with the sample supply path.
[0013]
The biosensor according to claim 3 is the biosensor according to claim 1 or 2 , wherein the electrically conductive layer is formed on the insulating substrate by a sputtering method. .
[0014]
The biosensor according to claim 4 is the biosensor according to any one of claims 1 to 3 , wherein the first slit and the second slit are formed by processing the electrically conductive layer with a laser. It is formed by doing so.
Moreover, the measurement method according to claim 5 is a measurement method using the biosensor according to any one of claims 1 to 4, wherein when the biosensor is inserted into a measuring instrument, A step of detecting presence / absence of conduction between the measurement unit and the correction unit; a step of determining information of correction data according to output characteristics by the measuring device according to the presence / absence of the conduction; and The measurement value corrected from the step of detecting an electrical change caused by the reaction between the sample solution and the reagent layer as a current value through the measurement unit, the correction data corresponding to the output characteristic, and the current value is obtained. And a step of outputting.
[0015]
DETAILED DESCRIPTION OF THE INVENTION
Embodiment 1 FIG.
The biosensor according to the first embodiment will be described with reference to the drawings.
[0016]
FIG. 1 is a diagram showing perspective views of the biosensor according to the first embodiment in the order of creation steps. FIG. 2 is a plan view showing a formation example of the second slit of the biosensor according to the first embodiment. FIG. 3 is a diagram showing a state in which the biosensor is inserted into the measuring instrument. 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 first slits provided in the electrically conductive layer 2. Reference numerals 5, 6 and 7 are electrodes formed by dividing the electrically conductive layer 2 by the first slits 3a, 3b, 3c, and 3d. The measurement electrode, the counter electrode, and the specimen are surely placed inside the specimen supply path. It is a detection electrode which is an electrode for confirming whether it was attracted | sucked to. Reference numerals 4a, 4b, and 4c denote second slits that divide the counter electrode 6, the detection electrode 7, and the measurement electrode 5, respectively. A spacer 8 covers the measurement electrode 5, the counter electrode 6, and the detection electrode 7. Reference numeral 9 denotes a rectangular notch that forms a sample supply path provided in the center of the front edge of the spacer 8. 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 5, the counter electrode 6, and the detection electrode 7 by dropping. A cover 12 covers the spacer 8. Reference numeral 13 denotes an air hole provided in the central portion of the cover 12. Reference numerals 26, 27, and 25 denote correction units provided at the terminal portions of the measurement electrode 5, the counter electrode 6, and the detection electrode 7 that are the respective electrodes. Reference numerals 35, 36, and 37 denote measurement units in the peripheral portion of the cover 12 that are exposed from the cover 12 of the measurement electrode 5, the counter electrode 6, and the detection electrode 7, respectively. 14 is a biosensor. Reference numeral 15 denotes a measuring instrument to which the biosensor 14 is attached. Reference numeral 16 denotes an insertion port of the measuring instrument 15 for inserting the biosensor 14. Reference numeral 17 denotes a display unit of the measuring instrument 15 that displays the measurement result.
[0017]
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.
[0018]
Next, as shown in FIG. 1B, the first 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 measuring electrode 5 and the counter electrode 6. And divided into detection electrodes 7. In addition, the second slits 4a, 4b, and 4c are formed in the electrodes of the measurement electrode 5, the counter electrode 6, and the detection electrode 7 using a laser. Here, the second slits 4a, 4b and 4c divide all the measurement electrodes 5, counter electrodes 6 and detection electrodes 7 which are electrodes, but how to provide the second slits 4a, 4b and 4c is as follows. For example, there are eight possible combinations as shown in FIG. FIG. 2A shows a case where the second slit is not provided, FIG. 2B shows a case where the second slit 4a is provided only on the counter electrode 6, and FIG. FIG. 2D shows the case where the second slit 4 c is provided only on the measurement electrode 5, and FIG. 2E shows the counter electrode 6 and the detection electrode 7. FIG. 2 (f) shows the case where the second slits 4c and 4a are provided in the measurement electrode 5 and the counter electrode 6, and FIG. 2 (g) shows the measurement. This is a case where the second slits 4 c and 4 b are provided in the electrode 5 and the detection electrode 7, and FIG. 2 (h) shows the second slit 4 c in all of the measurement electrode 5, the counter electrode 6, and the detection electrode 7. It is a figure which shows the case where 4a and 4b are provided. The combination of these second slits 4a, 4b and 4c enables the measuring device 15 to determine correction data information for correcting the difference in output characteristics for each production lot. For example, when the second slit of FIG. 2A is not provided, the biosensor having the output characteristic of the production lot number 1 is provided, and the second slit 4a is provided only on the counter electrode 6 of FIG. In this case, the biosensor having the output characteristics of the production lot number 2 is used.
[0019]
In addition, a printing plate or a masking plate in which a pattern necessary for forming the electrically conductive layer 2 having the first slits 3a, 3b, 3c, and 3d and the second slits 4a, 4b, and 4c is arranged in advance. The electrodes and the first slits 3a, 3b, 3c, and 3d and the second slits 4a, 4b, and 4c may be formed on the substrate 1 by the screen printing method or the sputtering method used.
[0020]
In addition, as a method of providing the first slits 3a, 3b, 3c, 3d and the second slits 4a, 4b, 4c in the electrically conductive layer 2, the electric conductive layer 2 can be formed with a jig having a sharp tip. A part may be shaved.
[0021]
Further, the second slits 4a, 4b, and 4c may be formed after the output characteristics of the biosensor 14 are examined, so that the sorting for each production lot can be reliably performed.
[0022]
Next, as shown in FIG. 1 (c), in the case of a blood glucose sensor, a reagent composed of glucose oxidase which is an enzyme and potassium ferricyanide or the like as an electron acceptor is dropped onto the measurement electrode 5, the counter electrode 6 and the detection electrode 7. Apply by.
[0023]
Next, a spacer 8 having a notch 9 for forming a specimen supply path is installed on the electrodes of the measurement electrode 5, the counter electrode 6 and the detection electrode 7.
[0024]
Next, the cover 12 is installed on the spacer 8. Here, one end of the notch 9 of the spacer 8 communicates with an air hole 13 provided in the cover 12.
In addition, after forming the spacer 8 on the electrode of the measurement electrode 5, the counter electrode 6, and the detection electrode 7, a reagent is dripped at the part exposed from the notch part 9 of the measurement electrode 5, the counter electrode 6, and the detection electrode 7. Thus, the reagent layer 11 may be formed.
[0025]
When measuring a specimen with a biosensor, first, the biosensor 14 is inserted into the insertion port 16 of the measuring instrument 15 as shown in FIG. When blood is supplied to the inlet 10 of the specimen supply path as a specimen liquid as a specimen, a certain amount of specimen is sucked into the specimen supply path by capillary action through the air holes 13, and on the counter electrode 6, the measurement electrode 5, and the detection electrode 7. To reach. 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 filled in the sample supply path, an electrical change occurs between the counter electrode 6 and the detection electrode 7. Thereby, it is confirmed that the specimen is sucked up to the detection electrode 7. In addition, since an electrical change also occurs between the measurement electrode 5 and the detection electrode 7, it may be confirmed that the specimen is sucked up to the detection electrode 7. After the specimen is aspirated to the detection electrode 7, 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 5 and the counter electrode 6 or both the counter electrode 6 and the detection electrode 7. To do. Since it is a blood glucose level sensor, a current proportional to the glucose concentration is generated, and the measuring device 15 measures the value. The measuring device 15 senses the electrical changes at the measurement electrode 5, the counter electrode 6, and the detection electrode 7 from the measurement units 35, 36, and 37.
[0026]
Further, the measuring instrument 15 checks whether or not the measurement electrode 5, the counter electrode 6 and the detection electrode 7 which are the respective electrodes of the biosensor 14 are divided by the second slits 4c, 4a and 4b. For example, by examining the electrical continuity between the measurement unit 35 and the correction unit 25, it can be determined whether or not the second slit 4c is formed. Similarly, if the electrical continuity between the measurement unit 36 and the correction unit 26 is examined, whether or not the second slit 4a is formed determines the electrical continuity between the measurement unit 37 and the correction unit 27. By examining it, it can be determined whether or not the second slit 4b is formed. For example, when the second slit is not formed in any electrode, the measuring device 15 is a pre-stored manufacturing lot because it is the state shown in FIG. A blood glucose level is obtained from the correction data corresponding to the output characteristic of No. 1 and the measured current value, and the blood glucose level is displayed on the display unit 17. Similarly, if the second slit 4a is formed only in the counter electrode 6, the blood glucose level is obtained from the correction data corresponding to the output characteristics of the production lot number 2 and the measured current value, and the blood glucose level is displayed. Displayed on the unit 17.
[0027]
Although the blood glucose level sensor has been described in the first embodiment, it can be used as a biosensor other than the blood glucose level sensor, for example, as a urea sensor or a lactose sensor by changing the components and the specimen of the reagent layer 11. Even in such a case, if the measuring instrument can discriminate information on the correction data corresponding to the output characteristics of the urea sensor or the lactose sensor according to the position of the second slit, the measuring instrument 15 stores in advance. The measured value is obtained from the correction data corresponding to the output characteristics of the urea sensor or the lactose sensor and the current value and displayed on the display unit 17.
[0028]
In the first embodiment, a biosensor having three electrodes has been described. However, the number of electrodes may be other than that. A plurality of second slits may be provided on one electrode.
[0029]
As described above, in the biosensor according to the first embodiment, it is possible to determine which manufacturing lot the biosensor is based on on which electrode the second slit that divides each electrode is formed. Therefore, since the measuring device can determine which correction data is required by inserting a biosensor into the measuring device, the operator does not need to input the correction data using a correction chip etc. This has the effect of preventing operation mistakes. In addition, a reagent layer formed of a reagent to be reacted with a sample solution, a spacer having a notch for forming a sample supply channel for supplying the sample solution to the electrode, and the sample supply channel disposed on the spacer And a cover having an air hole leading to, the sample liquid can be easily sucked into the sample supply path. In addition, since the electrically conductive layer is formed on the entire surface of the insulating substrate by the sputtering method and divided into a plurality of electrodes by the first slit, it is possible to create a highly accurate electrode and to increase the measurement accuracy. Have In addition, since the first slit and the second slit are formed by a laser, highly accurate processing can be performed, the area of each electrode can be defined with high accuracy, and the interval between the electrodes can be narrowed. Therefore, the biosensor can be miniaturized.
[0030]
【The invention's effect】
As described above, according to the biosensor according to claim 1 of the present invention, a plurality of electrically conductive layers formed on the whole surface or a part of the insulating substrate are divided by the first slit. A biosensor having an electrode and a reagent layer made of a reagent to be reacted with a sample solution, and outputting an electrical change caused by a reaction between the sample solution and the reagent layer, wherein each of the electrodes A measurement unit that outputs changes, and a correction unit that has correction data information corresponding to the output characteristics of the biosensor, and each electrode is divided between the measurement unit and the correction unit. Since the measuring instrument can determine the information on the correction data based on the presence or absence of slits, the measuring instrument can determine which correction data is necessary by inserting a biosensor into the measuring instrument. , The operator There is no need to input the information of the correction data using a like, it eliminates the need for tedious, prevent operation errors, has the effect that it is possible to obtain a correct result.
[0032]
Moreover, according to the biosensor according to claim 2 of the present invention, in the biosensor according to claim 1, a spacer having a notch portion that forms a specimen supply path for supplying the sample liquid to the electrode; Since the cover having the air hole leading to the sample supply path disposed on the spacer is provided, the sample liquid can be easily sucked into the sample supply path.
[0033]
Moreover, according to the biosensor according to claim 3 of the present invention, in the biosensor according to claim 1 or 2 , the electrically conductive layer is formed on the insulating substrate by a sputtering method. As a result, it is possible to form a highly accurate thin film, to produce a highly accurate electrode, and to increase the measurement accuracy.
[0034]
Moreover, according to the biosensor according to claim 4 of the present invention, in the biosensor according to any one of claims 1 to 3 , the first slit and the second slit are the electric conductivity. Since the layer is formed by processing with a laser, it is possible to perform processing with high accuracy and to define the area of each electrode with high accuracy. Moreover, since the space | interval of each electrode can be narrowed, it has the effect that size reduction of a biosensor can be achieved.
[Brief description of the drawings]
FIG. 1 is a diagram illustrating perspective views of a biosensor according to a first embodiment in the order of creation steps.
FIG. 2 is a plan view showing a formation example of a second slit of the biosensor according to the first embodiment.
FIG. 3 is a diagram showing a state where a biosensor is inserted into a measuring device.
FIG. 4 is a diagram showing perspective views of a conventional biosensor in the order of creation steps.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Substrate 2 Electrically conductive layer 3a 1st slit 3b 1st slit 3c 1st slit 3d 1st slit 4a 2nd slit 4b 2nd slit 4c 2nd slit 5 Measuring electrode 6 Counter electrode 7 Detection Electrode 8 Spacer 9 Notch 10 Entrance of sample supply path 11 Reagent layer 12 Cover 13 Air hole 14 Biosensor 15 Measuring device 16 Biosensor insertion port 17 Display unit 25 Correction unit 26 Correction unit 27 Correction unit 35 Measurement unit 36 Measurement unit 37 Measuring unit 101 Substrate 102 Electrically conductive layer 103a Slit 103b Slit 103c Slit 103d Slit 105 Measuring electrode 106 Counter electrode 107 Detection electrode 108 Spacer 109 Notch 111 Reagent layer 112 Cover 113 Air hole

Claims (5)

A plurality of electrodes formed by dividing an electrically conductive layer formed on the entire surface or a part of an insulating substrate by a first slit, and a reagent layer made of a reagent that reacts with the sample solution, the sample solution A biosensor that outputs an electrical change caused by a reaction between the reagent layer and the reagent layer,
Each of the electrodes includes a measurement unit that outputs the electrical change, and a correction unit that includes information on correction data corresponding to the output characteristics of the biosensor,
In each of the electrodes, the measuring instrument can determine the information of the correction data based on the presence or absence of a second slit that divides the measurement unit and the correction unit.
A biosensor characterized by that. The biosensor according to claim 1 , wherein
A spacer having a notch for forming a sample supply path for supplying the sample liquid to the electrode;
A cover that is disposed on the spacer and has an air hole leading to the sample supply path.
A biosensor characterized by that. The biosensor according to claim 1 or 2 ,
The electrically conductive layer is formed on the insulating substrate by a sputtering method.
A biosensor characterized by that. The biosensor according to any one of claims 1 to 3 ,
The first slit and the second slit are formed by processing the electrically conductive layer with a laser,
A biosensor characterized by that. A measurement method using the biosensor according to any one of claims 1 to 4,
When the biosensor is inserted into the measuring instrument, detecting the presence or absence of conduction between the measurement unit and the correction unit in each electrode;
The step of determining information of correction data according to output characteristics by the measuring instrument according to the presence or absence of the conduction;
A step of detecting an electrical change caused by a reaction between the sample solution and the reagent layer as a current value through the measurement unit by the measuring device;
And a step of outputting a corrected measurement value from the correction data corresponding to the output characteristic and the current value.

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