JP4518846B2 - Sensor chip manufacturing method and sensor chip - Google Patents

Description

  The present invention relates to a method of manufacturing a sensor chip that can easily determine and detect a chemical substance contained in a sample. The present invention also relates to a sensor chip manufactured by this manufacturing method, particularly a biosensor chip.

  The biosensor chip introduces a trace amount sample into a reaction part in the chip, causes a biochemical reaction such as an enzyme reaction or an antigen-antibody reaction in the trace amount sample in the chip, and obtains information obtained by the biochemical reaction. This is a sensor chip that outputs to the outside of the chip. This biosensor chip utilizes an excellent molecular identification function of a living body, and has been attracting attention as being capable of quick and simple measurement of a small amount of chemical substance. For example, the amount of glucose in blood ( As blood glucose level sensors and urine sugar level sensors for measuring blood sugar levels) and urine sugar levels, they are used for home health diagnosis (self-care) for self-management and prevention of diabetes.

  Japanese Patent Application Laid-Open No. 11-94791 discloses a biosensor chip that has a rising portion on a substrate, and by using this rising portion, the substrate and the cover layer are directly bonded without using a spacer layer, thereby forming a hollow reaction portion. It is disclosed. An example is described in which enzymes are arranged on both surfaces of the substrate and the cover layer in the hollow reaction part (paragraph 0021).

  As in this example, by arranging chemicals such as enzymes on both sides of the substrate and the cover layer in the sensor chip, for example, the following excellent effects (1) to (3) can be considered. . (1) Since the contact area between the sample introduced into the reaction part and the drug can be increased, the reaction time can be shortened. (2) When an enzyme or the like is placed in one place and a surfactant is placed in another place, even if the introduction port for introducing the sample into the reaction section is small, the surfactant introduces the sample into the reaction section. Is extremely smooth, and the distribution of the sample in the reaction section is made uniform, thereby shortening the inspection time and reducing the variation in inspection. (3) A biosensor chip having a detection function for a plurality of chemical substances can be created by disposing two or more different kinds of enzymes that react with different chemical substances.

  On the other hand, JP-A-10-2874 and JP-A-11-94791 disclose a multilayer biosensor chip in which a spacer layer having a hollow reaction portion is arranged on a substrate and a cover layer is further arranged. (Paragraph 0003). Such a stacked biosensor chip is widely used because its productivity is high, the size of the reaction part can be reduced, and the amount of a required sample can be reduced.

However, in the conventional laminated biosensor chip, the cover layer on the upper surface of the sensor chip and the substrate on the lower surface of the sensor chip are separately formed. Therefore, in order to dispose the chemicals on both the cover layer side and the substrate side of the hollow reaction part, it is necessary to apply each separately. Then, the number of processes is doubled, and the productivity is significantly reduced. Therefore, it is difficult for conventional multilayer biosensor chips to place a drug such as an enzyme on both sides while maintaining high productivity, and a solution to this problem has been desired.
JP-A-10-2874 Japanese Patent Application Laid-Open No. 11-94791

  The present invention is obtained by laminating a substrate, a spacer layer having a hollow reaction part, and a cover layer, and producing a laminated sensor chip in which a drug is arranged on both the cover layer side and the substrate side of the hollow reaction part with high production. It is an object of the present invention to provide a method of manufacturing a sensor chip that can be manufactured by the method, and a sensor chip manufactured by this method.

  As a result of studies, the present inventor has found that this problem can be achieved by the following configuration, and has completed the present invention.

  That is, the present invention is a method of manufacturing a sensor chip having a substrate folded in half and a spacer layer sandwiched between the substrates, and further having a hollow reaction part between the substrates and a detecting means in the hollow reaction part. On the substrate on which the detection means is formed, a sheet layer having at least one pair of grooves having a line symmetry with respect to a bend line that bisects the substrate is divided into at least one of the grooves. Lamination so that the book includes the detection means to obtain a laminate 1, a step of simultaneously applying a drug to a position on a substrate corresponding to each groove of the pair of grooves, and after the two steps And a step of folding the laminate 1 around the fold line and bonding the sheet layers together to form a spacer layer. Claim 1).

  The sensor chip manufactured by the manufacturing method of the present invention has a substrate folded in half and a spacer layer sandwiched between the substrates, and further includes a hollow reaction portion between the substrates and a detection means in the hollow reaction portion. It is a sensor chip having. The two-folded substrate corresponds to the substrate and the cover layer of the conventional multilayer sensor chip. Since the substrate and the cover layer are obtained from one substrate, both are bonded at one end, and both have the same material and thickness. As the material of the substrate, an insulating material film is selected. As the insulating material, ceramics, glass, paper, biodegradable materials (for example, polylactic acid microorganism-producing polyester), polyvinyl chloride, polypropylene, polystyrene, Examples thereof include thermoplastic materials such as polycarbonate, acrylic resin, polybutylene terephthalate and polyethylene terephthalate (PET), thermosetting resins such as epoxy resins, and plastic materials such as UV curable resins. A plastic material such as PET that can be folded is preferred because of its mechanical strength, flexibility, and ease of chip fabrication and processing, particularly ease of bi-folding. The preferable range of the thickness of the substrate varies depending on the application of the sensor chip and is not particularly limited. However, when manufacturing a biosensor chip such as a blood glucose level sensor, about 100 to 300 μm is preferable.

  When this substrate is expanded, it is folded in two around a folding line that bisects the substrate, and a spacer layer is sandwiched between the two folded substrates. In the method of folding in two around the fold line, in addition to the method of folding in two at the position of the fold line, the cross section is U-shaped at the position of two straight lines that are parallel to the fold line and equidistant from the fold line. The method of bending so as to form a mold is also included.

  The spacer layer being sandwiched between the two folded substrates means that both surfaces of the spacer layer are bonded to each of the two folded substrates. There may be other layers such as electrodes between the spacer layer and the substrate.

  In the sensor chip manufactured by the manufacturing method of the present invention, a hollow reaction part is formed between the two folded substrates. The hollow reaction part is a part where a sample is introduced when the sensor chip is used, and the introduced sample chemically reacts. This hollow reaction part can be formed by a groove of the spacer layer, and an electrode is contained therein as shown below, and a drug such as a catalyst and an enzyme is fixed therein, and thereby, Chemical reaction is promoted. In this invention, this chemical | medical agent is arrange | positioned at each side of a pair of groove | channel formed in the upper surface and lower surface of a hollow reaction part, ie, the substrate folded in half.

  In the case of a biosensor chip or the like, the arranged catalyst, enzyme and other chemicals are chemicals for causing a biochemical reaction, and various auxiliaries for facilitating the biochemical reaction may be included. Good. More specifically, in the case of a glucose biosensor chip that measures the amount of glucose in blood, glucose oxidase (GOD), glucose oxidase-electron acceptor (mediator) mixture, glucose oxidase-albumin mixture, or glucose oxidase-electron A receptor-albumin mixture and the like are exemplified. Moreover, enzymes other than glucose oxidase, for example, glucose dehydrogenase (GDH) etc. are mentioned. Buffers, hydrophilic polymers, etc. may be included in the drug as additives.

  A sample to be measured, for example, blood, urine, an aqueous solution sample extracted on the production line, and the like are introduced into the hollow reaction part from a sample introduction port. The sample introduction port is provided in the substrate or the cover layer, and may be connected to the hollow reaction part through the sample introduction path, or the hollow reaction part opens at at least one side of the spacer layer, and the sample introduction A mouth may be formed. A plurality of sample inlets may be provided. In particular, it is desirable that the hollow reaction portion crosses the spacer layer, and the opening portions at both ends thereof serve as sample introduction ports. By making such a straw shape, introduction of the reagent into the hollow reaction part can be facilitated by utilizing capillary action.

  The sensor chip manufactured by the manufacturing method of the present invention further has detection means in the hollow reaction part. Here, the detection means is composed of at least two electrodes. These electrodes are usually referred to as a working electrode and a counter electrode, but the detection means may further include other electrodes such as a reference electrode and other means. The electrode exerts the action of applying a predetermined voltage to the hollow reaction part, measuring the current value from the hollow reaction part, etc., and detecting and quantifying the chemical substance in the sample based on the signal from this electrode. It can be carried out.

  The electrode is exposed in the hollow reaction part, but a lead wire portion of the electrode is further formed in the substrate, the spacer layer, or between them, and can be electrically connected to the outside of the sensor chip. A predetermined voltage is applied through this lead wire portion, a current value is measured, and the like.

  In the manufacturing method of the present invention, the detection means is usually formed on the substrate before being folded in half. The detection means can be formed by screen printing, plating, vapor deposition, metal tape pasting, or the like. The detection means may be formed only on one side of the folding line or on both sides. Further, as described below, when a large number of sensor chips are manufactured in a series of processes, a large number of detection means are formed in parallel in the direction of the folding line. Here, one set of detection means is a set of electrodes included in one sensor chip, and has at least two working and counter electrodes.

  A sheet layer is laminated on the substrate on which the detection means is formed, and the laminate 1 is obtained. The sheet layer is composed of a single-layer spacer material or a laminate of a plurality of spacer materials. In the present invention, two sheet layers are bonded to form a spacer layer. The spacer material refers to a single layer film constituting the spacer layer.

  The sheet layer has one or more pairs of grooves, that is, two or more pairs, which are in a line-symmetric relationship with respect to the folding line. Lamination of the substrate and the sheet layer is performed so that at least one of the grooves of the sheet layer includes the detection means, that is, the electrodes are exposed in the grooves.

  In this sheet layer, since two or more grooves are present on the same plane, two or more grooves can be formed in the same step, and productivity can be improved as compared with the case where they are formed separately. As a method for stacking the sheet layers and forming the grooves, for example, a tape having an adhesive layer may be attached to the substrate on which the detecting means is formed, and both grooves may be formed.

  However, a method of applying a resin by a method such as screen printing is preferable in terms of productivity because a sheet layer having a pair of grooves or more can be laminated on a substrate in one step, that is, a single application. According to this method, it is possible to easily form two or more grooves by simply changing the shape of the printing plate with the same process load as that for forming one groove. Claim 2 corresponds to this preferred embodiment, and in the manufacturing method described above, the lamination of a sheet layer having at least one pair of grooves having line symmetry with respect to the folding line is a resin on the substrate. Thus, the present invention provides a method for manufacturing a sensor chip, which is performed in one step.

  In the production method of the present invention, a chemical agent such as a catalyst or an enzyme is applied to a position on the substrate corresponding to the groove. As described above, there are at least two grooves, but the manufacturing method of the present invention is characterized in that the drug is simultaneously applied to the portions corresponding to the at least two grooves. In the conventional manufacturing method, the chemical | medical agent was separately apply | coated to two places, and productivity was low. However, in the present invention, the above-described configuration enables two places to be applied simultaneously, and as a result, excellent productivity is achieved.

  By performing the step of laminating the sheet layers and the step of applying the drug, a laminate in which two or more grooves are formed on the substrate and the drug is applied in the two or more grooves can be obtained. Thereafter, the laminate is folded in two with the folding line as the center. As described above, it may be folded in half so that the cross section has a U-shape. Then, the sheet layers are overlapped with each other, and the overlapped sheet layers are bonded together to obtain a spacer layer, and a sensor chip in which the spacer layer is sandwiched between the two folded substrates is manufactured. Further, when the sheet is folded in two with the folding line as the center, the pair of grooves of the sheet layer overlap to form a hollow reaction part. Since the drug is already applied to each of the pair of grooves, the drug is arranged on both the upper surface and the lower surface of the hollow reaction portion.

  Any of the step of laminating the sheet layer and the step of applying the drug may be performed first. Claim 3 corresponds to an embodiment in which the step of applying a drug is performed first, and in the above manufacturing method, after the step of applying the drug, a step of forming a sheet layer having a pair of grooves to obtain a laminate 1 A method for manufacturing a sensor chip is provided. In this method, after the drug is applied, the sheet layer is formed by a method such as attaching a member of the sheet layer to the periphery or applying a resin.

  Further, claim 4 corresponds to an embodiment in which the step of laminating the sheet layers is performed first, and in the manufacturing method, the drug is added after the step of forming the sheet layer having a pair of grooves to obtain the laminate 1. The present invention provides a sensor chip manufacturing method characterized by performing a coating step. According to the method in which the step of laminating the sheet layers is performed first, the region of the hollow reaction part is clarified before folding in half. Therefore, the application area and application position of the drug can be easily defined before application, which is preferable from the viewpoint of ease of manufacture and is preferable for producing a high-quality biochip.

  The pair of grooves on the sheet layer that are symmetrical with respect to each other about the fold line are two parallel straight grooves that are equidistant from the fold line in the state before being folded in two. preferable. In this case, simultaneous application can be performed at positions corresponding to the two grooves with a simple structure coating machine in which two nozzles are fixed. That is, in this case, for example, a single applicator having two nozzles for the upper surface and the lower surface is used, and the distance between the two nozzles is simply fixed and the applicator or the laminate is moved in parallel. It is extremely economical because the drug can be applied to both application surfaces simultaneously and continuously. A fifth aspect of the present invention corresponds to this preferred embodiment, and provides the method for manufacturing a sensor chip, wherein the grooves constituting the pair are parallel to each other and linear. .

  The medicines applied to two or more grooves may be the same or different. As described above, when an enzyme is applied on one side and a surfactant is applied on the other side, the introduction of the sample into the reaction layer becomes very smooth even when the sample introduction port is small, and the distribution of the sample in the reaction part becomes uniform, The inspection time is shortened and the variation in inspection is also reduced. In addition, when the same enzyme is applied to both surfaces, the contact area between the reagent and the enzyme can be increased, so that the reaction time between the reagent and the enzyme can be shortened. Moreover, when different types of enzymes that react with different chemical substances are applied on both sides, a biochip having a plurality of reagent detection functions can be produced.

  In the present invention, in the above-described exemplary applicator, it is possible to apply different drugs without increasing the load on the process only by using different nozzles for different drugs. A sixth aspect of the present invention provides a method for manufacturing a sensor chip, which corresponds to a mode in which different drugs are applied, and different drugs are simultaneously applied to positions corresponding to the grooves constituting the pair. Is.

  In addition, even when the manufacturing method is performed in units of individual sensor chips, the productivity is low, and the distance between the substrate and the cover layer also varies greatly from sensor chip to sensor chip. The problem is that the variation of the volume of the reaction part becomes large and the variation of the measurement value becomes large. Therefore, a single large substrate corresponding to a large number of sensor chip substrates, that is, a substrate in which the individual sensor chip substrates are connected to each other, and a large number of detection means are formed thereon, and then the manufacturing described above. After the method is implemented and a large number of sensor chips are formed on one substrate, a method of cutting each individual sensor chip is preferable. By this method, productivity is improved and a large number of sensor chips are manufactured in a series of steps, so that problems such as variations in the volume of the reaction part can be prevented.

  In this method, multiple sets of detection means are formed in parallel with the direction of the fold line. Further, the substrate has a size and a shape capable of forming a large number of sets of detection means so as to be parallel to the direction of the bending line. Further, the size of the sheet layer, the position where the medicine is applied, and the like also correspond to this size. With respect to a single substrate on which a large number of sets of detection means are formed, sheet layers are laminated and chemicals are applied in the same manner as described above. Laminated bodies connected in parallel in the direction are obtained.

By cutting this laminated body along one or a plurality of straight lines perpendicular to the folding line, each individual sensor chip is separated, and a large number of sensor chips are obtained. The cutting is performed so that each of the cut individual sensor chips includes at least one set of detection means. Claim 7, the preferred correspond to embodiments, a the method for producing a detection means formed on the substrate, consists of a number of sets of sensing means in parallel in a direction perpendicular to said fold line, said The laminate 1 formed by folding the laminate 1 around the fold line and bonding the sheet layers together to form a spacer layer is formed along one or more straight lines perpendicular to the fold line. Further, the present invention provides a method for manufacturing a sensor chip, further comprising a step of cutting so that at least one set of detection means is included in each.

  In this method of manufacturing a large number of sensor chips, cutting into individual sensor chips is performed in two and after the sheet layers are bonded to each other. By this method, dust at the time of cutting enters the reaction part as a foreign substance. This can be prevented, and the folding process can be completed only once, which is advantageous in terms of productivity. Also in this method of manufacturing a large number of sensor chips, it is preferable that the application part of the medicine at the position corresponding to the groove or the groove is a straight line. In this way, for the same reason as described above, the operation of the coating machine is easy, and the amount of movement of the nozzle can be minimized and smoothly moved, so that it can be produced economically.

  In addition, a set of a plurality of detection means arranged in parallel in the direction of the fold line is formed on a single sheet as a substrate, and a plurality of sets are formed in a direction perpendicular to the fold line, and the sheet is formed in the same manner as described above After laminating layers and forming grooves, and further applying the drug in the same manner as described above, each group is separated by cutting in the direction of the fold line, and then each group is folded in two, and further individual A method of cutting into sensor chips can also be employed as a more productive method.

The present invention further provides a sensor chip manufactured by the above manufacturing method. Claim 8 corresponds to this sensor chip. This sensor chip is a blood glucose sensor that measures the glucose level (blood glucose level) and urine sugar level in blood as a biosensor chip that is a drug for causing the biochemical reaction of the drug applied onto the substrate , It is suitably used as a urine sugar value sensor or the like. Claim 9 corresponds to this preferred embodiment, and is the sensor chip, wherein the drug applied onto the substrate is a drug for causing a biochemical reaction, and is a biosensor chip. A sensor chip is provided.

  By the manufacturing method of the present invention, a stacked sensor chip in which a spacer layer is sandwiched between substrates and a drug is disposed on both the upper surface and the lower surface of the hollow reaction portion formed between the substrates is produced with high production. It can be manufactured with sex. That is, according to the production method of the present invention, since the medicine can be applied to both surfaces of the hollow reaction part in the same process, the productivity is lowered by applying the medicine to two places, which has been a problem in the prior art. There is no.

  Next, the best mode for carrying out the present invention will be described with reference to the drawings. Note that the present invention is not limited to this form, and can be changed to other forms as long as the gist of the present invention is not impaired.

  The example shown below is an example of the manufacturing method of the present invention for manufacturing a large number of sensor chips by a series of processes using a substrate on which a large number of sets of electrodes (detecting means) are formed. FIG. 1 is a plan view showing a state in which a plurality of sets of electrodes 2, 2 ′ (detecting means) are formed on a substrate 1. In this example, the pair of electrodes 2 and 2 ′ includes two electrodes and corresponds to a working electrode and a counter electrode, respectively. FIG. 2 is a side view showing a state in which the electrode 2 is formed on the substrate 1. In this example, the electrodes 2 and 2 'are made of carbon ink, and are formed on the substrate 1 made of PET resin by screen printing. The electrodes may be formed by a method other than screen printing, for example, a method of attaching a metal tape on the substrate.

  The dotted lines in FIGS. 1 and 2 indicate a fold line 3 that bisects the substrate 1 and two lines 3 ′ that are parallel to the fold line 3 and equidistant from the fold line 3. As shown in FIGS. 1 and 2, in this example, the electrodes 2, 2 ′ are formed on only one of the folding lines 3.

  Next, the sheet layer 4 is laminated on the substrate shown in FIGS. FIG. 3 is a plan view showing a state after the sheet layer 4 is laminated. The sheet layer 4 is formed with two linear grooves 5 and 5 ′ that are equidistant from the fold line 3 and parallel to the fold line 3. The formation of the sheet layer 4 having the grooves 5 and 5 ′ is performed by screen-printing and applying a resin onto the substrate. As the resin to be screen printed, urethane resin, epoxy resin, modified polyimide resin, acrylic resin, or the like is used.

  According to the method of screen printing the resin on the substrate, the sheet layer can be laminated by one application, which is preferable in terms of productivity. Also, the position and shape of the grooves 5, 5 'can be easily changed by simply changing the printing plate. The sheet layer 4 serves as a spacer when forming the sensor chip, masks the electrode surface by a predetermined area, and makes the electrode area constant, thereby reducing the variation in detection of the sensor. Generally referred to as a resist layer. When the sheet layer 4 is laminated, an adhesive material or an adhesive having a function of adhering both sides when folded in two may be simultaneously applied by screen printing. Here, as the adhesive material to be screen-printed, a rubber adhesive material, an acrylic adhesive material, a silicone adhesive material, or the like can be used. As the adhesive, an epoxy, vinyl acetate, silicone or the like can be used.

  Next, the chemical | medical agent is apply | coated to the groove | channels 5 and 5 'by application machines, such as a dispenser which has two nozzles. The two nozzles correspond to the positions of the grooves 5 and 5 ', but the grooves 5 and 5' are on two parallel straight lines. A wide range of drug applications can be easily performed in a single step. That is, according to the present invention, it is possible to apply the medicine to both the lower surface and the upper surface in the same process using the applicator using the fact that the two surfaces are on the same plane. In addition, you may apply a medicine to both grooves using one nozzle, but if two nozzles for the lower surface and the upper surface are arranged in one applicator, the medicine is applied to the groove on one side. Since it can be applied to the grooves on both sides in exactly the same application time as the case of application, it is economical. Different medicines in the grooves 5, 5 'can be applied by separating the medicine supply lines of the two nozzles, that is, by supplying different medicines to each. 4 and 5 are a plan view and a side view, respectively, showing the state after the drugs 6 and 6 'are applied.

  In this example, the drug 6, 6 'is applied after the formation in the grooves 5, 5'. However, after the drug 6, 6 'is applied, the groove 5, 5 ′ may be formed. However, the method of applying the drug after the formation in the grooves 5 and 5 ′ is preferable in this respect because the positioning of the application and the management of the application amount are easier.

  After the drug application, the substrate 1 is folded in two around the fold line 3. In this example, the substrate 1 is bent along two lines 3 ′ that are parallel to the bending line 3 and equidistant from the bending line 3, and is molded so that the cross section has a U shape. FIG. 6 is a side view showing a state after the folding. Although it is possible to perform the bending at normal temperature, the bent portion is preferably heat-treated after the bending in order to eliminate the residual stress.

  In general, the heat treatment temperature of the thermoplastic resin is preferably a temperature between the softening temperature of the resin (glass transition temperature) and the melting point and above and below the melting point. If the temperature is lower than the temperature between the resin softening temperature and the melting point, the residual stress at the bent portion is not sufficiently eliminated, and the bent state may change over time. On the other hand, if the melting point is exceeded, the deformation of the resin becomes large, and it may be impossible to maintain a beautiful bent surface. The resin softening temperature of the PET resin is about 70 ° C., and the melting point is about 250 ° C. Therefore, in the case of a substrate made of a PET resin, the bent portion is preferably heat-treated at 160 ° C. or higher and 250 ° C. or lower. Representative PET resins include Melinex and Tetron (trade names, manufactured by Teijin DuPont Films Ltd.), Lumirror (trade names, manufactured by Toray Industries, Inc.), and the like.

  On the other hand, enzymes such as GOD and GDH may deteriorate at a temperature of 60 ° C. or higher. In the case of biosensor chips using these enzymes, the temperature of the heat treatment should be such that the fixed portion of the enzyme does not exceed 60 ° C. It is desirable to take measures such as adjusting the distance between the hollow reaction part and the folding line by a sufficient distance.

  In the case of this example in which the substrate 1 is made of a PET resin, the bent back portion is abutted against a hot plate having a surface temperature of 200 ° C. while being bent at room temperature, and then heated for 1 second. The method is illustrated as a preferred embodiment. The use of a hot plate is advantageous in terms of both productivity and prevention of adverse effects due to heat because local heating is easy and the heating time may be short. Further, it is desirable that the position where the medicine 6 is applied is at least 5 mm away from the portion abutted against the hot plate. If the distance is 5 mm or more, even if heat treatment is performed under the above conditions, the portion where the drug 6 is applied does not reach 60 ° C. or higher. Even when the drug 6 is an enzyme with low heat resistance, There is no degradation.

  After folding in half, the folded sheet layer 4 is bonded with an adhesive 7 to form a spacer layer 8. As the adhesive material 7, the same rubber adhesive material, acrylic adhesive material, silicone adhesive material, and the like as described above are used. Grooves 5 and 5 'are also combined to form a hollow reaction portion 9, and drugs 6 and 6' are applied to the lower and upper surfaces, respectively. When the laminate thus obtained is cut along a line perpendicular to the fold line 3 (line 10 in FIG. 1), a large number of individual sensor chips having the side view shown in FIG. 6 are obtained. It is done. The cutting is performed so that each individual sensor chip includes at least one set of electrodes.

It is a top view which shows the board | substrate used for the manufacturing method of this invention. It is a side view which shows the board | substrate used for the manufacturing method of this invention. It is a top view which shows 1 process of the manufacturing method of this invention. It is a top view which shows 1 process of the manufacturing method of this invention. It is a side view which shows 1 process of the manufacturing method of this invention. It is a side view which shows the biosensor chip of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Substrate 2, 2 'Electrode 3 Folding line 4 Sheet layer 5, 5' Groove 6, 6 'Drug 7 Adhesive material 8 Spacer layer 9 Hollow reaction part 10 Line

Claims (9)

  A method of manufacturing a sensor chip having a substrate folded in half and a spacer layer sandwiched between the substrates, and further having a hollow reaction part and a detection means in the hollow reaction part between the substrates, On the formed substrate, a sheet layer having at least one pair of grooves symmetrical to each other about a folding line that bisects the substrate is divided into at least one groove so that at least one groove includes the detecting means. To obtain a laminated body 1, a step of simultaneously applying a drug to a position on a substrate corresponding to each groove of the pair of grooves, and after the two steps, the bending line as a center. A method of manufacturing a sensor chip, comprising: a step of folding the laminate 1 in two and bonding the sheet layers together to form a spacer layer.   The sheet layer having one or more pairs of grooves having line symmetry with respect to the folding line as an axis is laminated in one step by applying a resin on the substrate. Manufacturing method of the sensor chip.   3. The method of manufacturing a sensor chip according to claim 1, wherein a step of forming a sheet layer having a pair of grooves to obtain a laminate 1 is performed after the step of applying a medicine.   The method for manufacturing a sensor chip according to claim 1 or 2, wherein a step of applying a drug is performed after the step of forming a sheet layer having a pair of grooves to obtain the laminate 1.   5. The sensor chip manufacturing method according to claim 1, wherein the grooves constituting the pair are parallel to each other and linear.   6. The method of manufacturing a sensor chip according to claim 1, wherein different drugs are simultaneously applied to positions corresponding to the respective grooves constituting the pair. The detection means formed on the substrate is composed of a large number of detection means arranged in parallel in a direction perpendicular to the fold line, and the laminate 1 is folded in two around the fold line, and the sheet layers are attached to each other. And a step of cutting the laminate formed by the step of forming the spacer layer so as to include at least one pair of detection means along one or more straight lines perpendicular to the folding line. A method for manufacturing a sensor chip according to claim 1, comprising:   A sensor chip manufactured by the method for manufacturing a sensor chip according to claim 1. The sensor chip according to claim 8, wherein the drug applied on the substrate is a drug for causing a biochemical reaction, and is a biosensor chip.

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