JP2019078556A - Biosensor - Google Patents

Abstract

To suppress variations in a reagent dissolving time and dissolving state.SOLUTION: Provided is a biosensor used in measuring a measurement object component in a specimen, comprising: a separation membrane for separating between a tangible component and a liquid component in the specimen; a reservoir unit for storing a permeated substance having passed through the separation membrane; a flow path for the permeated substance that communicates with the reservoir; an electrode and a reagent arranged in one of a plurality of surfaces constituting the flow path; and a hydrophilic surface provided on a surface other than the surface where the electrode and the reagent are arranged among the plurality of surfaces, and in which the flow path is provided ranging from a position adjacent to the reservoir to a reaction region with the reagent and the permeated substance.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a biosensor.

  In the field of biosensors, there is a biosensor provided with a hydrophilic filter in the reagent flow channel, and plasma in the blood sample flowing into the reagent flow channel passes through the hydrophilic filter to reach the electrode and react with the reagent. For example, Patent Document 1). According to such a biosensor, it is avoided that red blood cells adhere to the electrode and the effective area of the electrode is reduced. As another prior art related to the present application, there is a technique described in Patent Document 2 below.

Unexamined-Japanese-Patent No. 2017-3585 Patent No. 4761688 gazette

  However, in the prior art described above, the plasma that has permeated the hydrophilic filter gradually reacts with the reagent. For this reason, the dissolution time of the reagent by plasma and the dissolution state of the reagent may vary, which may affect the measurement accuracy.

  An object of the present invention is to provide a biosensor capable of stabilizing the dissolution time of a reagent and the dissolved state of the reagent.

  One aspect of the present invention is a biosensor used to measure a component to be measured in a sample. This biosensor comprises a separation membrane for separating a tangible component and a liquid component in the sample, a storage unit for storing a permeate that has permeated the separation membrane, and a channel for the permeate stored in the storage unit. An electrode and a reagent disposed on one of a plurality of surfaces forming the flow channel, and a surface of the plurality of surfaces other than the surface on which the electrode and the reagent are disposed, and adjacent to the storage section And a hydrophilic surface provided over the reaction site of the reagent and the permeate from the

  Another aspect of the present invention is a biosensor used to measure a component to be measured in a sample. The biosensor includes a separation membrane for separating a tangible component and a liquid component in the sample, a storage unit for storing a permeate that has permeated the separation membrane, and a flow path of the permeate that communicates with the storage unit. And an electrode and a reagent disposed on the surface forming the flow path, and a hydrophilic surface provided on the surface forming the flow path and in contact with the storage section.

  According to the present invention, the dissolution time of the reagent and the dissolution state of the reagent can be stabilized.

FIG. 1 shows a plan view of a biosensor according to an embodiment. FIG. 2 is a cross-sectional view of the biosensor shown in FIG.

Hereinafter, the biosensor according to the embodiment will be described. The biosensor according to the embodiment is a biosensor used to measure a component to be measured in a sample. Biosensors include the following.
A separation membrane for separating the tangible component and the liquid component in the sample.
-A storage unit for storing the permeated material that has permeated the separation membrane.
A flow path of the permeate in communication with the reservoir;
An electrode and a reagent disposed on one of a plurality of surfaces forming the flow channel.
· Among the plurality of surfaces, provided on the surface other than the surface on which the electrode and the reagent are disposed, and the flow channel is provided from the position adjacent to the reservoir to the reaction site between the reagent and the permeate Hydrophilic surface.

  According to the biosensor according to the embodiment, the permeate (liquid component) from which the tangible component has been removed by the separation membrane is stored in the reservoir. When the permeate stored in the reservoir touches the hydrophilic surface adjacent to the reservoir, the permeate in the reservoir travels along the hydrophilic surface and rapidly moves to the reaction site, mixes with the reagent, and dissolves the reagent, React with reagents. The removal of the tangible component from the permeate can avoid or reduce the contact of the tangible component with the electrode to reduce the effective area of the electrode. By rapidly moving the permeate along the hydrophilic surface, it is possible to transport the collected amount (the amount appropriate for the reaction with the reagent) to the reaction site in a short time, so that the dissolution time of the reagent and the dissolved state of the reagent Can be reduced. That is, the dissolution time of the reagent and the dissolved state of the reagent can be stabilized.

  The sample is, for example, a biological sample. The biological sample is, for example, a liquid sample such as blood, interstitial fluid, urine or the like. The components to be measured in the sample include glucose (blood sugar) and lactate (lactate) values. The reagent contains at least an enzyme and may further contain a mediator. The formulation (component) of the reagent is appropriately selected depending on the sample and the component to be measured. In the following description, by way of example, blood (whole blood) is used as a sample, and a biosensor used to measure a glucose value is described. The biosensor for measuring blood glucose is a blood glucose sensor (glucose sensor) for self-monitoring of blood glucose (SMBG: Self Monitoring of Blood Glucose). When blood is a sample, the tangible component is blood cells (including red blood cells and white blood cells) and the liquid component is plasma.

  In the biosensor according to the embodiment, it is preferable that the hydrophilic surface is provided on a surface facing the surface on which the electrode and the reagent are disposed among surfaces forming the flow path. However, the surface located on the side of the surface on which the electrode and the reagent are disposed (the side surface of the flow channel) may be a hydrophilic surface. The hydrophilic surface may be provided on two or more surfaces of the plurality of surfaces forming the flow path, or may be provided on two or more surfaces.

  The flow channel may be formed by a plurality of surfaces (a combination of planes, a combination of curved surfaces, a combination of flat and curved surfaces, etc.). However, the flow path may be formed by a surface without clear boundaries (for example, the inner peripheral surface of a cylinder, a spherical surface, a combination of curved surfaces, etc.). In this case, the hydrophilic surface is provided on a surface that forms a flow path and is in contact with the flow path.

  In the biosensor according to the embodiment, the reservoir preferably has a volume according to the amount of the permeate to be reacted with the reagent in the flow channel. The hydrophilic surface is preferably formed to be in contact with the permeate when the reservoir is filled with the permeate. The volume of the storage section is defined, and when the desired amount of permeate (liquid component) is stored in the storage section, the permeated substance that overflows from the storage section to the flow path contacts the hydrophilic surface, which triggers the hydrophilic surface Let the movement of the permeate along it be started. In this way, a predetermined amount of permeate can be fed into the flow path, and the amount of permeate transported to the reaction site can be stabilized.

In the biosensor according to the embodiment, a sample storage unit for storing the sample is disposed above the separation membrane, the storage unit is disposed below the separation membrane, and the flow path is provided to the side of the storage unit. The configuration formed can be adopted. By arranging the separation membrane in a direction (horizontal direction) orthogonal to the falling direction, the sample can be separated into the tangible component and the liquid component through the dropping action of the sample. However, the separation membrane may be spread in the vertical direction, and the liquid component in the sample may be pushed to the opposite side of the separation membrane under pressure. In addition, a sample storage unit whose volume is adjusted is provided so that a desired amount of permeate is stored in the storage unit, and if the sample storage unit is filled with the sample, a configuration in which the liquid component of the desired amount of sample passes through the separation membrane. By adopting this method, it is possible to intuitively understand the amount of filling of the sample storage section as the amount of sample required for measurement.

  In the biosensor according to the embodiment, the separation film may have a single layer structure or a structure in which a plurality of films are stacked. For example, the separation membrane separates a first membrane that separates a tangible component and a liquid component in the sample, and a tangible component and a liquid component in a permeate that has permeated through the first membrane. A configuration may be adopted in which the permeant that has passed through the second membrane is stored in the storage section, including two membranes. In this case, tangible components that could not be removed by the first membrane can be removed by the second membrane, and the amount of tangible components in the permeate can be reduced. However, the number of membranes may be three or more as well as one or two.

  The separation membrane is used to permeate plasma, which is a liquid component, when the sample is, for example, blood, and remove blood cells (especially red blood cells), which are tangible components, from the blood. By removing the red blood cells by the separation membrane, it is possible to eliminate or reduce the amount of red blood cells introduced into the flow path which may affect the effective area of the electrode. When the first film and the second film are used, the removal rate of the tangible component of the second film can be configured to be higher than the removal rate of the tangible component of the first film. In this case, the second film may be disposed below the first film, and the reservoir may be disposed below the second film. The liquid component in the sample permeates through the first membrane and the second membrane and accumulates in the reservoir, and when a certain amount is stored, it contacts the side hydrophilic surface and moves to the reaction site Can be realized without applying an external force such as pressure application. The reservoir is, for example, formed to include at least a reservoir and a passage. The storage unit can adopt a configuration in which the liquid reservoir communicates with the flow path through the passage. Alternatively, the storage unit may adopt a configuration in which the passage of the permeate communicates with the flow passage through the liquid reservoir.

  As described above, when the sample storage portion, the separation membrane, and the storage portion are arranged in the height direction (the thickness direction of the membrane), the height of the sample storage portion is, for example, 0.1 mm to 0.5 mm. The inner diameter of the sample reservoir is, for example, 0.97 mm to 53.21 mm, and the height of the liquid reservoir included in the reservoir is, for example, 0.1 mm to 0.5 mm. The internal diameter of the reservoir included in the reservoir is, for example, 0.5 mm to 15.96 mm, the width of the flow path is, for example, 0.2 mm to 5.0 mm, and the height of the flow path is For example, it is 0.02 mm-0.5 mm, and channel length is 0.10 mm-100 mm.

  The thickness of the first film is preferably 0.1 mm to 0.5 mm, more preferably 0.2 mm to 0.3 mm. When a porous membrane is employed as the first membrane, the pore size of the porous membrane is preferably 0.5 μm to 20 μm, and more preferably 0.5 μm to 10 μm. The thickness of the second film is preferably 0.01 mm to 0.50 mm, more preferably 0.02 mm to 0.10 mm. When a porous membrane is employed for the second membrane, the pore size of the porous membrane is preferably 0.5 μm to 1.0 μm, and more preferably 0.5 μm to 0.8 μm. The width of the channel is preferably 0.2 mm to 5.0 mm, more preferably 1.0 mm to 3.0 mm. The height of the flow path is preferably 0.02 mm to 0.50 mm, more preferably 0.03 mm to 0.20 mm. The flow channel length is preferably 0.10 mm to 100 mm, more preferably 1.0 mm to 50 mm.

When the separation membrane has a single layer structure, the thickness of the membrane is preferably 0.01 mm to 0.5
It is 0 mm, more preferably 0.02 mm to 0.40 mm. The pore size of the membrane is preferably 0.5 μm to 20 μm, more preferably 0.5 μm to 10 μm.

  Hereinafter, a biosensor according to an embodiment of the present invention will be described with reference to the drawings. The configuration of the embodiment described below is an exemplification, and the present invention is not limited to the configuration of the embodiment.

  FIG. 1 shows a plan view of a biosensor according to an embodiment, and FIG. 2 is a cross-sectional view of the biosensor shown in FIG. 1 and 2, the biosensor 10 (hereinafter referred to as "sensor 10") has a longitudinal direction (X direction) having one end 10a and the other end 10b, and a width direction (Y direction). The sensor 10 is formed by laminating and bonding the insulating substrate 1 (hereinafter, "substrate 1"), the first cover 2 and the second cover 3 in the height direction (Z direction). Adhesive layers 4a and 4b made of an adhesive are shown in FIG.

  For the substrate 1, for example, a synthetic resin (plastic) is used. As the synthetic resin, for example, polyether imide (PEI), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene (PE), polystyrene (PS), polymethacrylate (PMMA), polypropylene (PP), polyimide resin, Various resins such as acrylic resin, epoxy resin, and glass epoxy can be applied. In addition, insulating materials other than synthetic resin are applicable to the substrate 1. Insulating materials include, in addition to synthetic resins, paper, glass, ceramics, biodegradable materials, and the like. The same material as the substrate 1 can be applied to the first cover 2 and the second cover 3.

  The biosensor 10 includes a separation membrane 20 disposed (held) between the first cover 2 and the second cover 3. The separation membrane 20 is, for example, a first membrane and a first membrane. It is formed by laminating the lower second film. The separation membrane 20 may have a single layer structure. A circular through hole is formed in a portion overlapping the separation membrane 20 of the second cover 3 in a plan view, and is used as a sample storage unit 11 for storing a sample supplied to the separation membrane 20.

  Further, a through hole 12 is provided in a portion corresponding to the separation membrane 20 of the first cover 2 (a portion overlapping the separation membrane 20 in a plan view). Below the through hole 12 is formed a region 7A which is a flat rectangular space where the adhesive layer 4b is not provided. The through hole 12 and the region 7A are used as a reservoir 13 for the permeate that has permeated the separation membrane 20. The area 7A may be formed in a planar circular shape having substantially the same diameter as the inner diameter of the through hole 12. However, the planar shape of the region 7A may be a shape other than a rectangle or a circle. The through hole 12 is used as a reservoir and the area 7A is used as a passage.

  With the configuration described above, the tangible component (blood cells) and the liquid component (plasma) in the blood stored in the sample storage unit 11 are separated by the separation membrane 20. That is, the tangible component in the sample remains in the sample reservoir 11, and the permeate (liquid component) comes out of the separation membrane 20. Here, the amount of plasma that permeates the separation membrane 20 is very small, and the inner surface of the through hole 12 (liquid reservoir) is hydrophobic. Thus, the surface tension applied to the permeate that has leaked to the lower surface of the separation membrane 20 is larger than the gravity (or capillary force) applied to the permeate. For this reason, the permeate does not immediately flow along the inner surface of the through hole 12 into the area 7A (passage). Therefore, the amount of the permeated material that has permeated the separation membrane 20 increases with the passage of time, and the through holes 12 (liquid reservoirs) are filled. Soon, the lump of permeate filling the through holes 12 protrudes into the area 7A (passage) and contacts the hydrophilic surface 9 of the flow path 14 communicating with the area 7A, the lump of permeate passes through the path 7A to the flow path 14 Flow into.

A porous membrane can be applied as the separation membrane 20. Among the first and second membranes forming the separation membrane 20, the pore diameter of the second membrane below the first membrane is smaller than the pore diameter of the first membrane, and the second membrane The removal rate of red blood cells in the membrane is higher than the removal rate of red blood cells in the first membrane.
The material of the separation membrane 20 is not particularly limited. For example, polyolefin resin such as polyethylene and polypropylene, acrylic or methacrylic resin such as polymethyl methacrylate (PMMA) and polyacrylonitrile (PAN), polyester resin such as polyethylene terephthalate (PET), epoxy resin, polysulfone, polyether sulfone, cellulose acetate Resin materials such as modified cellulose, cellulose, polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE) can be used.

  A key-shaped electrode 5 and an electrode 6 are provided on the top surface of the substrate 1. Each of the electrodes 5 and 6 has a portion extending in the width direction (Y direction) of the sensor 10 and a portion extending in the longitudinal direction (X direction), and the portions extending in the longitudinal direction are the lead portion 5a and the lead portion 6a I The lead portion 5a and the lead portion 6a are not covered by the first cover 2 and the second cover 3 and are used for electrical connection with a connector of a blood glucose meter (not shown).

  Each of the electrodes 5 and 6 is formed using, for example, a metal material such as gold (Au), platinum (Pt), silver (Ag), palladium, ruthenium, or a carbon material such as carbon. For example, each of the electrodes 5 and 6 can be formed as a metal layer having a desired thickness by depositing a metal material by physical vapor deposition (PVD, for example, sputtering) or chemical vapor deposition (CVD). . Alternatively, each of the electrodes 5 and 6 can be formed by printing an ink containing a carbon material on the substrate 1 by screen printing.

  The electrode 5 and the electrode 6 are an electrode pair used to measure a glucose value, for example, the electrode 6 is used as a working electrode, and the electrode 5 is used as a counter electrode. In addition, three or more electrodes may be provided. Furthermore, a reference electrode may be provided.

  The reagent 8 is immobilized on the electrode 6. Reagent 8 contains an enzyme. The reagent 8 may further contain a mediator. The enzyme is appropriately selected according to the type of sample and the component to be measured. When the component to be measured is glucose in blood or interstitial fluid, glucose oxidase (GOD) or glucose dehydrogenase (GDH) is applied. The mediator is, for example, ferricyanide, p-benzoquinone, p-benzoquinone derivative, phenazine methosulfate, methylene blue, ferrocene, ferrocene derivative, ruthenium complex and the like.

  A flow path 14 is formed between the substrate 1 and the first cover 2 for the sample (liquid component in the sample) to flow. The flow channel 14 is a space formed by bonding the substrate 1 and the first cover 2 with the adhesive layer 4 b while leaving the flat rectangular area 7 B including the electrode 5, the electrode 6 and the reagent 8, and one end 10 a side Open (see the opening 7a) and communicate with the region 7A (the reservoir 13) on the other end 10b side.

  The electrode 5, the electrode 6 and the reagent 8 are exposed in the flow path 14 and include a reaction site 15 with the permeate (the liquid component of the sample) moved from the reservoir 13. The flow path 14 has a plurality of surfaces including the upper surface of the substrate 1, the lower surface of the first cover 2, and both side surfaces formed by the adhesive layer 4 b. Among the plurality of surfaces, the lower surface of the first cover 2 is formed as a hydrophilic surface 9 having high hydrophilicity. Further, the lower surface of the first cover 2 is an example of a surface that forms the flow path 14 and is in contact with the storage portion 13. The contact angle of water on the hydrophilic surface 9 is, for example, 0 ° to 30 °.

  The hydrophilic surface 9 can be formed, for example, by surface modification by coating or coating of a surfactant (formation of a hydrophilic layer), irradiation of UV light, plasma treatment, corona discharge or the like. The hydrophilic surface 9 is formed on the entire part overlapping the area 7 B of the lower surface of the first cover 2. Thus, the hydrophilic surface 9 is formed across the reaction site 15 from the position where the flow path 14 is adjacent to the storage portion 13.

The volume of the reservoir 13 is defined based on the amount of the permeate (liquid component of the sample) used for the reaction with the reagent 8 at the reaction site 15 in the flow channel 14. When the through hole 12 (liquid reservoir) of the storage portion 13 is filled with the permeate and it protrudes into the passage 7A, the permeate comes into contact with the hydrophilic surface 9 and travels along the hydrophilic surface 9 and rapidly into the flow passage 14 It flows in and can move to the reaction site 15.

  The usage method of the biosensor 10 is as follows. The lead 5 a and the lead 6 a of the biosensor 10 are electrically connected to a blood glucose meter (measuring device) not shown. Next, a sample (for example, whole blood) is filled in the sample storage unit 11. Then, the separation membrane 20 separates the tangible component (blood cells) and the liquid component (plasma) in the sample. The permeated material of the separation membrane 20 (the liquid component of the sample (plasma): hereinafter referred to as the sample for the convenience of explanation) is stored in the through hole 12 (liquid reservoir) of the storage portion 13.

  When the through hole 12 (liquid reservoir) of the storage section 13 is filled with the sample (a certain amount of storage) and it protrudes into the passage 7A and contacts the hydrophilic surface 9, the sample in the storage section 13 passes through the hydrophilic surface 9 Move to 14 quickly. Thereby, the reaction site 15 is filled with the sample in a short time. The reagent 8 is dissolved by the sample, and electrons generated by the reaction of the enzyme in the reagent 8 with the sample reach the electrode directly or via the mediator contained in the reagent 8 at the electrode. In such a state, when a voltage is applied between the electrode 5 and the electrode 6, a current (response current) by the electrons reaching the electrode is detected. Since the response current depends on the glucose concentration in blood, the glucose concentration (glucose value) can be measured by converting the current value of the response current to the glucose concentration.

  That is, according to the biosensor 10 according to the embodiment, the blood plasma from which the sample (whole blood) is separated by the separation film 20 of the biosensor 10 is accumulated in a fixed amount in the through hole 12 (liquid reservoir) of the reservoir 13 After touching the hydrophilic layer (hydrophilic surface 9) on the inner surface of the flow channel 14, the reaction site 15 in the flow channel 14 is promptly moved. Therefore, a fixed amount of sample (plasma) is supplied to the reaction site 15 in a short time, so that there is no variation in the dissolution time or dissolution state of the reagent 8, and the measurement accuracy of the glucose value can be improved.

<Dimensional condition>
Sample storage portion 11 capable of securing 0.1 μL to 20 μL of plasma with a recovery rate (ratio of permeated material to the amount of supplied sample) of separation membrane 20 of 30%, through holes 12 (liquid reservoir portion) of storage portion 13 , And the dimension range of the flow path 14 are as follows. The following L1, L2, L4 to L6, φ1 and φ2 are illustrated in FIG. 1 and FIG.
(Sample storage unit 11)
Height (axial length of through hole) L1: 0.1 mm to 0.5 mm
Hole diameter (inner diameter of through hole) φ 1: 0.97 mm to 53. 21 mm
(Through hole 12 (liquid reservoir))
Height (axial length of through hole 12) L2: 0.1 mm to 0.5 mm
Hole diameter (inner diameter of through hole 12) φ2: 0.5 mm to 15.96 mm
(Channel 14)
Channel width L6: 0.2 mm to 5.0 mm
Height L4: 0.02 mm to 0.5 mm
Flow path length L5: 0.10 mm to 100 mm
In addition, the said dimension is not limited to the above, According to the recovery rate of the liquid component by the separation membrane 20, and the required plasma amount, it can set suitably.

  The dimensions of the above-described sample storage unit 11, the through holes 12 of the storage unit 13, and the flow path 14 are determined as follows. As described above, it is assumed that the recovery rate of the separation membrane 20 is 30%. The amount of permeate (plasma) to be collected is adjusted to 0.1 μL to 20 μL.

Here, it is assumed that 0.1 μL of plasma is obtained from blood having a hematocrit value (Hct value) of 70% (the upper limit of the Hct value) using the separation membrane 20. Because the above recovery rate is 30%,
The amount (theoretical value) of plasma supplied to the separation membrane 20 is 0.33 μL, and the amount of sample supplied to the separation membrane 20 is 1.11 μL. When 20 μL of plasma is obtained using separation membrane 20, the recovery rate is 30%, so the amount of plasma supplied to separation membrane 20 (theoretical value) is 66.77 μL, and the amount of sample supplied to separation membrane 20 is It will be 222.22 μL.

  Next, consider the case of obtaining 0.1 μL of plasma from blood having a hematocrit value (Hct value) of 10% (the lower limit of the Hct value) using the separation membrane 20. Since the recovery rate is 30%, the amount (theoretical value) of plasma supplied to the separation membrane 20 is 0.33 μL, and the amount of sample supplied to the separation membrane 20 is 0.37 μL. When 20 μL of plasma is obtained using separation membrane 20, the recovery rate is 30%, so the amount of plasma supplied to separation membrane 20 (theoretical value) is 66.77 μL, and the amount of sample supplied to separation membrane 20 is It will be 74.07 μL.

  The height (axial direction length of the through hole) L1 of the sample storage portion 11 is, for example, 0.1 mm to 0.5 mm from the thickness of the material. When the thickness of the sample storage portion 11 is set to 0.1 mm (the lower limit of the thickness), the inner diameter φ1 of the sample storage portion 11 (through hole) is 2.17 mm when the sample amount is 0.37 μL. Become. On the other hand, when the sample amount is 222.22 μL, the inner diameter φ1 of the sample storage portion 11 (through hole) is 53.21 mm.

  When the height (the axial length of the through hole) L1 of the sample storage portion 11 is set to 0.5 mm (the upper limit of the height), the sample storage portion 11 (through) when the sample amount is 0.37 μL The inner diameter φ1 of the hole) is 0.97 mm. On the other hand, when the sample amount is 222.22 μL, the inner diameter φ1 of the sample storage portion 11 (through hole) is 23.79 mm. Thus, the ranges of the height L1 and the inner diameter φ1 of the sample storage portion 11 (through hole) are 0.1 mm to 0.5 mm and 0.97 mm to 53.21 mm as described above.

  The size of the through hole 12 is calculated as follows. When the thickness of the first cover 2 is set to 0.1 mm (the lower limit of the thickness), the inner diameter φ2 of the through hole 12 is 0.1 μL when the sample amount (the amount of the permeate from the separation membrane 20) is 0.1 μL. It will be 1.13 mm. On the other hand, when the amount of sample (the amount of permeate from separation membrane 20) is 20 μL, the inner diameter φ2 of through hole 12 is 15.96 mm.

  When the thickness of the first cover 2 is set to 0.5 mm (the upper limit of the thickness), the inner diameter φ2 of the through hole 12 when the sample amount (the amount of the permeate from the separation membrane 20) is 0.1 μL It becomes 0.50 mm. On the other hand, when the amount of sample (the amount of permeate from the separation membrane 20) is 20 μL, the inner diameter φ2 of the through hole 12 is 7.14 mm. Thus, the range of the height (axial length) of the through hole 12 and the inner diameter φ2 is 0.1 mm to 0.5 mm, 0.50 mm to 15.96 mm as described above.

  When the amount of sample (the amount of permeate from separation membrane 20) is 0.1 μL, the width of channel 14 (channel width) is, for example, 0.2 mm to 4.0 mm (for example, 0.2 mm and 4.0 mm) Set Further, the height of the flow path 14 is set to, for example, 0.02 mm to 0.25 mm (for example, 0.02 mm and 0.25 mm). In this case, the flow path length is 0.10 mm to 25 mm.

  When the amount of sample (the amount of permeate from separation membrane 20) is 0.20 μL, the width of flow path 14 (flow path width) is, for example, 0.5 mm to 5.0 mm (for example, 0.5 mm and 5.0 mm) Set Further, the height of the flow path 14 is set to, for example, 0.4 mm to 0.5 mm (for example, 0.4 mm and 0.5 mm). In this case, the flow path length is 8.0 mm to 100 mm. From these, the dimensions of the flow channel 14 are as described above.

<Modification>
In the configuration of the biosensor 10 shown in FIG. 1 and FIG. 2, the storage portion 13 is located below the through hole 12 (liquid reservoir portion) provided below the separation membrane 20 and below the through hole 12 (liquid reservoir portion). And a certain area 7A (passage). A flow path 14 is formed on the side of the area 7A (passage), and the through hole 12 (liquid reservoir) communicates with the flow path 14 through the area 7A (passage). With such a configuration, the permeate from the separation membrane 20 is stored in the through hole 12. That is, in FIG. 1 and FIG. 2, the reservoir 13 is formed below the liquid reservoir (12) provided below the separation membrane 20 and the liquid reservoir (12) and in communication with the flow path 14 An aspect (first aspect) including the passage (7A) is shown as an example.

  Instead of the above-described aspect (first aspect) of the storage portion 12, the storage portion 13 is formed below the passage (12) provided below the separation membrane 20 and the passage (12) An aspect (second aspect) including the liquid reservoir (7A) communicating with the flow path 14 can also be applied. For example, the reservoir 13 includes a through hole 12 provided below the separation membrane 20, and a region 7A below the through hole 12 (see FIG. 2). However, in the second embodiment, the region 7A is used as a liquid reservoir, and the through hole 12 is used as a passage for the permeated material coming out of the separation membrane 20 to reach the region 7A. A flow path 14 is formed on the side of the area 7A (liquid reservoir), and the through hole 12 (passage), the area 7A (liquid reservoir), and the flow path 14 communicate with each other. The contact angle of the inner surface of the through hole 12 with water is set to be lower than that in the first aspect.

  In the second embodiment, the permeated material which has permeated the separation membrane 20 flows along the inner surface of the through hole 12 (passage) to the region 7A (liquid reservoir) and is stored in the region 7A. As time passes, the permeate stored in the region 7A (liquid reservoir) comes in contact with the hydrophilic surface 9, and the permeate flows into the flow path 14 along the hydrophilic surface 9. The size of the through hole 12 described in the first aspect can be applied to the size of the region 7A in the second aspect. The configurations described in the embodiments can be combined as appropriate.

5, 6 ... electrode 8 ... reagent 9 ... hydrophilic surface 10 ... biosensor 11 ... sample storage portion 12 ... through hole 13 ... storage portion 14 ... flow path 20 ... Separation membrane

Claims (14)

In a biosensor used to measure a component to be measured in a sample,
A separation membrane that separates the tangible component and the liquid component in the sample;
A storage unit for storing the permeated material that has permeated the separation membrane;
A flow path of the permeate in communication with the reservoir;
An electrode and a reagent disposed on one of a plurality of surfaces forming the channel;
Among the plurality of surfaces, it is provided on a surface other than the surface on which the electrode and the reagent are disposed, and the flow channel is provided from the position adjacent to the reservoir to the reaction site of the reagent and the permeate. And a hydrophilic surface. The biosensor according to claim 1, wherein the hydrophilic surface is provided on a surface facing the surface on which the reagent is disposed among surfaces forming the flow path. The biosensor according to claim 1, wherein the reservoir has a volume corresponding to an amount of the permeate to be reacted with the reagent in the flow path. The biosensor according to any one of claims 1 to 3, wherein the hydrophilic surface is formed to be in contact with the permeate when the reservoir is filled with the permeate. A sample storage unit for storing the sample is disposed above the separation membrane,
The reservoir is disposed below the separation membrane,
The biosensor according to any one of claims 1 to 4, wherein the flow path is formed on the side of the storage section. The biosensor according to claim 5, wherein the reservoir includes a liquid reservoir provided below the separation membrane, and a passage formed below the liquid reservoir and in communication with the flow path. The biosensor according to claim 5, wherein the reservoir includes a passage provided below the separation membrane, and a liquid reservoir formed below the passage and in communication with the flow passage. The separation membrane is
A first membrane that separates the tangible component and the liquid component in the sample;
The second membrane separating the liquid component and the tangible component in the permeate that has permeated through the first membrane;
The biosensor according to any one of claims 1 to 7, wherein the permeated material that has permeated the second membrane is stored in the storage section. The biosensor according to claim 8, wherein the removal rate of the tangible component of the second membrane is higher than the removal rate of the tangible component of the first membrane. The second membrane is disposed below the first membrane,
The biosensor according to claim 9, wherein the reservoir is disposed below the second membrane. The height of the sample reservoir is 0.1 mm to 0.5 mm,
The inner diameter of the sample reservoir is 0.97 mm to 53.21 mm,
The height of the liquid reservoir is 0.1 mm to 0.5 mm,
The inner diameter of the liquid reservoir is 0.5 mm to 15.96 mm,
The width of the flow path is 0.2 mm to 5.0 mm,
The biosensor according to any one of claims 6 to 10, wherein the height of the flow path is 0.02 mm to 0.5 mm, and the flow path length is 0.10 mm to 100 mm. The biosensor according to any one of claims 1 to 11, wherein the sample is blood. The biosensor according to any one of claims 1 to 12, wherein the component to be measured is glucose. In a biosensor used to measure a component to be measured in a sample,
A separation membrane that separates the tangible component and the liquid component in the sample;
A storage unit for storing the permeated material that has permeated the separation membrane;
A flow path of the permeate in communication with the reservoir;
An electrode and a reagent disposed on the surface forming the flow path;
A biosensor comprising: a hydrophilic surface provided on a surface that is in contact with the storage section while forming the flow path.

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