JP2008249538A - Detecting element - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a detecting element capable of detecting accurately a detection object. <P>SOLUTION: This detecting element 1 has a planar base part 2, a supply part 3 provided in the base part 2, and provided with a supply space 31 for supplying a specimen liquid containing the detection object and an inhibitor inhibiting the detection of the detection object, a flow channel 4 provided in the base part 2, communicated with the supply space 31, and passed therethrough with the specimen liquid, a solid matter 5 provided in the flow channel 4 to capture the inhibitor in the specimen liquid, a detecting part 6 provided in the base part 2, communicated with the flow channel 4, provided with a storage space 61 for storing the specimen liquid passed through the flow channel 4, and for detecting the detection object in the specimen liquid stored in the storage space 61, a promotion liquid charge part 7 provided with a charge space 71 for charging a promotion liquid 9 for promoting the detection object in the specimen liquid to pass it through the flow channel 4, the promotion liquid 9 charged in the charge space 71 of the promotion liquid charge part 7, a communication passage 84 for communicating the supply space 31 and the storage space 61, and a partitioning means 8 for opening and closing the communication passage 84. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a detection element.

For example, Patent Documents 1 and 2 disclose a blood glucose sensor chip that measures glucose concentration in blood. This blood glucose sensor chip includes a blood introduction part and a sensing electrode part, and detects the glucose concentration in the blood by introducing a sample solution filled in the blood introduction part into the sensing electrode part.
However, in such a blood glucose sensor chip, if a sample solution such as whole blood is used as it is, an interference substance (inhibitor that inhibits detection of a detection target) present in the sample solution, a solid component such as a blood cell component, etc. Due to the influence, the glucose concentration in blood, that is, the detection target may not be detected accurately.
In addition, when detecting the glucose concentration in the blood, it is known that the detection accuracy of the glucose concentration is more significantly affected by the presence of an inhibitor in the blood and is further lowered.

JP 2004-20465 A JP 2004-61496 A

  An object of the present invention is to provide a detection element that can accurately detect a detection target.

Such an object is achieved by the present invention described below.
The detection element of the present invention includes a flat base,
A supply unit provided in the base, and provided with a supply space for supplying a sample liquid containing a detection target and an inhibitor that inhibits detection of the detection target;
A flow path provided in the base, communicating with the supply space, and through which the analyte liquid passes;
A captured substance provided in the flow channel and capable of capturing the inhibitor in the analyte liquid;
The detection target in the analyte liquid that is provided in the base, includes a storage space that communicates with the flow path and stores the analyte liquid that has passed through the flow path, and is stored in the storage space. A detection unit for detecting
An accelerating liquid filling unit comprising a filling space for filling the accelerating liquid that promotes the detection object in the analyte liquid to pass through the flow path;
The accelerating liquid filled in the filling space of the accelerating liquid filling section;
A communication passage communicating the supply space and the filling space;
And an opening / closing means for opening and closing the communication path.
Thereby, the movement of the inhibitor to the detection unit can be prevented or suppressed, and the detection target can be accurately detected.

In the detection element of the present invention, the analyte liquid includes a solid component dispersed in the analyte liquid,
It is preferable that the detection element further includes a separation unit that separates the solid component from the analyte liquid.
Thereby, it is prevented that the solid component is clogged in the flow path. As a result, a reliable detection target can be detected.

In the detection element of the present invention, the detection element further has a branch channel that branches from the middle of the channel,
Preferably, the separation means includes a vibrator provided at a branch portion where the branch flow path branches from the flow path, and the solid component is guided to the branch flow path by operation of the vibrator.
Thereby, it is prevented that the solid component is clogged in the flow path. As a result, a reliable detection target can be detected.

In the detection element according to the aspect of the invention, the separation unit may be provided to partition the supply space of the supply unit into two spaces, the flow channel side and the opposite side of the flow channel, and may separate the solid component. It is preferable to have a separation membrane.
Thereby, it is prevented that the solid component is clogged in the flow path. As a result, a reliable detection target can be detected.

In the detection element of the present invention, it is preferable that the flow path has a portion whose cross-sectional area decreases from the supply unit side toward the detection unit side.
Thereby, the capillary phenomenon with respect to the sample liquid is efficiently exhibited.
In the detection element of the present invention, it is preferable that a cross-sectional area of the flow path gradually decreases from the supply unit side toward the detection unit side.
Thereby, the capillary phenomenon with respect to the sample liquid is more efficiently exhibited.
In the detection element according to the aspect of the invention, it is preferable that the captured material is formed of a granular solid and is filled in the flow path.
As a result, the contact area between the captured substance and the analyte liquid increases, so that the separation ability between the detection target and the inhibitor is improved.

In the detection element of the present invention, it is preferable that the average particle diameter of the solid matter is different on the supply unit side and the detection unit side, and is larger than the detection unit side on the supply unit side.
Thereby, the filling rate of the capture | acquisition in the flow path by the side of a detection part from the supply part side can be raised, ie, the volume (cross-sectional area) in a flow path can be made smaller by the detection part side than the supply part side. As a result, the capillary phenomenon with respect to the sample liquid can be more reliably generated.

In the detection element of the present invention, the detection target is a low-molecular substance, and the capture is composed of a porous body,
The porosity of the porous body is different between the supply unit side and the detection unit side, and is preferably larger on the supply unit side than the detection unit side.
As a result, the polymer in the sample liquid enters the pores of the trapped substance, and the movement (transfer) speed thereof is slowed down, so that it can be reliably separated from the low molecule such as the detection target. As a result, the detection target can be detected more reliably.

In the detection element of the present invention, the detection object is hydrophilic.
The hydrophobicity of the captured substance is different between the supply unit side and the detection unit side, and is preferably higher on the supply unit side than the detection unit side.
Thereby, the difference in speed between the detection target and the inhibitor moving in the flow path can be increased, and the separation can be performed reliably.

In the detection element of the present invention, the analyte liquid is whole blood or plasma, the detection target is glucose, and the inhibitor is alcorbic acid,
It is preferable that at least the surface of the trapped material is composed of hydrocarbon.
Thereby, the movement of ascorbic acid to the detection unit can be prevented or suppressed, and glucose in whole blood or plasma can be accurately detected.

Hereinafter, preferred embodiments of the detection element of the present invention shown in the accompanying drawings will be described.
<First Embodiment>
First, a first embodiment of the detection element of the present invention will be described.
1 is a plan view (partially cut away) showing a first embodiment of the detection element of the present invention, FIG. 2 is a cross-sectional view taken along line AA in FIG. 1, and FIG. 3 is shown in FIG. It is a figure which shows the state which connected the detection element to the measuring apparatus.
A measuring apparatus 100 shown in FIG. 3 is used by connecting the detection element 1, and includes an arithmetic unit 210 including a processing circuit 200 that analyzes a current value obtained by the detection element 1, and the detection element 1. A connector 300 to be mounted (connected) and a wiring 310 for connecting the processing circuit 200 and the connector 300 are provided.

  As shown in FIGS. 1 and 2, the detection element 1 includes a flat base 2, a supply unit 3 that supplies a sample liquid containing a detection target and an inhibitor, and a flow path 4 that communicates with the supply unit 3. And a solid material 5 that can capture an inhibitor, a detection unit 6 that detects an object to be detected, and an accelerating liquid that accelerates the passage of the analyte liquid through the channel 4. The accelerating liquid filling unit 7, the accelerating liquid 9 filled in the accelerating liquid filling unit 7, the communication path 84 that communicates the supply unit 3 and the accelerating liquid filling part 7, and the partition means that opens and closes the communication path 84 (opening and closing Means) 8.

  In the present invention, the detection target to be detected from the sample liquid includes, for example, sugars such as glucose and sucrose, lipids such as triglycerides and phospholipids, nitrogen containing urea nitrogen (BUN), uric acid and creatine. Examples include components, lipases, enzymes such as GOT (glutamate oxaloacetate transaminase), GPT (glutamate pyruvate transaminase), proteins such as albumin and hemoglobin A1c (HbA1c). In this embodiment, the detection target is The case of glucose will be described as a representative.

In this case, the accuracy of detection of glucose from the sample liquid is greatly increased by including ascorbic acid together with glucose in the whole blood as the sample liquid due to, for example, the influence of the subject's diet and vitamin intake. Affected (inhibited).
Therefore, in this embodiment, the case where ascorbic acid is contained in the sample liquid as an inhibitor will be described as a representative. In this embodiment, the case where whole blood (or plasma) is used as the sample liquid will be described as a representative.

The base 2 includes a lower substrate 21, a wiring system 22 provided on the lower substrate 21, and an upper substrate 23 provided so as to cover the wiring system 22 and joined to the lower substrate 21.
The lower substrate 21 supports each part constituting the detection element 1.
Examples of the constituent material of the lower substrate 21 include various resin materials such as polyethylene, polypropylene, polystyrene, polyethylene terephthalate (PET), polyethylene naphthalate (PES), polyimide (PI), various glass materials such as quartz glass, and alumina. Various ceramic materials such as zirconia and the like can be mentioned, and one or more of these can be used in combination.

The wiring system 22 includes a working electrode 221, a counter electrode 222, a reference electrode 223, three terminals 224 to 226 corresponding to the electrodes 221 to 223, each electrode 221 to 223, and each terminal 224 to 226 corresponding to these. The connection lines 227 to 229 are connected.
In a state where the detection element 1 is mounted on the connector 300 of the measuring apparatus 100, the electrodes 221 to 223 are electrically connected to the processing circuit 200 through the terminals 224 to 226 and the connection lines 227 to 229.

The constituent materials of the electrodes 221 to 223 are, for example, a metal material such as gold, silver, copper, platinum or an alloy containing these, a metal oxide material such as ITO, and a carbon material such as graphite. Etc.
Moreover, as a constituent material of each terminal 224-226 and each connection line 227-229, the same material as the constituent material of each electrode 221-223 can be used.
A reaction layer (sensitive layer) 62 that reacts with glucose is provided on the upper surface of the working electrode 221. The reaction layer 62 of the present embodiment performs an oxidation-reduction reaction of glucose, an enzyme that performs a reaction involving the emission of electrons (e ⁻ ) with glucose (detection target), and a working electrode of the electrons And a mediator (electron transfer substance) that performs transmission to 221.

Examples of the mediator include quinone derivatives, potassium ferricyanide, ferrocene derivatives, complex salts such as tris (bipyridyl) osnium complex, organic acids such as picric acid and 3,6-dinitrophthalic acid, and the like.
Moreover, as an enzyme, various oxidases, various dehydrogenases, etc. can be used according to the kind of detection target object, for example. When the detection target is glucose as in this embodiment, examples of usable enzymes include glucose oxidase and glucose dehydrogenase.

When a substance other than glucose is to be detected, examples of oxidase that can be used include galactose oxidase and pyruvate oxidase. On the other hand, as the dehydrogenase, for example, alcohol dehydrogenase and glutamate dehydrogenase can be used.
When electrons are transferred to the working electrode 221 through such a mediator, if ascorbic acid is present in whole blood, the transfer of electrons is inhibited, and glucose from the whole blood is inhibited. This greatly affects the detection accuracy.

  The reaction layer 62 is preferably configured to contain (impregnate) an enzyme and a mediator in a matrix (base material) composed of a polymer. Thereby, it is possible to prevent the enzyme and mediator from diffusing into other layers or the effluent (eluent) flowing out into the storage space 61. In the reaction layer 62, the reaction between glucose and the enzyme, The reaction between the electron and the mediator can be caused more reliably.

  The polymer constituting the matrix is not particularly limited. For example, a natural polymer such as a bio-related polymer (animal-derived polymer) or a plant-derived polymer, a synthetic polymer (synthetic resin), or These modification | denaturation things etc. are mentioned, Among these, it can use combining 1 type (s) or 2 or more types. Among them, the polymer constituting the matrix is preferably a polymer mainly composed of a bio-derived polymer or a modified product thereof. By constituting a matrix using these as a polymer, it is possible to suitably prevent the enzyme (or mediator) from being easily denatured and inactivated.

Examples of such bio-related polymers include modified albumin (for example, bovine serum albumin: BSA), a mixed polymer of carboxymethyl cellulose and BSA, a mixed polymer of polyvinyl pyrrolidone and BSA, and a mixed polymer of polyethylene glycol and BSA. Etc.
Examples of the modified product include those subjected to treatment for breaking the hydrophobic bond, hydrogen bond, and ionic bond of the biological polymer. Examples of such treatment include heat treatment, pressure treatment, pH adjustment treatment, treatment with a denaturing agent, and the like.

The matrix preferably has a cross-linked structure. As a result, the mediator can be firmly held (supported) on the matrix. Moreover, it contributes to the improvement of the mechanical strength of the reaction layer 62.
As the cross-linking agent that forms a cross-linked structure in the matrix, for example, when a polymer having a peptide as a main component is used, for example, glutaraldehyde, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, trinitromethane These can be used, and one or more of these can be used in combination.
The enzyme content in the reaction layer 62 is preferably 45 wt% or more, more preferably about 50 to 80 wt%. Thereby, sufficient reaction can be produced between glucose and an enzyme, and an electron can be discharge | released efficiently.

The counter electrode 222 is an electrode that applies a voltage between the working electrode 221. In the storage space 61 of the detection unit 6, the whole blood that has passed through the flow path 4 described later (hereinafter also simply referred to as “whole blood”) is stored, and the working electrode 221 and the counter electrode 222 are In the meantime, when a voltage is applied so that the working electrode 221 has a high potential, electrons are emitted from the reaction layer 62 according to the amount of glucose present in the whole blood. The amount of current flowing between the working electrode 221 and the counter electrode 222 changes according to the amount of emitted electrons. That is, the measuring device 100 measures a current value according to the amount of glucose present in the whole blood.
Further, the area of the counter electrode 222 is preferably at least twice as large as that of the working electrode 221, and more preferably at least 10 times. Thereby, the current value can be measured with higher accuracy.

The reference electrode 223 is an electrode that applies a voltage to the counter electrode 222. A voltage is applied between the reference electrode 223 and the counter electrode 222 in a state where whole blood is stored in a storage space 61 of the detection unit 6 described later. Then, by comparing the current value flowing between these electrodes with the current value flowing between the working electrode 221 and the counter electrode 222 described above, the change in the current value based on glucose in whole blood can be increased. It can be detected (measured) with accuracy.
As a constituent material of the reference electrode 223, for example, silver-silver chloride, mercury-mercury sulfate, or the like can be used in addition to the materials described above.

The upper substrate 23 includes a through hole 231 that penetrates in the thickness direction, a first recess 232, a first groove 233 that communicates with the through hole 231 and the first recess 232, and a second recess 234. A second groove 235 communicating with the first recess 232 and the second recess 234 is formed.
In a state where the upper substrate 23 is bonded to the lower substrate 21, the electrodes 221 to 223 are exposed inside the through hole 231. This portion constitutes the detection unit 6, and the space inside the through hole 231 constitutes the storage space 61.
A thin plate 24 is liquid-tightly bonded to the upper substrate 23 so as to cover the first groove 233. A space defined by the thin plate 24 and the first groove 233 constitutes the flow path 4.

A cylindrical portion 25 is provided at the edge of the first concave portion 232, and the first concave portion 232 and the cylindrical portion 25 constitute the supply unit 3, and the first concave portion 232 and the cylindrical portion 25 are provided. The inner space of the slab constitutes a supply space 31 for supplying whole blood.
Whole blood supplied into the supply space 31 is transferred through the flow path 4 and flows out into the storage space 61 by capillary action.

As shown in FIGS. 1 and 2, the flow path 4 is filled with a granular solid (captured matter) 5. This solid material 5 has a function of capturing ascorbic acid contained in whole blood. As a result, ascorbic acid is captured by the solid material 5 when whole blood is transferred through the flow path 4. Therefore, the whole blood that has passed through the flow path 4 flows into the storage space 61, but ascorbic acid is removed from the whole blood. As a result, it is possible to accurately detect glucose in whole blood.
Moreover, since the contact area of the solid 5 and whole blood increases by making the solid 5 granular, the separation ability of glucose and ascorbic acid is improved.

As such solid 5, those capable of selectively (specifically) capturing ascorbic acid and those having a lower capturing ability (affinity) for glucose than ascorbic acid can be used. Preferably used.
Examples of the former include a solid 5 in which a substance that specifically binds to ascorbic acid (for example, an antibody or the like) is solid-phased on the surface of the carrier. However, such a solid 5 tends to be expensive. .
On the other hand, the latter solid material 5 can be obtained relatively easily and inexpensively. As the solid 5, one having at least a surface composed of hydrocarbon is preferably used. Specific examples of the solid material 5 include those obtained by bonding a coupling agent having a hydrocarbon group to the surface of the inorganic oxide particles.

Examples of the inorganic oxide constituting the inorganic oxide particles include silica (SiO ₂ ) and alumina (Al ₂ O ₃ ).
Further, the carbon number of the hydrocarbon is appropriately set according to the combination of the inhibitor supplemented from the sample liquid and the detection target, and preferably about 1 to 50. Ascorbic acid and glucose are added. When separating, it is set to about 2-18.
In addition, the solid substance 5 which combined the coupling agent which has a hydrocarbon group on the surface of an inorganic oxide particle as mentioned above is available from Aldrich, for example.

Further, the composition of the solid material 5 may be constant in the longitudinal direction of the flow path 4, but may be different between the supply unit 3 side and the detection unit 6 side.
Specifically, when the detection target is hydrophilic, such as glucose, as in this embodiment, the hydrophobicity of the solid 5 may be higher on the supply unit 3 side than on the detection unit 6 side. Thereby, the difference in the speed | rate of glucose and ascorbic acid which moves the inside of the flow path 4 can be enlarged, and these isolation | separation can be performed reliably. That is, glucose can be preferentially discharged from the flow path 4 into the storage space 61 while ascorbic acid is supplemented to the solid matter 5. Furthermore, it is possible to reliably separate lipids and the like present in whole blood from glucose. For this reason, the detection unit 6 can more reliably detect glucose.

For example, in the solid substance 5 to which the coupling agent having a hydrocarbon group as described above is bonded, the hydrophobicity as the solid substance 5 can be easily changed by changing the carbon number of the hydrocarbon group. .
Specifically, as shown in FIG. 2, when three regions 41 a to 41 c having different hydrophobicity are provided from the supply unit 3 side in the longitudinal direction of the flow path 4, the carbon number of the hydrocarbon is, for example, the region 41 a. 13 to 18, 7 to 12 in the region 41b, and 2 to 6 in the region 41c.

The solid material 5 may be a dense body, but is preferably a porous body. Thereby, the contact area with the whole blood of the solid substance 5 can further be increased, and the separation ability of glucose and ascorbic acid is further improved.
In this case, the porosity of the solid material 5 may be constant in the longitudinal direction of the flow path 4, but may be different between the supply unit 3 side and the detection unit 6 side.

Specifically, when the detection target is a low-molecular substance such as glucose as in the present embodiment, the porosity of the solid material 5 is greater on the supply unit 3 side than on the detection unit 6 side. Good. Thereby, for example, macromolecules such as proteins in the whole blood enter into the pores of the solid material 5, the movement (transfer) speed thereof becomes slow, and can be reliably separated from low molecules such as glucose. As a result, it is possible to more reliably detect glucose in the detection unit 6.
For example, when the average particle size of the solid material 5 is made different in the three regions 41a to 41c, the region 41a is about 50 to 70%, the region 41b is about 30 to 50%, and the region 41c is 10 to 30%. Can be about.

Further, in the longitudinal direction of the flow path 4, the average particle size of the solid material 5 is preferably about 1 to 100 μm.
Further, the average particle diameter of the solid material 5 may be constant in the longitudinal direction of the flow path 4, but may be different between the supply unit 3 side and the detection unit 6 side.
Specifically, the average particle size of the solid material 5 may be larger on the supply unit 3 side than on the detection unit 6 side. Thereby, the filling rate of the solid material 5 in the flow path 4 on the detection section 6 side is increased from the supply section 3 side, that is, the volume (cross-sectional area) occupied by the gap formed in the flow path 4 is increased. It can be made smaller on the detection unit 6 side than on the side. As a result, capillary action on whole blood can be generated more reliably.
For example, when the average particle diameter of the solid material 5 is made different in the three regions 41a to 41c, the region 41a is set to about 70 to 100 μm, the region 41b is set to about 30 to 70 μm, and the region 41c is set to about 1 to 30 μm. be able to.

It is preferable that the condition of the solid material 5 as described above satisfies one, more preferably two or more, and still more preferably three or more.
Moreover, it is preferable that the flow path 4 has a part where the cross-sectional area itself decreases from the supply unit 3 side to the detection unit 6 side. In particular, in the present embodiment, the flow channel 4 has a detection unit 6 side. The cross-sectional area gradually decreases (the height of the first groove 233 is substantially constant and the width gradually decreases). Thereby, the capillary phenomenon with respect to the whole blood is exhibited more efficiently, and the outflow of the whole blood from the flow path 4 to the detection unit 6 can be performed more reliably. Further, the flow path 4 having such a configuration has an advantage that it is easy to form.
The width of such a flow path 4 is not particularly limited from the supply unit 3 side toward the detection unit 6 side, but is preferably about 5 to 20 mm at the end on the supply unit 3 side. It is preferable that it is about 2-10 mm in the edge part of the side.

The flow path 4 may have a configuration in which the cross-sectional area gradually decreases from the supply section 3 side toward the detection section 6 side, and is provided only in a part of the flow path 4 in the longitudinal direction. May be. Even with such a configuration, capillary action on whole blood is more efficiently exhibited.
Moreover, the length (full length) of the flow path 4 is not particularly limited, but is preferably about 30 to 200 mm, and more preferably about 50 to 100 mm. By setting the length of the flow path 4 in such a range, it is possible to detect glucose more accurately without requiring a long time for glucose detection.

  The second recess 234 and the second groove 235 are liquid-tightly sealed by the thin plate 26. The accelerating liquid filling portion 7 is configured by the second recess 234 and the thin plate 26, and a space defined by the thin plate 26 and the second recess 234 constitutes the filling space 71. The filling space 71 is filled with the accelerating liquid 9. A space defined by the second groove 235 and the thin plate 26 constitutes the communication path 84.

  When detecting glucose in whole blood, the accelerating liquid 9 is supplied into the first recess 232 (supply unit 3) via the communication path 84. The accelerating liquid 9 dilutes whole blood and is introduced into the flow path 4 after introduction of the whole blood into the flow path 4, so that the whole blood is removed from the first recess 232 in the flow path 4. Since it exerts the function of extruding to each other, it facilitates each component (particularly glucose) in the whole blood to pass through the flow path 4.

  Examples of the accelerating solution 9 include, but are not limited to, triethanolamine hydrochloric acid-sodium hydroxide buffer, veronal (sodium 5,5-diethylbarbiturate) -hydrochloric acid buffer, tris-hydrochloric acid buffer, Glycylglycine-sodium hydroxide buffer, 2-amino-2-methyl-1,3-propanediol-hydrochloric acid buffer, diethanolamine-hydrochloric acid buffer, boric acid buffer, sodium borate-hydrochloric acid buffer, glycine- Sodium hydroxide buffer, sodium carbonate-sodium bicarbonate buffer, sodium borate-sodium hydroxide buffer, sodium bicarbonate-sodium hydroxide buffer, potassium dihydrogen phosphate-disodium hydrogen phosphate buffer, phosphorus Disodium acid-sodium hydroxide buffer, potassium chloride-sodium hydroxide buffer, Ton - Robinson buffer, etc. plus the various buffers or their physiological saline of GTA buffer and the like.

The amount of the accelerating liquid 9 is not particularly limited, but is preferably about 0.5 to 100 times that of whole blood (subject liquid), and more preferably about 5 to 20 times.
Further, the accelerating liquid 9 preferably contains a treatment agent that suppresses coagulation of whole blood. By adopting a configuration in which the accelerating liquid 9 includes such a treatment agent, clogging of the flow path 4 due to solidification of whole blood when passing through the flow path 4 can be reliably prevented. .

Examples of the treatment agent include blood anticoagulants such as heparin sodium, citric acid, and ethylenediaminetetraacetic acid, and thrombolytic agents such as urokinase, and one or more of these are used in combination. be able to.
A partition unit (opening / closing unit) 8 is provided between the supply space 31 of the supply unit 3 and the filling space 71 of the accelerating liquid filling unit 7, that is, in the middle of the communication path 84.

  In a state before the detection element 1 is used, the supply space 31 and the filling space 71 are separated by the partition unit 8. On the other hand, when the detection element 1 is in use, the supply space 31 and the filling space 71 communicate with each other by releasing the separation by the partition unit 8. That is, the partitioning means 8 switches the opening and closing of the communication path 84 between a state before use and a state before use.

In the present embodiment, a through hole 261 is formed at a position corresponding to the communication path 84 of the thin plate 26. A partition plate 81 is inserted into the communication path 84 through the through hole 261. The partition plate 81 is configured by the partition plate 81.
Before use of the detection element 1, a separation state (closed state) in which the partition plate 81 is liquid-tightly inserted into the communication path 84 through the through hole 261 and the supply space 31 and the filling space 71 are separated from each other. It has become. On the other hand, when the partition plate 81 is removed during use, the spaces 31 and 71 communicate with each other via the communication path 84 (open state). As a result, the accelerating liquid 9 is supplied into the first recess 232 (supply unit 3) via the communication path 84.

  Examples of the constituent material of the partition plate 81 include polyamide resin, polyester resin, polyurethane resin, polystyrene resin, polyurethane elastomer, polyolefin elastomer, ethylene propylene rubber, latex rubber, and silicone resin. One or more of these can be used in combination. By comprising with such a material, the partition plate 81 can be made excellent in elastic force. As a result, when the partition plate 81 is inserted into the communication path 84 through the through hole 261, liquid tightness between the partition plate 81 and the communication path 84 is ensured, and the accelerating liquid 9 is surely placed in the filling space 71. Can be stored.

Moreover, as a constituent material of the thin plates 24 and 26, for example, one kind or a combination of two or more kinds of various resin materials and various glass materials can be used. In addition, what has transparency (light transmittance) is suitable for this constituent material. Thereby, the state in the flow path 4 and the promotion liquid filling part 7 can be visually recognized.
Further, as the constituent material of the upper substrate 23, for example, in addition to the constituent material of the lower substrate 21 described above, a silicone resin, a fluorine resin such as polytetrafluoroethylene, an epoxy resin, and the like can be given. These can be used alone or in combination of two or more.

Among these, as a constituent material of the upper substrate 23, a material mainly composed of a silicone resin is preferable. A material mainly composed of a silicone-based resin is preferable because it can be easily processed finely, has self-adhesiveness, has high transparency, and has low interaction with various biological substances (detection objects). . In addition, since a material mainly composed of a silicone-based resin has high hydrophilicity, whole blood moves smoothly (transfers) in the flow path 4 by forming the upper substrate 23 with such a material. ).
Examples of such silicone resins include polydimethylsiloxane (PDMS) and silicone thermoplastic elastomers. Among these, PDMS is particularly preferable. PDMS is particularly excellent in the effects described above.

Next, a usage method (action) of such a detection element 1 will be described.
<I> First, the detection element 1 is connected to the connector 300 of the measuring apparatus 100.
<II> Next, whole blood is supplied into the supply space 31 of the supply unit 3. Thereby, the whole blood is transferred in the flow path 4 by capillary action.
<III> Also, at substantially the same time, the partition plate 81 is removed from the communication path 84. Thereby, the supply space 31 of the supply part 3 and the filling space 71 of the accelerating liquid filling part 7 communicate with each other, and the accelerating liquid 9 is transferred in the second groove 233 by capillary action.
Then, the accelerating liquid 9 reaches the supply space 31 of the supply unit 3, dilutes the whole blood, and is further transferred through the flow path 4 by capillary action. Thereby, the transfer of whole blood in the second groove 233 is promoted, and as a result, the supply of whole blood into the storage space 61 is also promoted.

<IV> Each component in whole blood moves at different moving speeds due to the difference in affinity for the solid material 5 and the accelerating liquid (developing solvent) 9 and flows into the storage space 61 of the detection unit 6 ( Elution) and stored.
<V> In the present embodiment, by appropriately setting the configuration of the flow path 4 and the solid material 5, the glucose outflow time (retention time) is configured to be earlier than that of ascorbic acid. For this reason, even if the ascorbic acid which inhibits the detection of glucose is not contained or contained in the effluent that flows into the storage space 61 of the detection unit 6, it is extremely small. For this reason, glucose in whole blood can be detected more reliably, and the detection accuracy of glucose from whole blood can be improved.

Second Embodiment
Next, a second embodiment of the detection element will be described.
Hereinafter, although the detection element of 2nd Embodiment is demonstrated, it demonstrates centering around difference with the said 1st Embodiment, and the description is abbreviate | omitted about the same matter.
FIG. 4 is a longitudinal sectional view showing the configuration of the partition means included in the detection element of the second embodiment.

The detection element 1 of the second embodiment is the same as the first embodiment except for the configuration of the partitioning means (opening / closing means) 8.
That is, the partitioning means 8 shown in FIG. 4 is filled in the second groove 235 and melted by heating, and is provided below the second groove 235 and heating means for heating the filling 82. 83.

As the filling material 82, a material that melts when heated by the heating means 83 is used, but a material that melts at about 40 to 50 ° C. is preferably used. Examples of such materials include aliphatic hydrocarbons having about 20 to 25 carbon atoms, and various waxes composed mainly of fluorine atoms substituted for hydrogen atoms contained in these aliphatic hydrocarbons. It is done.
When such various waxes are used as the filling material 82, as shown in the first embodiment, the solid material 5 has a structure in which a coupling agent having a hydrocarbon group is bonded to the surface thereof. In this case, the filler 82 has a high affinity for the solid material 5. Therefore, it is possible to reliably prevent the filler 82 from flowing into the storage space 61 together with glucose.
Moreover, even if the processing agent demonstrated in the said 1st Embodiment is added to the filler 82 so that it may be gradually released in the liquid mixture of whole blood and the acceleration | stimulation liquid 9 by melting of the filler 82, it may be added. Good.

On the other hand, examples of the heating means 83 include a micro heater, high-frequency heating, and laser heating.
Further, it is preferable that the heating unit 83 is turned on when the detection element 1 is connected to the connector 300 of the measuring apparatus 100.
Also by the detection element 1 of this embodiment, the same operation and effect as the detection element 1 of the first embodiment can be obtained.

<Third Embodiment>
Next, a third embodiment of the detection element will be described.
Hereinafter, although the detection element of 3rd Embodiment is demonstrated, it demonstrates centering around difference with the said 1st Embodiment, and the description is abbreviate | omitted about the same matter.
FIG. 5 is a longitudinal sectional view of a supply unit included in the detection element of the third embodiment.

The detection element 1 of the third embodiment is different from that of the first embodiment except that the detection element 1 includes a separation unit that separates solid components.
That is, the supply unit 3 shown in FIG. 5 is provided with a separation membrane (separation means) 32 so as to cover the first recess 232, and the cylindrical portion 25 so as to fix the edge of the separation membrane 32 to the upper substrate 23. Is provided. That is, the separation membrane 32 includes a first space (lower space) 311 on the flow channel 4 side and a second space (upper space) 312 on the opposite side of the flow channel 4 in the supply space 31 of the supply unit 3. It is provided to partition into two spaces.

The separation membrane 32 has a function of separating solid components such as red blood cells and white blood cells in whole blood. By providing the separation membrane 32, solid components of the whole blood supplied to the first space 311 cannot pass through the separation membrane 32 and remain on the separation membrane 32. Plasma moves into the second space 312 and is transferred into the flow path 4 by capillary action.
When removing solid components from whole blood, for example, a blood cell removal filter is suitably used as the separation membrane 32. In addition, when using another analyte liquid, a filter having an opening diameter corresponding to the size of the solid component to be removed may be used.
Also by the detection element 1 of this embodiment, the same operation and effect as the detection element 1 of the first embodiment can be obtained.
In addition, with this configuration, solid components such as red blood cells and white blood cells are prevented from clogging in the flow path 4. As a result, reliable glucose detection can be performed.

<Fourth embodiment>
Next, a fourth embodiment of the detection element will be described.
Hereinafter, although the detection element of 4th Embodiment is demonstrated, it demonstrates centering around difference with the said 1st Embodiment, and the description is abbreviate | omitted about the same matter.
FIG. 6 is a perspective view showing the configuration of the separating means included in the detection element of the fourth embodiment.
That is, the separating means shown in FIG. 6 includes a branch channel 42 that branches from the middle of the channel 4 and a vibrator 44 that is provided in a branch part 43 where the branch channel 42 branches from the channel 4. Yes.

In addition, on the side opposite to the branching portion 43 of the branching channel 42, there is a recovery unit 45 that recovers a solid component communicating with the branching channel 42.
With such a configuration, when the vibrator 44 is operated and the wall surface (in this embodiment, the thin plate 24) that defines the flow path 4 is vibrated at a specific frequency, a solid having a relatively large specific gravity contained in whole blood. Components (for example, solid matter solidified by red blood cells, white blood cells, fibrin, etc.) are aggregated by the microcentrifugation effect.

The vibration direction of the vibrator 44 is arranged along the longitudinal direction of the branch flow path 42, and the aggregate is guided to the branch flow path 42 side along the vibration direction of the vibrator 44. Is recovered by the recovery unit 45. As a result, the solid component is prevented from clogging in the flow path 4.
Although it does not specifically limit for the vibrator | oscillator 44, For example, a piezoelectric element etc. are used suitably.
The vibrator 44 is preferably configured to be turned on when the detection element 1 is connected to the connector 300 of the measuring apparatus 100.
Even with such a configuration, the same effect as the third embodiment can be obtained.

The detection element of the present invention has been described based on the illustrated embodiment, but the present invention is not limited to this.
For example, in the detection element of the present invention, the configuration of each part can be replaced with an arbitrary configuration that exhibits the same function, and an arbitrary configuration can be added.
In addition, for example, when the analyte (sample) is a liquid, the analyte liquid can be obtained as it is or by adjusting the volume (for example, diluting) as necessary.

Examples of liquid subjects include whole blood (or plasma) as described above, for example, body fluids such as urine, sweat, lymph, cerebrospinal fluid, bile, saliva, wastewater such as domestic wastewater and industrial wastewater, pool water, Examples thereof include stored water such as water in a water storage tank, or processed liquid obtained by subjecting these liquids to various treatments.
When using a solid sample such as cells, soil, or mineral, for example, the sample solution may be pulverized and suspended in the buffer solution as described above. it can.

Further, the detection target is not limited to glucose, and the inhibitor is not limited to ascorbic acid. As a combination of a detection target and an inhibitor that inhibits detection of the detection target, for example, glucose and A combination with uric acid, a combination of uric acid and ascorbic acid, and the like can be mentioned.
Further, the trapped material can be constituted by a solid material such as a block shape or a pellet shape instead of the granular solid material.

Moreover, when the hydrophobicity of the detection target is high, the composition of the captured substance may be higher on the detection unit side than on the supply unit side.
Moreover, the detection method of the detection target in a detection part is not limited to the method of measuring an electric current value like the said embodiment, For example, with the change of the mass (weight) and layer thickness (film thickness) of a reaction layer You may make it measure (detect) the change of a numerical value.

It is a top view which shows 1st Embodiment of the detection element of this invention. It is the sectional view on the AA line in FIG. It is a figure which shows the state which connected the detection element shown in FIG. 1 to the measuring apparatus. It is a longitudinal cross-sectional view which shows the structure of the partition means which the detection element of 2nd Embodiment has. It is a longitudinal cross-sectional view of the supply part which the detection element of 3rd Embodiment has. It is a perspective view shown in the structure of the isolation | separation means which the detection element of 4th Embodiment has.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Detection element 2 ... Base 21 ... Lower board 22 ... Wiring system 221 ... Working electrode 222 ... Counter electrode 223 ... Reference electrode 224-226 ... Terminal 227-229 ... Connection line 23 ... Upper substrate 231... Through-hole 232... First recess 232... First groove 234... Second recess 235... Second groove 24 ... Thin plate 25 ... Cylindrical portion 26 ... Thin plate 261 …… Through hole 3 …… Supply part 31 …… Supply space 32 …… Separation membrane 4 …… Flow path 41a to 41c …… Area 42 …… Branch flow path 43 …… Branch part 44 …… Oscillator 45 …… Recovery Part 5 …… Solid matter 6 …… Detecting part 61 …… Reserving space 62 …… Reaction layer 7 …… Promoting liquid filling part 71 …… Filling space 8 …… Partitioning means 81 …… Partition plate 82 …… Packing substance 83 …… … Heating means 84 …… communication passage 9 …… Susumueki 100 ...... measuring device 200 ...... processing circuit 210 ...... computing device 300 ...... connector 310 ...... wiring 311 ...... first space 312 ...... second space

Claims (11)

A flat base, and
A supply unit provided in the base, and provided with a supply space for supplying a sample liquid containing a detection target and an inhibitor that inhibits detection of the detection target;
A flow path provided in the base, communicating with the supply space, and through which the analyte liquid passes;
A captured substance provided in the flow channel and capable of capturing the inhibitor in the analyte liquid;
The detection target in the analyte liquid that is provided in the base, includes a storage space that communicates with the flow path and stores the analyte liquid that has passed through the flow path, and is stored in the storage space. A detection unit for detecting
An accelerating liquid filling unit comprising a filling space for filling the accelerating liquid that promotes the detection object in the analyte liquid to pass through the flow path;
The accelerating liquid filled in the filling space of the accelerating liquid filling section;
A communication passage communicating the supply space and the filling space;
A detection element comprising: opening / closing means for opening and closing the communication path. The sample liquid includes a solid component dispersed in the sample liquid,
The detection element according to claim 1, further comprising separation means for separating the solid component from the analyte liquid. The detection element further has a branch channel that branches from the middle of the channel,
The separation means includes a vibrator provided at a branch portion where the branch flow path branches from the flow path, and the solid component is guided to the branch flow path by operation of the vibrator. The detection element as described.   The separation means includes a separation membrane that is provided so as to partition the supply space of the supply section into two spaces of the flow path side and the opposite side of the flow path, and can separate the solid component. The detecting element according to 1.   The detection element according to any one of claims 1 to 4, wherein the flow path has a portion whose cross-sectional area decreases from the supply unit side toward the detection unit side.   The detection element according to claim 5, wherein a cross-sectional area of the flow path gradually decreases from the supply unit side toward the detection unit side.   The detection element according to any one of claims 1 to 6, wherein the trapped substance is formed of a granular solid and is filled in the flow path.   The detection element according to claim 7, wherein an average particle diameter of the solid matter is different between the supply unit side and the detection unit side, and is larger on the supply unit side than the detection unit side. The detection target is a low molecular substance, and the capture is composed of a porous body,
The detection element according to claim 7 or 8, wherein the porosity of the porous body is different between the supply unit side and the detection unit side, and is larger on the supply unit side than the detection unit side. The detection object is hydrophilic,
The detection element according to any one of claims 7 to 9, wherein the hydrophobicity of the captured substance is different between the supply unit side and the detection unit side, and is higher on the supply unit side than the detection unit side. The analyte fluid is whole blood or plasma, the detection target is glucose, and the inhibitor is alcorbic acid,
The detection element according to claim 7, wherein at least a surface of the trapped substance is made of hydrocarbon.

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