JP2004245734A - Disposable sensor card for measuring blood component - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a disposable sensor card for measuring blood components allowing required amount of blood to be led into a flow passage without requiring the fine adjustment of a suction pressure and preventing the blood from leaking to the outside. <P>SOLUTION: This disposable sensor card for measuring the blood components comprises a substrate having an electrode with a reaction reagent to measured components to be measured in the blood and a terminal capable of taking out signals from the electrode from a separate measuring device. The sensor card also comprises at least a flow passage passing over the measured part of the electrode, a blood lead-in part allowing the blood to be measured therein formed at the upstream end of the flow passage, a suction opening for sucking the blood led into the blood lead-in part through the flow passage formed at the downstream end of the flow passage, and a sealing member having both properties of gas permeability and liquid non-permeability installed between the electrode and the suction opening in the flow passage. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an improvement in a disposable sensor card used for measuring a specific component in blood.
[0002]
[Prior art]
Conventionally, various sensors have been proposed for quickly and simply quantifying a specific component in a biological sample solution such as blood.
Specifically, a biomaterial having a space containing a reaction layer that reacts with a specific component to be measured is provided on a substrate, and an inlet for a sample liquid and an outlet for discharging gas in the space are provided in this space. A sensor has been proposed (see Patent Document 1).
[0003]
[Patent Document 1] Japanese Patent Publication No. 06-58338
[Problems to be solved by the invention]
In the above-described conventional biosensor, when the sample liquid is brought into contact with the sample liquid inlet, the sample liquid is guided into the interior of the space by capillary action, and the sample liquid is discharged onto the electrode while discharging the air in the space from the outlet. Therefore, there is an effect that the electrode surface can be uniformly wetted with the sample solution without bubbles remaining on the electrode.
However, specific components in the blood include not only components that can be measured in the state of so-called whole blood by directly introducing blood, as in this conventional biosensor, but also, for example, cholesterol and neutral fats. As described above, there are components in which the measurement reaction system is easily affected by blood cells themselves or exudates from inside the blood cells. In addition, there is also a problem that the measurement value is usually susceptible to hematocrit when measuring in the state of whole blood. Some components such as high-density lipoprotein (hereinafter, HDL) cannot be measured without removing contaminants such as non-HDL components in addition to blood cells.
As described above, in order to remove blood cells and contaminants from blood, usually, the blood is subjected to some pretreatment (eg, a pretreatment such as adding a coagulation reagent of a specific component and then centrifuging), or the blood to be measured is removed. Must pass through some filter. However, in a sensor configured to carry a sample solution to above an electrode only by a capillary phenomenon as in the above-described conventional biosensor, for example, even if a filter is provided between a sample solution inlet and an electrode, the sample can be sampled. There is a problem that it is difficult to make the liquid proceed more than filling the voids of the filter, and it is extremely difficult to introduce a sufficient amount of exudate from the filter onto the electrode.
In order to solve this problem, the inventor has adopted a method of physically suctioning blood introduced from an air outlet, and repeated trial and error such as suction conditions. It is extremely difficult to keep the amount of suction constant for blood with different individual blood cell volume ratios, and as a result, a sufficient amount of sample solution may not reach the electrode, or the sample solution may reach the electrode. The problem is that the amount of sample liquid varies, resulting in variations in the measurement results, and the problem that the sample liquid leaks out from the air outlet when the amount of sample liquid suctioned is too large. There is.
The present invention solves the above-mentioned conventional problems, and can introduce a required amount of blood into a flow path without requiring fine adjustment of a suction pressure, and does not leak blood to the outside. The purpose is to provide a disposable sensor card for measurement.
[0005]
[Means for Solving the Problems]
In order to achieve the above-mentioned object, the disposable sensor card for measuring blood components according to the present invention can be connected to a measurement unit provided with a reaction reagent for a measurement component to be measured in blood and a separate measurement device. A substrate on which an electrode having an appropriate terminal portion is formed, at least a flow path passing over a measurement site of the electrode, and a blood introduction capable of introducing blood to be measured to an upstream end of the flow path. A portion is provided, and at the downstream end of the flow channel, a suction opening for allowing blood introduced into the blood introduction portion to be suctioned through the flow channel is formed, and the electrode and the suction opening in the flow channel are formed. A sealing member having both properties of gas permeability and liquid impermeability is provided therebetween.
The method of suction from the suction opening may be any method, for example, a suction pump device may be provided on the measurement device side on which the sensor card is set, or a suction pump that can be manually operated by a measurer may be provided. Alternatively, suction may be performed manually.
The suction opening may preferably be provided in the measurement substrate. By providing the suction opening in the measurement substrate in this way, for example, in a sensor that configures a flow path by laminating and bonding a plurality of films having openings formed in a liquid-tight and air-tight manner, the measurement substrate is formed with a flow path. It can be used as one component of a film.
A filter may be provided between the electrode and the blood introduction unit to remove components that inhibit measurement and / or blood cells from the introduced blood. As this filter, for example, when measuring cholesterol or neutral fat, a filter that can remove blood cells is used. When measuring HDL, a filter that removes non-HDL components in addition to blood cells is used. Can be
As the sealing member having both the gas-permeable property and the liquid-impermeable property, for example, a sealing member formed by using a fiber made of a water-absorbing polymer or a fiber made of a hydrophobic polymer can be used. Specifically, for example, a sealing member can be formed by coating the fiber with an appropriate core material. When a water-absorbing polymer is used, the water-swelling polymer swells with blood and does not pass through the blood any more. When a hydrophobic polymer is used, blood does not pass through due to surface tension.
As the water-absorbing polymer, for example, a polysaccharide and / or a derivative thereof, an acrylic polymer, polyvinyl alcohol, gelatin, a block copolymer containing collagen or maleic anhydride, or the like can be used.
As the hydrophobic polymer, for example, polyester, silicone, fluororesin, polyethylene, or the like can be used.
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, an embodiment of a disposable sensor card for measuring blood components (hereinafter, simply referred to as a sensor card) according to the present invention will be described with reference to an embodiment shown in the accompanying drawings.
[0007]
FIG. 1 is an exploded perspective view of one embodiment of a sensor card according to the present invention.
This sensor card is configured to measure cholesterol, neutral fat and HDL in blood.
As shown in the drawing, this sensor card
Eight films 1 to 8 forming a flow path of the sample liquid;
Three filters 9-11,
It comprises a single substrate 12 on which electrodes and terminals are formed.
[0008]
The uppermost film 1 is a polyethylene terephthalate film (hereinafter, PET film) having a thickness of 0.125 mm.
The second film 2 is made of a single-sided pressure-sensitive adhesive tape having a thickness of 0.15 mm and having an adhesive surface on an upper surface, and a notch 2a for forming a blood introduction holding portion A at one end thereof, and a film 3 described later. And two independent openings 2b and 2c communicating with the notches 3a.
The third film 3 is made of a double-sided pressure-sensitive adhesive tape having a thickness of 0.3 mm having an adhesive surface on both sides, and a notch for forming a blood introduction holding portion together with the notch 2a of the film 2 at one end thereof. 3a are formed. The notch 3a is notched widely inside the notch 2a of the film 2 so as to communicate with openings 2b and 2c of the film 2 and openings 4a and 4b of the film 4 described later.
The fourth film 4 is made of a PET film having a thickness of 0.125 mm, and has an opening 4a forming the first flow path and an opening 4b forming the second flow path.
The fifth film 5 is made of a double-sided adhesive tape having a thickness of 0.725 mm and having adhesive surfaces on both sides, and has an opening 5a communicating with the opening 4a of the film 4 at one end thereof. An opening 5b communicating with the opening 4b is formed.
[0009]
A glass fiber nonwoven fabric 9 is fitted into the opening 5a. The glass fiber non-woven fabric 9 has the same thickness as the film 5, has a pore diameter of 1 to 10 μm, and has a cross-sectional shape formed to have the same shape and the same size as the opening 5a. Functions as a progress delay filter. In addition, the glass fiber nonwoven fabric 9 previously holds a lectin as a blood cell separation promoting agent in a dry state, and the reaction with the lectin increases the effect of delaying the progress speed of blood cells.
Similarly, the glass fiber nonwoven fabric 10 is fitted into the opening 5b. This glass fiber nonwoven fabric 10 has the same thickness as the film 5, has a hole diameter of 1 to 10 μm, and is formed to have the same cross-sectional shape as the opening 5b. In addition, the glass fiber nonwoven fabric 10 has a non-HDL precipitant dried and held in advance, so that the glass fiber nonwoven fabric 10 can delay the progression of blood cells, and can also be used to delay non-HDL components. Functions as an HDL component removal filter.
A porous polyester membrane 11 is provided between the film 5 (that is, the two independent filters 9 and 10 described above) and a film 6 described below. The porous polyester membrane 11 is provided with a large number of pores extending in the vertical direction (that is, the flow direction of the flow path) and having a pore diameter in the range of 0.5 to 4 μm. And functions as a blood cell removal filter that traps blood cells that pass through the plasma.
[0010]
The sixth film 6 is made of a double-sided pressure-sensitive adhesive tape having a thickness of 0.06 mm and having adhesive surfaces on both sides, and has, at one end thereof, the glass fiber nonwoven fabrics 9 and 10 fitted in the openings 5a and 5b. Independent openings 6a and 6b communicating with the openings 4a and 4b of the film 4, respectively, are formed via the and the porous polystyrene membrane 11.
The seventh film 7 is made of a PET film having a thickness of 0.125 mm, and has independent openings 7a and 7b communicating with the openings 6a and 6b of the film 6, respectively.
The eighth film 8 is made of a 0.1 mm thick double-sided pressure-sensitive adhesive tape having adhesive surfaces on both sides.
In this film 8,
One end communicates with the opening 7a, passes through the upper surface of a first measuring section B of the substrate 12 described later, and extends along the longitudinal direction of the film to a suction opening D formed in the substrate 12; ,
One end communicates with the opening 7b, passes through the upper surface of a second measuring section C of the substrate 12 described later, and extends along the longitudinal direction of the film to a suction opening E formed in the substrate 12; Are respectively formed.
The elongated openings 8a and 8b are formed such that portions corresponding to the measurement portions B and C of the substrate 12 described later are formed wide, and after narrowing from the wide portion to the downstream, a suction opening D of the substrate 12 described later. And E are formed so as to be wider again.
A narrow flow path portion between the wide portion corresponding to the measuring portion B and the wide portion corresponding to the suction opening C in the elongated opening 8a has a seal having both gas-permeable and liquid-impermeable properties. A member 13a is provided.
Similarly, the narrow flow path portion between the wide portion corresponding to the measurement portion C and the wide portion corresponding to the suction opening E in the elongated opening 8b has both properties of gas permeability and liquid impermeability. A sealing member 13b is provided.
As the sealing members 13a and 13b, for example, those formed using fibers made of a water-absorbing polymer or fibers made of a hydrophobic polymer are used. Specifically, the sealing members 13a and 13b can be formed by, for example, coating an appropriate core material with the fibers. When the water-absorbing polymer is used, when the blood comes into contact, the water-absorbing polymer absorbs the blood and swells, and does not pass through the blood any more. When the hydrophobic polymer is used, the blood does not pass through due to surface tension.
As the water-absorbing polymer, for example, a polysaccharide and / or a derivative thereof, an acrylic polymer, polyvinyl alcohol, gelatin, a block copolymer containing collagen or maleic anhydride, or the like can be used.
As the hydrophobic polymer, for example, polyester, silicone, fluororesin, polyethylene, or the like can be used.
[0011]
Lastly, the substrate 12 will be described with reference to FIGS.
FIG. 2 is an enlarged view of the substrate 12 in FIG.
The substrate 12 is made of a polyester film, and has a first measuring section B and a second measuring section C formed thereon.
The first measurement unit B includes a pair of electrodes B1 and B2 for measuring cholesterol, a pair of electrodes B3 and B4 for measuring neutral fat, and a counter electrode B5.
The second measuring section C includes a pair of electrodes C1 and C2 for HDL measurement and a counter electrode C3.
A cholesterol measuring reagent, cholesterol esterase, cholesterol oxidase, and an electron acceptor are held on the measurement site of one electrode B1 of the pair of electrodes B1 and B2 for measuring cholesterol by drop drying, and the other electrode Cholesterol esterase and an electron acceptor are held on the measurement site of B2.
A lipase, a glycerol kinase, a glycerophosphate oxidase, and an electron acceptor are held as a neutral fat measurement reagent on a measurement site of one electrode B3 of the pair of electrodes B3 and B4 for the neutral fat measurement. On the measurement site of the other electrode B4, glycerol kinase, glycerophosphate oxidase, and an electron acceptor are held.
On the measurement site of one electrode C1 of the pair of electrodes C1 and C2 for HDL measurement, cholesterol esterase, cholesterol oxidase, and an electron acceptor are held by drop drying for HDL measurement, and the other is held. Cholesterol esterase and an electron acceptor are held on the measurement site of the electrode C2.
As described above, a pair of electrodes is provided for each measurement item, one reagent holds all reagents necessary for measurement, and the other electrode removes one reagent from all reagents required for measurement. By holding the sample, the cholesterol, neutral fat, and HDL components can be measured from the difference between the reaction values obtained at both electrodes by the measuring device.
As for the HDL component, the non-HDL component is removed by the glass fiber nonwoven fabric 10 in advance, and the blood cells are removed in advance by the combination of the glass fiber nonwoven fabric 10 and the porous polyester membrane 111. It is possible to measure components.
Each of the above-mentioned electrodes is formed by bonding a copper foil on a substrate and then forming a desired pattern by a photolithography method.
Gold or platinum plating is applied to the surface of the measurement site of the measurement electrodes B1, B2, B3, B4, C1, and C2. On the counter electrodes B5 and C3, a conductive layer made of a conductive paste containing silver powder and silver chloride powder is further formed on the pattern by screen printing.
Also, an insulating resist made of a UV-curable polyester resin was formed on the electrode by photolithography so that only the measurement site and the terminal site were exposed. In the present example, the diameter of the exposed portion of each measurement site could be reduced to 0.6φ by using the photolithography method for forming the insulating resist. As described above, by reducing the exposed portion of the measurement site, the amount of blood required for measurement can be greatly reduced, and the effect of reducing the burden on the patient can be achieved.
[0012]
The films 1 to 8 and the three filters 9 to 11 are all laminated on the substrate 12.
As described above, the films 2, 3, 5, 6, and 8 sandwiched between the films or between the film and the substrate are simply made of single-sided tape or double-sided tape, so that they are simply aligned and stacked. Each film is liquid-tightly and air-tightly adhered to the substrate only by stacking, so that the sensor card can be easily manufactured.
When all the films 1 to 8 and the filters 9 to 11 are laminated on the substrate 12, the blood introduction holding portion A is formed by the notch 2a of the film 1, the notch 2, the notch 3a of the film 3, and the film 4. A substance that inhibits blood coagulation, such as heparin, is previously applied to a portion of the film 1 and the film 4 corresponding to the blood introduction holding section A, so that the blood introduction holding section A has a certain amount of time. It is possible to keep blood.
When all the films 1 to 8 and the filters 9 to 11 are laminated on the substrate 12, the openings 4a, the glass fiber nonwoven fabric 9 fitted in the openings 5a, the porous polyester membrane 11, the openings 6a, the openings 7a, All of the elongated opening 8a and the suction opening D communicate with each other to form the first flow path F. The upstream end of the first flow path F communicates with the blood introduction holding section A, passes through the upper surface of the first measurement section B formed on the substrate 12, and reaches the suction opening D.
At the same time, the opening 4b, the glass fiber nonwoven fabric 10, the porous polyester membrane 11, the opening 6b, the opening 7b, the elongated opening 8b, and the suction opening E which are fitted in the opening 5b all communicate with each other, and the second flow path G Is formed. The upstream end of the second flow path G communicates with the blood introduction holding section A, passes through the upper surface of the second measurement section C formed on the substrate 12, and reaches the suction opening E.
The first flow path F and the second flow path G are, as shown in FIG. 1, the substrate 12 from the blood introduction holding section A to the first measurement section B and the second measurement section C on the same plane. Perpendicular to the substrate 12, from which it is horizontal with respect to the substrate 12, and further opened vertically to the substrate 12 via suction openings D and E. Then, the glass fiber nonwoven fabrics 9 and 10 and the porous polyester membrane 11 functioning as filters are all arranged in the portions of the flow paths F and G perpendicular to the substrate.
[0013]
Hereinafter, a usage example of the sensor card configured as described above will be briefly described.
This sensor card is set in a measuring device having an input section to which a terminal can be connected, and a pump configured to be able to independently suction the test liquid in the two flow paths via the two suction openings. Used as
After setting the sensor card in the measuring device, the user introduces blood into the blood introduction holding part A, one of which is open to the outside.
The blood immediately after the introduction is held by the blood introduction holding unit A without flowing to the first flow path F and the second flow path G due to surface tension.
Here, first, the blood in the blood introduction holding section A flows through the second flow path G against the surface tension, and flows through the suction opening E on the second flow path G side until it contacts the filter 10. Through the pump. When blood comes into contact, the filter 10 absorbs the blood itself until it fills its capacity.
Next, the blood in the blood introduction holding section A flows into the first flow path F against the surface tension, and is sucked by the pump through the suction opening D on the first flow path F side until it contacts the filter 9. . When the blood comes in contact, the filter 9 absorbs the blood by itself until it fills the capacity.
In this state, the apparatus waits until the blood cell separation promoting agent and the blood in the filter 9 sufficiently react with each other, and after a sufficient reaction time has elapsed, the blood in the filter 9 again passes through the filters 6 through the openings 6a, 7a, and 8a. It flows in order and is sucked by the pump through the suction opening D on the first flow path F side until it reaches the sealing member 13a of the opening 8a through the first measuring portion B of the substrate 12.
Thereby, only the plasma from which the blood cells have been removed by the action of the filter 11 is filled in the first flow path F from the downstream of the filter 11 to the sealing member 13a. At this time, in addition to the blood cell progression delaying action of the filter 9 and the reaction with the blood cell separation promoting agent, the blood cell progression in the filter 9 is sufficiently delayed with respect to the plasma. The filter 11 does not get clogged with blood cells before reaching the sealing member 13a above the first measuring section B.
Next, after a sufficient reaction time between the non-HDL precipitant and the blood has passed, the blood in the filter 10 flows again through the filter 11 in the order of the openings 6b, 7b, and 8b, and flows on the second measuring section C of the substrate 12 again. The liquid is sucked by the pump of the measuring device through the suction opening E on the second flow path G side until the gas reaches the sealing member 13b of the opening 8b.
As a result, the filter 10 removes the non-HDL component, the filter 11 removes the blood cells, and only the blood plasma from which the blood cells and the non-HDL component have been removed is sealed from the downstream of the filter 11 in the second flow path G by the sealing member 13b. Will be charged until
As described above, in this sensor card, the plasma to be measured (or the plasma from which non-HDL components have been removed) is filled over the first measuring unit B and the second measuring unit C to the sealing members 13a and 13b. The configuration is such that a constant amount of plasma can be guided onto the electrodes without worrying about overshoot, regardless of the wetting of the electrode surface of each electrode, so that the measurement is very stable.
[0014]
As described above, the sensor card according to the present embodiment is provided with the two flow paths F and G connected to one blood introduction holding part A, and the flow paths F and G are placed on the corresponding measurement parts B and C, respectively. , And to the respective suction openings D and E, and necessary filters 9, 10, 11 between the blood introduction holding unit A and the measurement units B and C in the respective flow paths F and G. And sealing members having both gas-permeable and liquid-impermeable properties are provided between the measurement sections B and C and the suction openings D and E in each of the flow paths F and G, respectively. However, the number of flow paths in the sensor card is not limited to the present embodiment, and may be one, or three or more. Naturally, the number of measurement units corresponds to the number of flow paths. A number is fine. Further, the presence or absence or type of the filter can be arbitrarily determined according to the measurement item in the measurement unit.
Further, in the above-described embodiment, the description has been made that the flow paths F and G are suctioned by the pump of the measuring apparatus. However, it is needless to say that this pump may be an automatic type or a manual type.
[0015]
【The invention's effect】
As described above, the disposable sensor card for measuring a blood component according to the present invention includes a measurement unit provided with a reaction reagent for a measurement component to be measured in blood, and a terminal unit connectable to a separate measurement device. A substrate having an electrode formed thereon, having at least a flow path passing over a measurement site of the electrode, and an upstream end of the flow path being provided with a blood introducing portion capable of introducing blood to be measured. At the downstream end of the flow path, while forming a suction opening for allowing blood introduced into the blood introduction unit to be suctioned through the flow path, between the electrode and the suction opening in the flow path, Since a sealing member having both gas-permeability and liquid-impermeable properties is provided, a stable amount of blood can always be supplied to the electrode simply by applying a negative pressure to the suction opening. For this reason, it is possible to obtain a stable measurement result without requiring fine control of the negative pressure.
In addition, with the configuration described above, when the disposable sensor card for measuring blood components is used by being set in an analyzer provided with a pump, the sucked blood or plasma flows into the analyzer by mistake. No more.
[Brief description of the drawings]
FIG. 1 is a developed perspective view of one embodiment of a sensor card according to the present invention.
FIG. 2 is an enlarged view of a substrate in FIG.
[Description of References]
A blood introduction holding section B first measurement section B1 cholesterol measurement electrode B2 cholesterol measurement electrode B3 triglyceride measurement electrode B4 triglyceride measurement electrode B5 counter electrode C second measurement section C1 HDL measurement electrode C2 HDL measurement Electrode C3 Counter electrode D Suction opening E Suction opening F First channel G Second channel 1 Film (PET film)
2 Film (single-sided tape)
2a notch 2b opening 2c opening 3 film (double-sided tape)
3a Notch 4 film (PET film)
4a Opening 4b Opening 5 Film (double-sided tape)
5a Opening 5b Opening 6 Film (double-sided tape)
6a Opening 6b Opening 7 Film (PET film)
7a opening 7b opening 8 film (double-sided tape)
8a Elongated opening 8b Elongated opening 9 Glass fiber nonwoven fabric (holds blood cell separation promoter lectin)
10 Glass fiber nonwoven fabric (holds non-HDL precipitant)
DESCRIPTION OF SYMBOLS 11 Porous polyester membrane 12 Substrate 13a Sealing member 13b Sealing member

Claims (6)

A measurement unit provided with a reaction reagent for a measurement component to be measured in blood, and a substrate provided with an electrode having a terminal unit connectable to a separate measurement device,
At least, having a flow path passing over the measurement site of the electrode,
At the upstream end of the flow path, a blood introduction unit capable of introducing blood to be measured is provided,
At the downstream end of the flow path, while forming a suction opening for allowing blood introduced into the blood introduction unit to be suctioned through the flow path,
A disposable sensor card for measuring blood components, wherein a sealing member having both gas permeability and liquid impermeability is provided between an electrode and a suction opening in the flow path. The disposable sensor card for measuring blood components according to claim 1, wherein the suction opening is formed in the substrate. The blood component measurement disposable device according to claim 1 or 2, wherein a filter is provided between the electrode and the blood introduction unit to remove components that inhibit measurement and / or blood cells from the introduced blood. Sensor card. The disposable sensor for measuring blood components according to any one of claims 1 to 3, wherein the sealing member is formed using at least a fiber made of a water-absorbing polymer or a hydrophobic polymer. card. The blood according to claim 4, wherein the water absorbing polymer is any one of a polysaccharide and / or a derivative thereof, an acrylic polymer, polyvinyl alcohol, gelatin, collagen, and a block copolymer containing maleic anhydride. Disposable sensor card for component measurement. The disposable sensor card for measuring blood components according to claim 4, wherein the hydrophobic polymer is polyester, silicon, fluororesin, or polyethylene.

Images