CN203551502U - Biosensor - Google Patents
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- CN203551502U CN203551502U CN201320150703.3U CN201320150703U CN203551502U CN 203551502 U CN203551502 U CN 203551502U CN 201320150703 U CN201320150703 U CN 201320150703U CN 203551502 U CN203551502 U CN 203551502U
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Abstract
The utility model aims to provide a biosensor which comprises an insulating bottom plate and an electrode system positioned on the insulating bottom plate, wherein a reaction reagent which can react with a detection sample is contained in the electrode system; the electrode system comprises a functional electrode used for detection and auxiliary diffusion electrodes used for controlling diffusion of the reaction reagent; the functional electrode is positioned between the auxiliary diffusion electrodes. Because the auxiliary diffusion electrodes can overcome the surface tension of the insulating bottom plate, the reagent can smoothly and uniformly diffuse on the electrode system and reach a preset position.
Description
Technical field
The utility model relates to the biology sensor for detection of physical signs content.
Background technology
In recent years, from utilizing at first clinical labororatory's pattern detection to only need realizing fast detecting at one's side in doctor's office or patient, there is great variety in medical health care detection field.Disposable biological sensor with electrode system is often used in the middle of fast detecting.Take diabetic's daily glucose detection as example, patient only need utilize disposable biological sensor to detect at home now, just can obtain tested patient glucose level at that time, help patient understand in time the health of self and adjust accordingly the dietary structure of oneself, or allow doctor according to the data of daily monitoring, dosage be adjusted to hospital.Therefore in the daily monitoring of disease, the accuracy of this kind disposable biology sensor seems particularly important.
This class can be for the detection of various materials with the biology sensor of electrode system, and according to the difference of analyte, the reaction reagent adding on electrode system is also different.For example measure the biology sensor of Glucose in Blood by Cyclic, first be that the reaction reagents such as glucose oxidase are added on working electrode, when blood sample drops is added in working electrode, because enzyme reaction agent dissolves is in blood, glucose in blood will with working electrode on oxidase react, electron accepter reduces thereupon.After enzyme reaction finishes, by the electron accepter electrochemical oxidation of reduction, by calculating oxidation current value, obtain the content of glucose in sample.
The basic structure of this class biology sensor comprises: an insulating base; On this insulating base, have electrode system, this electrode system at least comprises working electrode and to electrode; Contain and according to measured matter content in sample, produce the reaction reagent that can survey signal and cover at least one working electrode; A detection sample channel being formed by separation layer, this sample channel is positioned at working electrode and on electrode, reacts and produce the signal that can be detected while detecting sample through this call with the reaction reagent in passage.Instrument, according to this signal, draws testing result.
In passage, the amount of the reaction reagent of participation and detection example reaction has a great impact testing result tool.Therefore, how accurately the amount of the reaction reagent of control and participate in reaction is a large technical barrier of this area.The area that the amount of reaction reagent that participates in reaction equals sample channel is multiplied by the thickness of reaction reagent layer, therefore, accurately controlling the size of the sample channel between the different product of same batch of production and control reaction reagent thickness homogeneity is mainly to need the problem that solves.
Accurately the size of Quality control passage can and select suitable material to solve by the precision of raising mould, but the homogeneity of control reaction reagent thickness is a relatively scabrous technical matters.
As shown in Fig. 1 of U.S. Pat 7655119, on electrode, add an insulcrete 16 with rectangle diffusion of reagents control zone 18, it is the active region of electrode that described rectangle diffusion of reagents control zone exposes the electrode part that need to add reaction reagent, reaction reagent drip in this control zone 18 and and electrode contact, and the part of other non-participation reactions of electrode is owing to there being the covering of cover plate 16, and do not have above reagent is added on, reaction reagent is just limited at the needed position of working electrode like this.When we find to add reaction reagent by this way, often there will be added reaction reagent can not cover the phenomenon of whole rectangular region completely, for example reagent can not arrive four drift angle ends in rectangle diffusion control district.This also just means the product of same batch of production, and the area that its reaction reagent covers is unequal.In the case of drip reaction reagent volume equal, will there is deviation in the thickness of the reaction reagent of the product of same batch of production, therefore, participate in reaction reaction reagent amount also can be unequal.So utilizing these products to detect obtained testing result will be inaccurate.While adopting these class methods to add reaction reagent on electrode, occur sometimes even more serious bad phenomenon, reaction reagent not only can not cover completely whole rectangular region, even has part reagent to overflow the dual-side of rectangle diffusion of reagents control zone.
When sample is tested with biology sensor, conventionally only need very little sample size, for example, only need the amount of liquid of 0.5 microlitre to 1 microlitre.Biology sensor is also made into very little structure, covers reaction reagent on electrode just less.Improving in the research of test accuracy, people do not notice that reaction reagent spread condition on the electrode of small size so presents diversity, and the impact of these diversity on test result.People often make a search to improve the detection accuracy of biology sensor from the structure of electrode, material selection, test methodology and the tester of electrode.And we notice when adopting rectangle diffusion of reagents control zone to control the distribution of reaction reagent on electrode, the area of rectangle control zone is very tiny, reagent can be because surface tension effects forms a semisphere droplet-like in the groove of rectangle control zone, cause the reagent on electrode in uneven thickness, forming thick middle around has inhomogeneous or reaction reagent to concentrate on the phenomenon in the centre in electrode activity region in the edge of thin result, particularly coating area.And the existence of semisphere droplet-like edge surface tension force has stoped further diffusion towards periphery of reagent, thereby occur between reagent edge and four drift angles reserving reagent blank district phenomenon, four drift angle places can not be filled up by reaction reagent.It is full that the biology sensor of producing by this way there will be the electrode activity region on the sensor having evenly to be covered by reaction reagent, and the drift angle in some electrode activities region does not have the became uneven one of reaction reagent or covering.Some position of electrode does not have reaction reagent can cause sample segment not participate in reaction, and the variation that the reaction reagent became uneven covering on electrode makes reaction rate occur does not for a moment meet predefined mode, and these all can cause the inaccurate of testing result.
And for example in Chinese 200480023924.8 patents, do not adopt insulcrete to hide the method for adding reagent, but directly reaction reagent is coated on electrode by die slot dispense tip, create continuous reagent strip.Because the reagent area of coating is very large, even comprised the part that does not need to add reaction reagent.This can cause the waste of reagent, increases cost of products.On the other hand, due to the surface tension effects of insulativity base plate, make reagent diffusion thereon can be subject to certain resistance, this resistance has hindered the even diffusion of reaction reagent on electrode system, makes reaction reagent not arrive predefined position.
Because the biology sensor size of the concentration of glucose in blood for detection of the mankind is very little, testing mechanism is very complicated, and the blood sample amount adopting is conventionally between 0.3-1.0 microlitre, therefore current technical merit can only obtain relatively accurate testing result.The legal requirements of U.S. food and drug surveilance office (FDA) biology sensor to the concentration of glucose in blood for detection of the mankind is: as long as more than 95% testing result and the positive and negative deviation of standard glucose concentration be in 20%, it is qualified that product is considered to.As can be seen here, the technical difficulty that lifting detects concentration of glucose accuracy in human blood with biology sensor is very high.
Statisticss demonstrations in 2011 of IDF (IDF), global diabetic has increased to 3.66 hundred million people at present, estimates will reach nearly 600,000,000 people in 20 years.In China, the morbidity rate of diabetes was turned over nearly twice at nearly 10 years.In 2010, Chinese Adult diabetes prevalence was 9.7%, and diabetic has reached people more than 100,000,000 4 thousand.Because radix is huge, even if test accuracy rate only improves 1%, so, in the whole world, will reduce by the mistaken diagnosis of 3,600,000 person-times, the whole world will have 3,600,000 people therefrom to benefit, and this will bring sizable economic benefit and social benefit.
Medical expert reminds, diabetes are the important component part of Non Communicable Diseases (NCD), if rationally do not monitored and being treated, diabetic's long-term hyperglycemia state can cause the infringement of whole body multisystem, cause various acute and chronic complication, such as angiocardiopathy, diabetic nephropathy, the change of diabetes nerve venereal disease, DRP etc.Therefore, the accuracy of test is extremely important, and it can effectively guarantee that patient and doctor find change of illness state early, revises in time dosage and eating habit, prevents that patient from, for a long time in hyperglycemia state, avoiding the generation of fearful complication.Whether reaction reagent correctly distributes and is one but by people, to be ignored be to guarantee whole test result one of key factor accurately on electrode.
Utility model content
In order to overcome above-mentioned shortcoming, one of the purpose of this utility model is to provide a kind of accurately location and few biology sensor of consumption of reaction reagent that have, this biology sensor, comprise insulativity base plate and be positioned at the electrode system on insulativity base plate, on electrode system, include reaction reagent and the insulation course that can react with detection sample, this insulation course cover part electrode system, but form a closed region that there is no insulation course in the position at reaction reagent place, on the electrode part that reaction reagent is positioned at this closed region divides, the described closed region being surrounded by insulation course has a closed boundary of not having a wedge angle, reaction reagent covers this closed region, and do not exceed this closed boundary.
As further improvement of the utility model, described closed boundary be shaped as relative oval or four rectangles that drift angle is circular arc of circle, ellipse, two.
As further improvement of the utility model, reaction reagent is filled full described closed region just, and the area of reaction reagent overlay area equates with the area of closed region.
As further improvement of the utility model, the thickness of described insulation course is 1-50 micron.
As further improvement of the utility model, the thickness of described insulation course is 3-30 micron.
As further improvement of the utility model, the material of described insulation course is hydrophobic material.
As further improvement of the utility model, two sides of the electrode part covering at the detected reagent of electrode system also respectively comprise an auxiliary diffusion electrode, and the electrode part that described auxiliary diffusion electrode and detected reagent cover is arranged side by side.
Two of the purpose of this utility model is to provide a kind of method of manufacturing biology sensor, comprising:
1) on insulativity base plate, form electrode system;
2) on electrode system, form an insulation course, this insulation course cover part electrode system, and form a closed region that there is no insulation course, this closed region has a closed boundary of not having a wedge angle;
3) to described closed region, add reaction reagent, make reaction reagent cover this closed region, but do not exceed the closed boundary of this closed region;
4) dry described reaction reagent.
As further improvement of the utility model, the closed boundary of described closed region be circular, oval or four drift angles to be circular arc square.
As further improvement of the utility model, the thickness of described insulation course is 3-30 micron.
Three of the purpose of this utility model is to provide a kind of biology sensor, comprise insulativity base plate and be positioned at the electrode system on insulativity base plate, on electrode system, include the reaction reagent that can react with detection sample, it is characterized in that, described electrode system comprise for detection of functional electrode and for controlling the auxiliary diffusion electrode of reaction reagent diffusion, functional electrode is between auxiliary diffusion electrode.
As further improvement of the utility model, comprise at least two auxiliary diffusion electrodes.
As further improvement of the utility model, described at least two auxiliary diffusion electrodes lay respectively at the outside of functional electrode.
As further improvement of the utility model, the distance between auxiliary diffusion electrode and functional electrode, just in time makes the front end that is added on the reaction reagent on functional electrode can touch this auxiliary diffusion electrode.
As further improvement of the utility model, functional electrode comprises working electrode, to electrode and reference electrode, and these functional electrodes and auxiliary electrode are arranged side by side, and are roughly parallel to each other.
As further improvement of the utility model, described auxiliary electrode is two, lays respectively at the outside of functional electrode.
As further improvement of the utility model, comprise the insulation course of cover part electrode system, this insulation course forms a closed region that there is no insulation course in the position at reaction reagent place, on the electrode part that reaction reagent is positioned at this closed region divides, the described closed region being surrounded by insulation course has a closed boundary of not having a wedge angle, reaction reagent covers this closed region, and does not exceed this closed boundary.
As further improvement of the utility model, described closed boundary be shaped as relative oval or four rectangles that drift angle is circular arc of circle, ellipse, two.
As further improvement of the utility model, the thickness of described insulation course is 3-30 micron.
The beneficial effects of the utility model are: by a large amount of experiments, show, biology sensor described in the utility model is not had an application of sample pattern of diffusion of reagents control zone of wedge angle owing to adopting, effectively overcome the edge effect of reaction reagent, make reaction reagent can be distributed to equably the respective regions of electrode, thereby can control exactly the homogeneity of the reaction reagent thickness of the biology sensor of same batch production, and then improve the accuracy of testing result.In the production run of biology sensor, the reaction reagent adding is filled the full reaction reagent identical with its shape and is added district, has avoided reaction reagent to add the phenomenon that four, district drift angle is not filled up by reaction reagent.Manufacture method described in the utility model is simple on the other hand, without the consumption of controlling reaction reagent through complicated step.The electrode system of biology sensor of the present utility model has at least two auxiliary diffusion electrodes on the one hand again, this auxiliary diffusion electrode can overcome the surface tension effects of insulativity base plate, make the reagent can smooth and easy even diffusion on electrode system, and arrive predefined position.And reaction reagent can not overflow predefined region yet.
Accompanying drawing explanation
Fig. 1 is the utility model the first biology sensor;
Fig. 2 A-2E is the production stage of the biology sensor shown in Fig. 1;
Fig. 3 is the exploded view of the biology sensor shown in Fig. 1;
Fig. 4 is the electrode microphoto after the biology sensor dropwise reaction reagent shown in Fig. 1;
Fig. 5 is the utility model the second reaction reagent diffusion-controlled layer structural drawing;
Fig. 6 is the electrode microphoto utilizing after the structure dropwise reaction reagent of Fig. 5;
Fig. 7 is the biology sensor exploded view with auxiliary diffusion electrode;
Fig. 8 is the electrode microphoto utilizing after the structure dropwise reaction reagent of Fig. 7;
Fig. 9 is the third reaction reagent diffusion-controlled layer structural drawing;
Figure 10 is the electrode microphoto utilizing after the structure dropwise reaction reagent of Fig. 9;
Figure 11 is the 4th kind of reaction reagent diffusion-controlled layer structural drawing;
Figure 12 is the electrode microphoto utilizing after the structure dropwise reaction reagent of Figure 11;
Figure 13 is the exploded view of the biology sensor of prior art;
Figure 14 is the electrode microphoto utilizing after the structure dropwise reaction reagent of Figure 13;
Figure 15 is the linear graph that utilizes biosensor assay glucose standard solution of the present utility model;
Figure 16 is the linear graph of the biosensor assay glucose standard solution of prior art.
Figure 17 is that biology sensor is combined use constitutional diagram with blood examination instrument.
Figure 18 is the schematic diagram that detects diffusion of reagents situation in prior art.
Figure 19 is the schematic diagram that detects diffusion of reagents situation in the utility model.
Embodiment
Below in conjunction with concrete accompanying drawing, the utility model is described in detail.These specific embodiments are only limited the enumerating under the utility model spirit, do not get rid of one of ordinary skill in the art prior art and the utility model in conjunction with and other specific embodiments of producing.
Alternatively say, biology sensor of the present utility model comprises insulativity base plate 1 and is positioned at the electrode system on insulativity base plate, on electrode system, include reaction reagent and the insulation course 5 that can react with detection sample, these insulation course 5 cover part electrode systems, but in the position at reaction reagent place, forming one does not have the 6(Ci closed region, closed region of insulation course to be equal to reaction reagent diffusion control district 6), on the electrode part that reaction reagent is positioned at this closed region 6 divides, the described closed region being surrounded by insulation course has a closed boundary of not having a wedge angle, reaction reagent covers this closed region, and do not exceed this closed boundary.The shape of closed boundary can be circular, oval, two relative oval or rectangles that four drift angles are circular arc etc.At one, preferably in scheme, reaction reagent is filled full described closed region just, and the area of reaction reagent overlay area equates with the area of closed region.The thickness of insulation course is 1-50 micron.The thickness of insulation course is that 3-30 micron can be better.The material of insulation course is hydrophobic material.As further improvement of the utility model, two sides of the electrode part covering at the detected reagent of electrode system also respectively comprise an auxiliary diffusion electrode, and the electrode part that described auxiliary diffusion electrode and detected reagent cover is arranged side by side.
Above scheme is commonly called parallel capillary application of sample technology.In another embodiment, also can take the scheme of vertical application of sample, that is, the upper cover with well sticks on key-course 5, and the well of upper cover is just in time positioned on diffusion of reagents control zone and is identical or smaller with the aperture area of this control zone.Also when sample drop is added in well, samples vertical flows and contacts and react with the reagent in control zone.
Reaction reagent diffusion control district 6 is the holes without wedge angle, and the reaction reagent of interpolation spreads and can arrive the All Ranges that this control zone is set in this control zone.The shape of diffusion of reagents control zone can be the hole with circular arc limit, the shapes such as for example circle, ellipse, Pear-Shaped.Can also be other shapes that do not occur wedge angle, for example four quadrilaterals that drift angle is circular arc in diffusion control district.By a large amount of tests, we are surprised to find and utilize diffusion of reagents described in the utility model control zone, can form and spread reagent layer even, consistency of thickness, and reagent layer lid has been expired the whole active region of electrode when reaction reagent is added on electrode.
Amount of reagent is according to actual needs determined the degree of depth and the size in reaction reagent diffusion control district 6.The degree of depth of diffusion of reagents control zone is 1-50 micron in one embodiment, and preferably the degree of depth is 3-30 micron, and the preferred degree of depth is 5-20 micron.
When upper cover 8 covers described space, manufacture on layer 7, the groove of manufacturing layer 7 with space has formed a path 10 that adds sample.In order to make sample flow channel arriving on electrode system smoothly, upper cover 8 is also with the vent port 11 of application of sample path 10.
Fig. 2 is the method for manufacturing the utility model biology sensor embodiment illustrated in fig. 3.But manufacture method described in the utility model is not limited to step shown in Fig. 2.
As shown in Figure 2 A, provide an insulating base 1, and add electrode system on insulativity base plate, the electrode system described in the present embodiment comprises working electrode 2, to electrode 3 and reference electrode 4.In another embodiment, electrode system comprises working electrode 2, to electrode 3 and reference electrode 4, also comprises auxiliary diffusion electrode 12 as shown in Figure 7.
Insulating base 1 can be selected but be not limited to following various material: the insulativity materials such as carbon, polystyrene, polycarbonate, Corvic and polyester.In an embodiment, base plate can be made with polyethylene terephthalate (PET).Described base plate thickness is 3-10 mil, and the PET band of for example 5 mils (long measure, 1 mil equals mil, 0.0254 millimeter for mil, mil) can provide suitable support, and the PET tunica albuginea of 14 mils is applicable equally.Certainly, much different thickness also can play good effect in the utility model.Insulating base is that electrode and electrode cable provide support.
Alternatively say, the method for manufacture biology sensor of the present utility model, comprises the following steps:
1) on insulativity base plate, form electrode system;
2) on electrode system, form an insulation course, this insulation course cover part electrode system, and form a closed region that there is no insulation course, this closed region has a closed boundary of not having a wedge angle;
3) to described closed region, add reaction reagent, make reaction reagent cover this closed region, but do not exceed the closed boundary of this closed region;
4) dry described reaction reagent.
Can adopt variety of way that electrode is placed on insulating base 1.These modes include but not limited to that serigraphy, ink jet printing, bonding agent are bonding, lithography and laser carved method etc.Silver or silver chloride, graphite, palladium, gold, platinum, iridium stainless steel and other suitable conductive materials can be served as the material of electrode.Electrode also can be formed by these combinations of materials, and is not single composition.For example, adopt graphite with the electrode of reaction reagent contact jaw, the rear end of this electrode and detecting instrument contact jaw adopt ag material.
As shown in Figure 2 B, when electrode system after dry forming, is placed on reaction reagent diffusion-controlled layer 5 on electrode system on insulating base 1, and the diffusion of reagents control zone 6 on this key-course is just in time positioned on the active region of electrode system.Reaction reagent 200 is added in diffusion of reagents control zone 6, and evenly diffusion on electrode activity region, and actual to cover reagent area on electrode identical with preliminary election setting area.
Reaction reagent diffusion-controlled layer 5 is placed on electrode system by bonding, heat-sealing, ultra-sonic welded or the mode such as roll.Reaction reagent diffusion-controlled layer 5 is selected from hydrophobic material, for example, be selected from the polystyrene of insulation, hydrophobic inks or the glue of insulation.Described glue can be double faced adhesive tape, one side glue or transfer adhesive etc.In one embodiment, reaction reagent diffusion-controlled layer 5 is a double faced adhesive tape material, and its one side can stick to key-course on the base plate with electrode system, and another side and upper cover 8 are bonding or bonding with space manufacture layer 7.
Whether in reaction reagent, contain one or more exists for detection of analyte in fluid sample or the chemical composition of its content.For example, the reaction reagent of electrochemica biological sensor comprises oxidoreducing enzyme and electron acceptor, and the two is used for detecting sample and producing the reaction product that a kind of electronic detection system can be surveyed.In the embodiment of detection Glucose in Blood by Cyclic, reaction reagent contains glucose oxidase, chlorination six ammino rutheniums (III), BSA, CaSO4, TritonX-100 and PVP etc.The techniques such as the spraying by serigraphy, liquid dropping, scraper for coating and nozzle slot are added on reaction reagent on electrode.
As shown in Figure 2 C, when be added on reaction reagent on electrode dry after, layer 7 is manufactured in the space with fluted 9 and is placed on the base plate with electrode system and reaction reagent.In this one end with reaction reagent layer, space is manufactured layer and is covered the electrode part not contacting with sample, and reaction reagent layer is exposed in groove 9.Space manufacture layer does not cover the electrode with the relative other end with reaction reagent layer, this part exposed electrode can be contacted with the pin on detecting instrument 300, connected mode as shown in figure 17.Space is manufactured layer and is placed on electrode system by bonding, heat-sealing, ultra-sonic welded or the mode such as roll.Its material is insulation hydrophobic material, the material of for example bonding agent.When the polystyrene of layer employing insulation is manufactured in space, can be in the equal coated with adhesive in the two sides of this layer to stick to diffusion of reagents key-course 5 and upper cover 8.In one embodiment, for sample is flowed smoothly in groove, can carry out hydrophilic treatment to groove 9, for example surperficial coating surface activating agent or the plasma treatment to groove, gives the groove surfaces contacting with sample and has water wettability.
As shown in Figure 2 D, upper cover 8 is placed on to space and manufactures on layer 7, make biology sensor.As shown in Figure 2 E, upper cover 8 cover be with reeded space manufacture layer upper after, make groove 9 become sample to enter the path 10 of biology sensor.Sample enters biology sensor from feeder connection, and utilizes the capillarity that groove forms to enter smoothly and contact with reaction reagent.Upper cover material can be the hydrophobic material of insulation or the material of other character.Upper cover 8 has vent port 11, and described vent port 11 is positioned at groove 9 tops and away from sample channel inlet end.
Fig. 7 is another kind of biology sensor 100 described in the utility model, comprises insulativity base plate 1, on insulativity base plate, includes electrode system.Described electrode system comprises working electrode 2, to functional electrodes such as electrode 3 or reference electrodes 4.On insulativity base plate, also comprise auxiliary diffusion electrode 12, this auxiliary diffusion electrode can assist to drip the reaction reagent diffusion equably rapidly on electrode on functional electrode.Both sides at the electrode system that need to add reaction reagent have auxiliary diffusion electrode.For example, functional electrode is between auxiliary diffusion electrode, and auxiliary diffusion electrode is positioned at functional electrode outside.Distance between auxiliary diffusion electrode and functional electrode is moderate, and this distance makes the front end that drips the reaction reagent on functional electrode can touch this auxiliary diffusion electrode.
In preferential scheme, auxiliary diffusion electrode is made by porous material, for example carbon electrode.The utility model people of present patent application finds through research, the porous structure of electrode material can form capillary effect, make to arrive solution diffusion rapidly on this auxiliary electrode under capillarity of this electrode, the power that this diffusion on auxiliary diffusion electrode produces is greater than the surface tension effects of liquid, impels the rapid diffusion of solution on electrode to reach predefined scope.Therefore, when oval in shape after reaction reagent diffusion, sub-elliptical shape, rectangle, when approximate rectangular or other the size aspect certain is greater than the shape of size of another aspect, in the central point of the shape apart from after reaction reagent diffusion position far away (such as the double-pointed outside of transverse, rectangle is compared with the outside of minor face) when diffusivity electrode is set, reagent can be faster than that direction that diffusivity electrode is not set in the rate of propagation of this direction, therefore, be conducive to make reagent in all directions, to arrive the profile border of shape simultaneously, thereby be conducive to improve the homogeneity of diffusion of reagents.For reaching this object, one or more can be set in the relatively slow any position of diffusion of reagents speed increases the auxiliary diffusion electrode of diffusion of reagents speed.In another preferred version, auxiliary diffusion electrode, according to the character that drips solution, does hydrophilic treatment to auxiliary diffusion electrode in advance.
In embodiment as described in Figure 7, biology sensor is also included on electrode system and is coated with reaction reagent diffusion-controlled layer 5, comprises the reaction reagent diffusion control district 6 with opening on this key-course 5.The aperture area of diffusion of reagents control zone 6 is with need to be added on reagent area on electrode identical and be just in time positioned on electrode activity region.On reaction reagent diffusion-controlled layer 5, have space with groove 9 and manufacture layer 7, upper cover 8 covers that described space is manufactured on layer 7 and has formed a path 10 that adds sample with groove 9 that layer 7 is manufactured in space.Upper cover 8 is also with vent port 11, and when sample flows in passage by capillary action, the gas that is positioned at sample front end is discharged from passage by vent port 11, has guaranteed sample flowing smoothly in passage.
Reaction reagent diffusion control district 6 is the holes without wedge angle, and the reaction reagent of interpolation spreads and can arrive the All Ranges that this control zone is set in this control zone.The shape of diffusion of reagents control zone can be the hole with circular arc limit, the shapes such as for example circle, ellipse, Pear-Shaped.Can also be other shapes that do not occur wedge angle, for example four quadrilaterals that drift angle is circular arc in diffusion control district.
Can adopt the biology sensor shown in the shop drawings of method shown in Fig. 27.In manufacture process, when this step of Fig. 2 A is added electrode system or afterwards or before, auxiliary diffusion electrode 12 is added on insulating base.Biology sensor shown in Fig. 7 also can be manufactured with additive method.
Alternatively say, biology sensor of the present utility model comprises insulativity base plate 1 and is positioned at the electrode system on insulativity base plate, on electrode system, include the reaction reagent that can react with detection sample, described electrode system comprise for detection of functional electrode (2,3,4) and for controlling the auxiliary diffusion electrode (10,12) of reaction reagent diffusion, functional electrode is between auxiliary diffusion electrode.The utility model comprises at least two auxiliary diffusion electrodes.Described at least two auxiliary diffusion electrodes lay respectively at the outside of functional electrode.Distance between auxiliary diffusion electrode and functional electrode, just in time makes the front end that is added on the reaction reagent on functional electrode can touch this auxiliary diffusion electrode.Functional electrode comprises working electrode, to electrode and reference electrode, these functional electrodes and auxiliary electrode are arranged side by side, and are roughly parallel to each other.Described auxiliary electrode is two, lays respectively at the outside of functional electrode.Comprise the insulation course of cover part electrode system, this insulation course forms a closed region that there is no insulation course in the position at reaction reagent place, on the electrode part that reaction reagent is positioned at this closed region divides, the described closed region being surrounded by insulation course has a closed boundary of not having a wedge angle, reaction reagent covers this closed region, and does not exceed this closed boundary.Described closed boundary be shaped as relative oval or four rectangles that drift angle is circular arc of circle, ellipse, two.The thickness of described insulation course is 3-30 micron.
Explain again principle of work of the present utility model below.
Please refer to Figure 18.Figure 18 is a kind of situation of reaction reagent diffusion in prior art.Wherein, label 200 is the reaction reagents after diffusion, label 6 is the closed regions (being referred to as again in this application reaction reagent diffusion control district) that surrounded by insulating material, label 7 is that layer is manufactured in space, label 9 is that layer 7 groove forming are manufactured in space, and space is manufactured layer 7 and is used to form the sidewall of this groove 9 and insulating base 1 and upper cover 8 and jointly formed sample channel 10.Through research and experiment, we find, those are positioned at reaction reagent outside path 10 (such as being manufactured by space the part reagent that layer is covered) and substantially do not participate in and detect the reaction of sample, only have those reaction reagents that are positioned at path 10 just to participate in and detect the reaction of sample, the amount of the reaction reagent in path 10 is the key factor that affects testing result.Therefore the deviation that, effectively reduces the amount of the reaction reagent in passage between the different product of same batch of production will be conducive to the accuracy of the testing result that improves these products.
In the prior art, because the closed region 6(being formed by insulation course is referred to as again reaction reagent diffusion control district in this application) be square, the shape with wedge angle such as rectangle, the different product of same batch of production is when adding reaction reagent, the shape difference opposite sex of reaction reagent after the interior diffusion in closed region 6 large (because reaction reagent is not easy to cover all wedge angle regions), the otherness of the area between different product after reaction reagent diffusion is also larger, and the reaction reagent total amount of adding equates substantially, therefore, there is larger difference in the thickness between different product after reaction reagent diffusion, thereby cause the amount of the reaction reagent in path 10 to have larger difference.That is,, between different product, the consistance of the amount of the reaction reagent in path 10 is poor.This will cause the different product with same batch of production to detect identical sample, and the testing result deviation obtaining is larger, thereby causes testing result inaccurate.
Please refer to Figure 19.In the utility model, because the closed region 6(being formed by insulation course is referred to as again reaction reagent diffusion control district in this application) be circular, oval or other shape with wedge angle not, when adding liquid reaction reagent, reaction reagent is more easily filled full whole closed region 6 than prior art, and is not easy to stay " dead angle " that some are not covered by reaction reagent.Therefore, the different product of same batch of production is when adding reaction reagent, the shape difference opposite sex of reaction reagent after the interior diffusion in closed region 6 less (substantially consistent with the shape of closed region), the otherness also less (being substantially equal to the area of closed region) of the area between different product after reaction reagent diffusion, and the reaction reagent total amount of adding equates substantially, therefore, thickness between different product after reaction reagent diffusion equates substantially, thereby the amount of the reaction reagent in path 10 equates substantially.That is,, between different product, the consistance of the amount of the reaction reagent in path 10 is better.This will make the different product with same batch of production detect identical sample, and the testing result deviation obtaining is less, thereby has improved the accuracy of testing result.
In the employing of the utility model, increase in the technical scheme of auxiliary electrode, research and experimental result show: when reaction reagent spreads, be not easy to arrive (comprise and often can not arrive within the predetermined time and can not arrive once in a while) or will improve the diffusivity of reaction reagent in these region than the technical scheme of region (this region should be covered by reaction reagent) the increase auxiliary electrode of the obvious more late arrival in other region, therefore this scheme is conducive to promote reaction reagent evenly to spread in closed region and covers whole closed region, but do not exceed the border of closed region, thereby reach the object that makes the even thickness after reaction reagent diffusion.In present patent application, (include but not limited to instructions and claim), that reaction reagent is filled, filled is full, it is full just to fill, just fill, cover, just cover (or other similar terms) closed region 6 refers to that reaction reagent has covered the entire area of closed region 6 substantially completely, but does not substantially exceed or overflow again the border of this closed region 6.According to analysis above, this technical scheme has improved the accuracy of testing result.
Biology sensor as shown in Figure 3 comprises insulativity base plate 1, working electrode 2, to electrode 3 and reference electrode 4.On electrode system, be coated with reaction reagent diffusion-controlled layer 5, on this key-course 5, comprise that has an oval-shaped reaction reagent diffusion control district 6, the reagent area of the aperture area of this diffusion of reagents control zone 6 and the required interpolation of electrode is identical and be just in time positioned on electrode activity region.Biology sensor described in the present embodiment also comprises space manufacture layer 7 and the upper cover 8 with vent port.
Method by a liquid in biology sensor manufacture process is added reaction reagent on electrode to by oval-shaped diffusion of reagents control zone.After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Fig. 4 shows, the reaction reagent being added on electrode spreads evenly, does not also have reagent to overflow the sideline 6-1 that diffusion of reagents control zone limits.And reaction reagent 200 is paved with the whole reagent area of being set by sideline 6-1, and whole control zone has all shown the color of reaction reagent.Therefore the consistance that in the biology sensor described in the present embodiment, reaction reagent distributes on electrode is good.
The circular reaction reagent diffusion-controlled layer 5 of being shaped as of reaction reagent diffusion control district 6 as shown in Figure 5.Method by a liquid in biology sensor manufacture process is added reaction reagent on electrode to by circular diffusion of reagents control zone.After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Fig. 6 show, the reaction reagent of interpolation at working electrode 2, to electrode 3 and reference electrode on evenly diffusion, do not have yet reagent overflow diffusion of reagents control zone limit sideline 6-1.And reaction reagent 200 is paved with whole reagent area, whole control zone has all shown the color of reaction reagent.Therefore the consistance that in the biology sensor described in the present embodiment, reaction reagent distributes on electrode is good.
The electrode system of biology sensor as shown in Figure 7 comprises functional electrode 2,3,4 and auxiliary electrode 12.This biology sensor also comprises the reaction reagent diffusion-controlled layer 5 with oval 6.Method by a liquid in biology sensor manufacture process is added reaction reagent on electrode to by oval-shaped diffusion of reagents control zone.After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Fig. 8 shows, the reaction reagent of interpolation is evenly diffusion on electrode, does not also have reagent to overflow the sideline 6-1 that diffusion of reagents control zone limits.And reaction reagent 200 is paved with whole reagent area, whole control zone has all shown the color of reaction reagent.Therefore the consistance that in the biology sensor described in the present embodiment, reaction reagent distributes on electrode is good.
The reaction reagent diffusion-controlled layer 5 with Double Circle 6 as shown in Figure 9.Double Circle diffusion of reagents key-course head to head can be used for manufacturing two biology sensors simultaneously.Manufacturing in the process of biology sensor, on insulating base, electrode system is overlapped in placement two head to head, comprises working electrode 2, to electrode 3 and reference electrode 4, and comprises auxiliary diffusion electrode 12.As Fig. 9 comprises three auxiliary diffusion electrodes 12, wherein two outermost end at the functional electrode of two covers (working electrode 2, to electrode 3 and reference electrode 4), another in the middle of the functional electrode of two covers as the auxiliary diffusion electrode sharing.After reaction reagent diffusion layer shown in Fig. 9 is placed on this electrode system, toward dropwise reaction reagent on electrode system.
Method by a liquid in biology sensor manufacture process is added reaction reagent on electrode to by oval-shaped diffusion of reagents control zone.After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Figure 10 shows, the reaction reagent diffusion of interpolation evenly, does not have reagent to overflow the sideline 6-1 that diffusion of reagents control zone limits yet.And reaction reagent 200 is paved with whole reagent area, whole control zone has all shown the color of reaction reagent.Therefore the consistance that in the biology sensor described in the present embodiment, reaction reagent distributes on electrode is good.
It is that the double square diffusion of reagents control zone of arc is in conjunction with the design of auxiliary diffusion electrode that embodiment 5 adopts drift angle
That drift angle is the reaction reagent diffusion-controlled layer 5 of the double square diffusion of reagents control zone 6 of arc as shown in figure 11.This double square diffusion of reagents key-course can be used for manufacturing two biology sensors simultaneously.Manufacturing in the process of biology sensor, on insulating base placement two head to head overlap electrode system comprise working electrode 2, to electrode 3 and reference electrode 4.Also comprise auxiliary diffusion electrode 12.As Figure 11 comprises three auxiliary diffusion electrodes 12, wherein two outermost end at the functional electrode of two covers, another centre at the functional electrode of two covers is the auxiliary diffusion electrode sharing.After reaction reagent diffusion layer shown in Figure 11 is placed on this electrode system, toward dropwise reaction reagent on electrode system.
Add on electrode the diffusion of reagents control zone of the rectangle by having circular arc drift angle by reaction reagent of the method by a liquid in biology sensor manufacture process.After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Figure 12 shows, the reaction reagent diffusion of interpolation evenly, does not have reagent to overflow yet.And reaction reagent is paved with whole reagent area, whole control zone has all shown the color of reaction reagent.Therefore the consistance that in the biology sensor described in the present embodiment, reaction reagent distributes on electrode is good.
To manufacture biology sensor according to the method for prior art as shown in figure 13.On insulativity base plate 1, add electrode system, will cover on electrode with the diffusion-controlled layer 5 of rectangle diffusion of reagents control zone 6, and rectangle diffusion of reagents control zone is just in time positioned at the active region of electrode, electrode need to add the region of reaction reagent.Method by a liquid is added reaction reagent on electrode to by this slotted eye of diffusion of reagents control zone, then covers space and manufactures layer 7 and upper cover 8.
After reaction reagent adds on electrode system, with digital Stereo microscope (microscope model MOTICAM 2306, Mike's Christian Dior Industry Group Co.,Ltd of manufacturer) distribution situation to reagent on electrode takes pictures, the distribution situation figure with observing response reagent on electrode.As Figure 14 shows, the reaction reagent of interpolation can not cover whole rectangle region, at 50 places, four tops in rectangle diffusion control district, does not all have reagent to arrive, and has the reagent of interpolation to overflow in rectangle region both sides, and this has just caused the reagent on electrode in uneven thickness.
The analysis of the accuracy that embodiment 7 biology sensors are measured glucose content in standard items
Configuration dextrose standard sample solution, and with the glucose content in this standard solution of biosensor assay in embodiment 3 and embodiment 6.
Table 1 and Figure 15 are the glucose contents utilizing in the biosensor assay standard items of embodiment 3 described in the utility model.Its electrode system of biology sensor in embodiment 3 comprises auxiliary diffusion electrode, and comprises the reaction reagent diffusion-controlled layer with oval diffusion control district.Measurement result shows, the coefficient R of its mensuration
2value has reached 0.9993.Table 2 and Figure 16 are the glucose contents utilizing in the biosensor assay standard items of embodiment 6 in prior art.Biology sensor in embodiment 6 does not comprise auxiliary diffusion electrode, and reaction reagent diffusion control district is a rectangle that drift angle is right angle.Measurement result shows, the coefficient R of its mensuration
2value is only 0.9941.
Table 1 utilizes the measurement result of glucose content in the biosensor assay standard items in embodiment 3
| Glucose configuration concentration (mg/dL) | 55.7 | 84.0 | 117.9 | 177.9 | 223.5 | 298.0 | 448.7 | 575.0 |
| Measurement result (mg/dL) | ||||||||
| |
57 | 82 | 116 | 177 | 223 | 298 | 449 | 565 |
| |
55 | 84 | 118 | 178 | 226 | 294 | 454 | 582 |
| |
55 | 81 | 120 | 177 | 223 | 293 | 441 | 582 |
| |
56 | 80 | 122 | 180 | 218 | 293 | 448 | 566 |
| |
56 | 82 | 119 | 175 | 222 | 295 | 439 | 577 |
| |
56 | 83 | 119 | 183 | 229 | 295 | 449 | 563 |
| |
57 | 82 | 122 | 179 | 224 | 303 | 458 | 566 |
| |
56 | 82 | 119 | 178 | 224 | 294 | 459 | 565 |
| |
57 | 84 | 121 | 175 | 223 | 309 | 455 | 581 |
| |
57 | 84 | 120 | 174 | 226 | 296 | 449 | 585 |
| Mean value | 56.2 | 82.4 | 119.6 | 177.6 | 223.8 | 297.0 | 450.1 | 573.2 |
| SD | 0.8 | 1.3 | 1.8 | 2.7 | 2.9 | 5.2 | 6.6 | 8.9 |
| CV | 1.4% | 1.6% | 1.5% | 1.5% | 1.3% | 1.7% | 1.5% | 1.6% |
Table 2 utilizes the measurement result of glucose content in the biosensor assay standard items in embodiment 7
| Glucose configuration concentration (mg/dL) | 51.5 | 86.0 | 105.4 | 170.6 | 215.2 | 283.2 | 444.4 | 560.9 |
| Measure concentration (mg/dL) | ||||||||
| |
57 | 74 | 122 | 173 | 195 | 276 | 470 | 543 |
| |
57 | 73 | 112 | 188 | 204 | 272 | 472 | 540 |
| |
58 | 74 | 109 | 183 | 197 | 279 | 462 | 560 |
| |
57 | 77 | 121 | 183 | 196 | 302 | 435 | 537 |
| |
55 | 73 | 115 | 170 | 214 | 280 | 485 | 531 |
| |
54 | 75 | 122 | 180 | 215 | 279 | 440 | 577 |
| |
54 | 75 | 117 | 172 | 203 | 305 | 433 | 551 |
| |
54 | 76 | 111 | 184 | 203 | 294 | 436 | 576 |
| |
56 | 77 | 119 | 169 | 214 | 274 | 439 | 569 |
| |
55 | 77 | 110 | 173 | 196 | 274 | 449 | 571 |
| Mean value | 55.7 | 75.1 | 115.8 | 177.5 | 203.7 | 283.5 | 452.1 | 555.5 |
| SD | 1.5 | 1.6 | 5.1 | 6.8 | 8.0 | 12.2 | 18.7 | 17.3 |
| CV | 2.7% | 2.1% | 4.4% | 3.8% | 3.9% | 4.3% | 4.1% | 3.1% |
From experimental result, can find out, in embodiment 3, adopted auxiliary diffusion electrode, and comprise the biology sensor of the reaction reagent diffusion-controlled layer with oval diffusion control district, the coefficient of variation (CV) and the standard variance (SD) of the result that the coefficient of variation (CV) of its test result and standard variance (SD) are all measured than biology sensor of the prior art (do not adopt auxiliary diffusion electrode, and diffusion of reagents control zone being rectangle design) are worth low.Therefore utilize glucose content in biosensor assay sample of the present utility model, the favorable reproducibility of its content measuring (, with multiple biology sensors of same batch of production, detect the sample of same batch, otherness between the testing result obtaining is less than prior art), test result is more accurate.
Claims (9)
1. biology sensor, comprise insulativity base plate and be positioned at the electrode system on insulativity base plate, on electrode system, include the reaction reagent that can react with detection sample, it is characterized in that, described electrode system comprise for detection of functional electrode and for controlling the auxiliary diffusion electrode of reaction reagent diffusion, functional electrode is between auxiliary diffusion electrode.
2. biology sensor according to claim 1, is characterized in that, comprises at least two auxiliary diffusion electrodes.
3. biology sensor according to claim 2, is characterized in that, described at least two auxiliary diffusion electrodes lay respectively at the outside of functional electrode.
4. according to the biology sensor described in any one of claims 1 to 3, it is characterized in that, the distance between auxiliary diffusion electrode and functional electrode, just in time makes the front end that is added on the reaction reagent on functional electrode can touch this auxiliary diffusion electrode.
5. biology sensor according to claim 1, is characterized in that, functional electrode comprises working electrode, to electrode and reference electrode, and these functional electrodes and auxiliary electrode are arranged side by side, and are roughly parallel to each other.
6. biology sensor according to claim 5, is characterized in that, described auxiliary electrode is two, lays respectively at the outside of functional electrode.
7. biology sensor according to claim 1, it is characterized in that, comprise the insulation course of cover part electrode system, this insulation course forms a closed region that there is no insulation course in the position at reaction reagent place, on the electrode part that reaction reagent is positioned at this closed region divides, described closed region has a closed boundary of not having a wedge angle, and reaction reagent covers this closed region, and does not exceed this closed boundary.
8. biology sensor according to claim 7, is characterized in that, described closed boundary be shaped as relative oval or four rectangles that drift angle is circular arc of circle, ellipse, two.
9. biology sensor according to claim 8, is characterized in that, the thickness of described insulation course is 3-30 micron.
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| CN201320150703.3U CN203551502U (en) | 2013-03-28 | 2013-03-28 | Biosensor |
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