CN1460852A

CN1460852A - Multifunctional blood detection chip

Info

Publication number: CN1460852A
Application number: CN 03137571
Authority: CN
Inventors: 郝鹏飞; 姚朝晖; 陈强; 史海滨
Original assignee: Tsinghua University; Nankai University
Current assignee: Tsinghua University; Nankai University
Priority date: 2003-06-18
Filing date: 2003-06-18
Publication date: 2003-12-10
Anticipated expiration: 2023-06-18
Also published as: CN1194223C

Abstract

The multifunctional blood detection chip capable of simultaneously detecting the concentrations of four different component of glucose and cholesterol, etc. includes upper layer base plate, lower layer base plate, sampling hole, exhausting hole and intermediate sandwich with cruciform groove between upper layer base plate and lower layer base plate, on the described lower base plate four pairs of enzyme electrodes which are cross-arranged are set, every pair of enzyme electrodes is respectively connected with every pair of wires, the tail end of the wire is equipped with wiring terminal.

Description

A kind of multi-functional blood testing chip

Technical field

The present invention relates to a kind of biology sensor, relate in particular to a kind of structural design of multi-functional blood testing chip, belong to the biosensor technology field.

Background technology

At present, the whole world has 100,012,000 diabetics, and developed countries onset diabetes rate has reached 2%-10%, domesticly should the disease population size have also surpassed 4,000 ten thousand people, accounts for about 4% of total population. and diabetes have become human the 3rd dead killer.At present onset diabetes rate every year is with 10% speed increase, but recall rate has only 20%, that is to say, has 80% patient to get diabetes but do not know, and these people overwhelming majority are early stage patients, because of not knowing that the state of an illness very easily increases the weight of.In addition, along with variations such as diet, habits and customs, working pressures, the people who suffers from high fat of blood is more and more.China is populous, and hyperlipemia has reached 2.16 hundred million more than at present, and the trend of rejuvenation is gradually arranged.Among this crowd, the people who suffers from angiocardiopathies such as high fat of blood, heart disease is quite a lot of, accounts for more than 70% of this age level more than 40 years old.One of effective means that solves hyperglycaemia and high fat of blood is the frequent test to compositions such as blood sugar in the patient blood and blood fat, and auxiliary with drug therapy and diet control.Ketoboidies is the fatty product that decomposes in a large number and fail abundant oxidation, comprises acetoacetate, acetone and beta-hydroxybutyric acid.If human body produces a large amount of ketoboidies at short notice and piles up in vivo, will cause metabolic acidosis, severe patient is with threat to life, and therefore the periodic monitoring ketoboidies is extremely important in case of necessity.The acidaemia that lactate can rapider reflection than acidity or oxygen chlorine saturation degree produces because of tissue oxygenation is on the low side, lactic acid content is to judge the various after one's own heart important indicators of the criticality of the state of an illness such as burst infraction, ventricular fibrillation, septic shock of situation of being critically ill.

In the prior art in the detection by quantitative blood method of composition such as blood sugar mainly contain colourimetry and electrochemical process.Utilize the colourimetry precision of optical reflection principle lower, light path system and apparatus structure more complicated.And the biochemical sensor that utilizes enzyme electrode to make is easy to use, and the measurement sensitivity height can obtain test result fast.The biology sensor of existing measuring blood and cholesterol comes out both at home and abroad at present.China invention invention (invention number: 99108434.9) disclose a kind of biology sensor, this sensor is made up of two pole plates up and down, on one of them pole plate pair of electrodes is arranged, scribble enzyme reagent and the reagent layer that contains electron transmitter on the electrode, but this sensor all can only detect a physiochemical indice, and two leads that link to each other with electrode lay respectively on the different pole plates, and structure is relatively complicated, what electrode processing method adopted is sputtering method, and cost is higher.

In actual applications, often need to measure simultaneously (index) concentration of multiple composition in the blood, have only the large-scale Medical Instruments of the complex and expensive utilized just can accomplish this point at present, testing cost is very high.

Summary of the invention

The purpose of this invention is to provide a kind of multi-functional blood testing chip that can measure many index in the blood simultaneously simple in structure, with low cost, different enzyme reagent is solidificated on the different electrodes of same substrate, utilize this multi-functional blood testing chip can measure blood sugar in the blood simultaneously, cholesterol, lactic acid, ketoboidies or the content of other four kinds of materials in blood.

The objective of the invention is to be achieved through the following technical solutions: a kind of multi-functional blood testing chip, comprise upper strata substrate, lower floor's substrate and annotate sample hole and vent port, it is characterized in that: an intermediate course that has the cruciform groove is set between upper strata substrate and lower floor's substrate, on described lower floor substrate, be provided with four pairs of enzyme electrodes that are cross layout, each joins with couple of conductor respectively to enzyme electrode, and wire end is a connection terminal; Described four pairs of enzyme electrodes are positioned at two substrates up and down and have the space that the intermediate course of cross groove constitutes.

Feature of the present invention also is: described vent port is arranged on the substrate of upper strata, is four vent ports and cross symmetric offset spread, communicates with the cruciform groove of intermediate course; Described notes sample hole is arranged on the substrate of upper strata, and corresponding with the center of cross groove.

Multi-functional blood testing chip provided by the present invention, be that four kinds of different enzyme reagent are solidificated on the different enzyme electrodes of same substrate, therefore can once realize measuring four physiochemical indices such as blood sugar, cholesterol, lactic acid, ketoboidies or other four kinds of physiochemical indices.Simple in structure, cost is low.The cross space that the present invention is positioned at four pairs of enzyme electrodes to have up and down two substrates and intermediate course constitute, blood sample is diffused on four pairs of enzyme electrodes by on-chip notes sample hole, upper strata.Adopt this design can dwindle the volume of chip, reduce blood using amount, only need splash into once bleeding and to be full of whole measured zone; Because four pairs of enzyme electrodes lay respectively on four limits of cruciform groove, do not contact mutually each other, have suppressed influence each other to greatest extent.

Description of drawings

Fig. 1 is one-piece construction synoptic diagram of the present invention (a main cut-open view).

Fig. 2 is the structural representation of upper strata substrate.

Fig. 3 is the structural representation of the intermediate course of band cruciform groove.

Fig. 4 is the structural representation of lower floor's substrate.

Wherein:

1-annotates 2-upper strata, sample hole substrate 3-vent port 4-cross groove 5-intermediate course

6-working electrode 7-is to the substrate 9-of electrode 8-lower floor connection terminal 10 leads

Embodiment

Further specify concrete structure of the present invention and enforcement below in conjunction with accompanying drawing.

Fig. 1 is the structural representation of multi-functional blood testing chip provided by the invention, and this chip comprises upper strata substrate 2, lower floor's substrate 8 and an intermediate course 5 that has cruciform groove 4.Four pairs of enzyme electrodes are arranged on lower floor's substrate 8, and each is made up of electrode 7 working electrode 6 and one enzyme electrode.3, four vent ports of four vent ports are set on the substrate of upper strata are cross symmetric offset spread, corresponding with the position of the cruciform groove of intermediate course respectively.Annotate sample hole 1 and be arranged on the upper strata substrate 2, and corresponding with the center of cross groove.The enzyme and the biological reagent of different types of participation generation redox reaction on every pair of enzyme electrode, have been solidified respectively, because intermediate course 5 is very thin, so in the middle of upper and lower layer substrate, form a criss-cross lamella space, four pairs of enzyme electrodes on lower floor's substrate 8 all are positioned at the cross space that is made of up and down two substrates and intermediate course, and lay respectively on four limits of cruciform groove.Blood sample is diffused on four pairs of enzyme electrodes by on-chip notes sample hole, upper strata 1.Because capillary action blood can be from annotating 1 diffusion of sample hole and being full of whole cross groove, unnecessary air can be discharged from four vent ports 3 of upper strata substrate.Adopt this design can dwindle the volume of chip, reduce blood using amount, only need splash into once bleeding and to be full of whole measured zone; Because four pairs of enzyme electrodes lay respectively on four limits of cruciform groove, do not contact mutually each other, have suppressed influence each other to greatest extent.

The last subtegulum of multi-functional blood testing chip and interlayer can be made by high molecular polymerization materials such as polycarbonate, poly-ethyl esters, and these materials are non-conductive, and are pliable and tough, and certain rigidity and intensity are arranged.Utilize silver-colored paste on lower floor's substrate 8, to form and working electrode 6 and lead 10 that electrode 7 is linked to each other and connection terminal 9, with the working electrode 6 of carbon paste formation rectangular shape with to electrode 7 by the method for serigraphy.Enzyme reagent and electron transfer mediator are solidificated in electrode surface formation biological elements, when applying certain voltage when the working electrode of on-chip four pairs of enzyme electrodes with between to electrode to lower floor, different electrochemical reactions can take place with four pairs of enzyme electrodes respectively in the blood in the cruciform groove, produce electric current at the working electrode of every pair of enzyme electrode with between, and link to each other with the external testing instrument with connection terminal 9 by lead 10 to electrode; These biological elements respectively with blood in material generation redox reactions such as blood sugar, cholesterol, lactic acid, ketoboidies, produce oxidation current, can measure the concentration of materials such as blood sugar in the blood, cholesterol, lactic acid and ketoboidies by the size of measuring electric current.

Embodiment:

With thickness is the polycarbonate plate cut growth 32mm of 0.2mm millimeter, the small pieces of wide 16mm, be used for forming the upper strata substrate 2 and the intermediate course 5 of multi-functional blood testing chip, wherein on upper strata substrate 2, have notes sample hole 1 and four vent ports 3 that diameter is 1mm of a diameter 2mm, these four vent ports are cross arrangement, the position is corresponding with the position of the cruciform groove of intermediate course 5, annotates the center that sample hole 1 is positioned at cross.

Then at the polycarbonate plate cut growth 32mm that with thickness is the 0.5mm millimeter, the small pieces of wide 16mm form lower floor's substrate 8 of multi-functional blood testing chip.Utilize silver-colored paste on lower floor's substrate 8, to form and working electrode 6 and lead 10 that electrode 8 is linked to each other and connection terminal 9 by the method for serigraphy, with the working electrode 6 of carbon paste formation rectangular shape with to electrode 8, the length of electrode and wide 1.8mm and the 1.5mm of being respectively.Wherein the enzyme reagent that solidifies on the working electrode of first pair of enzyme electrode is glucose oxidase, be used for measuring the concentration of glucose in the blood, the enzyme reagent that solidifies on the working electrode of second pair of enzyme electrode is Lactate Oxidase, be used for measuring concentration of lactic acid in the blood, the enzyme reagent that solidifies on the working electrode of the 3rd pair of enzyme electrode is cholesterol oxidase and cholesterol ester hydrolase, be used for measuring the concentration of cholesterol in the blood, the enzyme reagent that solidifies on the working electrode of the 4th pair of enzyme electrode is b-hydroxybutyric dehydrogenase (HBD) and reducibility coenzyme, is used for measuring the concentration of ketoboidies in the blood.Electron transport enzyme medium adopts potassium ferricyanide solution, above enzyme reagent and solution is added cementing agent such as gelatin and is sprayed on the working electrode on the bottom substrate at room temperature dry then 4-8 hour.At last upper strata substrate, the intermediate course and the lower floor substrate that have a cross groove are in the same place with adhesive bond, finish the making of whole multi-functional blood testing chip.

Claims

1. multi-functional blood testing chip, comprise upper strata substrate (2), lower floor's substrate (8) and annotate sample hole (1) and vent port (3), it is characterized in that: an intermediate course (5) that has cruciform groove (4) is set between upper strata substrate and lower floor's substrate, on described lower floor substrate, be provided with four pairs of enzyme electrodes that are cross layout, each joins with couple of conductor (10) respectively to enzyme electrode, and wire end is connection terminal (9); Described four pairs of enzyme electrodes are positioned at two substrates up and down and have the space that the intermediate course of cross groove constitutes.

2. according to the described multi-functional blood testing chip of claim 1, it is characterized in that: described vent port (3) is arranged on the substrate of upper strata, is four vent ports and cross symmetric offset spread, and is corresponding with the position of the cruciform groove of intermediate course.

3. according to claim 1 or 2 described multi-functional blood testing chips, it is characterized in that: described notes sample hole (1) is arranged on the substrate of upper strata, and corresponding with the center of cross groove.