A kind of electrochemical method and its device detecting in-vivo tissue liquid concentration of glucose informationTechnical field
The present invention relates to a kind of electrochemical methods and its device for detecting in-vivo tissue liquid concentration of glucose information, belong to doctorTreat detection technique field.
Background technique
The abnormal carbohydrate metabolisms person such as diabetes or hyperglycemia needs frequently detection concentration of glucose level to cooperate medication at presentAnd diet, this is the key link for the treatment of diabetes, and it is diabetes that whether internal glucose level, which obtains being monitored and controlled in time,The deciding factor for the treatment of.
The glucose to be detected is present in internal liquid environment in the form of glucose solution, hereinafter referred to as body fluid.Concentration of glucose is detected to need first then to establish glucose signals intensity with algorithm with the glucose signals in instrument detection body fluidWith the relationship of concentration of glucose.
Common detection method is external detection, i.e., first turns the body fluid such as blood or tissue fluid using the method for extracting or permeatingIt moves on in vitro, then it is detected again.
In view of the frequent feeling of pain of external detecting glucose signal and not convenient operation, and it can not achieve continuous survey, there is the method for internal detection glucose signals in amount.
The body fluid for being used to detect concentration of glucose at present has vessel inner blood, subcutaneous tissue liquid, aqueous humor (tissue fluid in eyesOne kind).There are body fluid circulatory between blood-tissue liquid, concentration of glucose substantially reaches unanimity, however after intake sugar notConcentration of glucose variation with body fluid has differences, relative to the concentration of glucose in blood, in some cases in tissue fluidConcentration of glucose contacted with treating diabetes it is even closer, increasingly by medical field pay attention to.
Therefore, it is necessary to a better methods to overcome a series of above-mentioned disadvantages, and this method requirement: internal detection replaces externalDetection；Detect interstitial fluid glucose signal rather than blood glucose Sugar signal.
For United States Patent (USP) US6181957 using the aqueous humor of optical means detection eyes, aqueous humor is interior to be free of blood vessel, can be to avoid bloodThe influence of liquid signal, however proposed method have safety the problem of.
The existing method for even penetrating skin detection concentration of glucose using skin, such as use up across ear-lobe or handRefer to, or with being needled into subcutaneously, however the tissue at these positions contains a large amount of blood vessels, and these methods are not all mentioned and how to be avoidedThe interference of blood signal, even without recognizing dividing tissue liquid and blood.
Current method all ignores the feasibility and necessity of interstitial fluid glucose signal in detection corium.Blood in coriumIt manages and is mainly enriched in the intersection of upper surface and epidermis and the intersection of lower surface and subcutaneous tissue, by protein inside skin coriumFiber forms space structure, wherein being filled with tissue fluid, if it is possible to only collect the signal inside skin corium, so that it may haveEffect reduces the signal for carrying out autoblood, and safe and convenient.
Summary of the invention
The present invention is intended to provide a kind of electrochemical method and its device for detecting in-vivo tissue liquid concentration of glucose information, leads toIt crosses and gives chemical pumping effect to interstitial fluid glucose in dermal layer of the skin, so that it is generated current signal, to obtain glucoseConcentration information.
The invention is realized by the following technical scheme:
A kind of electrochemical method detecting in-vivo tissue liquid concentration of glucose information, comprising:
Glucose excitation enzyme is loaded into conducting probe；
Conducting probe is pierced into detected part skin, the piercing depth of the conducting probe is 0.5 ~ 1.5mm；By glucokinaseEnzyme is encouraged to be trapped in dermal layer of the skin；
Make the glucose in glucose excitation enzyme excitation dermis layer tissue liquid, makes the glycoxidative generation current signal of grape, and pass throughCurrent signal is passed to analytical equipment by the electrode sensor of conducting probe, and analytical equipment passes through the size of analysis current signal,Obtain interstitial fluid glucose concentration information in detected part dermal layer of the skin.
In above-mentioned technical proposal, the glucose excitation enzyme includes glucose dehydrogenase or glucose oxidase.
A kind of conducting probe can be used in the electrochemical method for implementing detection in-vivo tissue liquid concentration of glucose information, instituteStating conducting probe includes at least one set of electrode, and the electrode includes at least working electrode and to electrode, and electric with the workThe glucose that pole connects motivates zymophore, and the glucose excitation zymophore is for carrying glucose excitation enzyme.
In above-mentioned technical proposal, the electrode further includes reference electrode.
In above-mentioned technical proposal, the conducting probe further includes puncture needle and the delay needle that is set in outside the puncture needle,The delay needle is cylindrical, and the electrode is arranged on the delay needle outer wall.
A kind of electrochemical appliance can be used in the electrochemical method for implementing detection in-vivo tissue liquid concentration of glucose information,Including conducting probe and analytical equipment, the conducting probe includes at least one set of electrode, and the electrode includes at least working electrodeWith to electrode, and the glucose excitation zymophore to connect with the working electrode, glucose excitation zymophore is for takingBand glucose motivates enzyme；The analytical equipment is connected with the electrode.
In above-mentioned technical proposal, the electrode further includes reference electrode.
In above-mentioned technical proposal, the conducting probe further includes puncture needle and the delay needle that is set in outside the puncture needle,The delay needle is cylindrical, and the electrode is arranged on the outer wall for being detained needle.
The present invention has the following advantages and beneficial effects: injecting glucose by conducting probe and enzyme is motivated to make Portugal in tissue fluidGrape sugar, which reacts, generates electric current, and analyzes to obtain concentration of glucose information by collected current, and method is simple, reliable.
Detailed description of the invention
Fig. 1 is human skin tissue according to the present invention and detection principle schematic diagram.
Fig. 2 is the conducting probe schematic diagram of one of embodiment according to the present invention.
Fig. 3 is the conducting probe schematic diagram of another embodiment according to the present invention.
Fig. 4 is the electrode current test schematic diagram of Fig. 3.
In figure: 1-analyzer；2-conducting probes；21-to electrode；22-working electrodes；23-glucose motivate zymophore；24-reference electrodes；25-puncture needles；26-are detained needle；3-epidermis；4-skin coriums；5-subcutaneous tissues.
Specific embodiment
A specific embodiment of the invention and the course of work are further described with reference to the accompanying drawing.
The positional terms such as the upper, lower, left, right, front and rear in present specification be positional relationship based on the figure andIt establishes.Attached drawing is different, then corresponding positional relationship is also possible to change therewith, therefore cannot be interpreted as with this to protection modelThe restriction enclosed.
The invention discloses a kind of electrochemical methods for detecting in-vivo tissue liquid concentration of glucose information, and this method is using such asElectrochemical appliance shown in FIG. 1, electrochemical appliance include conducting probe 2 and analyzer 1, carry out excitation to detected part and obtain skinSkin dermis layer tissue liquid concentration of glucose information.
As shown in Fig. 2, conducting probe 2 includes at least one group of bipolar electrode, i.e. working electrode 22 and to electrode 21, and settingGlucose between bipolar electrode motivates zymophore 23.Glucose motivates enzyme to select glucose dehydrogenase or glucose oxidase.
As shown in figure 3, conducting probe 2 can also include puncture needle 25 and cover the delay needle 26 outside puncture needle 25.It is detainedNeedle 26 is cylindrical, and electrode setting is on being detained 26 outer wall of needle.Electrode include three, i.e., working electrode 22, to electrode 21 and ginsengThan electrode 24.
One of embodiment is to select conducting probe 2 as shown in Figure 3, including puncture needle 25 and cover in puncture needle 25Outer delay needle 26.Wherein it is detained needle 26 to be made of polyester film, the length for being pierced into skin is 1.5mm, is less than this position of armDermis thickness 2mm.Being detained printing on 26 outer wall of needle is working electrode 22(W respectively there are three electrode), to electrode 21(C) andReference electrode 24(R).Relative to dual-electrode sensor (working electrode with to electrode), three electrode sensors are introduced to stabilizationThe reference electrode of working electrode.Wherein graphite is as working electrode and to electrode, silver/silver chloride as reference electrode,Working electrode lower end loads glucose oxidase and the potassium ferricyanide, fixed with polyethylene oxide gel, and making it in retardation, let the acupuncture needle remain at a certain pointThe distribution in direction is less than 1mm, to ensure that it acts only on intradermal.Puncture needle 25 and delay needle 26 are pierced into vivo, pulls out and wearsPricker 25, the glucose oxidase being detained on needle 26 start to motivate the glucose in tissue fluid, glucose oxidase (GOD) catalysisGrape in tissue fluid is glycoxidative, and the cooperation potassium ferricyanide generates gluconic acid and potassium ferrocyanide, later as electron mediatorPotassium ferrocyanide can also lose electronics and revert to the potassium ferricyanide, which is accompanied by the gain and loss of electronics, form current signal.ElectricityStream flows through working electrode and to electrode, and reference electrode is used to keep the stability of current potential.As shown in figure 4, working electrode 22 and ginsengThan 24 no power of electrode, the electrode potential of fixed voltage, working electrode 22 and the system that an energization is constituted to electrode 21 are constituted,The electric current that working electrode passes through can be measured.By analyzing the size of the electric current, the information of concentration of glucose can be obtained.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this fieldFor art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repairChange, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.