CN108120755A - Detection device and its application - Google Patents
Detection device and its application Download PDFInfo
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- CN108120755A CN108120755A CN201711385284.0A CN201711385284A CN108120755A CN 108120755 A CN108120755 A CN 108120755A CN 201711385284 A CN201711385284 A CN 201711385284A CN 108120755 A CN108120755 A CN 108120755A
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Abstract
The present invention relates to in-vitro diagnosis medical instruments fields, more particularly to detection device and its preparation method and application.The invention discloses a kind of POCT diagnostic cards.Calibration reagent, reagent valves, electrode array chip and waste liquid storage chamber etc. are integrated on the diagnostic card, so that it no longer needs to carry out reagent pipetting volume in detection process, also additional Biohazard Waste is no longer generated, all fluid, pipeline are all integrated in test card, the convenience used of the raising of high degree also avoids the blocking risk of instrument fluid path.Diagnostic card Applied Electrochemistry principle, it can be used for the in-vitro diagnosis to Disease, some biology, chemical substances in analysis detection blood of human body sample, multiple medical diagnostic fields, such as biochemical project test, the test of vim and vigour project testing, metabolin, hematology test, blood coagulation test, immunology test (cardiac marker) can be used in.
Description
Technical field
The present invention relates to in-vitro diagnosis medical instruments fields, more particularly to detection device and its application.
Background technology
POCT quick diagnosis technologies have become a development trend of medical diagnosis, corresponding to diagnose card or diagnosis test paper
Have very much；Mainly include colloid gold test paper, immunofluorescence test paper, blood sugar test paper etc., their common feature is exactly disposably to make
With.
Colloid gold test paper and immunofluorescence test paper due to instrument used by test methodology limitation, measurement accuracy is relatively low, one
As be qualitative or Quasi-quantitative measurement.
And electrochemical techniques are since the response, transmission and acquisition of signal can be realized by pure hardware circuit, as PCB manufactures skill
The rapid development of art, a multi-channel electrochemical tester size can make 1 hand size, be very suitable for POCT and quickly examine
The development need of disconnected technology；And with the development of solid-state dry type electrochemical sensor technology, highly integrated micro- electrochemical sensing
Device array has been applied to clinical detection, for example, blood sugar test, vim and vigour electrolysis quality detection etc..
The making of blood sugar test paper is to use screen printing technique layer printed circuit board in PET base material, and the sensing formed in printing
Chemical reagent in device region coating, then drying and moulding.Blood sugar test paper test has that precision is higher, instrument using electrochemical principle
The advantages of device is small；But blood sugar test paper is all single test event, and multiple test events can not be completed in same test strips；And
No calibration solution is calibrated before blood sugar test paper test, so that measuring accuracy is limited.
Therefore it provides a kind of highly integrated, simple for process, easy to operate detection device has important practical significance.
The content of the invention
In view of this, the present invention provides a kind of detection device and its application.The detection device is integrated with calibration reagent, electrode sensing
Device array and all runners and control element contacted with liquid, based on electrochemical principle, can be used for the body to Disease
Outer diagnosis, analysis detect some biology, chemical substances in blood of human body sample, can be used in multiple medical diagnostic fields,
Such as biochemical project test, the test of vim and vigour project testing, metabolin, hematology test, blood coagulation test, immunology test (heart mark
Remember object etc.).
In order to realize foregoing invention purpose, the present invention provides following technical scheme：
The present invention provides a kind of detection devices, and including base material, the base material is integrated with liquid fluid channel and electrode sensor battle array
Row, the liquid fluid channel include calibration reagent fluid channel, sample fluid channel, electrode sensor area fluid channel；Further include reagent
Storage unit, the reagent storage unit are closely connected with the calibration reagent runner.
In some specific embodiments of the present invention, the reagent storage unit includes at least two membranes；First tunic is close
The inner wall for telling calibration reagent runner is arranged at, cavity is formed by punch forming；Second tunic is arranged in parallel in described first
On tunic, by hot pressing or ultrasonic welding and first layer film combination, the cavity being fully sealed is formed, obtains the reagent storage part
Part.
In some specific embodiments of the present invention, the electrode sensor array includes metal layer and insulating layer；
The metal layer includes the electrode sensor site of electro-chemical activity and the conduction contacts of electrode sensor signal；
The insulating layer is equipped with through hole in the corresponding region in the electrode sensor site, is passed with the electrode of the metal layer
Sensor site forms well shape blind hole, and by coating selective sensor film in the well shape blind hole, acquisition can be applied to multi-parameter
The electrode sensor array of test.
In some specific embodiments of the present invention, the junction of the reagent storage unit and the calibration reagent runner is set
Valve block is equipped with, the connection and partition of the reagent storage unit and the calibration reagent runner are controlled by valve block.
In some specific embodiments of the present invention, the detection device further includes calibration reagent buffer unit, the calibration
Reagent buffer unit is arranged between the reagent storage unit and the calibration reagent runner.
In some specific embodiments of the present invention, the detection device further includes injection port and micro-fluidic sample introduction runner, leads to
Capillary siphonage is crossed to carry out peripheral blood sampling or pass through syringe sampling.
In some specific embodiments of the present invention, the surrounding of the injection port of the detection device sets to exclude sample
The groove of bubble in this.
In some specific embodiments of the present invention, the injection port of the detection device is additionally provided with c-type component, described
C-type component is closely connected with the injection port, reduces the resistance of syringe sampling.
In some specific embodiments of the present invention, the detection device further includes devil liquor recovery component, the devil liquor recovery
One end of component is connected with the liquid fluid channel, and the other end is in communication with the outside, and ensures that liquid flowing is smooth.
The present invention also provides the detection device in biochemical project test, the test of vim and vigour project testing, metabolin, hematology
Application in test, blood coagulation test, immunology test.
The invention discloses a kind of POCT diagnostic cards.Calibration reagent, reagent valves, electrode array chip are integrated on the diagnostic card
And waste liquid storage chamber etc. so that it no longer needs to carry out reagent pipetting volume in detection process, also no longer generates additional Biohazard Waste,
All fluid, pipeline are all integrated in test card, and the convenience used of the raising of high degree also avoids instrument fluid path
Blocking risk.Diagnostic card Applied Electrochemistry principle can be used for the in-vitro diagnosis to Disease, analysis detection blood of human body
Some biology, chemical substances in sample, can be used in multiple medical diagnostic fields, such as biochemical project test, vim and vigour project
Test, metabolin test, hematology test, blood coagulation test, immunology test (cardiac marker etc.).
Description of the drawings
It in order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing skill
Attached drawing is briefly described needed in art description.
Fig. 1 shows diagnostic card front projection view；
Fig. 2A shows calibration reagent area front projection view；
Fig. 2 B show calibration reagent area cross section of fluid channel schematic diagram；
Fig. 3 shows injection port front projection view；
Fig. 4 A show chip and flow channel for liquids front projection schematic diagram；
Fig. 4 B show chip and flow channel for liquids schematic cross-section；
Fig. 5 A show the response curve of pH electrodes；
Fig. 5 B show pO2The response curve of electrode；
Fig. 6 A show pH test comparison results；
Fig. 6 B show pO2Test comparison result；
Wherein, 1- injection ports (sample inlet)；2- calibrations storage unit (calibration reagent bag)；3- electrode sensor arrays (electricity
Pole sensor array chip area)；4- valves；5- waste liquid recovery apparatus (waste liquid chamber)；(reagent buffers 6- calibration reagents buffer unit
Area)；7- circular holes；8- reagents flow to the runner in sensor chip area；9th, it is used for when 10- is respectively and seals what head and the tail both ends were reserved
Filling calibration reagent, filling completion rear enclosed passage；11- circular holes exclude aluminum plastic film and diagnostic card base during for putting up aluminum plastic film
Bubble between body；The identical aluminum plastic film of two layers of material above and below 12a, 12b-；13rd, 14- is two layers of common plastics film；15th, 16- is convex
Block；17th, 18- is respectively upper and lower getting stuck of being contacted with diagnostic card of instrument；19-C shape sequins；20th, 23- electrodes of different shapes pass
Sensor；The good basis material of 21- chip insulation performances；22- sensor array chips region runner；Metal layer gold-plated 24-；
25~27- is the three-layer insulated material for being provided with concentric pylone, and from 25 to 27, opening diameter is sequentially increased, shown in diagram 24
Metal layer, which forces together, forms the sensor region of back taper；Reagent components in 28- films；29- possesses electro-chemical activity or life
Object activity sensor film；30- is for adhering chip and the double faced adhesive tape of test card.
Specific embodiment
The invention discloses a kind of detection device and its application, those skilled in the art can use for reference present disclosure, be suitably modified
Technological parameter is realized.In particular, it should be pointed out that all similar substitutions and modifications be for a person skilled in the art it is aobvious and
It is clear to, they are considered as being included in the present invention.The method of the present invention and application are retouched by preferred embodiment
It states, related personnel can substantially not depart from present invention, method described herein and application changed in spirit and scope
Dynamic or appropriate change is with combining, to realize and using the technology of the present invention.
In order to realize the diagnostic card of said structure and function, the diagnostic card matrix with flow channel for liquids groove is devised first.Base
Body material can be PET, PBT or PP material.Entire card can be divided into calibration reagent area, electrode sensor array area, sample introduction
Area and waste liquid memory block.In order to which entire test card is made to use up minimizing thickness, and smooth outflow of the liquid in test card is not influenced,
Electrode sensor array area runner and other runners can be distributed in the tow sides of test card.Sensor array area runner
Width depend on electrode sensor array chip on electrode size, generally between 800-1500 μm；Calibrate reagent area stream
The length in road determines the size for the amount of reagent that diagnostic card is carried with width, usually in 75-110 μ L；Sample introduction zone runner is with passing
The size of required sample size when the length of sensor array area runner determines diagnostic card test with width, generally in 60-100 μ L；
And the design of waste runner depends on the size of the calibration amount of reagent and sample size designed front, in order to ensure in test process
Calibrate reagent or sample will not overflow test card, the Capacity design of waste liquid chamber is beyond calibration amount of reagent and sample size summation
20%.
Calibration reagent area main flow paths chamber is designed as two parallel wide runners, passes through a tiny runner phase between two wide runners
Even.It is designed close to one end of electrode sensor there are one reagent valves area, reagent valves one end passes through tiny runner and calibration
Reagent is connected, and the other end is connected with electrode sensor.In order to ensure in the long-time stability of reagent, especially vim and vigour calibration reagent
The O2 and the stability of CO2 gases contained is, it is necessary to use aluminum plastic film to wrap up reagent cavity.The present invention is by the way of gluing first by one
Layer aluminum plastic film is fixed on diagnostic card matrix, is then stamped and formed out aluminum plastic film/matrix flow path groove, and is also formed in valve block area
One groove is used to place valve block；Second layer aluminum plastic film and first layer aluminum plastic film are bonded in one by heat-sealing or ultrasonic welding again
The cavity for forming an all round closure is acted, valve block is also closed in reagent bag simultaneously；During heat-sealing two are reserved at head and the tail both ends
A passage is used for filling calibration reagent, filling completion rear enclosed passage.The switch control of valve calibrates reagent to electrode sensor
The flowing in region.Before use, valve is in normally off.After diagnosing card start-up test, valve is automatically opened by test equipment,
Then two wide flow passage areas of reagent area are pushed, reagent is made to flow to sensor array area.
The technical solution that sensor array chip uses refers to the manufacturing technology of intelligent card chip.
Intelligent card chip technology is quite ripe, due to a large amount of need of electronics industry (such as SIM cards of mobile phones chip, IC card chip)
It asks, intelligent card chip cost is comparatively inexpensive.
The basic structure of intelligent card chip includes insulating layer and metal layer.Gluing knot can be used between insulating layer and metal layer.It bonds
It can also be several layers of that layer, which can be one layer,.
By getting through hole on insulating layer, glue line, the biographies of various different structures then can be formed with metal bonding layer again
Sensor chip.After bonding, the reaction contact surface of bioelectrochemical sensor, material are used as by the through hole exposing metal covering of insulating layer
Matter is generally Au or Pt.The well that insulating layer through hole is formed plays key effect to the preparation of sensor film.Under normal conditions, it is raw
Object electrochemical sensor is all to have multilayer film composition, and the thickness per tunic has different requirements, such as conducting electrolyte layer
Generally several μm to tens μm, ion selectivity thicknesses of layers is usually 20~40 μm, and ventilative layer film thickness is generally several μm.
The well shape border that insulating layer or adhesive layer through hole are formed can prepare the random flowing of time limit film formula solution in sensor film,
When each one timing of amount of liquid being added dropwise in border, since border limits, the sensor area to be formed is certain, the thickness of film
Degree is also controlled well, and film thickness is the key parameter for influencing sensor performance.It is also positive because there is the limitation on through hole border,
It need not be as in many traditional sensors membrane process, it is necessary to carry out stringent surface etc. by contacting surface to Au or Pt etc.
Gas ions handle to achieve the purpose that control film shape and thickness.According to the requirement of specific sensor, different-thickness can be selected
Insulating layer and adhesive linkage, opening the size in hole can also design according to actual requirement, thus can be very easily same micro-
(such as 30mm × 10mm) Integrated Conductivity type sensor, voltage sensor, amperometric sensor on small chip.
Sensor layer, respectively in the tow sides of same sheet metal, greatly reduces sensor chip with signal acquisition articulamentum
Size.Sensor layer is contacted with sample to be tested, since size sensor can be designed to hundreds of microns of microsize, flows through biography
The runner of sensor surfaces can also be designed to it is hundreds of microns wide, test required sample size also just considerably less (representative value：20~
100 μ L), it can thus save substantial amounts of blood sample.
It is very convenient to be used to mass produce since chip is small and thin (the general 0.15mm~0.2mm of thickness).It and can be in chip
Optical detection marks on silk-screen, production batch identification, vision positioning, vision QC during for automated production etc..0.15mm~
The thickness of 0.2mm is also also very convenient with dispensing to the cutting of follow-up chip.
Micro-fluidic POCT diagnostic cards provided by the invention, Applied Electrochemistry principle can be used for the in-vitro diagnosis to Disease,
Some biology, chemical substances in analysis detection blood of human body sample, can be used in multiple medical diagnostic fields, such as biochemical item
Estimate examination, the test of vim and vigour project testing, metabolin, hematology test, blood coagulation test, immunology test (cardiac marker etc.).
This diagnostic card includes：
Diagnostic card base material：For a size, thickness and the comparable plastic cards of bank card.Liquid fluid channel is integrated on card, is determined
Mark reagent storage area, reagent valves, electrod-array installing zone and waste liquid memory block.
Reagent bag：It is pressed by two aluminum plastic films, wherein one layer of aluminum plastic film is close to diagnostic card upscaling reagent storage area stream
On the inner wall in road, the cavity size formed by punch forming determines the amount of storage of reagent on diagnostic card；Second layer plastic-aluminum
Film is placed in parallel on first layer aluminum plastic film, is combined together, has been formed with first layer aluminum plastic film by hot pressing or ultrasonic welding
Hermetically sealed cavity.
Electrode array chip：Using the lamination, printing and lithographic technique of flexible PCB.By one layer of metal layer and a few layer insulatings
It suppresses；Metal layer two sides is gold-plated, is on one side the electrode sensor site of electro-chemical activity, and another side is believed for electrode sensor
Number conduction contacts.Insulating layer is provided with through hole in the corresponding region in electrode sensor site, is passed after pressing with metal layer top electrode
Sensor site forms the blind hole of well shape together.By the various selective sensor films of sensor site region coating in well shape,
Just the electrochemical sensor of test relevant parameter has been obtained can be applied to.Multiple sensors are in juxtaposition, and composition can be applied
In the sensor array of multi-parameters test.
Preferably, the size of card, thickness are suitable with bank card, calibration reagent bag, reagent valves, electrode are integrated on card and is passed
Sensor array, calibration reagent fluid channel, sample fluid channel, electrode sensor area fluid channel, waste liquid chamber etc..
Preferably, sample and electrode sensor area fluid channel are distributed in the upper and lower faces of diagnostic card with sample fluid channel, by examining
Groove on disconnected card base material is formed with plastic film seal.The material of diagnostic card base material and plastic foil can be PET, PBT or PP.
Preferably, calibration reagent bag is made of upper and lower two layers of aluminum plastic film；Calibration reagent bag cleverly make use of diagnostic card base material
On cavity support, not only ensure structural stability, but also can be very easily by reagent bag and the test runner phase on diagnostic card
Connection；In order to ensure the long-time stability of reagent in reagent bag, reagent bag cavity and the minimum range of test card surrounding should be 5-
10mm。
Preferably, reagent bag and the junction of test runner are packaged with a valve block, during test, by valve block by the reagent of sealing
Bag is opened, and calibration reagent can flow to electrode sensor array region, and the material of valve block can be have certain degree of hardness stainless
Steel disc or the epoxy sheet containing glass.
Preferably, diagnostic card is also containing calibration reagent buffering area.Reagent bag valve opens reagent bag, when reagent is begun to flow out,
It is easily mixed with the micro-air of valve region, and makes to be mixed with bubble in calibration reagent；The calibration reagent buffering of diagnostic card
Area is used to collect the calibration reagent that front end is mixed with air.
Preferably, diagnostic card is also integrated with electrochemical sensor array, do not have a sensor site to correspond to one on array
Measurement parameter based on different clinical requirements, can realize different clinical trial projects combos.
Preferably, diagnostic card is also integrated with micro-fluidic sample introduction runner；Corona or plasma surface treatment are carried out to runner, and
Hydrophilic polymer-modified is done in runner inner surface, ensures that diagnostic card can carry out peripheral blood sampling by capillary siphonage.Together
When can also use syringe sampling.
Preferably, the injection port of diagnostic card is there are one fine structure, before the resistance and exclusion during for reducing syringe sampling
The micro bubble at end.
Preferably, diagnostic card is also integrated with waste liquid chamber；The end of waste liquid chamber is communicated with air, ensures that liquid flowing is smooth.
With reference to Fig. 1~Fig. 6 A/6B, specific implementation to the present invention and the application during diagnosing in vitro are described in detail.
Fig. 1 is diagnostic card front projection view.Diagram 1 is sample inlet.Diagram 2 is calibration reagent bag, by several segment length and
The cavity that width differs is formed.On the top of calibration reagent bag, there are one circular reagent valve (diagrams 4)；It will by reagent valves
Electrode sensor array chip region (diagram 3) is connected with reagent buffering area (diagram 6)；Reagent buffering area (diagram 6) is act as
Calibration reagent and bubble that original segment squeezes out are excluded, ensures the reliability of test result.Diagram 7 is sample introduction runner and calibration reagent
Runner intersection, for calibration reagent runner on upper strata, sample introduction runner is distributed in lower floor, tiny circular hole of the sample shown in by diagram 7
It is upwardly into sensor test region.The diameter design of 7 circular holes is illustrated as 200-400 μm, is only upper strata calibration solution width of flow path
1/10 to 1/15, so calibration solution when flowing through this region, since flow resistance is larger, is poured into without counter in sample introduction runner.It surveys
After the completion of examination, discarded calibration solution and sample are stored in the waste liquid intracavitary illustrated shown in 5.There are one oblique angles in the test card upper right corner
For fool-proof design.
Fig. 2A is calibration reagent area front projection view.First one layer of aluminum plastic film is pasted onto from bottom to top by the way of gluing and is examined
On disconnected card matrix, aluminum plastic film/matrix flow path groove (region shown in diagram 2) is then stamped and formed out, it is illustrated that circular hole is used for shown in 11
The bubble between aluminum plastic film and diagnostic card matrix is excluded when putting up aluminum plastic film, ensure aluminum plastic film it is smooth and smooth be posted in groove
Inner wall；Meanwhile a groove is also formed in border circular areas shown in diagram 4, valve block is placed in groove, then by heat-sealing by the
Two layers of aluminum plastic film are bonded together into the cavity of an all round closure with first layer aluminum plastic film, and valve block is also closed in examination simultaneously
In agent bag；It is reserved during heat-sealing at head and the tail both ends there are two passage (diagram 9 and diagram 10) for filling calibration reagent, filling completion
Rear enclosed passage.Runner shown in diagram 6 and diagram 8 is respectively the stream that reagent buffering area passage and reagent flow to sensor chip area
Road positioned at the upper surface of diagnostic card, passes through the valve shown in diagram 4 and the calibration reagent runner phase positioned at diagnostic card lower surface
It is logical.
Fig. 2 B are cross-sectional views of the Fig. 2A along AA ' directions.It illustrates 12a and illustrates 12b as the identical aluminum plastic film of upper and lower two layers of material.
Diagram 13 and diagram 14 are two layers of common plastics film, can be PP or PET materials, be respectively adhered on diagnostic card upper and lower surface, with
The groove of diagnostic card upper and lower surface forms the liquid flow path of closing together.During test, inside diagnostic card inserting instrument, figure
Show 17 and diagram 18 represent that instrument contacted with diagnostic card upper and lower gets stuck respectively.After instrument receives test card insertion trigger signal,
It is up moved by the convex block shown in electrode drive diagram 16, the reagent valves shown in open-top diagram 4 so that reagent bag and diagram
Passage connection shown in 8.Then, then by the convex block shown in electrode drive diagram 15 move upwards, squeeze the examination shown in diagram 2
Agent bag region so that calibration reagent carries out calibration test by 8 flow direction sensor region of passage.Due to the region shown in diagram 4
A small amount of air would generally be remained and influence whether test result, especially pO2、pCO2Etc. gas projects test, it is necessary to will be initial
The calibration reagent of extrusion exhausts.Calibration reagent buffering area shown in diagram 6 in Fig. 2A just solves the problems, such as this well.By
In (800-1500 μm) width of flow path (200-400 μm) being much larger than shown in diagram 8 of width of flow path shown in diagram 6, just start, examination
The flow resistance that agent flows to buffering area will be much smaller than the flow resistance in flow direction sensor area, as air is compressed in buffering area, reagent flow direction
The flow resistance of buffering area can be increasing, the flow resistance until being more than flow direction sensor area, and subsequent calibration reagent will smoothly flow
To sensor region, it is achieved thereby that the purpose of emptying leading portion reagent and bubble.
Fig. 3 is injection port front projection view.Injection port surrounding is provided with many sulculuses, lacks for exclude to bring in sample
Measure bubble.C-shaped sequin shown in diagram 19 can play the role of reducing resistance during syringe sampling.
Injection port runner design is micron order, carries out corona or plasma surface treatment to runner, and is done in runner inner surface
Hydrophilic polymer-modified, to ensure that diagnostic card can carry out peripheral blood sampling by capillary siphonage.
Fig. 4 A are chip and flow channel for liquids front projection schematic diagram.By chip groove fitting corresponding on diagnostic card, just formed
Sensor array chip region runner, as shown 22, the width of runner is usually 800 μm~2mm.Diagram 20 and 23 is difference
The electrode sensor of shape, each circular dot or strip form point in Fig. 4 A correspond to an electrode sensor, shown in the present invention
Array chip on can at most integrate 14 different types of sensors.Diagram 21 is the good matrix material of chip insulation performance
Material, generally epoxy resin or polyimide material.
Fig. 4 B are cross-sectional views of the chip figure 4A along BB ' directions.Diagram 24 is gold-plated metal layer, and upper strata is contacted with sensor film
Electric signal is generated, lower floor exports contact for signal.Diagram 25,26,27 is to be provided with the three-layer insulated material of concentric pylone, from 25 to
27, opening diameter is sequentially increased, and is forced together with the metal layer shown in diagram 24 and is formed the sensor region of back taper.Diagram
30 i.e. for adhering chip and the double faced adhesive tape of test card, and thickness is usually in 0.05~0.08mm.Diagram 29 is to possess electrochemistry
Activity or biological activity sensors film, the test event and performance of sensor depend entirely on the formula composition of film 29, thickness, table
Face energy, homogeneity etc..Sensor film key component is typically the high molecular polymer of some doping；These films usually have well
Waterproof and breathable performance, can effectively reagent components (diagram 28) be outwards lost in and good steam, pO in block film2、
pCO2Wait Gas permeabilities；To ensure when fluid sample flows through TCH test channel, these sensors can be become moistening from dry state
Hygrometric state, thus form an electrochemical measurement circuit with good conductivity.
Raw materials used and reagent can be bought by market in detection device provided by the invention and its application.
With reference to embodiment, the present invention is further explained：
Embodiment 1 is with pH and pO2The present invention will be described in detail exemplified by electrode sensor
It is prepared by pH electrodes：
PH electrode structures are：Reference/electrolyte layer/ion selectivity film layer in Ag/AgCl；
Solid electrolyte of the present invention adds in NaCl the or KCl conducts of 100-500mM using PVP or PVA as solid phase carrier
Supporting electrolyte, while PBS or Hepes are added in as pH buffer reagents；
Ion selective membrane is configured to：1 (1%by of PVC (66%by wt.%)+NPOE (33%by wt.%)+H+ carriers
Wt.%)
Each sensor film layer is uniformly coated in the border circular areas of sensor chip by way of Microdispensing.
pO2It is prepared by electrode：
pO2Electrode structure is：Electrolyte membrane layer/air penetrating film layer；
Electrolyte layer is using hydrophilic gel as solid phase supporting carrier, such as PEG, trehalose, D4, while adds in KCl or NaCl conducts
Supporting electrolyte, and Hepes is added in as pH buffer reagents；
Air penetrating film layer is preferably dimethyl silicone polymer Type of Collective object；
Each sensor film layer is uniformly coated in the border circular areas of sensor chip by way of Microdispensing.
Calibrate preparation of reagents：
50mM Hepes+150mM NaCl+ preservatives adjust pH value to pH=7.35 with NaOH, then pass to 21%O2+N2 and put down
The gas of weighing apparatus obtains pO in calibration reagent2For 150mmHg.
Electrode test curve
Fig. 5 show integrated pH electrodes and pO2The test response curve of electrode.Diagnostic card is inserted into our company's independent development
After measuring and analysing meter GSI-100, instrument automatically opens reagent valve, pushes calibration solution and enters electrode sensor region；Work as sensor
After detecting that electrode zone is completely covered in calibration solution, start gathered data, i.e. zero point on test curve；It can start standard at this time
Standby sample, and the variation of instrument monitors sensor signal always, after 60s, after slope of curve variation is stablized, instrument prompting
It can start sample introduction.The requirement control of sample introduction opportunity will warn optimal sample introduction opportunity within 60-240s more than 240s instruments
It crosses, diagnostic card please be replace.Fig. 5 A show the response curve example of pH electrodes, and at 37 DEG C, electrode response sensitivity is in 54-
62mV/pH；Fig. 5 B are pO2The response curve example of electrode.By the pH and pO that test different known concentration Grad2Sample,
PH electrodes and pO can be established respectively2The calibration curve of electrode.
PH electrodes calibrate principle：
According to Nernst equation, Δ V=s* (pHSample–pHCalibration),
So pH samples=Δ V*s '+b '；By testing a series of known pHI (i=0,1,2 ...)Δ under concentration samples
VI (i=0,1,2 ...)Value, can establish calibration curve, obtain slope s ' and intercept b '；
When testing unknown sample, it is only necessary to substitute into electrode response signal delta V, you can acquire the pH value of unknown sample.
pO2Electrode calibrates principle：
Define normalized rate-aided signal：D=iSample/iCalibration(the reaction electricity in the kinetic current divided by calibration solution i.e. in sample
Stream), then：
pO2, sample=pO2, calibration*s*(D–a)/(1–a)
By testing a series of known pO2, i (i=0,1,2 ...)D under concentration samplesI (i=0,1,2 ...)Value, can establish calibration curve,
Obtain slope s and intercept a；
When testing unknown sample, it is only necessary to substitute into electrode response signal D, you can acquire the pO of unknown sample2Value.
PH and pO2The linear dependence result of electrode test：
Fig. 6 is to test pH and pO using measuring and analysing meter GSI-100 of the diagnostic card shown in the present invention in our company's independent development2
Result and the ABL800 test results of Lei Du Mitt USA Corporation of industry mark post Denmark compare.
The pO shown in pH test results and Fig. 6 B shown in Fig. 6 A2Test result compares display, relative coefficient R2Both greater than
0.99, there is good linear dependence.
The above is only the preferred embodiment of the present invention, it is noted that is come for those skilled in the art
It says, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should be regarded as
Protection scope of the present invention.
Claims (10)
1. a kind of detection device, including base material, the base material is integrated with liquid fluid channel and electrode sensor array, the liquid
Fluid channel includes calibration reagent fluid channel, sample fluid channel, electrode sensor area fluid channel；It is characterized in that, further include reagent
Storage unit, the reagent storage unit are closely connected with the calibration reagent runner.
2. detection device according to claim 1, which is characterized in that the reagent storage unit includes at least two membranes；
First tunic is closely arranged at the inner wall for telling calibration reagent runner, and cavity is formed by punch forming；Second tunic is parallel to be set
It is placed on first tunic, by hot pressing or ultrasonic welding and first layer film combination, forms the cavity being fully sealed, obtain institute
State reagent storage unit.
3. detection device according to claim 1 or 2, which is characterized in that the electrode sensor array includes metal layer
And insulating layer；
The metal layer includes the electrode sensor site of electro-chemical activity and the conduction contacts of electrode sensor signal；
The insulating layer is equipped with through hole in the corresponding region in the electrode sensor site, is passed with the electrode of the metal layer
Sensor site forms well shape blind hole, and by coating selective sensor film in the well shape blind hole, acquisition can be applied to multi-parameter
The electrode sensor array of test.
4. detection device according to any one of claims 1 to 3, which is characterized in that the reagent storage unit with it is described
The junction of calibration reagent runner is provided with valve block, and the reagent storage unit and the calibration reagent runner are controlled by valve block
Connection and partition.
5. detection device according to any one of claims 1 to 4, which is characterized in that calibration reagent buffer unit is further included,
The calibration reagent buffer unit is arranged between the reagent storage unit and the calibration reagent runner.
6. detection device according to any one of claims 1 to 5, which is characterized in that further include injection port and it is micro-fluidic into
Sample runner carries out peripheral blood sampling by capillary siphonage or passes through syringe sampling.
7. detection device according to claim 6, which is characterized in that the surrounding of the injection port sets to exclude sample
In bubble groove.
8. the detection device according to claim 6 or 7, which is characterized in that the injection port is additionally provided with c-type component, institute
It states c-type component to be closely connected with the injection port, reduces the resistance of syringe sampling.
9. according to claim 1 to 8 any one of them detection device, which is characterized in that devil liquor recovery component is further included, it is described
One end of devil liquor recovery component is connected with the liquid fluid channel, and the other end is in communication with the outside, and ensures that liquid flowing is smooth.
10. according to claim 1 to 9 any one of them detection device in biochemical project test, vim and vigour project testing, metabolin
Application in test, hematology test, blood coagulation test, immunology test.
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| CN201711385284.0A CN108120755B (en) | 2017-12-20 | 2017-12-20 | Detection device and application thereof |
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