CN116106390A - Continuous arterial blood oxygen detection chip based on microfluidic technology and preparation process thereof - Google Patents
Continuous arterial blood oxygen detection chip based on microfluidic technology and preparation process thereof Download PDFInfo
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- CN116106390A CN116106390A CN202310057148.8A CN202310057148A CN116106390A CN 116106390 A CN116106390 A CN 116106390A CN 202310057148 A CN202310057148 A CN 202310057148A CN 116106390 A CN116106390 A CN 116106390A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
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- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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Abstract
The invention provides a continuous arterial blood oxygen detection chip based on a microfluidic technology and a preparation process thereof, wherein the chip comprises an integrated electrochemical sensor element and an integrated microfluidic channel element, adopts a Clark type limiting current sensor principle of a double-electrode system, takes a salt bridge as a conductive medium and an oxygen permeable membrane as a gas filter, adopts a microfluidic pipeline design, controls flow resistance and blood flow velocity through the microfluidic pipeline, and enables blood to continuously flow through the surface of an oxygen sensor, so that the continuous detection of arterial blood oxygen is realized; the chip solves the problems of volatilization of liquid caused by heating in the processing process, overlarge chip volume caused by sealing in the packaging process and the like, and is beneficial to reducing the sensing area, thereby reducing the blood consumption.
Description
Technical Field
The invention relates to the technical field of blood gas detection, in particular to a continuous arterial blood oxygen detection chip based on a microfluidic technology and a preparation process thereof.
Background
Oxygen is one of the substances essential for maintaining biological life activities. Physiological oxygen is one of the fundamental sources of human energy. Japanese Koukou world doctor has said "hypoxia is the source of ten thousand diseases".
Clinically, one of the tests that must be done to determine oxygenation and to determine the severity of respiratory failure and guide treatment is to measure blood oxygenation. The partial pressure of oxygen (PO 2) refers to the tension (so-called oxygen tension) generated by oxygen molecules dissolved in the plasma in a physical state. Normally, the arterial partial pressure (PaO 2) is about 100mmHg and the venous partial pressure (PvO 2) is about 40mmHg. PaO2 is primarily dependent on the partial pressure of oxygen in the inhaled gas and the external respiratory function of the lungs, pvO2 then reflects the internal respiratory conditions. Blood oxygen analysis refers to measuring the oxygen content dissolved in human blood by using a blood oxygen analyzer to understand the respiratory function of the human body.
The current clinical blood oxygen detecting instrument needs to be intermittently sampled and then sent to an analyzer or a laboratory for detection. The detection mode belongs to in-vitro single-point detection, blood is extracted once, and only blood physiological state information at one time point can be obtained by using a test card. The detection result is lagged, and accurate information of continuous real-time change of the blood physiological state of the patient cannot be reflected. Therefore, achieving continuous real-time detection of blood oxygen is currently a necessary research direction.
The continuous blood oxygen detection proposed in the market at present can be divided into a minimally invasive detection and a non-invasive detection, wherein the minimally invasive detection comprises: intravascular implantation, intramuscular implantation, and subcutaneous implantation. Since there is a difference in the value of PO2 in human tissue and PO2 in arterial blood, new diagnostic criteria are required for intramuscular and subcutaneous implantation. Although the intravascular implantation can realize continuous online blood oxygen detection and reflect the blood oxygen change trend, thrombus is easy to form, so that the blood flow around the sensor is reduced or even interrupted, and intermittent vasospasm is generated. Non-invasive detection is percutaneous oximetry, which has time delay and measurement bias, and cannot replace arterial blood oxygen.
Disclosure of Invention
The invention aims to provide a continuous arterial blood oxygen detection chip based on a microfluidic technology.
The invention aims to provide a preparation process of the continuous arterial blood oxygen detection chip based on the microfluidic technology.
In order to solve the technical problems, the technical scheme of the invention is as follows:
a continuous arterial blood oxygen detection chip based on a microfluidic technology comprises an integrated electrochemical sensor element and an integrated microfluidic channel element, adopts a C l arm type limiting current sensor principle of a double-electrode system, takes a salt bridge as a conductive medium, takes an oxygen permeable membrane as a gas filter, adopts a microfluidic pipeline design, and controls flow resistance and blood flow velocity through the microfluidic pipeline so that blood continuously flows through the surface of an oxygen sensor to realize continuous detection of arterial blood oxygen.
Preferably, the integrated electrochemical sensor element is sequentially composed of a glass substrate (1), an electrode layer (2), a salt bridge (3) and a filter layer (4), wherein the glass substrate (1) is used as a substrate, the electrode layer (2) is arranged on the upper surface of the glass substrate, the salt bridge (3) which is electrically contacted with the electrode is arranged on an electrode reaction area of the electrode layer (2), and the filter layer is formed on the salt bridge (3); the principle of a C l arm type limiting current sensor of a double-electrode system is adopted, a salt bridge is used for filling an electrolyte tank and covering the double electrodes, and a filter layer (4) is suitable for blocking other components except oxygen in a gas medium.
Preferably, the continuous arterial blood oxygen detection chip based on the microfluidic technology is characterized in that the electrodes are double electrodes, namely a working electrode and a reference electrode, each electrode comprises a lead (2-1) and a reaction area (2-2), and the lead (2-1) is in contact connection with the reaction area (2-2).
Preferably, the electrode is prepared on a glass substrate by using an inkjet printing, evaporation, screen printing or magnetron sputtering technology, and then chloridizing the reference electrode.
Preferably, the continuous arterial blood oxygen detection chip based on the microfluidic technology is characterized in that the reference electrode is an Ag/AgC l reference electrode.
Preferably, the continuous arterial blood oxygen detection chip based on the microfluidic technology is characterized in that the salt bridge is hydrogel containing salt ions, such as zinc sulfate (ZnSO 4 ) Is a hydrogel of (a).
Preferably, the continuous arterial blood oxygen detection chip based on the microfluidic technology is prepared by the following method: each 1.229g of sulfobetaine methacrylate (SBMA) was dissolved in 1mL of 0.1M anhydrous zinc sulfate, 6.78mg of monobromoacetic acid (MBAA) was added, the ice water bath was 30min, 2mg of ammonium sulfate (APS) and 2. Mu.L of tetramethyl ethylenediamine (TEMED) were added, and finally, the salt bridge was formed by polymerization at 37 ℃.
The common electrolyte is a solution containing salt ions, so that the unavoidable heating procedure in the chip processing process can cause volatilization of the electrolyte, the liquid electrolyte has large volume, the packaging is difficult or the chip volume after the packaging is overlarge, a salt bridge is selected as the electrolyte, the salt bridge can realize the conduction between a working electrode and a reference electrode while fixing an oxygen permeable membrane and the electrode, and the current base line of the integrated electrochemical sensor is improved; meanwhile, the upper surface of the salt bridge and the oxygen permeable membrane after heating and polymerization is flat, so that the micro-fluidic chip has a good sealing effect, and is beneficial to miniaturization of the micro-fluidic chip, thereby reducing the consumption of blood.
Preferably, in the continuous arterial blood oxygen detection chip based on the microfluidic technology, the filter layer (4) is an oxygen permeable membrane, and the size of the filter layer is the same as that of the salt bridge, and the filter layer is completely covered and attached on the upper surface of the salt bridge.
Preferably, the integrated microfluidic channel element of the continuous arterial blood oxygen detection chip based on the microfluidic technology sequentially comprises an electrolyte tank (5) and a packaging layer (6), wherein the packaging layer (6) is arranged above the electrolyte tank (5); the electrolyte tank (5) is located locally above the electrode layer of the integrated electrochemical sensor element.
Preferably, in the continuous arterial blood oxygen detection chip based on the microfluidic technology, the glass substrate and the integrated microfluidic channel element are made of Polydimethylsiloxane (PDMS), and the glass substrate, the electrolyte tank and the packaging layer are bonded layer by oxygen Plasma (Plasma).
Preferably, the continuous arterial blood oxygen detection chip based on the microfluidic technology is characterized in that the electrolyte tank (5) is a cavity with an annular structure, a hole groove is reserved in the middle of the electrolyte tank, the hole groove is positioned right above the electrode layer reaction area, a part of the cavity is positioned right above the lead wire of the electrode layer, a salt bridge is filled in the hole groove, the salt bridge is liquid before heating and polymerization, after the liquid salt bridge is filled in the internal cavity of the electrolyte tank, the salt bridge and the oxygen permeable membrane are heated and polymerized, a completely sealed cavity structure is formed on the upper surface of the electrolyte tank, and the electrolyte tank is electrically contacted with the electrode layer in the electrode reaction area.
Preferably, in the continuous arterial blood oxygen detection chip based on the microfluidic technology, a microfluidic flow path (7) is arranged on the lower surface of the packaging layer (6), the packaging layer is in direct contact with the upper surface of the filter layer (4), and liquid inlet holes and liquid outlet holes are respectively arranged at two ends of the microfluidic flow path.
Preferably, in the continuous arterial blood oxygen detection chip based on the microfluidic technology, the microfluidic flow path (7) adopts a curve type regulating flow path.
The preparation process of the continuous arterial blood oxygen detection chip based on the microfluidic technology comprises the following specific processing processes:
(1) Attaching an electrode layer to a glass substrate by inkjet printing; filling polydimethylsiloxane into a micro-fluid flow path (curve type adjusting flow path) on the lower surface of the packaging layer through a die, heating (80 degrees, 1 h) and solidifying to obtain the micro-fluid flow path;
(2) Bonding the electrolyte tank, the electrode layer and the glass substrate together, wherein Plasma (300W, 30 s) is adopted to treat the glass substrate, the electrode layer and the electrolyte tank respectively, and heating is carried out after bonding (80 ℃ for 30 min);
(3) Dropping the salt bridge into the middle hole groove of the electrolyte tank, covering a filter layer (oxygen permeable film) with the same size as the hole groove, heating at 37 ℃ to solidify the salt bridge, so that the filter layer is adhered to the upper surface of the salt bridge, and sealing and flattening the middle of the electrolyte tank are realized;
(4) Bonding the packaging layer and the electrolyte tank together, adopting Plasma (100W, 30 s) for treatment, and heating (80 ℃ for 30 min) after bonding;
(5) Preparation of conductive and insulating portions: the conductive wire is glued at the tail end of the lead wire of the electrode layer by conductive silver glue and is heated at 60 ℃ for solidification; and (3) dripping ultraviolet curing glue on the connection area of the conductive wire and the lead wire, and irradiating for 5min by using an ultraviolet lamp to realize curing, so that the purpose of insulation is achieved.
Preferably, in the preparation process of the continuous arterial blood oxygen detection chip based on the microfluidic technology, the electrolyte tank and the packaging layer are made of Polydimethylsiloxane (PDMS), and after the surface of the electrolyte tank and the packaging layer is modified by oxygen Plasma (Plasma), the hydrophilicity of the surface of the Polydimethylsiloxane (PDMS) is improved, so that the anti-adsorption performance of the Polydimethylsiloxane (PDMS) is improved, and the anticoagulation function of the chip is improved.
Preferably, the preparation process of the continuous arterial blood oxygen detection chip based on the microfluidic technology comprises the following preparation processes of an electrode layer: gold ink and silver ink are printed on a glass substrate by adopting an ink-jet printing technology, and are heated and sintered, and 100 mu L of 50mmol/L FeCl is added dropwise on a reference electrode 3 The electrode 20s was chloridized, and after jet printing, sintered for 2h at 250℃using a heating plate (C-MAG HP 10, IKATIHERM, germeny).
The adopted ink-jet printer is a Jetlab4 ink-jet printing system of MicroFab company in the United states; the gold Ink was UTDAuIJ Ink of UT Dots, and the silver Ink was Smart' Ink S-CS01130 Ink of Sigma Co.
The beneficial effects are that:
the novel structural design of the oxygen partial pressure detection chip enables real-time and continuous detection of arterial blood oxygen and miniaturization of blood oxygen analysis instruments to be possible for the first time. By adopting a salt bridge (solid hydrogel) to replace common electrolyte, the problems of volatilization of liquid caused by heating in the processing process, overlarge chip volume caused by sealing in the packaging process and the like are solved, and the reduction of a sensing area is facilitated, so that the blood consumption is reduced; the flow resistance is controlled by adopting a curve type regulating flow path, so that the real-time information of PO2 in arterial blood can be measured under the drive of arterial pressure, and the continuous detection of arterial blood oxygen is realized.
Drawings
Fig. 1 is a schematic diagram of the whole structure of a continuous arterial blood oxygen detection chip based on the microfluidic technology, including a top view and a side view.
Fig. 2 is a schematic diagram of the operation of the continuous arterial blood oxygen detection chip based on the microfluidic technology according to the present invention.
Fig. 3 is a top view of an electrode layer structure of the continuous arterial blood oxygen detection chip based on the microfluidic technology.
FIG. 4 is a top view of an electrolyte tank structure of the continuous arterial blood oxygen detection chip based on the microfluidic technology.
Fig. 5 is a top view of a packaging layer structure of a continuous arterial blood oxygen detection chip based on the microfluidic technology according to the invention.
Fig. 6 is a graph showing the change of the current values of different quality control fluids of the continuous arterial blood oxygen detection chip based on the microfluidic technology.
FIG. 7 shows the current values and PO obtained by different quality control fluids of the continuous arterial blood oxygen detection chip based on the microfluidic technology of the invention 2 Is a linear regression line of (2).
In the figure: 1-glass substrate 2-electrode layer 2-1-lead 2-2-reaction region 3-salt bridge 4-filtration layer 5-electrolyte tank 6-encapsulation layer 7-microfluidic flow path
Detailed Description
Example 1
As shown in fig. 1-5, the continuous arterial blood oxygen detection chip based on the microfluidic technology comprises an integrated electrochemical sensor element and an integrated microfluidic channel element, adopts the principle of a C l arm type limiting current sensor of a double-electrode system, takes a salt bridge as a conductive medium and an oxygen permeable membrane as a gas filter, adopts a microfluidic pipeline design, and controls flow resistance and blood flow velocity through the microfluidic pipeline so that blood continuously flows through the surface of the oxygen sensor, thereby realizing continuous detection of arterial blood oxygen. The specific structure is as follows:
the integrated electrochemical sensor element sequentially comprises a glass substrate 1, an electrode layer 2, a salt bridge 3 and a filter layer 4, wherein the glass substrate 1 is used as a substrate, the electrode layer 2 is arranged on the upper surface of the glass substrate, the salt bridge 3 which is electrically contacted with an electrode is arranged on an electrode reaction area of the electrode layer 2, and the filter layer is formed on the salt bridge 3; the electrodes are double electrodes, namely a working electrode and a reference electrode respectively, the reference electrode is an Ag/AgC l reference electrode, each electrode respectively comprises a lead wire 2-1 and a reaction area 2-2, the lead wires 2-1 are in contact connection with the reaction areas 2-2, the electrodes are prepared on a glass substrate through an ink-jet printing technology, the reference electrode is subjected to chlorination treatment, the salt bridge is used for filling an electrolyte tank and covering the double electrodes, and the salt bridge is hydrogel containing salt ions, such as zinc sulfate (ZnSO) 4 ) The salt bridge is prepared by the following method: each 1.229g of sulfobetaine methacrylate (SBMA) was dissolved in 1mL of 0.1M anhydrous zinc sulfate, 6.78mg of monobromoacetic acid (MBAA) was added, the ice water bath was 30min, 2mg of ammonium sulfate (APS) and 2 μl of tetramethyl ethylenediamine (TEMED) were added, and finally polymerized at 37 ℃ to form a salt bridge; the filter layer (4) is an oxygen permeable membrane and is suitable for blocking other components except oxygen in a gas medium.
The integrated micro-fluidic channel element sequentially comprises an electrolyte tank 5 and a packaging layer 6, and the packaging layer 6 is arranged above the electrolyte tank 5; the electrolyte tank 5 is located locally above the electrode layer of the integrated electrochemical sensor element. The electrolyte tank 5 is a cavity with an annular structure, a hole groove is reserved in the middle of the electrolyte tank, the hole groove is located right above the electrode layer reaction area, part of the cavity is located right above the lead wire of the electrode layer, a salt bridge is filled in the hole groove, the electrolyte tank is in a liquid state before heating and polymerization, after the liquid salt bridge is filled in the internal cavity of the electrolyte tank, the salt bridge and the oxygen permeable membrane are heated and polymerized, the surface area of the oxygen permeable membrane is identical to the surface area of the salt bridge, the surface area of the oxygen permeable membrane is completely covered and attached to the upper surface of the salt bridge, a completely sealed cavity structure is formed on the upper surface of the electrolyte tank, and the electrolyte tank is electrically contacted with the electrode layer on the electrode reaction area. The lower surface of the packaging layer 6 is provided with a microfluidic flow path 7, the microfluidic flow path 7 adopts a curve-shaped adjusting flow path and is in direct contact with the upper surface of the filter layer 4, and two ends of the microfluidic flow path are respectively provided with a liquid inlet hole and a liquid outlet hole.
The materials of the glass substrate and the integrated microfluidic channel element are Polydimethylsiloxane (PDMS), and the glass substrate, the electrolyte tank and the encapsulation layer are bonded layer by oxygen Plasma (Plasma). The electrolyte tank and the packaging layer are made of Polydimethylsiloxane (PDMS), and after the surface of the electrolyte tank and the packaging layer is modified by oxygen Plasma (Plasma), the hydrophilicity of the surface of the Polydimethylsiloxane (PDMS) is improved, so that the anti-adsorption performance of the Polydimethylsiloxane (PDMS) is improved, and the anti-coagulation function of the chip is improved. The common electrolyte is a solution containing salt ions, so that the unavoidable heating procedure in the chip processing process can cause volatilization of the electrolyte, the liquid electrolyte has large volume, the packaging is difficult or the chip volume after the packaging is overlarge, a salt bridge is selected as the electrolyte, the salt bridge can realize the conduction between a working electrode and a reference electrode while fixing an oxygen permeable membrane and the electrode, and the current base line of the integrated electrochemical sensor is improved; meanwhile, the upper surface of the salt bridge and the oxygen permeable membrane after heating and polymerization is flat, so that the micro-fluidic chip has a good sealing effect, and is beneficial to miniaturization of the micro-fluidic chip, thereby reducing the consumption of blood.
The preparation process of the continuous arterial blood oxygen detection chip based on the microfluidic technology comprises the following specific processing processes:
(1) Attaching an electrode layer to a glass substrate by inkjet printing; a microfluidic flow path (curve type regulating flow path) on the lower surface of the packaging layer is obtained by pouring polydimethylsiloxane (which is a commercial product and is used after the brand of the product is Dow Corning, PDMS and a curing agent are mixed according to the ratio of 10:1) on a die, and heating (80 degrees, 1 h) for curing;
(2) Bonding an electrolyte tank with the electrode layer and the glass substrate, wherein Plasma (300W, 30 s) is adopted to respectively treat the glass substrate, the electrode layer and the electrolyte tank, heating is carried out after bonding (80 ℃ for 30 min), and a 1cm multiplied by 0.5cm hole tank is reserved in the middle of the electrolyte tank;
(3) Dropping the salt bridge into the middle hole groove of the electrolyte tank, covering an oxygen permeable film (for example, PTFE film) with the same size as the hole groove, heating at 37 ℃ to polymerize and solidify the salt bridge, so that the filter layer is adhered to the upper surface of the salt bridge, and sealing and flattening the middle of the electrolyte tank are realized;
(4) Bonding the packaging layer with the electrolyte tank, treating with Plasma (100W, 30 s), heating (80deg.C, 30 min) after bonding, arranging a curve flow path of 1cm×0.1cm on the lower surface of the packaging layer, and arranging liquid inlet and liquid outlet at two ends of the flow path respectively;
(5) Adhering conductive silver adhesive and a lead: the conductive wire is glued at the tail end of the lead wire of the electrode layer by conductive silver glue and is heated at 60 ℃ for solidification; and (3) dripping ultraviolet curing glue on the connection area of the conductive wire and the lead wire, and irradiating for 5min by using an ultraviolet lamp to realize curing, so that the purpose of insulation is achieved.
The preparation flow of the electrode layer is as follows: gold ink and silver ink are printed on a glass substrate by adopting an ink-jet printing technology, and are heated and sintered, and 100 mu L of 50mmol/L FeCl is added dropwise on a reference electrode 3 The electrode 20s was chloridized, and after jet printing, sintered for 2h at 250℃using a heating plate (C-MAG HP 10, IKATIHERM, germeny). The ink-jet printer used was a Jetlab4 ink-jet printing system from micro fab, usa; the gold Ink was UTDAuIJ Ink of UT Dots, and the silver Ink was Smart' Ink S-CS01130 Ink of Sigma Co.
As shown in FIG. 2, co is the oxygen partial pressure at the outer side of the oxygen permeable membrane, and Ci is the oxygen partial pressure at the inner side of the oxygen permeable membrane. When in measurement, a certain voltage is applied between the two electrodes, after a period of power-on, the concentration of dissolved oxygen in the sensor is basically reduced to zero, at the moment, due to the action of concentration difference, the dissolved oxygen in the solution outside the sensor enters the sensor through the polymer membrane, and is diffused to the surface of the working electrode through electrolyte between the oxygen permeable membrane and the working electrode, and oxidation-reduction reaction occurs on the electrode. The potential and current signals are detected by an electrochemical workstation and other instruments, and the oxygen partial pressure in the solution is measured.
For testing the detection performance, the continuous arterial blood oxygen detection chip based on the microfluidic technology is applied as follows:
the blood gas quality control liquid flows in from the liquid inlet hole of the packaging layer, flows out from the liquid outlet hole after filling the microfluidic flow path, adopts 3 standard-level blood gas quality control liquids ( level 1,2 and 3 of Denmark Rey company) and takes 5 solutions which are formed by mixing level1 and level2 and level3 according to the volume ratio of 1:1 as the solution to be measured (PO) 2 Ranging from 0 to 200 mmHg). It can be seen that PO 2 Response current value and PO of sensor 2 The values have good linear correlation, the average absolute error of the measured value of PO2 compared with the true value is not more than 5mmHg, and the measured results are shown in table 1, fig. 6 and fig. 7.
Table 1 PO 2 Test results of sensor
It can be seen that the continuous arterial blood oxygen detection chip based on the microfluidic technology has the following advantages:
(1) An integrated electrochemical sensor element is designed. PO detection in blood by using membrane-covered electrode method 2 The prepared Clark type dissolved oxygen sensor has simple principle and high precision; the salt bridge is adopted to replace the traditional liquid electrolyte, and the manufactured chip has small volume and low blood consumption; and the oxygen is selectively detected by adopting an oxygen permeable membrane. The high-precision and selective detection of arterial blood oxygen is realized as a whole.
(2) The integrated micro-fluid channel element is designed, the structural size of the micro-pipeline is optimized, so that blood can smoothly flow through the surface of the oxygen permeable membrane, and a curve flow path structure is adopted, so that the contact area between the blood and the oxygen permeable membrane is increased as much as possible, and the sensitivity of the chip is improved. The continuous and real-time detection of arterial blood oxygen is realized as a whole.
(3) Each structure inside the chip is bonded layer by layer, so that the package inside the chip is realized, the sensor element inside the chip is protected, and the service life of the chip is prolonged.
In conclusion, the continuous arterial blood oxygen detection chip integrally realizes high-precision, selective, continuous and real-time detection of arterial blood oxygen.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. A continuous arterial blood oxygen detection chip based on a microfluidic technology is characterized in that: the device comprises an integrated electrochemical sensor element and an integrated micro-fluid channel element, adopts the Clark type limiting current sensor principle of a double-electrode system, adopts a salt bridge as a conductive medium, adopts an oxygen permeable membrane as a gas filter, adopts a micro-fluid pipeline design, and controls flow resistance and blood flow velocity through the micro-fluid pipeline so that blood continuously flows through the surface of the oxygen sensor, thereby realizing continuous detection of arterial blood oxygen.
2. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 1, wherein: the integrated electrochemical sensor element sequentially comprises a glass substrate (1), an electrode layer (2), a salt bridge (3) and a filter layer (4), wherein the glass substrate (1) is used as a substrate, the electrode layer (2) is arranged on the upper surface of the glass substrate, the salt bridge (3) which is electrically contacted with an electrode is arranged on an electrode reaction area of the electrode layer (2), and the filter layer is formed on the salt bridge (3); the salt bridge is used for filling the electrolyte tank and covering the double electrodes, and the filter layer (4) is suitable for blocking other components except oxygen in a gas medium.
3. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 2, wherein: the electrode is a double electrode, namely a working electrode and a reference electrode, each electrode comprises a lead (2-1) and a reaction area (2-2), and the lead (2-1) is in contact connection with the reaction area (2-2).
4. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 2, wherein: the salt bridge is hydrogel containing salt ions.
5. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 2, wherein: the filter layer (4) is an oxygen permeable membrane, the size of the filter layer is the same as that of the salt bridge, and the filter layer is completely covered and attached on the upper surface of the salt bridge.
6. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 1, wherein: the integrated micro-fluidic channel element sequentially comprises an electrolyte tank (5) and a packaging layer (6), wherein the packaging layer (6) is arranged above the electrolyte tank (5); the electrolyte tank (5) is located locally above the electrode layer of the integrated electrochemical sensor element.
7. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 6, wherein: the electrolyte tank (5) is a cavity with an annular structure, a hole groove is reserved in the middle of the electrolyte tank, the hole groove is located right above the electrode layer reaction area, part of the cavity is located right above the lead wire of the electrode layer, a salt bridge is filled in the hole groove, the salt bridge is liquid before heating and polymerization, after the liquid salt bridge is filled in the internal cavity of the electrolyte tank, the salt bridge and the oxygen permeable membrane are heated and polymerized, a completely sealed cavity structure is formed on the upper surface of the electrolyte tank, and the electrolyte tank is in electrical contact with the electrode layer on the electrode reaction area.
8. The microfluidic technology-based continuous arterial blood oxygen detection chip according to claim 6, wherein: the lower surface of the packaging layer (6) is provided with a micro-fluid flow path (7) which is in direct contact with the upper surface of the filter layer (4), and two ends of the micro-fluid flow path are respectively provided with a liquid inlet hole and a liquid outlet hole.
9. The process for preparing the continuous arterial blood oxygen detection chip based on the micro-fluidic technology according to any one of claims 1 to 8, wherein the process comprises the following steps: the specific processing technology is as follows:
(1) Attaching an electrode layer to a glass substrate by inkjet printing; pouring polydimethylsiloxane on a die through a microfluidic flow path on the lower surface of the packaging layer by the die, and heating and curing to obtain the micro-fluidic packaging layer;
(2) Bonding the electrolyte tank, the electrode layer and the glass substrate together, wherein Plasma is adopted to treat the glass substrate, the electrode layer and the electrolyte tank respectively, and heating is carried out after bonding;
(3) Dropping the salt bridge into the middle hole groove of the electrolyte tank, covering a filter layer with the same size as the hole groove, heating at 37 ℃ to solidify the salt bridge, so that the filter layer is adhered to the upper surface of the salt bridge, and sealing and flattening the middle of the electrolyte tank are realized;
(4) Bonding the packaging layer and the electrolyte tank together, adopting Plasma to process, and heating after bonding;
(5) Preparation of conductive and insulating portions: the conductive wire is glued at the tail end of the lead wire of the electrode layer by conductive silver glue and is heated at 60 ℃ for solidification; and (3) dripping ultraviolet curing glue on the connection area of the conductive wire and the lead wire, and irradiating for 5min by using an ultraviolet lamp to realize curing, so that the purpose of insulation is achieved.
10. The preparation process of the continuous arterial blood oxygen detection chip based on the micro-fluidic technology according to claim 9, which is characterized in that: the electrolyte tank and the packaging layer are made of polydimethylsiloxane, and after the oxygen plasma surface is modified, the hydrophilicity of the polydimethylsiloxane surface is improved, so that the anti-adsorption performance of the polydimethylsiloxane is improved, and the anticoagulation function of the chip is improved.
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| CN101881749A (en) * | 2010-06-25 | 2010-11-10 | 浙江大学 | All-solid state dissolved oxygen sensor and preparation method thereof |
| CN103424451A (en) * | 2013-08-26 | 2013-12-04 | 深圳市希莱恒医用电子有限公司 | Card type potassium ion sensor and method for preparing card type potassium ion sensor |
| CN111948275A (en) * | 2020-08-27 | 2020-11-17 | 江苏农林职业技术学院 | Dissolved oxygen detection device based on micro-fluidic chip |
| CN113588739A (en) * | 2021-06-17 | 2021-11-02 | 天津大学 | Continuous arterial blood detection system |
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- 2023-01-17 CN CN202310057148.8A patent/CN116106390A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101881749A (en) * | 2010-06-25 | 2010-11-10 | 浙江大学 | All-solid state dissolved oxygen sensor and preparation method thereof |
| CN103424451A (en) * | 2013-08-26 | 2013-12-04 | 深圳市希莱恒医用电子有限公司 | Card type potassium ion sensor and method for preparing card type potassium ion sensor |
| CN111948275A (en) * | 2020-08-27 | 2020-11-17 | 江苏农林职业技术学院 | Dissolved oxygen detection device based on micro-fluidic chip |
| CN113588739A (en) * | 2021-06-17 | 2021-11-02 | 天津大学 | Continuous arterial blood detection system |
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