CN104132969A - Novel portable thrombus detection device - Google Patents
Novel portable thrombus detection device Download PDFInfo
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- CN104132969A CN104132969A CN201410362663.8A CN201410362663A CN104132969A CN 104132969 A CN104132969 A CN 104132969A CN 201410362663 A CN201410362663 A CN 201410362663A CN 104132969 A CN104132969 A CN 104132969A
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Abstract
The invention relates to a design and manufacture method of a portable thrombus detection device, and is characterized in that a silicon-based graphene material and an advanced micro-nano processing technology are utilized, and the difference of phase change inversion points of normal blood and thrombus patient blood in a blood coagulation process is utilized to achieve early detection and diagnosis of thrombus diseases. The portable detection device has the width of about 3-5 cm and the length of about 8-11 cm, and a power supply device, a signal processor and an in-vitro blood detection chip are all integrated in the portable detection device. The portable device is a disposable type single-use medical diagnostic device. When in use, a patient or a medical worker only requires to perform fingertip blood sampling of 2-5 microliters of blood on the patient, the blood is placed at the middle of the detection chip, the power supply is turned on, the blood coagulation process is completed in 2-3 minutes, and a detection result is displayed and prompted in voice and digital forms by a processing circuit.
Description
Technical field
The present invention relates to a kind of novel advanced Portable thrombus detection system and method for making, specifically, is to utilize semiconductor micro-nano processing technology to realize the miniature integrated chip manufacturing of Portable thrombus sensing in conjunction with semiconductor and grapheme material.By metal lead wire, detection chip is connected with process chip with power supply and signals collecting, realize in coagulation process, the monitoring that blood phase transformation transforms, thus provide detected blood and suffer from the diagnosis reference frame of thrombus disease.The invention belongs to medical instruments field.
Background technology
Thrombus is the clot forming in blood vessel, in the circulation system, can hinder or blocking blood flow.Work as vascular injury, the blood platelet in blood and fibrin can be assembled and form clot and repair it, lose blood or cause blood vessel further to injure because blood flow impacts avoiding.If but clot comes off, just probably become thrombus.The elderly's blood vessel aging, vascular wall is impaired, easily suffers from hypertension, artery sclerosis, diabetes.After vascular endothelial cell is impaired, the thromboplastin of generation increases, and promotes fibrin ferment to form, and blood coagulation flavine A2 also increases, and manufactures anticoagulant substances prostacyclin simultaneously and reduces, and easily brings out thrombosis.While increasing as blood sugar, the haemoglobin of sugar in red blood cell is combined, and makes body tissue's anoxic, and at this moment platelet aggregation strengthens, and viscosity increases, and easily promotes thrombosis.If thrombus occurs in cardia, clinical manifestation is heart thromboembolism or miocardial infarction so; If thrombus occurs in cerebral vessels, clinical manifestation is cerebral thrombus or headstroke so.
The formation of thrombus, generally has endothelium, clotting factor, and blood platelet, fibrinogen participates in, and these can form thrombus.Body has very strong balanced capacity, do not allow thrombus continue to increase, form immediately Fibrinolysis system, carry out thrombus, reach mobile equilibrium, body is all at every moment like this, and the formation thrombus of doing is exactly that balance has been destroyed, blood fat just causes blood viscousness, a link of slow blood flow, endothelial function certainly, hypercoagulative state is also reason.More thickness, blood flow is slower, easier thrombus.
Thrombus more complicated, has involved too many levels, and the patient that hospital seeks medical advice generally falls ill, or high-risk patient, treats fairly simplely, is exactly antithrombotic, has a lot of medicines.Key is, the thrombus high-risk patient that you measure, and parameter is a lot of in vivo; can not be which link is out of joint certainly to hospital exactly; unless as myocardial infarction or cerebral thrombus, these are that blood platelet is out of joint more certainly, or lower limb vein thrombus, coagulation function is out of joint.
In general thrombosis is mainly by three factors: 1 slow blood flow, 2 hypercoagulative state 3 endothelial injuries.
It is the hot issue of global medical domain research that thrombus detects with early warning always.Along with the increase of China's aging proportion, the morbidity rate of thrombus and apoplexy also significantly improves.Last the follow-up investigation to cerebral apoplexy in 3 years according to authoritative institution.The existing Patients with Stroke 3,000,000 of China, annual dead up to 1,000,000.The incidence of disease occupies second place of the world, is only second to Russia.China News Service on July 19th, 2012, annual new Patients with Stroke approximately 2,000,000 people of China, and to be often close on 9% speed rising.According to the World Health Organization's 2011 annual datas: just have 1 people may suffer from apoplexy in every 6 people in the whole world; within every 6 seconds, just there is 1 people to die from apoplexy; be faced with the crisis of " people's apoplexy " whole family paralysis in ten million paralytic family of China, paralytic has become China first " unhappy colony ".How effectively preventing and treating harm that apoplexy brings becomes the to be separated problem of pendulum in face of in the whole society, needs that society is common to be paid close attention to and rescue.
Existing thrombus checkout equipment is mainly divided into following a few class:
1, mechanical transmission-type thrombus detection system: this system comprises machine driven system, temperature-controlling system, microcomputer program control system, change operating room and the most of composition of film face-plate display system five.It detects principle is that the temperature of controlling in instrument is 37 degree, is the same with human temperature. the speed that instrument rotates is the same with the speed of blood circulation of human body.By the centrifugation technique of instrument, the thrombus factor of carrying in one milliliter of blood in body is flocked together, see thrombosed length, the dry weight of thrombus and weight in wet base, thus judge the weight of disease.The method is because need machine driven system, so expensive, maintenance cost is expensive, and equipment failure rate is high.
2, thrombus alignment sensor: go out a kind of flexibility memory apparatus of being made by laser diode and spiral fashion high molecular polymer by advanced sensor network technological development, utilize the accurate positioning instant of CT can take out embolus after being inserted into arteria carotis.Equipment is made up of microsensor unit and smart mobile phone.Microsensor can real time record under patient's physiological signal comprise cardiogram, temperature, blood sugar, blood pressure etc., sight sensor has comprised the accelerometer of surveying motion, surveys temperature, the noise transducer of environment, the skin conductance meter of thought-read reason etc.Finally, these integrated datas can pass to patient, family numbers of patients and related doctor by smart mobile phone.This detecting sensor is only in the conceptual phase, and need to implant at arteria carotis, and operation cost is all relative very large with risk.
3, the data collector of thrombus elastic force detector (CN 203203993 U): comprise the sensor measurement output module, A/D conversion circuit, single-chip microcomputer and the serial communication circuit that connect successively, on single-chip microcomputer, be also connected with crystal oscillating circuit, A/D conversion circuit, single-chip microcomputer and serial communication circuit are also connected with power circuit respectively.Adopt single-chip microcomputer to analog/digital converter carry out at a high speed, real-time data acquisition and controlling, reasonable in design, simple in structure, can be at a distance, Real-time Collection conversion detects data with sending, strong adaptability to environment simultaneously, cost stable and reliable for performance is lower, highly versatile, safe.Although this method is state-of-the-art detection method, equipment cost costliness, single detects patient's cost and exceedes 1500 yuans.And apparatus expensive, maintenance cost is high, makes a definite diagnosis use so this equipment is only suitable for hospital clinical, and is not suitable for portable household and ambulance, the preliminary screening diagnosis of hospital.
4, (CN 1878504 A of the thrombus checkout equipment based on ultrasonic transducer, JP-A-2001-327495): this ultrasonic transducer thrombus checkout equipment mainly comprises: transducer, be attached to the monitor portion of detected object, and transmit and receive ultrasound wave; Transmitter and receiver unit, launches and applies driving pulse to transducer, and receiving from the echoed signal of transducer output; And use hyperacoustic detecting device, process the output signal of transmitter and receiver unit (11), and detect by the thrombus of blood vessel; And/or light source, produce biopsy light; Probe, is attached to the monitor portion of detected object, and irradiates biopsy light from light source to detected object; Light receiving unit, receives from probe and irradiates and pass through the biopsy light of detected object, and according to the biopsy light intensity receiving, output electrical signals; And the detecting device of use live body light, process the output signal of light receiving unit, and detect by the thrombus of blood vessel.This equipment volume is huge, and simultaneously cost costliness needs ultrasonic transducer and the optical detection use that combines.
Several existing equipments above, all can not realize miniaturization, and portable thrombus detects.Novel portable thrombus checkout equipment involved in the present invention, semiconductor based on advanced and grapheme material, by advanced micro-nano process technology, realize the wafer level low-cost production of thrombus detection chip, in conjunction with miniaturization button-type battery and highly integrated signals collecting and process chip, form a set of portable quick thrombus detection system.
Summary of the invention
The object of the present invention is to provide a kind of method for making of novel portable checkout equipment.
In structure, advanced Portable thrombus checkout equipment provided by the invention comprises power supply unit, thrombus detection chip and signals collecting and treatment circuit.This Portable thrombus detection system one-piece construction as shown in Figure 1, its thrombus detection chip fabrication processing as shown in Figure 2:
1, adopt high resistant silicon chip, or other high resistivity substrate, the standard cleaning of first carrying out micro-nano processing;
2, will transfer on HR-Si substrate through graphene film high growth temperature or plasma deposition growth;
3, carry out gluing, adopt micro-resistance mask plate of design, realize the graphical of photoresist by uv-exposure development;
4, by oxygen gas plasma chemical etching or argon plasma physical etchings, realize the figure of photoresist is transferred on graphene film, form the micro-resistance of Graphene;
5, adopt the methods such as acetone wet method or plasma dry to remove photoresist;
6, by methods such as magnetron sputtering or electron beam evaporations, realize metallic film deposit;
7, resist coating again, and utilize the photolithography plate of metal interconnection lead-in wire carry out ultraviolet photolithographic and develop, realize the graphical of photoresist;
8,, by dry etching or the wet etching of metal, realize the graphical of metal interconnection lead-in wire;
9, adopt the methods such as acetone wet method or plasma dry to remove photoresist, the wafer level that completes thrombus detection chip is made.
In sum, the invention provides a kind of novel portable thrombus and detect micro-system, based on the power supply of button level [D1] power supply, thrombus detection chip is for the detection of liquid phase in blood clotting process and solid transformation process, by data sampling and processing and the quantitative Graphical output of data acquisition and processing (DAP) chip.The principle of work of thrombus detection chip is that in blood clotting process, liquid phase and solid transformation process cause that the micro-resistance resistance value of graphene film changes, realize the micro-resistance resistance change of Graphene by Wheatstone bridge testing circuit, and then provide detected blood and exist the quantitatively graphical testing result output of potential thrombus risk.
The present invention has adopted Graphene advanced material, makes micro-resistive element by micro-processing technology, the sensitive element detecting as thrombus.And in conjunction with Wheatstone bridge data acquisition and processing (DAP) chip, realize the output of testing result.By blood simulated experiment, this device rate of accuracy reached to 99.9%, can be quantitative provide is detected the existing thrombus disease risk of blood, early detection and early treatment for thrombus disease have breakthrough contribution, can greatly reduce the great pain that thrombus and paralytic and household thereof bear.
The application of Portable thrombus checkout equipment involved in the present invention mainly comprises:
1, hospital clinical early diagnosis thrombus application;
2, the Portable thrombus such as family expenses and medical ambulance diagnostic application;
3, wartime field emergency, first aid etc. beyond the disasters such as earthquake, is directed to the application that the situation is critical detects of injury blood.
In view of the superior device performance of the present invention and application widely, illustrate that this method is a kind of effectively Portable thrombus detection chip and equipment making method, can realize batch production, be with a wide range of applications, far-reaching social benefit and considerable economic benefit.
With existing method comparison, the Portable thrombus checkout equipment that method for making provided by the invention is made has following characteristics:
1, adopt advanced grapheme material, and utilize its resistance intrinsic property to realize the sensitivity for thrombus;
2, just there is advanced micro-nano processing technology, realize the miniaturization of detection chip;
3,, based on Wheatstone bridge testing circuit, realize accurate detection and the output of detection signal;
4, by the making of wafer level sensing chip, can greatly reduce the cost of manufacture of sensing chip, improve consistance and the yield rate of device;
5, apply feedback compensation signal, can further realize higher device detection resolution by Wheatstone bridge testing circuit;
6, compared with existing device, it is little that this device has volume, low in energy consumption, simple in structure, accuracy of detection is high, use the significant advantage such as simple operation;
7, adopt advanced micro-nano process technology to make, be conducive to the mass production of device, reduce device cost;
9, this device can be widely used in the every field such as field emergency in hospital's blood testing, family's blood health monitoring and extraordinary situation.
Brief description of the drawings
Fig. 1: Portable thrombus detection system structural representation, in figure: 1 is thrombus detection chip, 2 is signals collecting and process chip, 3 is power supply (button cell etc.);
Fig. 2: thrombus detection chip fabrication processing, a high resistant silicon chip substrate is cleaned, and b graphene film is transferred to HR-Si substrate, c resist coating photoetching development, d graphene film etching is graphical, and e removes photoresist, the deposit of f metallic film, g resist coating photoetching development, h metal erosion is graphical, and I removes photoresist, and 4 is high resistant silicon chip, 5 is Graphene, and 6 is photoresist, and 7 is that metal level (can be gold, platinum, titanium, tungsten, chromium, silver, the combination of wherein one or more such as aluminium);
Fig. 3: be the electron scanning micrograph of the micro-resistance of Graphene;
Fig. 4: be the quantitative level graphic output of this Portable thrombus checkout equipment.
Claims (7)
1. a novel portable thrombus checkout equipment, is characterized in that described thrombus checkout equipment is to be made up of power supply, thrombus detection chip and signals collecting and process chip.
2. by thrombus detection chip claimed in claim 1, be the blood coagulation performance by testing and contrast normal blood and tested blood, show blood from liquid state to solid-state phase transformation difference, thereby provide the risk of detected thrombus disease that blood is suffered from.
3. by thrombus detection chip claimed in claim 1, its making is to adopt advanced micro-nano processing technology to make, and technique used comprises that backing material cleans, membraneous material growth deposit, material are graphical, metal lead wire making etc.
4. by signals collecting claimed in claim 1 and process chip, its making is that the ic manufacturing process of employing standard is made, and has the functions such as electrical signal collection, timer timing, signal speech and demonstration output.
5. by power supply claimed in claim 1, be standard commercial button cell, realize the opening and closing control of power supply and signals collecting and process chip and thrombus detection chip by device global switch.
6. the thrombus detection chip of preparation as described in claim 2,3, the difference of sticking the resistive performance under state in conjunction with grapheme material in difference, comprising: the 1. making of the micro-resistance of silica-based Graphene, the 2. making of micro-resistance lead,
Its concrete steps are:
(1) buy the silica-based substrate of high resistivity, substrate also can be the other materials with high resistivity, comprises quartz, glass, high resistivity compound semiconductor substrate, high resistivity polymer substrate or film etc.;
(2) buy the graphene film material based on metal or other materials;
(3) by graphene film material transfer to high resistivity substrate;
(4) by spin coating or spraying, photoresist is applied to the graphene film on HR-Si substrate uniformly, and the photoetching of developing, realize the graphical of photoresist;
(5), by the chemical/physical plasma etching of oxygen or argon gas and other plasma gass, realization is graphical the little graphene film of photoresist mask, realizes the making of the advanced micro-resistance of Graphene;
(6), by the technique such as sputter or electron beam evaporation, realize the making of metal level on the micro-resistance of Graphene;
(7) again by spin coating or spraying, photoresist is applied on the metal level of deposit uniformly, and the photoetching of developing, realize the graphical of photoresist;
(8) by dry etching or wet etching, realize the graphical making of metal lead wire/electrode;
(9) disk of making is carried out to scribing and test resistance signal pre-detection, the thrombus detection chip having completed as described in claim 2,3 is made.
7. the method for making of thrombus detection chip as claimed in claim 6, it is characterized in that having utilized fully high resistant silicon-based substrate and the distinctive resistance phase transformation of advanced grapheme material response characteristic, realize the micro-resistance of Graphene and the interconnected making of metal lead wire by advanced micro-nano processing technology, realize the high-performance of this advanced thrombus detection chip, high integrated, wafer level making cheaply.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114235911A (en) * | 2021-12-23 | 2022-03-25 | 重庆大学 | Electrochemical sensor for choline detection and preparation method thereof |
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| CN202256503U (en) * | 2011-09-23 | 2012-05-30 | 北京大学 | Blood impedance analysis instrument |
| WO2013134107A1 (en) * | 2012-03-06 | 2013-09-12 | Emory University | Nanoenhanced hemostatic device and methods for making a layer having hemostatic properties |
| JP2013221782A (en) * | 2012-04-13 | 2013-10-28 | Sony Corp | Blood coagulation system analyzer, blood coagulation system analysis method and program |
| CN203745411U (en) * | 2014-03-31 | 2014-07-30 | 西门子（中国）有限公司 | Blood coagulation comparison device and blood coagulation comparison components |
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- 2014-08-27 CN CN201410362663.8A patent/CN104132969A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN202256503U (en) * | 2011-09-23 | 2012-05-30 | 北京大学 | Blood impedance analysis instrument |
| WO2013134107A1 (en) * | 2012-03-06 | 2013-09-12 | Emory University | Nanoenhanced hemostatic device and methods for making a layer having hemostatic properties |
| JP2013221782A (en) * | 2012-04-13 | 2013-10-28 | Sony Corp | Blood coagulation system analyzer, blood coagulation system analysis method and program |
| CN203745411U (en) * | 2014-03-31 | 2014-07-30 | 西门子（中国）有限公司 | Blood coagulation comparison device and blood coagulation comparison components |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114235911A (en) * | 2021-12-23 | 2022-03-25 | 重庆大学 | Electrochemical sensor for choline detection and preparation method thereof |
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Application publication date: 20141105 |