A kind of minimally-invasive wireless blood glucose detecting systemTechnical field
Blood glucose technical field is surveyed the present invention relates to human body minimally-invasive in medicine equipment, is specifically the daily survey blood glucose for being combined with MEMS sensor and wireless detector and reaching diabetes patient, can be used for medical institutions and family uses.
Background technology
Diabetes are to endanger one of four big diseases of human health, and it is that insulin is relative in human body or definitely not enough and target cell, to a kind of chronic disease caused by insulin sensitivity reduction, is clinical multiple illness.
Diabetic in order to avoid diabetes complication, it is necessary to continually measure and control blood sugar concentration, there is presently no the method for thorough radical cure diabetes, the method for diabetic's measurement blood sugar concentration is largely the blood-glucose meter using aculeus blood-taking.Two relatively conventional major class blood-sugar detecting instruments in the market：Electrochemical process and light lift-off technology, electrochemical process detect blood glucose value using the principle of the current signal produced in detection course of reaction, and the electronics that enzyme is produced with glucose response reads the quantity of electronics, be then converted into readings of glucose concentration by electric current numeration facility.Reflection method is to detect the color change of strip in course of reaction to react blood glucose value, the intermediate produced by the reaction of enzyme and glucose, with the intensity of the transmitting light of detector Test paper reflecting surface, by the intensity of these reflected lights, changes into concentration of glucose.
This current two classes blood-sugar detecting instrument is all mainly that the blood glucose in blood samples of patients is measured using directly detection blood, but frequently blood sampling carries out the measurement of blood glucose concentration and on the one hand brings huge financial burden and medical expense to diabetic, the risk of huge body and mental anguish and infectious disease is on the other hand also brought to diabetic.
The invention provides a kind of minimally-invasive wireless blood glucose detecting system based on hydrogel.By minimally-invasive and contact human skin, then just blood glucose can be surveyed with the method for wireless exploration within a certain period of time, the problem of to solve to propose in above-mentioned background technology, so that the very big pain that must reduce patient frequently in blood collection procedure, while enough blood glucose level datas can be obtained.After this hydrogel comes out from nineteen ninety, certain attention is caused【Document 1】.But the response speed and volume of this hydrogel are directly proportional, volume causes response speed slack-off compared with conference.The present invention is successfully integrated with the hydrogel and MEMS of micron level, so as to considerably improve the response speed of sensor, and sensor is had enough signal susceptibilitys.
Simultaneously, compared with enzyme process sensor, hydrogel does not bring heterologous organisms macromolecular into, and the biocompatibility of hydrogel is also used widely in other fields such as contact lenses etc., the stability and the repeatable advantage for bringing cost and accumulating condition of its physical properties for product yet.
The content of the invention
To achieve the above object, the present invention provides following technical scheme：Minimally-invasive wireless blood glucose detecting system, including MEMS sensor (1) and wireless detector (2) on the basis of hydrogel.MEMS sensor wherein on the basis of hydrogel includes hydrogel (4), microporous barrier (5), spring glass film (6), capacitor board (7), inductance coil (8), and silicon substrate (9).Microporous barrier (5) can accomplish that diameter is less than 0.5 millimeter, and skin contacts and slightly punctures skin, so as to reach effect of the body fluid pervious by microporous barrier.Hydrogel (4) and body fluid are contacted with each other, and the concentration of glucose in body fluid can make this special hydrogel produce Volume Changes.With the spring glass film (6) of Hydrogel contact flexibility change is produced under the hydrogel effect of expansion.In the opposite side of spring glass film, integrated a pole of capacitor board (7), the capacitor board of bending makes capacitance change.And electric capacity and inductance coil (8) form the miniature resonant lc circuit of a closure.
The micropore membrane volume of MEMS sensor can be made smaller than 0.5 millimeter of diameter, slightly puncture after skin just can and bioresorbable, in order to not influence the daily life of diabetes patient, sensor can be attached on skin with mackintosh.Within a certain period of time, such as 14 days to one month, patient can read blood glucose value with portable wireless detector.
External wireless detector includes transmitting coil, in the operating condition, and transmitting coil can repeatedly send wireless RF pulse signal (than the pulse signal of the 10MHz if any the 10kHz repetition periods).When pulse signal frequency and sensor miniature resonant lc circuit intrinsic frequency resonance when, transmitting coil senses signal, by amplifying circuit, and signal is input to phase-locked loop (PLL).When lockin signal occurs, output signal can just read the frequency of resonant LC-circuit.This technology can make the portable unit of very little, so as to be convenient for carrying and the measured value of pickup exactly.
It is used as further scheme of the invention：Wireless detector can make the module being connected with mobile phone, and such patient can read blood glucose value and store with mobile phone, or by bluetooth, the method for WIFI or wireless telecommunications uploads data on the net, can be referred to for doctor.
Compared with prior art, the beneficial effects of the invention are as follows：
1. the present invention process and manufacture sensor using advanced semiconductor fabrication process, by a minimally-invasive puncture skin it is shallower in the state of be attached on body, within a certain period of time just can with wireless exploration method read blood glucose value at any time.So as to greatly mitigate and eliminate the pain of frequent blood collection procedure, especially to the daily measurement of diabetes patient, it is to avoid the pain that traditional blood sampling measurement is brought.
2. the MEMS sensor of the present invention can be attached to each position of body; such as forearm and thigh; the micro volume of sensor and the defencive function of mackintosh can not influence the daily life of patient to greatest extent; great convenience and safety are brought to user, while reducing the infection risk frequently taken a blood sample.
Brief description of the drawings
Fig. 1 is the minimally-invasive wireless blood glucose detecting system of the present invention, including MEMS sensor and the structural representation of wireless detector on the basis of hydrogel.In figure：1- MEMS sensors, 2- wireless detectors, 3- skins.
Fig. 2 be hydrogel on the basis of MEMS sensor structural representation.In figure：4- hydrogels, 5- microporous barriers, 6- spring glass film, 7- capacitor boards, 8- inductance coils, 9- silicon substrates.
Response diagrams of the Fig. 3 for a kind of molecular formula of polyphenyl boric acid hydrogel and with glucose molecule.
Fig. 4 is the polyphenyl boric acid hydrogel volume and the change measured value of blood sugar concentration used in the present invention.
Fig. 5 is the schematic diagram of the test device circuit used in the present invention.In figure：Variable capacitance in the transmitting coils of 10- wireless detectors, the inductance coil of 11- MEMS sensors, 12- MEMS sensors.
Fig. 6 is the impedance phase value and the variation diagram of scan frequency of the wireless detector measured by the present invention.The corresponding frequency of minimum point of phase impedance curve is consistent with sensor intrinsic frequency.
Fig. 7 is the frequency and the changing value of concentration of glucose measured by the present invention.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described, it is clear that described embodiment is only a part of embodiment of the invention, rather than whole embodiments.Based on the embodiment in the present invention, the every other embodiment that those of ordinary skill in the art are obtained under the premise of creative work is not made belongs to the scope of protection of the invention.
Referring to Fig. 1, a kind of minimally-invasive wireless blood glucose detecting system in the embodiment of the present invention, including MEMS sensor and wireless detector on the basis of hydrogel.The microporous barrier of sensor one end can accomplish that diameter is less than 0.5 millimeter, and skin contacts and slightly punctures skin, so as to reach effect of the body fluid pervious by microporous barrier.The hydrogel that this sensor is used is the hydrogel to glucose-sensitive, is contacted with each other when with body fluid, and the concentration of glucose in body fluid can make this special hydrogel produce Volume Changes.Microporous barrier has certain mechanical strength, and deformation comparison is small.When hydrogel expands, and the spring glass film of Hydrogel contact occurs to change than significantly flexibility.In the opposite side of spring glass film, integrated a pole of capacitor board.Because capacitance is inversely proportional with the distance of two ends capacitor board, the capacitor board of bending makes capacitance change.And electric capacity and inductance coil (5) form the miniature resonant lc circuit of a closure, so that the intrinsic frequency of resonance circuit changes.So far the change of blood sugar of body fluid changes with regard to that can be converted into the frequency of resonance circuit in sensor.
The micropore membrane volume of MEMS sensor can be made smaller than 0.5 millimeter of diameter, and very slight pain can be brought to patient by so puncturing skin, and also imperceptible in daily life.It is slight puncture after skin just can and bioresorbable, in order to not influence the daily life of diabetes patient, sensor can be attached on skin with mackintosh.Within a certain period of time, such as 14 days to one month, patient can read blood glucose value with portable wireless detector.The bore dia of very little, such as 1~5 micron can be used in microporous barrier.Glucose so in body fluid, moisture and other small molecules can pass through, but cannot pass through than larger cell etc., so as to avoid cell from being attached on hydrogel, extend the service life of hydrogel.
External wireless detector includes transmitting coil, in the operating condition, and transmitting coil can repeatedly send wireless RF pulse signal (than the pulse signal of the 10MHz if any the 10kHz repetition periods).When pulse signal frequency and sensor miniature resonant lc circuit intrinsic frequency resonance when, transmitting coil senses signal, by amplifying circuit, and signal is input to phase-locked loop (PLL).When lockin signal occurs, output signal can just read the frequency of resonant LC-circuit.Schematic diagram such as Fig. 5 of test device circuit used in the present invention：The transmitting coil of wireless detector can send electromagnetic wave, and so as to be coupled with the inductance coil in MEMS sensor, and the capacitance of resonance circuit is changed as concentration of glucose changes.When the frequency of electromagnetic wave and the resonant circuit frequency of MEMS sensor resonate, there is a minimum point in the impedance phase value of wireless detector, and the corresponding frequency of this minimum point is consistent with sensor intrinsic frequency.When Fig. 6 is shown in different concentration of glucose, the frequency of minimum point is offset.The frequency of resonant LC-circuit can directly be read with detector by using the technology of phase-locked loop (PLL).The technology of above detector can make the portable unit of very little, so as to be convenient for carrying and the measured value of pickup exactly.Before this product use, the frequency of sensor is needed to be calibrated, and corresponding frequency can be just found out using the serum of different blood glucose values, so as to reach the corresponding degree of accuracy.Fig. 7 is the frequency and the changing value of concentration of glucose measured by the present invention.As concentration of glucose is raised, the frequencies go lower of measurement.By changing the volume of hydrogel, the thickness of spring glass film and the parameter of other MEMS sensors, the sensitivity value of frequency and concentration of glucose can be improved a lot, so as to measure the blood glucose minor variations in diabetes patient's body.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, and without departing from the spirit or essential characteristics of the present invention, the present invention can be realized in other specific forms.Therefore, no matter from the point of view of which point, embodiment all should be regarded as exemplary, and be nonrestrictive, the scope of the present invention is limited by appended claims rather than described above, it is intended that all changes fallen in the implication and scope of the equivalency of claim are included in the present invention.Any reference in claim should not be considered as to the claim involved by limitation.
In addition, it should be understood that, although the present specification is described in terms of embodiments, but not each embodiment is only comprising an independent technical scheme, this narrating mode of specification is only for clarity, the skilled in the art should refer to the specification as a whole, and the technical solutions in the various embodiments may also be suitably combined, and other embodiments which can be understood by those skilled in the art for formation.
【Document 1】Chen, G.H., et al., A glucose sensing polymer.Nature Biotechnology, 1997.15：p.354-357.