CN100450436C - Impedance tomography apparatus based on microneedle electrodes and micro-traumatic measuring method thereof - Google Patents
Impedance tomography apparatus based on microneedle electrodes and micro-traumatic measuring method thereof Download PDFInfo
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- CN100450436C CN100450436C CNB2006101146006A CN200610114600A CN100450436C CN 100450436 C CN100450436 C CN 100450436C CN B2006101146006 A CNB2006101146006 A CN B2006101146006A CN 200610114600 A CN200610114600 A CN 200610114600A CN 100450436 C CN100450436 C CN 100450436C
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Abstract
The invention relates to a resistance chromatography imager based on micro electrode, and relative micro-cut measurement, wherein it uses micro electrode to span the horny layer with high resistance; it can replace traditional surface electrode, to be used as current activator and sensor to sense voltage signal; the measured signal via magnification and filter is input into PC to be processed and displayed via gray diagram or colorful diagram, to represent the resistance distribution. The invention can reduce the effect of skin resistance in current activation and voltage signal collection, with high signal-noise ratio and reduced error, to improve the calculation accuracy and image resolution.
Description
Technical field
The present invention relates to a kind of electrical impedance tomography (EIT) equipment and measuring technique, particularly a kind of impedance tomography apparatus and micro-traumatic measuring method thereof based on microneedle electrodes belong to medical science micro-system and biomedical detection technique field.
Background technology
Electrical impedance tomography technology (electrical impedance tomography, EIT) be the difference of organizing electrical characteristic parameter (as resistivity, dielectric constant) according to interior of articles, by its surface is applied safe exciting current or voltage, the voltage or the current signal on Measuring Object surface are known the distribution of interior of articles electrical characteristic parameter simultaneously, and then reconstruct the image of reflection internal structure of body.This is significant to organism internal electrical The Characteristic Study, and this image has not only comprised abundant anatomic information, and can obtain the information that the electrical characteristics of some tissue and organ change with its pathology, states of physiologic function.And this mode is harmless, can repeatedly measure, and reuses, can become to the patient carry out for a long time, on-line monitor and can not cause damage or bring hospital's custodial care facility of discomfort to the patient.Add with low costly, do not require special working environment etc., thereby be a kind of comparatively ideal, medical imaging technology with broad prospect of application.
Modern mathematics proves, can adopt the electrical impedance inverse problem to find the solution for the successive situation of the anti-distribution single order of regional internal resistance, and then reconstruct obtains electrical impedance distribution figure.For not being that the successive situation of single order will be similar to processing in the actual measurement when calculating inverse problem, so electrical impedance distribution difference is more little, the degree of approximation is good more, and computational accuracy will be high more, and image quality will be good more.Therefore the high impedance layer in measured zone can directly influence the propinquity effect of model, causes computational accuracy to reduce, and the imaging resolution capability greatly reduces.
All adopt the external electrode metering system at present in electrical impedance tomography (EIT) technology, in measurement, electrode directly contacts with human body, is positioned at system foremost.Event on electrode comprises useful information, noise, artifact, contact impedance, polarizing voltage etc., all can enter subsequent conditioning circuit as signal to be exaggerated, to transmit, and participates in signal processing, influences the image reconstruction result.Electrode system structure and performance thereof are for the influence of effective extraction, system's timeliness and the image resolution ratio of EIT front-end information, particularly very big to the extraction of the relatively poor center useful information of EIT detection sensitivity influence, be one of the most responsive and crucial part of whole EIT system.And skin high impedance layer and surface electrode pattern are to cause the immediate cause of high contact impedance, and the external electrode metering system of EIT is a bottleneck of EIT system.The electrical impedance tomography technology that adopts external electrode to measure exists following deficiency and defective:
1. because the outermost horny layer of skin has the characteristic of high impedance, surface electrode is very big with the skin resistance of getting an electric shock indirectly, and very big uncertainty is arranged, and easily introduces to exchange and disturbs, and directivity is poor, and measured signal is very faint and dynamic range is bigger.These all are the sources of causing error, have hindered the accuracy of exciting current, make to calculate and image result inaccurate, and imaging resolution and signal to noise ratio are difficult to balance.
2. existing EIT restructing algorithm is all found the solution based on the electrical impedance continuous model, and surface electrode is high impedance layer when using surface electrode at the electrode-tissue interface, and but existing solving model requires the electrical impedance distribution single order continuous, so surface electrode can not finely satisfy existing continuous model, the approximate processing of this moment will make model accuracy and image resolution ability greatly reduce.
3. EIT measures needs to settle a large amount of electrodes, carry out image reconstruction with mass data, and at present the image reconstruction of EIT is mostly based on point electrode, the surface electrode contact area is big, be similar to and be reconstructed processing according to point electrode this moment, also caused certain error of calculation.
4. because the restriction of its physical dimension, surface electrode has limitation to the measuring object overall size, and the EIT that now can only be applied to macrostructure measures, and the EIT that can't be applied to the microchannel transverse section of using on micro-cell or cell cluster sample and the biochip measures.
As seen, the surface electrode metering system is a bottleneck of restriction EIT system development, and the error that high impedance surface causes is the clinical practice of EIT technological direction, to the necessary problem that solves of practical research development.
Summary of the invention
The objective of the invention is deficiency and defective at the prior art existence, micropin technology among the MEMS is combined with the bio-electrical impedance imaging technology, a kind of electrical impedance tomography device and micro-traumatic measuring method thereof based on microneedle electrodes is provided, solving in the existing electrical impedance imaging technology owing to the computational accuracy that can't avoid the skin high impedance layer to cause is poor, problem such as the low and measurement result of image resolution ability is inaccurate.
Technical scheme of the present invention is as follows:
A kind of impedance tomography apparatus based on microneedle electrodes, comprise the electrode group of forming by exciting electrode and acquisition electrode, single chip machine controlling circuit, signals collecting amplification filtering module and the exciting current control module that links to each other with outfan with the input of described single-chip microcomputer respectively, and the PC that contains control and software for calculation program, described PC carries out two-way data communication by communication module and described single-chip microcomputer, it is characterized in that: described electrode group adopts the microneedle electrodes group.
Microneedle electrodes group of the present invention is made of substrate and the microneedle array that is arranged on this substrate, described substrate and micropin adopt silicon materials to make, on silicon substrate, be provided with through hole, and adhere to conductive metal layer at silicon substrate upper and lower surface, micropin surface, internal surface of hole; Micropin distributes and is spaced apart 50～150 μ m.
In technique scheme of the present invention, described substrate and micropin can also adopt the silicon materials that are mixed with conducting metal to make.
Technical characterictic of the present invention also is: each micropin on the described microneedle array is wedge shape, and the micropin height is 100～300 μ m, and micropin tip portion width is 5～30 μ m.
The invention provides a kind of micro-traumatic measuring method of the electrical impedance tomography based on microneedle electrodes, it is characterized in that this method carries out as follows:
1) a plurality of microneedle array electrode groups is affixed on body surface, penetrates horny layer, thrust skin epidermis, and make electrode retaining collar be around in the same cross section of object to be measured;
2) control sequence of startup PC is selected measurement pattern, i.e. single measurement or continuous detecting pattern;
3) at PC control interface by the input value coordinate or use mouse point in given coordinate grid to get each electrode position, and setting exciting current parameter and continuous monitoring sampling time interval, exciting current working range 10 μ A～60 μ A, power frequency 0.1～10kHz;
4) in measuring operation, wherein two microneedle electrodes groups are as exciting electrode, remaining electrode is as the voltage sample electrode, finish an excitation-sampling circulation, select two other microneedle electrodes as exciting electrode then, repeat actuation-sampling circulation was till all microneedle electrodes all had been used;
5) analog quantity that microneedle electrodes is collected is converted into digital quantity, carries out date processing and reconstructed image through amplification, filtering after import PC after the single-chip microcomputer processing, with the electrical impedance distribution situation of each point on gray-scale map or the coloured picture reflection tomography; Simultaneously send instruction, exciting current is controlled by communication module and single-chip microcomputer by PC.
The present invention compared with prior art, have the following advantages and the salience effect: 1. the present invention in measurement owing to adopted microneedle electrodes, this kind electrode can be crossed over the horny layer of skin surface high electrical resistance, high impedance influence when having reduced current excitation and voltage signal acquisition, make that the signal directivity is good, signal to noise ratio is high, reduced the uncertainty of signal fluctuation, thereby reduced signal excitation and gathered the error of bringing.2. because microneedle electrodes is crossed high impedance layer, it is continuous to make that the interior electrical impedance distribution of actual measurement subject area more is tending towards single order, the degree of approximation improved greatly when application had the mathematics solving model now, made that then calculating is more accurate, and reconstruct gained image resolution ratio is higher, confidence level is high more.3. adopted microneedle electrodes, made and measure the restriction overcome the geometric electrode size, made measuring object not only be confined to macroscopic tissue, more can measure at the microchannel transverse section of using on the individual cells of microcosmic or cell cluster and the biochip.4. the microneedle electrodes base material that designs among the present invention is a silicon, has improved the hardness of micropin, has avoided simple metal micropin hardness not high flexible and micropin that cause thrusts difficulty.5. the microneedle electrodes surfacing that designs among the present invention is silver or platinum coating, has taken into account and the biocompatibility of organizing direct contact material in not strong having overcome the silicon materials conductive capability.6. in a square substrate, a large amount of micropins are arranged among the present invention, guaranteeing enough big foundation area, simultaneously still can operate as normal when certain micropin breakdown, improved the reliability of microneedle electrodes work.Unique minimally-invasive metering system incorporates in traditional electric impedance imaging system, because the architectural feature of microneedle electrodes is very little to the damage that human body skin causes, and can not produce the pain sensation, it is a kind of metering system of hommization, and (the micropin technology in the undisciplined electric system is dissolved in the bio-electrical impedance imaging technology with MEMS in the present invention can well to solve skin high impedance measurement error, microneedle electrodes can replace surface electrode, exactly can address the above problem.According to the micropin operation principle, micropin can be avoided the outermost high impedance layer horny layer of skin, reach the epidermal area under following 10～15 μ m degree of depth, this one deck has electric conductivity and does not have blood vessel and nerve, therefore micropin thrusts and can not cause damage and the pain sensation, is a kind of ideal minimally-invasive intervening mode.The mode of present this Wicresoft is medically having more and more wide application, except gathering the electrical characteristics signal, can also be used for fields such as medicine transmission, targeted therapy.
Compare conventional electrodes and microneedle electrodes and skin surface contacting electronic model as can be seen, it is simple many that the microneedle electrodes model is wanted, and can reduce contact impedance and electrochemistry noise greatly.
Description of drawings
Fig. 1 is the electrical impedance tomography apparatus structure theory diagram based on microneedle electrodes.
Fig. 2 is the axonometric chart of micropin.
Fig. 3 is square microneedle electrodes array.
The micropin that Fig. 4 makes through wet etching for the silicon base material.
Fig. 5 is a software program flow process block diagram of the present invention.
The specific embodiment
Below in conjunction with accompanying drawing concrete structure of the present invention, measuring principle, process and embodiment are further described.
Impedance tomography apparatus and measuring method thereof based on microneedle electrodes provided by the invention, its principle is based on the medical science characteristic of skin surface, can cross over the outermost high impedance layer horny layer of human body skin (thickness 10～15 μ m), arrival is made up of living cells, have electric conductivity, permeability, and do not comprise the epidermal area of neural and blood vessel, be equivalent to electrolyte (thickness 50～100 μ m), do not thrust and can produce the pain sensation and hemorrhage, thereby realize the superior conducting function of invasive.
Fig. 1 is the impedance tomography apparatus structural principle block diagram based on microneedle electrodes, this imager comprises the microneedle array electrode group of being made up of exciting electrode and acquisition electrode, the single-chip microcomputer change-over circuit, signals collecting amplification filtering module and the exciting current control module that links to each other with outfan with the input of described single-chip microcomputer respectively, and the PC that contains control and software for calculation program, described PC carries out two-way data communication by communication module and described single-chip microcomputer.PC relies on USB port or serial line interface to be connected with communication module, carries out two-way data communication; Single-chip microcomputer relies on data/address bus to be connected with communication module, carries out two-way data communication; Communication module only plays the effect of information encoding buffer, to adapt to two kinds of interfaces of PC and single-chip microcomputer.Control instruction to current excitation is passed toward the communication module repeated transmission toward single-chip microcomputer by PC; Metrical information behind digital coding is passed toward PC through communication module by single-chip microcomputer.The single-chip microcomputer change-over circuit is connected by the I/O interface with the exciting current control module, and information is by single-chip microcomputer and change-over circuit single flow direction exciting current control module.Single-chip microcomputer and change-over circuit will convert analogue signal to by the digital controlled signal that PC transmits, and pass toward the exciting current control module by the I/O interface again.The single-chip microcomputer change-over circuit is connected by the I/O interface with signals collecting, amplification, filtration module, and information is by signals collecting, amplification, filtration module single flow direction single-chip microcomputer and change-over circuit.Signal imports single-chip microcomputer and change-over circuit by after signals collecting, amplification, the filtration module pretreatment into by the I/O interface, and analog signal conversion is become digital coding.The microneedle electrodes group comprises exciting electrode group and acquisition electrode group, and in once excitation-collection circulated, the exciting current control module outputed current to two microneedle electrodes groups, makes it and measurand formation current loop; Meanwhile, remove the voltage signal that all the microneedle electrodes groups beyond above-mentioned two microneedle electrodes groups that are used as exciting electrode all detect as acquisition electrode in all electrode groups, and input to signals collecting amplification filtering module respectively.Finish after the circulation of excitation-collection this time, electrode group role is switched in system, uses adjacent another counter electrode group as exciting electrode, and other electrode groups are as acquisition electrode, repeat above-mentioned cycling, till all exciting electrodes that need all had been used to compound mode.
The microneedle electrodes group is the direct part that contacts and act on measuring object (human body or individual cells, cell cluster).Described microneedle electrodes group is made of substrate 2, the microneedle array that is arranged on this substrate, and each micropin 1 on the described microneedle array is wedge shape (as shown in Figure 2), and the micropin height is 100～300 μ m, and micropin tip portion width is 5～30 μ m.Micropin uniform distribution in the microneedle array, its distribution are spaced apart 50～150 μ m (as shown in Figure 3).Described substrate and micropin can adopt silicon materials to make, and make (as shown in Figure 4) by wet etching, are distributed on the dull and stereotyped base.On silicon substrate, be provided with through hole 3, conductor layer is guided to the substrate dorsal part; And adhere to conductive metal layer at silicon substrate upper and lower surface, micropin surface, internal surface of hole, as the conductive layer of conduction of current; Conductive metal layer generally adopts silver or platinum coating.Substrate and micropin also can adopt the silicon materials that are mixed with conducting metal to make.Microneedle array is diced into the square of the length of side (diameter) 0.5～10mm together with substrate, as shown in Figure 4, has been coated with the through hole lead-in wire of conductive layer, be connected with the electrode base at substrate dorsal part (no micropin one side).Packaged electrode can be invested and be fixed in the elastic fabric inner face, so that be close to the measuring object surface.The microneedle electrodes that designs among the present invention is disposable equipment.
Measuring process of the present invention is as follows:
A plurality of microneedle array electrode groups are affixed on body surface, penetrate horny layer, thrust skin epidermis, and make electrode retaining collar be around in the same cross section of object to be measured, as around breast, one week of arm etc.; Also electrode can be fixed in elastic fabric circle (similar wrister, headgear etc.) inboard, be placed in extremity, trunk, breast etc. again and locate.
Start the hardware device power supply, and open software interface, and select measurement pattern.Selectable measurement pattern is single measurement or continuous monitoring.When selecting single measurement,, on PC, show a two field picture by system's one-shot measurement operation.When selecting continuous monitoring, needs are preset the time in sampling interval and are measured the finish time, time in sampling interval is the interval that system carries out twice measuring operation, after beginning to measure, system was just measured once every the default time period, exported a two field picture, finished up to measuring, then can obtain a series of images this moment, but reflected measurement object electrical impedance distribution in time changes.Before beginning to measure, the relative position coordinates of each electrode of input on above-mentioned plane in PC control interface can be selected the input value coordinate or use mouse point in given coordinate grid to get each electrode position.For the different measuring object, can make within the specific limits that exciting current is adjustable continuously, the exciting current parameter can directly be adjusted at PC control interface.Measurement electric current for tissue is big slightly, and is slightly little for the measurement electric current of micro-cell, cell cluster; Increase exciting current when measure signal intensity is not enough, reduce exciting current when measuring-signal is bigger than normal.When measuring a two field picture when continuous monitoring (or) will experience several excitations-sampling circulation in measuring operation each time, in each excitation-sampling circulation, two microneedle electrodes group seat current excitation electrodes, remaining electrode is as the voltage sample electrode, after finishing a circulation, change the combination repeat actuation-sampling circulation of exciting electrode, till all exciting electrodes that need all had been used to compound mode.
PC and relevant software programs: can on operation interface, comprehensively be provided with to whole measurement, comprise electrode position demarcation (can or use mouse point in given coordinate grid to get each electrode position) by the input value coordinate, the exciting current parameter adjustment, single measurement and continuous monitoring are selected, continuous monitoring sampling time interval etc.In addition, measuring-signal through amplification, the input PC carries out date processing after the filtering, finds the solution the inverse problem of electrical impedance distribution with D-bar algorithm or layer strip, and reconstructed image is at last with the electrical impedance distribution situation of each point on gray-scale map or the RGB coloured picture reflection tomography.Image finally is stored in the storage medium on the PC, and in the display demonstration or from printer output.When actual measurement, can adjust electrode riding position, exciting current parameter etc. according to the result who has measured and measure repeatedly more afterwards.
Communication module: by serial line interface or USB interface PC and single-chip microcomputer are connected, the control instruction of exciting current is passed toward single-chip microcomputer by PC, the signal that collects is through amplifying, then passing past PC from single-chip microcomputer after the filtering.
Single-chip microcomputer and change-over circuit: the analog quantity that collects is converted into digital quantity, and coding mails to PC, buffer memory is carried out in the instruction that PC is transmitted simultaneously, control exciting current control module.
Exciting current control module: by the control of single-chip microcomputer and control circuit, adjust the exciting current parameter, and can switch each exciting electrode, export electric current to the excitation microneedle electrodes.Obtain from experiment, adopt microneedle electrodes, crossed skin high impedance horny layer, the exciting current scope can adopt 10 μ A～60 μ A, and little than the surface electrode measuring method, power frequency is at low-frequency range 1～10kHz.The design adopts functional generator chip (as the ICL8038 chip) that sine voltage signal takes place, and uses Voltage-controlled Current Source (VCCS) circuit as shown in Figure 6 to convert voltage signal to exciting current.
Signals collecting, amplification, filtration module: from measuring microneedle electrodes (when a pair of microneedle electrodes group during as exciting electrode, all the other each microneedle electrodes groups are measures microneedle electrodes) detectable voltage signals, and to signal amplify, pretreatment such as filtering, the signal after the pretreatment is passed toward single-chip microcomputer.The design adopts high-precision AD620 to amplify chip, takes the high and low logical passive filtering network of single order, and as accompanying drawing 7: through the high-pass filtering network, filtering polarization of electrode voltage is to prevent that amplifier is saturated earlier for input signal; After amplifying through the AD620 chip again, by low-pass filter network to remove high-frequency noise.For avoiding and the physiology signal aliasing, the circuit free transmission range of design is 1～100kHz.
Claims (2)
1. impedance tomography apparatus based on microneedle electrodes, comprise the electrode group of forming by exciting electrode and acquisition electrode, the single-chip microcomputer change-over circuit, signals collecting amplification filtering module and the exciting current control module that links to each other with outfan with the input of described single-chip microcomputer change-over circuit respectively, and the PC that contains control and software for calculation program, described PC carries out two-way data communication by communication module and described single-chip microcomputer change-over circuit, it is characterized in that: described electrode group adopts the microneedle electrodes group, this microneedle electrodes group is made of substrate (2) and the microneedle array that is arranged on this substrate, described substrate and micropin adopt silicon materials to make, on silicon substrate, be provided with through hole (3), and in the silicon substrate upper and lower surface, micropin (1) surface and internal surface of hole adhere to conductive metal layer; Micropin distributes and is spaced apart 50～150 μ m.
2. according to the described impedance tomography apparatus based on microneedle electrodes of claim 1, it is characterized in that: each micropin on the described microneedle array is wedge shape, and the micropin height is 100～300 μ m, and micropin tip portion width is 5～30 μ m.
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Families Citing this family (11)
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| CN102217933A (en) * | 2011-06-10 | 2011-10-19 | 中国人民解放军第四军医大学 | Electrode placing device of electrical impedance tomography |
| CN102445574B (en) * | 2011-10-12 | 2013-10-09 | 中国人民解放军第四军医大学 | Annular arrangement type multi-needle biological tissue dielectric spectrum characteristic measuring probe and method |
| CN102512169B (en) * | 2011-12-31 | 2013-06-05 | 重庆邮电大学 | Adaptive control method and device for deviation in skin electrical signal testing |
| CN102586092B (en) * | 2012-02-10 | 2013-07-31 | 浙江大学 | Cell impedance imaging system and cell impedance imaging method for dynamically monitoring wound healing |
| CN105748065B (en) * | 2016-01-21 | 2019-10-29 | 天津工业大学 | A kind of moisturizing micropin matrix array surface biological electricity electrode |
| US11092567B2 (en) * | 2017-03-21 | 2021-08-17 | International Business Machines Corporation | Biosensor electrode having three-dimensional structured sensing surfaces |
| WO2018209711A1 (en) * | 2017-05-19 | 2018-11-22 | 深圳市得道健康管理有限公司 | Microneedle electrode, meridian detecting device and customizing method therefor |
| KR102264402B1 (en) * | 2019-02-21 | 2021-06-14 | 주식회사 바이랩 | Measuring device using eit electrode |
| CN112043375B (en) * | 2020-09-30 | 2022-03-08 | 深圳半岛医疗有限公司 | Radio frequency microneedle array control method and device and radio frequency microneedle therapeutic apparatus |
| CN112568890A (en) * | 2020-11-30 | 2021-03-30 | 武汉中针智能科技有限公司 | Minimally invasive multi-electrode bioelectrical impedance detection system and detection method |
| CN113143242A (en) * | 2021-04-12 | 2021-07-23 | 浙江大学 | Circuit system for measuring human body spinal bone reactance |
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