CN100450436C - Electrical Impedance Tomography Based on Microneedle Electrodes and Its Minimally Invasive Measurement Method - Google Patents

Abstract

An electrical impedance tomography imager based on a microneedle electrode and a minimally invasive measurement method thereof belong to the technical field of medical microsystems and biomedical detection. In the present invention, microneedle electrodes are used to cross the high-impedance stratum corneum of human skin and replace traditional surface electrodes as current excitation devices and sensors for measuring voltage signals. Or the color map reflects the distribution of electrical impedance at each point on the fault. The present invention effectively reduces the influence of the high-impedance layer of the skin during current excitation and voltage signal collection by means of minimally invasive measurement, so that the signal directivity is good, the signal-to-noise ratio is high, and the uncertainty of signal fluctuation is reduced, thereby reducing the signal The error caused by excitation and acquisition; at the same time, the electrical impedance distribution in the measured object area tends to be more continuous, so that the calculation is more accurate, and the reconstructed image has higher resolution and higher confidence.

Description

Electrical Impedance Tomography Based on Microneedle Electrodes and Its Minimally Invasive Measurement Method

technical field

The invention relates to an electrical impedance tomography (EIT) device and measurement technology, in particular to an electrical impedance tomography instrument based on a microneedle electrode and a minimally invasive measurement method thereof, belonging to medical microsystem and biomedical detection technology field.

Background technique

Electrical impedance tomography (electrical impedance tomography, EIT) is based on the different electrical characteristic parameters (such as resistivity, permittivity) of the internal tissue of the object, by applying a safe excitation current or voltage to the surface, and simultaneously measuring the voltage or voltage on the surface of the object. The current signal is used to obtain the distribution of the internal electrical parameters of the object, and then reconstruct an image reflecting the internal structure of the object. This is of great significance to the study of the internal electrical properties of organisms. Such images not only contain rich anatomical information, but also can obtain information about the changes in electrical properties of certain tissues and organs with their pathological and physiological functional states. Moreover, this method is harmless to the human body, can be measured multiple times and used repeatedly, and can become a hospital monitoring device for long-term and continuous monitoring of patients without causing damage or discomfort to patients. Coupled with low cost and no special working environment, it is an ideal medical imaging technology with broad application prospects.

Modern mathematics proves that the inverse problem of electrical impedance can be used to solve the first-order continuous electrical impedance distribution in the region, and then the electrical impedance distribution diagram can be reconstructed. For the situation that is not first-order continuous in actual measurement, it will be approximated when calculating the inverse problem, so the smaller the difference in electrical impedance distribution, the better the approximation, the higher the calculation accuracy, and the better the imaging quality will be. Therefore, the high-impedance layer in the measurement area will directly affect the approximation effect of the model, resulting in reduced calculation accuracy and greatly reduced imaging resolution.

At present, in the electrical impedance tomography (EIT) technology, the body surface electrode measurement method is adopted. During the measurement, the electrode is directly in contact with the human body and is located at the front end of the system. Events that occur on the electrodes, including useful information, noise, artifacts, contact impedance, polarization voltage, etc., will be amplified and transmitted into subsequent circuits as signals, participate in the signal processing process, and affect the image reconstruction results. The electrode system structure and its performance have a great impact on the effective extraction of EIT front-end information, system timeliness and image resolution, especially on the extraction of useful information in the central area with poor EIT detection sensitivity, which is the most sensitive and important aspect of the entire EIT system. One of the key parts. The high impedance layer of the skin and the surface electrode pattern are the direct causes of high contact impedance, and the EIT body surface electrode measurement method is a bottleneck of the EIT system. The electrical impedance tomography technology using body surface electrode measurement has the following deficiencies and defects:

①Because the outermost stratum corneum of the skin has high impedance characteristics, the contact resistance between the surface electrode and the skin is very large, and there is great uncertainty, it is easy to introduce AC interference, the directivity is poor, the measured signal is very weak and the dynamic range is relatively small big. These are the sources of errors, which hinder the accuracy of the excitation current, make the calculation and image results inaccurate, and make it difficult to balance the imaging resolution and signal-to-noise ratio.

②The existing EIT reconstruction algorithms are all based on the continuous model of electrical impedance, and the surface electrode is a high-impedance layer at the electrode-tissue interface when the surface electrode is used, and the existing solvable model requires the first-order continuity of the electrical impedance distribution, so the surface electrode The existing continuous model cannot be well satisfied, and the approximate processing at this time will greatly reduce the accuracy of the model and the image resolution ability.

③EIT measurement requires a large number of electrodes to be placed, and image reconstruction is carried out with a large amount of data. At present, most of the image reconstruction of EIT is based on point electrodes, and the contact area of surface electrodes is large. There is a certain calculation error.

④ Due to its geometric size limitation, the surface electrode has limitations on the outline size of the measurement object, and it can only be applied to the EIT measurement of macroscopic tissues, and cannot be applied to the EIT of microscopic cells or cell cluster samples and microchannel cross-sections used on biochips Measurement.

It can be seen that the surface electrode measurement method is a bottleneck restricting the development of the EIT system, and the error caused by the high surface impedance is a problem that must be solved when EIT technology is moving towards clinical application and practical research.

Contents of the invention

The purpose of the present invention is to aim at the deficiencies and defects of the prior art, combine microneedle technology in MEMS with bioelectrical impedance imaging technology, and provide an electrical impedance tomography device based on microneedle electrodes and its minimally invasive A measurement method to solve the problems of poor calculation accuracy, low image resolution and inaccurate measurement results in the existing electrical impedance imaging technology due to the inability to avoid the high impedance layer of the skin.

Technical scheme of the present invention is as follows:

An electrical impedance tomography instrument based on a microneedle electrode, comprising an electrode group composed of an excitation electrode and an acquisition electrode, a single-chip microcomputer control circuit, a signal acquisition amplification filter module connected to the input end and the output end of the single-chip microcomputer and an excitation A current control module, and a PC containing control and calculation software programs, the PC performs two-way data communication with the single-chip microcomputer through the communication module, and it is characterized in that: the electrode group adopts a microneedle electrode group.

The microneedle electrode group of the present invention is composed of a substrate and a microneedle array arranged on the substrate. The substrate and the microneedles are made of silicon material, and through holes are arranged on the silicon substrate, and the upper and lower surfaces of the silicon substrate 1. A conductive metal layer is attached to the surface of the microneedle and the inner surface of the hole; the distribution interval of the microneedle is 50-150 μm.

In the above technical solution of the present invention, the substrate and the microneedle can also be made of silicon material doped with conductive metal.

The technical feature of the present invention is that each microneedle on the microneedle array is wedge-shaped, the height of the microneedle is 100-300 μm, and the width of the tip part of the microneedle is 5-30 μm.

The invention provides a minimally invasive measurement method based on electrical impedance tomography of a microneedle electrode, which is characterized in that the method is carried out as follows:

1) Paste multiple microneedle array electrode groups on the body surface, penetrate the stratum corneum, pierce the epidermis of the skin, and make the electrodes surround the same cross-section of the object to be measured;

2) Start the control program of the PC and select the measurement mode, that is, single measurement or continuous detection mode;

3) On the PC control interface, enter the numerical coordinates or use the mouse to click in the given coordinate grid to obtain the position of each electrode, and set the excitation current parameters and the continuous monitoring sampling time interval. The excitation current working range is 10μA to 60μA, and the current frequency is 0.1 ~10kHz;

4) In the measurement operation, two of the microneedle electrode groups are used as excitation electrodes, and the remaining electrodes are used as voltage sampling electrodes, an excitation-sampling cycle is completed, and then the other two microneedle electrodes are selected as excitation electrodes, and the excitation-sampling cycle is repeated, Until all microneedle electrodes have been used;

5) The analog quantity collected by the microneedle electrode is converted into a digital quantity, and after being amplified and filtered, it is processed by a single-chip microcomputer and then input to a PC for data processing and reconstruction of the image, reflecting the resistance of each point on the fault with a grayscale or color map Anti-distribution; at the same time, the PC sends instructions to control the excitation current through the communication module and the single-chip microcomputer.

Compared with the prior art, the present invention has the following advantages and outstanding effects: ① The present invention uses microneedle electrodes in the measurement, which can cross the stratum corneum with high electrical impedance on the skin surface, reducing the current excitation and voltage The high impedance effect during signal acquisition makes the signal directivity good, the signal-to-noise ratio is high, and the uncertainty of signal fluctuation is reduced, thereby reducing the error caused by signal excitation and acquisition. ②Because the microneedle electrode crosses the high-impedance layer, the electrical impedance distribution in the measured object area tends to be more continuous, and the approximation degree is greatly improved when the existing mathematical solution model is applied, which makes the calculation more accurate and the image resolution obtained by reconstruction Higher, higher confidence. ③Using microneedle electrodes, the measurement overcomes the limitation of electrode geometry, so that the measurement object is not limited to macroscopic human tissue, but can also be used for microscopic single cells or cell clusters and the cross-section of microchannels used on biochips. Measurement. ④ The base material of the microneedle electrode designed in the present invention is silicon, which improves the hardness of the microneedle and avoids the difficulty in penetrating the microneedle caused by the low hardness and easy bending of the pure metal microneedle. ⑤ The surface material of the microneedle electrode designed in the present invention is silver or platinum coating, which not only overcomes the weak conductivity of silicon materials, but also takes into account the biocompatibility of materials in direct contact with tissues. ⑥In the present invention, there are a large number of microneedles on a square base to ensure a sufficiently large base area, and at the same time, it can still work normally when a certain microneedle is broken, which improves the reliability of the microneedle electrode. The unique minimally invasive measurement method is integrated into the traditional electrical impedance imaging system. Due to the structural characteristics of the microneedle electrode, the damage to the human skin is very small, and it does not cause pain. It is a humanized measurement method and can be easily A good solution to the measurement error of skin high impedance is to integrate the microneedle technology in the MEMS (discipline-violating electrical system) into the bioelectrical impedance imaging technology in the present invention, and the microneedle electrode can replace the surface electrode, which can solve the above problems. According to the microneedle work In principle, microneedles can avoid the high-impedance stratum corneum of the outermost layer of the skin, and reach the epidermis at a depth of 10-15 μm below. This layer is conductive and has no blood vessels and nerves, so microneedle penetration will not cause damage It is an ideal minimally invasive intervention method. At present, this minimally invasive method has been widely used in medicine. In addition to collecting electrical characteristic signals, it can also be used in drug delivery, targeted therapy and other fields. .

Comparing the electronic models of conventional electrodes and microneedle electrodes in contact with the skin surface, it can be seen that the microneedle electrode model is much simpler, which can greatly reduce contact impedance and electrochemical noise.

Description of drawings

Fig. 1 is a schematic block diagram of the structure of an electrical impedance tomography device based on microneedle electrodes.

Fig. 2 is a perspective view of a microneedle.

Figure 3 is a square microneedle electrode array.

Fig. 4 is a microneedle prepared by wet etching of a silicon base material.

Fig. 5 is a flow chart of the software program of the present invention.

Detailed ways

The specific structure, measurement principle, process and implementation of the present invention will be further described below in conjunction with the accompanying drawings.

The electric impedance tomography instrument and its measurement method based on microneedle electrodes provided by the present invention are based on the medical characteristics of the skin surface, and can cross the high-impedance stratum corneum (thickness 10-15 μm) of the outermost layer of human skin, Reach the epidermal layer composed of living cells, which is conductive and permeable, and does not include nerves and blood vessels. It is equivalent to electrolyte (thickness 50-100 μm), and it will not cause pain and bleeding when piercing, so as to achieve superior minimally invasiveness Conductive function.

Fig. 1 is the block diagram of the electrical impedance tomography instrument structure principle based on microneedle electrode, and this imager comprises the microneedle array electrode group that is made up of excitation electrode and collection electrode, single-chip microcomputer conversion circuit, respectively with the input end and output of described single-chip microcomputer The terminal is connected to a signal acquisition, amplification and filtering module, an excitation current control module, and a PC containing control and calculation software programs, and the PC performs two-way data communication with the single-chip microcomputer through the communication module. PC and communication module are connected by USB port or serial interface for two-way data communication; MCU and communication module are connected by data bus for two-way data communication; communication module only plays the role of information coding buffer to adapt to PC And two kinds of interface of the one-chip computer. The control command for current excitation is transmitted from the PC to the communication module and then to the single-chip microcomputer; the digitally coded measurement information is transmitted from the single-chip microcomputer to the PC through the communication module. The conversion circuit of the single-chip microcomputer is connected with the excitation current control module through the I/O interface, and the information flows from the single-chip microcomputer and the conversion circuit to the excitation current control module in one direction. The single-chip microcomputer and conversion circuit convert the digital control signal from the PC into an analog signal, and then transmit it to the excitation current control module through the I/O interface. The conversion circuit of the single-chip microcomputer is connected with the module of signal acquisition, amplification and filtering through the I/O interface, and the information flows from the module of signal acquisition, amplification and filtering to the single-chip microcomputer and the conversion circuit in one direction. After the signal is preprocessed by the signal acquisition, amplification, and filtering modules, it is transmitted to the single-chip microcomputer and the conversion circuit through the I/O interface, and the analog signal is converted into a digital code. The microneedle electrode group includes the excitation electrode group and the collection electrode group. In an excitation-acquisition cycle, the excitation current control module outputs current to the two microneedle electrode groups to form a current loop with the measured object; at the same time, all All the microneedle electrode groups in the electrode group except the above two microneedle electrode groups used as excitation electrodes are used as the voltage signals detected by the collecting electrodes, and are respectively input to the signal collecting, amplifying and filtering module. After the excitation-acquisition cycle is completed, the system switches the role of the electrode group, uses another pair of adjacent electrode groups as the excitation electrode, and other electrode groups as the acquisition electrode, and repeats the above cycle until all the required combinations of excitation electrode pairs have been has been adopted.

The microneedle electrode group is the part that directly contacts and acts on the measurement object (human body or single cell, cell cluster). The microneedle electrode group is composed of a substrate 2 and a microneedle array arranged on the substrate. Each microneedle 1 on the microneedle array is wedge-shaped (as shown in FIG. 2 ), and the microneedle height is 100 ～300 μm, the width of the microneedle tip part is 5～30 μm. The microneedles in the microneedle array are evenly distributed, and the distribution interval is 50-150 μm (as shown in FIG. 3 ). The substrate and microneedles can be made of silicon material through wet etching (as shown in FIG. 4 ), and distributed on the flat base. A through hole 3 is provided on the silicon substrate to lead the conductor layer to the back side of the substrate; and a conductive metal layer is attached to the upper and lower surfaces of the silicon substrate, the surface of the microneedle, and the inner surface of the hole as a conductive layer for current conduction; the conductive metal layer is generally Available in silver or platinum plating. The substrate and microneedles can also be made of silicon material doped with conductive metal. Slice the microneedle array together with the substrate into squares with a side length (diameter) of 0.5 to 10 mm, as shown in Figure 4, lead wires at the through holes that have been plated with a conductive layer on the back side of the substrate (the side without microneedles), and connect with the electrodes. base connection. The packaged electrode can be attached and fixed on the inner surface of the elastic fabric so as to be close to the surface of the measurement object. The microneedle electrode designed in the present invention is a disposable device.

The measurement process of the present invention is as follows:

Paste multiple microneedle array electrode groups on the body surface, penetrate the stratum corneum, pierce the skin epidermis, and make the electrodes surround the same cross-section of the object to be measured, such as around the breast, the arm, etc.; the electrodes can also be fixed Put it on the inner side of the elastic fabric circle (similar to wristbands, headgear, etc.), and then put it on the limbs, torso, breasts, etc.

Start the power of the hardware device, open the software interface, and select the measurement mode. Selectable measurement modes are single measurement or continuous monitoring. When single measurement is selected, one frame of image will be displayed on the PC through one measurement operation of the system. When continuous monitoring is selected, it is necessary to preset the sampling interval time and the end time of the measurement. The sampling interval time is the time interval between two measurement operations by the system. After the measurement is started, the system will measure once every preset time period and output a frame of image , until the end of the measurement, a series of images can be obtained at this time, which can reflect the change of the electrical impedance distribution of the measured object over time. Before starting the measurement, enter the relative position coordinates of each electrode on the above plane in the PC control interface, and you can choose to input numerical coordinates or use the mouse to click in the given coordinate grid to get the position of each electrode. For different measurement objects, the excitation current can be continuously adjusted within a certain range, and the excitation current parameters can be directly adjusted on the PC control interface. The measurement current for human tissue is slightly larger, and the measurement current for microscopic cells and cell clusters is slightly smaller; increase the excitation current when the measurement signal strength is insufficient, and reduce the excitation current when the measurement signal is too large. In each measurement operation (or when measuring a frame of image during continuous monitoring), it will go through several excitation-sampling cycles. In each excitation-sampling cycle, two microneedle electrode groups seat current excites the electrodes, and the remaining electrodes serve as Voltage sampling electrodes, after completing a cycle, repeat the excitation-sampling cycle by changing the combination of excitation electrodes until all required combinations of excitation electrode pairs have been used.

PC and related software programs: comprehensive settings for the entire measurement can be made on the operation interface, including electrode position calibration (each electrode position can be obtained by inputting numerical coordinates or using the mouse to click in a given coordinate grid), excitation current parameter adjustment, Single measurement and continuous monitoring selection, continuous monitoring sampling interval, etc. In addition, after the measurement signal is amplified and filtered, it is input to the PC for data processing, and the inverse problem of the electrical impedance distribution is solved by the D-bar algorithm or the layer peeling method, and the image is reconstructed, and finally the grayscale image or RGB color image is used to reflect the fault on the fault. The distribution of electrical impedance at each point. The image is finally stored in the storage medium on the PC, and displayed on the monitor or output from the printer. In the actual measurement, the electrode placement position, the excitation current parameters, etc. can be adjusted according to the measured results, and then the measurement can be repeated.

Communication module: establish a connection between the PC and the single-chip microcomputer through the serial interface or USB interface, the control command for the excitation current is transmitted from the PC to the single-chip microcomputer, and the collected signal is transmitted from the single-chip microcomputer to the PC after being amplified and filtered.

Single-chip microcomputer and conversion circuit: convert the collected analog quantity into digital quantity, encode and send it to the PC, and at the same time cache the instructions from the PC to control the excitation current control module.

Excitation current control module: through the control of the single-chip microcomputer and the control circuit, the excitation current parameters are adjusted, and each excitation electrode can be switched, and the current is output to the excitation microneedle electrode. It is obtained from the experiment that the microneedle electrode is used to cross the high-impedance stratum corneum of the skin. The excitation current range can be 10 μA to 60 μA, which is smaller than that of the surface electrode measurement method, and the current frequency is in the low frequency range of 1 to 10 kHz. This design uses a function generator chip (such as ICL8038 chip) to generate a sinusoidal voltage signal, and uses a voltage-controlled current source (VCCS) circuit as shown in Figure 6 to convert the voltage signal into an excitation current.

Signal acquisition, amplification, and filtering module: detect voltage signals from measuring microneedle electrodes (when a pair of microneedle electrode groups are used as excitation electrodes, the remaining microneedle electrode groups are measuring microneedle electrodes), and amplify and filter the signals Wait for preprocessing, and transmit the preprocessed signal to the single-chip microcomputer. This design uses the high-precision AD620 amplifier chip, and adopts a first-order high- and low-pass passive filter network, as shown in Figure 7: The input signal first passes through the high-pass filter network to filter out the polarization voltage of the electrode to prevent the amplifier from being saturated; then passes through the AD620 After the chip is amplified, it passes through a low-pass filter network to remove high-frequency noise. In order to avoid aliasing with human physiological signals, the passband range of the designed circuit 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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