Synthesis of a digitally controlled impedance element

A practical design for the synthesis of a digitally controlled electrical impedance element is presented. The impedance element comprises a real impedance element in series with a voltage source whose magnitude is determined by the applied voltage multiplied by a factor k. The value of k is shown strongly to affect the circuit's performance. Results are presented which demonstrate the correspondence between circuit models and practical measurements. When negative values for k were employed the circuit element offered a controlled impedance range of 1:1000 and was stable to at least 1.5MHz, providing that low source impedance values were used. With a positive k, a restricted range of impedance values could be obtained and the value of source impedance was less critical, though the circuit's performance was acceptable only to about 100 kHz. Consideration is given to the specification of a multiplier that would permit the circuit's range of application to be extended to low megahertz frequencies.     

Micro coulter counters with platinum black electroplated electrodes for human blood cell sensing

We demonstrated a novel micro Coulter counter featuring platinum-black electrodes for human blood cell counting application. Two designs of micro Coulter counter were fabricated using two distinct technologies: integrated parylene and soft lithography. Platinum-black enhanced detection in the intermediate frequency range (∼100 Hz to 7 MHz), which is the operation frequency suitable for sensing the cells flowing by the electrodes. A detailed theoretical modeling of the sensing mechanism has been performed for the design of the electrodes, and electrical impedance spectra measurements confirmed the theoretical model. The surface morphology and roughness of the platinum black electroplated surface were characterized by SEM and AFM measurements. Polystyrene beads of various sizes were initially used to validate the operation of the devices, and using excitation frequency of 10 kHz, the signal magnitude was found to be correlated with the volume of the individual bead. Human blood cell sensing was successfully demonstrated with diluted whole blood and leukocyte rich plasma under the same excitation frequency. The histogram of impedance magnitude of the cells matched well with volume distributions of erythrocytes and leukocytes measured by conventional counting techniques. Micro Coulter counters have the advantages of small foot-print, low sample volume, and reduced cost of operation. Further development of the devices can lead to the development of a highly-sensitive and high-throughput handheld blood counting system for point-of-care applications.     

Dielectrophoresis assisted concentration of micro-particles and their rapid quantitation based on optical means

The detection and counting of micro particles having sizes comparable to biological entities can provide a tremendous impetus to rapid diagnostics and clinical applications. MEMS technology has already been used in capture and detection of such micron size entities in miniscule concentrations. For this purpose a concentration step is normally added prior to the detection process. A variety of methodologies are used for quantization of such micron size particles/entities including change in permittivity, medium impedance, magnetic permeability and other means. Although optical studies have been extensively performed prior to this, it has not been used for quantization of the micro particles. We have designed, developed and characterized a MEMS counter which captures micron size fluorescent beads using delectrophoresis (DEP) and monitors their accumulation in a 12 μm × 230 μm size channel and monitors this accumulation as growth of overall fluorescence. The field is generated by a set of finely placed interdigitated microelectrodes. As we apply an alternating voltage at 10 V_pp for a range of different frequencies we are able to capture the flowing beads and concentrate them by several orders of magnitude. This is also followed by their quantification in terms of growing fluorescence signal. For quantitating the fluorescence values a CCD (charge couple device) module fitted over an inverted fluorescence microscope is used that visualizes the whole capture process and a Labview based image acquisition software simultaneously calculates the signal intensity over these frames and arranges it temporally. Our work will have tremendous utility in developing a rapid bacterial counting procedure and will be a valuable tool in microbiological laboratories.     

便携式生物复阻抗信息检测仪的设计

目的 设计一种高精度、简单方便的生物复阻抗信息检测仪器,可提取人体局部肌肉组织损伤的电阻抗特征,指导临床治疗与康复.方法 采用四电极模式,一对电流注入激励电极和一对电压检测电极;设计了基于AD5933与AD844的激励电流源、屏蔽驱动电路、放大电路及数字解调电路,研发了便携式生物复阻抗信息检测仪器.结果 以三元件模型作为测量对象,将笔者设计的生物复阻抗信息检测仪与安捷伦4294A阻抗分析仪进行测量对比分析,结果显示,在频率为1～100 kHz,阻抗模量信息相对误差与阻抗分析仪基本相同,相位误差小于1..以1例大腿后侧肌群中度拉伤患者作为测量对象进行的连续跟踪测量,结果符合临床诊断与生理学意义.结论 本研究设计的生物复阻抗信息检测仪具有测量精度高、操作简单、使用方便等优点,可用于指导人体局部组织损伤过程的临床诊断、治疗与康复监测.     

Selective trapping of live and dead mammalian cells using insulator-based dielectrophoresis within open-top microstructures

The manipulation of biological cells is essential to many biomedical applications. Insulator-based dielectrophoresis (iDEP) trapping consists of insulating structures which squeeze the electric field in a conductive solution to create a non-uniform electric field. The iDEP trapping microchip with the open-top microstructures was designed and fabricated in this work. For retaining the merit of microfabrication, the microelectrodes were deposited on the substrate to reduce the voltage required, due to the shortened spacing between them. The dielectrophoretic responses of both live and dead HeLa cells under different frequencies (100 Hz, 1 kHz and 1 MHz) have been investigated herein. The live cells exhibited negative dielectrophoresis at low frequencies of 100 Hz and 1 kHz, but a positive dielectrophoretic response with the frequency at 1 MHz. As for dead cells, positive dielectrophoretic responses were shown at all the frequencies applied. Therefore, selective trapping of dead HeLa cells from live cells was achieved experimentally at the frequency of 1 kHz. The open-top microstructures are suitable for trapping cells or biological samples, and easily proceeding to further treatment for cells, such as culturing or contact detection. The intensity of the emitted light during fluorescent detection will not suffer interference by a cover, as it does not exist herein.     

A Microfluidic Device for Electrofusion of Biological Vesicles

This paper reports a microfabricated device with high aspect-ratio electrodes and low power consumption for the electrofusion of liposomes and cells. The applications may range from gene transfection or cell tracking to biophysical studies of membrane proteins. The device consists of 250 microm thick silicon electrodes bonded to a glass substrate and covered by a PDMS-coated glass slide. Liposomes were first aligned by AC voltage at 300 kHz and then fused with short DC pulses. The fusion yield can reach 75% and is globally better for liposome diameters larger than 10 microm. The encapsulation of microbeads inside liposomes has also been demonstrated and opens up the route towards fusion-based delivery of artificial microstructures into cells.     

基于体外阻抗测量的恶性胶质瘤介电特性

目的研究脑胶质瘤生物电阻抗特性,探索出恶性胶质瘤组织与正常脑组织的特征性电参数,为区分恶性胶质瘤与正常脑组织提供依据。方法基于四电极法阻抗测量设计了一种体外阻抗测量传感器,利用普林斯顿阻抗分析仪Versa STAT3对10例裸鼠脑胶质瘤和脑组织进行阻抗测量,并对20Hz~250 k Hz范围内阻抗频谱特性曲线进行定量分析;结合生物阻抗谱理论,建立体外脑胶质瘤等效电路模型,并利用ZSimp Win对等效阻抗电路进行拟合仿真,以探讨脑胶质瘤在阻抗电路中的特性。结果胶质瘤的阻抗模值在20 Hz~250 k Hz范围内随频率的增大而减小,幅值曲线在200 Hz和50 k Hz附近各存在一个斜坡,这两个斜坡的斜度都小于对应的正常鼠脑组织的斜度。10组裸鼠体外实验中,胶质瘤和脑组织的虚部-实部图中有两个时间环节,可以用两个时间常数的等效电路代替,并且电路元件中的参数R1对于胶质瘤和脑组织差异明显。结论体外鼠脑胶质瘤与正常脑组织可以用阻抗特性曲线的斜坡值进行定量区别。此外,等效电路电参数中的R1也可以作为一个区分胶质瘤和脑组织的指标,这为临床检测和区分胶质瘤组织开拓了新的研究思路。     

Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells

In this paper, we describe interactions between neural cells and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) toward development of electrically conductive biomaterials intended for direct, functional contact with electrically active tissues such as the nervous system, heart, and skeletal muscle. We introduce a process for polymerizing PEDOT around living cells and describe a neural cell-templated conducting polymer coating for microelectrodes and a hybrid conducting polymer-live neural cell electrode. We found that neural cells could be exposed to working concentrations (0.01 m) of the EDOT monomer for as long as 72 h while maintaining 80% cell viability. PEDOT could be electrochemically deposited around neurons cultured on electrodes using 0.5-1 microA/mm(2) galvanostatic current. PEDOT polymerized on the electrode and surrounded the cells, covering cell processes. The polymerization was impeded in regions where cells were well adhered to the substrate. The cells could be removed from the PEDOT matrix to generate a neural cell-templated biomimetic conductive substrate with cell-shaped features that were cell attracting. Live cells embedded within the conductive polymer matrix remained viable for at least 120 h following polymerization. Dying cells primarily underwent apoptotic cell death. PEDOT, PEDOT+live neurons, and neuron-templated PEDOT coatings on electrodes significantly enhanced the electrical properties as compared to the bare electrode as indicated by decreased electrical impedance of 1-1.5 orders of magnitude at 0.01-1 kHz and significantly increased charge transfer capacity. PEDOT coatings showed a decrease of the phase angle of the impedance from roughly 80 degrees for the bare electrode to 5-35 degrees at frequencies >0.1 kHz. Equivalent circuit modeling indicated that PEDOT-coated electrodes were best described by R(C(RT)) circuit. We found that an RC parallel circuit must be added to the model for PEDOT+live neuron and neuron-templated PEDOT coatings.     

Impedimetric sensing of cells on polypyrrole-based conducting polymers

Polypyrrole (PPy) is a conducting polymer that may be electrochemically generated with the incorporation of any anionic species, including net-negatively charged biological molecules such as proteins and polysaccharides. In this article, dermatan and chloride-loaded PPy films were prepared on gold sputter-coated coverslips and various skin derived cells were studied on them by electrochemical impedance spectroscopy. Impedance spectra in the frequency range 1-100 kHz were either determined at specific times or impedance was monitored continuously at specific frequencies. An equivalent impedance circuit was fitted to the recorded impedance spectra to obtain parameters whose contributions could be mapped to intracellular and intercellular current pathways, and the membrane properties of cells. Results show cell-induced impedance changes were detected over PPy modified electrodes and were dependent on cell density and type, monitoring frequency, material composition, and treatment. Lower cell densities were detected on PPy when compared with bare gold. Keratinocyte confluence, as determined by impedimetric analysis, was reached more rapidly on PPy than on gold. This was consistent with previous, more cumbersome, biochemical assays. Electrical equivalent circuit analysis provided evidence that the technique may be extended to discriminate cell type because of the intracellular and intercellular resistance, and cell membrane capacitance being related to cell morphology.     

Comparison of optical, electrical, and centrifugation techniques for haematocrit monitoring of dialysed patients

Haematocrits were measured as a function of ultrafiltration in a simulated haemodialysis circuit using bovine blood (plasma conductivity 12 mS cm-1) and hypotonic (8.6 mS cm-1) or hypertonic (16 mS cm-1) dialysates as well as in the absence of dialysate. A comparison was made between measurements by light absorption due to haemoglobin, by impedance in the blood line at 5 kHz using Hanai's model of blood conductivity, by conductivity measurements of blood samples at 1.2 kHz using a conductimeter, by centrifugation of blood samples and by calculations using fluid conservation. The validity of Hanai's model was verified to be satisfactory by direct blood and plasma conductivity measurements. In the absence of ionic transfer the impedance device underestimated the haematocrit by 5 to 7%. This underestimation reached 18% in the case of hypertonic dialysate, but this effect can be minimised if the haematocrit necessary for calibration is measured by centrifugation after 15 min of dialysate circulation when ionic balance is achieved. It was found that the optical method monitors haemoglobin concentration rather than red cell volume changes and is not affected by osmotic red cell swelling in the case of hypotonic dialysate. It can be concluded that the light absorption technique is both more accurate and more convenient to use than impedance.     

Specific impedance of canine blood

The specific impedance of canine erythrocytes suspended in plasma was measured in the frequency range from 5 kHz to 1 MHz in samples from three animals in the hematocrit range from zero to packed cells at a temperature of 39°C; measurements were made with a conductivity cell using four electrodes and a current density of 21 μA/cm². With the use of impedance spectroscopy, data were fitted to an equivalent circuit model; model parameters in turn were fitted as functions of hematocrit. The resultant model can be used to predict specific impedance (real and reactive components) as a function of hematocrit and frequency over a frequency range from 5 kHz to 1 MHz and a hematocrit range from 0 to 80. Over a normal range of hematocrits and at frequencies less than 100 kHz., the current is almost exclusively confined to the plasma, and the specific impedance is nearly equal to the real component; however, at higher frequencies, the complex nature of specific impedance becomes important.     

Measurement of middle ear pressure with a single transducer and a half-wavelength acoustic transmission line

A simple inexpensive electroacoustic instrument utilising the transforming properties of a half-wavelength acoustic transmission line has been developed for performing a simple screening test of the middle-ear pressure. This device monitors changes in the magnitude of the acoustic impedance of the tympanic membrane as the pressure difference across it is varied. A 25 db h.l. hearing test at 4 kHz is also included.     

Specific impedance of canine blood

The specific impedance of canine erythrocytes suspended in plasma was measured in the frequency range from 5 kHz to 1 MHz in samples from three animals in the hematocrit range from zero to packed cells at a temperature of 39°C; measurements were made with a conductivity cell using four electrodes and a current density of 21 μA/cm². With the use of impedance spectroscopy, data were fitted to an equivalent circuit model; model parameters in turn were fitted as functions of hematocrit. The resultant model can be used to predict specific impedance (real and reactive components) as a function of hematocrit and frequency over a frequency range from 5 kHz to 1 MHz and a hematocrit range from 0 to 80. Over a normal range of hematocrits and at frequencies less than 100 kHz., the current is almost exclusively confined to the plasma, and the specific impedance is nearly equal to the real component; however, at higher frequencies, the complex nature of specific impedance becomes important.     

Improvement in cell capture throughput using parallel bioactivated microfluidic channels

Optimization of targeted cell capture with microfluidic devices continues to be a challenge. On the one hand, microfluidics allow working with microliter volumes of liquids, whereas various applications in the real world require detection of target analyte in large volumes, such as capture of rare cell types in several ml of blood. This contrast of volumes (microliter vs. ml) has prevented the emergence of microfluidic cell capture sensors in the clinical setting. Here, we study the improvement in cell capture and throughput achieved using parallel bioactivated microfluidic channels. The device consists of channels in parallel with each other tied to a single channel. We discuss fabrication and testing of our devices, and show the ability for an improvement in throughput detection of target cells.     

剩余电压检测的关键技术研究

剩余电压是指用插头连接电源的设备在拔掉插头的瞬时,由设备内部的储能元件产生的存在于插头上各插脚之间的残余电压。若人体触摸到插头且该电压大于某一限值,就会产生触电危险。制定剩余电压、剩余能量的限值是为了保护患者、操作者或其他人员的人身安全,防止在断电瞬间触及带电部件而发生危险。故准确地检测医疗设备的剩余电压值具有十分重要的意义。本文解决了剩余电压测量的一个关键技术问题,即设计一个零电位检测的关键电路,与可调延时设计配合能使设备在交流峰值处准确断电。这种峰值时刻断电检测系统,用于一种单片机控制的新型剩余电压测量装置,该装置将具有较好的重复性、稳定性,以克服现有的剩余电压测试仪器不能准确地在峰值处断电、测试重复性差等缺陷。该检测电路结构简单,性能稳定,能够在整流波过零的时刻可靠地产生宽度很窄的触发脉冲。采用可调延时设计,能够解决元器件带来的时延。     

Comparison of optical, electrical, and centrifugation techniques for haematocrit monitoring of dialysed patients

Haematocrits were measured as a function of ultrafiltration in a simulated haemodialysis circuit using bovine blood (plasma conductivity 12mScm⁻¹) and hypotonic (8. 6 mS cm⁻¹) or hypertonic (16mScm⁻¹) dialysates as well as in the absence of dialysate. A comparison was made between measurements by light absorption due to haemoglobin, by impedance in the blood line at 5 kHz using Hanai's model of blood conductivity, by conductivity measurements of blood samples at 1.2 kHz using a conductimeter, by centrifugation of blood samples and by calculations using fluid conservation. The validity of Hanai's model was verified to be satisfactory by direct blood and plasma conductivity measurements. In the absence of ionic transfer the impedance device underestimated the haematocrit by 5 to 7%. This underestimation reached 18% in the case of hypertonic dialysate, but this effect can be minimised if the haematocrit necessary for calibration is measured by centrifugation after 15 min of dialysate circulation when ionic balance is achieved. It was found that the optical method monitors haemoglobin concentration rather than red cell volume changes and is not affected by osmotic red cell swelling in the case of hypotonic dialysate. It can be concluded that the light absorption technique is both more accurate and more convenient to use than impedance.     

Sensitivity improvements of a resonance-based tactile sensor

Resonance-based contact-impedance measurement refers to the application of resonance sensors based on the measurement of the changes in the resonance curve of an ultrasonic resonator in contact with a surface. The advantage of the resonance sensor is that it is very sensitive to small changes in the contact impedance. A sensitive micro tactile sensor (MTS) was developed, which measured the elasticity of soft living tissues at the single-cell level. In the present paper, we studied the method of improving the touch and stiffness sensitivity of the MTS. First, the dependence of touch sensitivity in relation to the resonator length was studied by calculating the sensitivity coefficient at each length ranging from 9 to 40?mm. The highest touch sensitivity was obtained with a 30-mm-long glass needle driven at a resonance frequency of 100?kHz. Next, the numerical calculation of contact impedance showed that the highest stiffness sensitivity was achieved when the driving frequency was 100?kHz and the contact-tip diameter of the MTS was 10?μm. The theoretical model was then confirmed experimentally using a phase-locked-loop-based digital feedback oscillation circuit. It was found that the developed MTS, whose resonant frequency was 97.030?kHz, performed with the highest sensitivity of 53.2?×?10⁶?Hz/N at the driving frequency of 97.986?kHz, i.e. the highest sensitivity was achieved at 956?Hz above the resonant frequency.     

Skin impedance measurements using simple and compound electrodes

We have studied the effect of the electrode configuration on the measurement of body impedance and found that the electrode configuration greatly affects the impedance measurement using the four-electrode method. We studied the characteristics of the compound electrode and found that the compound electrode provides the four-electrode method in a compact form. A new method of measuring the skin impedance using simple electrodes at low frequencies was developed. At high frequencies where the effect of internal tissue impedance is not negligible, we used the compensation method using compound electrodes, because they measure the voltage right under the skin. At 50 kHz, we measured the real part of the skin impedance of less than 80 Ω on the thorax. We propose a simple instrument which can measure accurate skin impedance at various frequencies.     

体外人脑胶质瘤电阻抗特性及等效电路

目的 研究人脑胶质瘤的电阻抗特性并建立其等效电路,可为进一步区分人脑胶质瘤和正常脑组织的阻抗特性差异提供依据.方法 利用英国Solartron公司的阻抗分析仪（1260）,采用四端法,在10 Hz ～ 10 MHz范围内,对4例体外人胶质瘤组织进行电阻抗测量.通过分析其频率特性并结合已有的人脑组织的等效电路,建立了体外胶质瘤的等效电路,利用阻抗分析软件Z-VIEW对其进行仿真.结果 体外人脑胶质瘤的阻抗模值在10 Hz～10 MHz范围内随频率的增大而下降,相位角在该范围内随频率的增大而增大.体外人脑胶质瘤组织在10 kHz ～ 10 MHz范围内电阻抗实部比较稳定,其中在10Hz～ 10 kHz范围内,实部随频率的增大而减小.电阻抗虚部在20 kHz ～ 10 MHz范围内较稳定,而在10Hz ～ 20 kHz范围内,虚部随频率增大而增大.样本的等效电路仿真曲线与实际曲线相比较,等效电路模型能较好地反映体外人脑胶质瘤的电阻抗特性.结论 体外人脑胶质瘤与已知的正常脑组织的电阻抗特性及等效电路差别明显,这为探索生物电阻抗技术应用于区别胶质瘤与正常脑组织的临床应用提供了研究基础.     

Impedance magnetocardiogram

We have developed an impedance magnetocardiogram (IMCG) system to detect the change of magnetic field corresponding to changes in blood volume in the heart. A low magnetic field from the electrical activity of the human heart--the so-called magnetocardiogram (MCG)--can be simultaneously detected by using this system. Because the mechanical and electrical functions in the heart can be monitored by non-invasive and non-contact measurements, it is easy to observe the cardiovascular functions from an accurate sensor position. This system uses a technique to demodulate induced current in a subject. A flux-locked circuit of a superconducting quantum interference device has a wide frequency range (above 1 MHz) because a constant current (40 kHz) is fed through the subject. It is shown for the first time that the system could measure IMCG signals at the same time as MCG signals.