Dec 15, 2003 - frequency 10KHz), actuator-electrodes, catcher-electrodes and an amplifier. The figure 1 shows the Schematic of every parts of the minimal ...
Proceedings of the 2nd IEEE International Conference on Nano/Micro Engineered and Molecular Systems January 16 - 19, 2007, Bangkok, Thailand
Minimally Invasive Electrical Impedance Measurements of Ovum Exemplified Using Microelectrodes Ran Liu', Jing Liu', Xia Di', Guangzhi Wang' , and Datian Ye2
*
'Department ofBiomedical Engineering, Medical School, Tsinghua University, Beijing, China 2Research Center ofBiomedical Engineering, Graduate School at Shenzhen Campus, Tsinghua University, Shenzhen, China. Abstract-It is commonly accepted that electrical impedance provides relevant information about the physiological condition of living tissues. Currently, impedance measurements are performed with relatively large surface electrodes not suitable for studies in micro tissue due to their poor spatial resolution and high ESEI that they cause on the surface of skin. A minimally invasive electrical impedance measurement technique of living tissues using needle shaped electrode is described in this paper. A series of experiments in ovum gallinaceums was performed to demonstrate the feasibility of the probes and the measurement system to decrease diagnostics uncertainty. Ovum impedance measurements with the minimally invasive probe showed that the effect of the outer layer membrane (the stratum corneum of skin) was substantially reduced compared to regular non-invasive impedance. Minimally invasive probes resulted in significant changes of all measured parameters.
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INTRODUCTION
It has been demonstrated that electrical impedance is a useful parameter to determine the physiological condition of living tissues [1]. Electrical impedance tomography (EIT) technique is one of important application of electrical impedance in the biomedical engineer field. The EIT is considered to be very useful clinically because structures, physiological function, the local tissue, and physiological state of the tissue caused by cell activities can be monitored. Bioimpedance information has been found great application potential for function measurements. Pathological diagnose using electrical impedance is of special interest since it is an objective, fast, straightforward, and inexpensive technique that captures fundamentally different information than optical techniques[2]. Though many researches have been reported to realize the EIT for practical use, there remain several problems to be solved. It is necessary to develop the electrical impedance technique in order to facilitate a diagnostic decision tool to reduce biological variations not related to the lesions and to enhance the malignant signals. This article describes such a technical enhancement. Currently, impedance measurements are performed with relatively large surface electrodes, and its major limitations are its low spatial resolution, and in the medical field diagnostics uncertainty. One important reason is that impedance measurements is based on the standard surface electrodes which results in long application times, long stabilization times, and high ESEI (Electrode-Skin-Electrode Impedances). Human skin This project was funded by the Tsinghua Basic Research Foundation (Project code. 052203008). *Contact authors:
liuran(mail.tsinghua.edu.cn.
1-4244-0610-2/07/$20.00 C)2007 IEEE
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has high impedance problems associated with layers of the outer skin (the Stratum Corneum, SC) which lead to the measuring uncertainty. The precise measurement of bioimpedance is required urgently to realize the clinical applications. One way to access electrical impedance of the viable tissue beneath the SC is to remove the SC with e.g. tape stripping. Another possibility is to penetrate the SC and measure the impedance below using microneedle electrodes. They can be made in silicon using micro-electro-mechanical system (MEMS). The SC is a dead tissue that acts as a fluid barrier and therefore has electrical isolation characteristics. Below lies the viable epidermis (50-100gm), a tissue containing living cells, but which is devoid of blood vessels and contains few nerves. Thus, the microneedles which penetrate the skin more than 1015gm but less than 50-100gm should provide electrical transport pathways across the stratum corneum. The spikes must not reach the tissue layers below the epidermis (containing nerves and blood vessels) so as to avoid pain or bleeding. For a microneedle electrode the electrical model is less complex compared to a wet standard electrode. This is mainly due to the fact that the microneedles create a direct interface with the epidermis, thereby circumventing the influence of the electrolytic gel and the SC. The overall impedance of the microneedle electrode is expected smaller than the overall impedance of the standard one. Furthermore, lower electrochemical noise can be anticipated for a microneedle[3]. In the arithmetic of EIT, the complete electrode model is more precise than the continuum model. In the complete model, 'K =z0(r)+z zj(Q) = 0)+ziy(rQ)an0' ),Sr
(1)
The zi is available contact impedance and reflects the high impedance between the electrode and the object. We can expect that zi will influence the result of the whole model. So the low contact impedance is needed. The EIT electromagnetic field models under the minimal invasive and non-invasive electrode contact modes on human body were built and analysed in previous paper[5]. The results of electromagnetic field analysis indicated that the effect of the stratum corneum in the minimally invasive mode was substantially reduced compared to regular surface mode. In this article the experiments are described to further study the minimally invasive electrical impedance measurements.
METHODOLOGY of minimal invasive bioelectrical The essential theory impedance measurement has been found same as the principle of non-invasive impedance measurement. We design and carry out a system of measuring bioelectrical impedance, and analyse the method of minimal invasive measurement by experimental way. First a experimental system for electric impedance measurement is built, consist of constant current source (low frequency 10KHz), actuator-electrodes, catcher-electrodes and an amplifier. The figure 1 shows the Schematic of every parts of the minimal invasive impedance measurement system. Compared to regular non-invasive impedance, minimal invasive impedance measurement system uses minimal invasive electrodes instead of surface electrodes measures signal based on a insertion model. The actuator-electrodes and catcher-electrodes are spiked electrodes made of Ag. The diameter of the spiked electrode is about 0.9mm. In order to show clearly, we used this small electrodes study for the microneedle electrodes. The fresh ovum gallinaceums are selected as the experimental objects because they are intact living tissue same as the intact skin and simpler than skin. Thus the experiments are avoided the effect of other physiology of organism. And the ovum can stand for one kind of cells, the studies of which are also subjects we care about. The figure 2 shows that the spiked electrodes are penetrated into the ovum. The four electrode techniques are used in the measurement system. II.
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Based on the system, we designed and took a series of contrastive experiments. The four placement modes of actuatorelectrodes and catcher-electrodes electrode are built to analyse the effect of electrode placement. RESULTS One pair of actuator electrodes was used for electrical current injection at the low frequency 10KHz. The current ranges vary from 0-1 5QOA. Figure 4 shows the results of impedance measurement. We obtain that at every different stimulative current the impedance in the minimal invasive model is further lower than in the noninvasive model. The result accords with the previous expectation. The spiked electrodes are penetrated through the SC and succeed in avoiding the high impedance layer. The results demonstrated the low ESEI could be obtained in the minimal invasive model using the microelectrodes and the effect of the outer layer membrane (the stratum corneum of skin) was substantially reduced compared to regular nonIII.
invasive impedance. It can be considered that the useful stimulative current band goes from 10[tA to 60tA in the minimal invasive impedance measurement using the microelectrodes for those ovum experiments exemplified from figure 5. Figure 6 shows that the effect of the different placement modes of actuator-electrodes and catcher-electrodes electrode to the results is not statistically evident from the curves. And the impedances vary following the penetrating depth. A sudden change happens on the point of piercing which can explain the difference of the non invasive mode and minimally invasive mode. Otherwise, we measure the impedances of ovum cells with the different freshness. Figure 7 shows that the impedance of fresh ovum cell is further lower than the ovum cell which is placed in 3 hours. So the freshness can be one of factors influencing the biology impedance.
.-
Schematic of the minimal invasive impedance Figure 1. measurement system: compared to regular non-invasive impedance, it uses needle microelectrodes instead of surface electrodes measures signal based on a insertion model. It is made up of constant current source (low frequency), actuator-electrodes, catcher-electrodes and an amplifier.
Figure 2. Schematic of needle microelectrodes are penetrated into the ovum cell. The fresh ovum gallinaceums are selected as the experimental objects The four electrode techniques are used in the measurement system.
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IV. CONCLUSION The minimally invasive electrical impedance tomography is described as a novel minimally invasive technique to decrease diagnostics uncertainty. The results of minimally invasive electrical impedance measurement experiment analysis of ovum exemplified indicate that at same applied stimulative current the impedance in the minimal invasive model is further lower than in the non-invasive model. The result accords with the previous expectation. The minimal invasive electrodes succeed in avoiding the high impedance layer and the low ESEI can obtain in this mode. We find the impedances vary following the penetrating depth and a sudden change happens on the point of piercing which can explain the difference of the non invasive mode and minimally invasive mode. The minimal invasive impedance measurement based on microneedle electrode is a new approach to enhance the precision and feasible attempt for many innovative applications. Otherwise, more biology experimental and theoretical analyses are waiting to be solved to realize clinical applications of EIT.
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Figure 6. Penetrating depth vs. impedance in four electrode modes. [5]
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Gomez, R.; Noguera, N.; Villa, R.; Sola, A.; Palacios, L.; Hotter, G.; Aguilo, J., "Minimally invasive silicon probe for electrical impedance measurements in small animals," Biosensors and Bioelectronics, v 19, n 4, Dec 15, 2003, pp. 391-399 Aberg, P.; Nicancer, I.; Ollmar, S.; "Minimally invasive electrical impedance spectroscopy of skin exemplified by skin cancer assessments," Engineering in Medicine and Biology Society, 2003. Proceedings of the 25th Annual International Conference of the IEEE, vol4, 17-21 Sept.2003, pp. 3211 - 3214 Patrick Griss, Peter Enoksson, Heli K. Tolvanen-Laakso, Pekka Merilainen, Stig Ollmar, Goran Stemme, "Micromachined electrodes for biopotential measurements," Journal of Microelectromechanical System, 10,2001,pp. 10-16 Griss, Patrick, Enoksson. Peter, Stemme. Goran, "Micromachined barbed spikes for mechanical chip attachment," Sensors and Actuators, A: Physical, v 95, n 2-3, Jan 1,2002, pp. 94-99 R. Liu, J. Liu, G. Z. Wang, "Minimally Invasive Electrical Impedance Tomography-Promising Way to Decrease Diagnostics Uncertainty," The
Proceeding of IEEE Int. Conf. on Nano/Micro Engineered and Molecular Systems 2006, Review of Advancements in Micro and NanoTechnologie [6] Xu GZ, Yang QX, Yang S, et al. , "Electrical characteristics of real head model based on electrical impedance tomography," IEEE Transactiona on applied superconductivity 14 (2), 2004, ppl617-1620 [7] Cherepenin V, Karpov A, Korjenevsky A, et al., "Preliminary static EIT images of the thorax in health and disease," Physiological Measurment 23 (1), 2002, pp33-41 [8] Frerichs I, Braun P, Dudykevych T, et al. , "Distribution of ventilation in young and elderly adults determined by electrical impedance
tomography," Respiratory Physiology & neurobiology 143 (1), 2004, pp 63-75 [9] Armstrong S, Jennings D, "Current injection electrodes for electrical impedance tomography," Physiological measurement 25 (4), 2004, pp797-802 [10] Allessandrini G, Rosset E, "Volume bounds of inclusions from physical EIT measurements", Inverse Problems 20 (2), 2004, pp575-588 [11] Tossavainen OP, Vauhkonen M, Heikkinen LM, et al. , "Estimating with shapes and free surfaces electrical impedance tomography,"Measurment Science & Technologyl5 (7), 2004, ppl4021411
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