Finite Element Simulation of Microelectrodes for Bio-impedance Sensor Applications Alberto Olmo Escuela Superior de Ingenieros (ESI), Dto. Física Aplicada III, Universidad de Sevilla Av. de los Descubrimientos s/n.41092. Sevilla. SPAIN e-mail: albertoolmo@esi.us.es albertoolmo@esi.us.es Alberto Yúfera Instituto de Microelectrónica de Sevilla (IMSE), Centro Nacional de Microelectrónica (CNM-CSIC) Universidad de Sevilla Av. Américo Vespucio s/n. 41092. Sevilla. SPAIN yufera@imse-cnm.csic.es Abstract - Electrical models for microelectrode-cell interfaces are essential to match electrical simulations to real bio-systems performance and correctly to decode the results obtained experimentally. The accurate performance simulation of a microelectrode sensor to changes in the cell-electrode system, such as cell growth, enables the optimum microelectrode design process. We report the use of COMSOL quasi-static mode, contrary to other DC modes frequently used, including magnetic fields to calculate the bioimpedance of the system. A fully electrode-cell model has been built, and the effect of fibroblasts of different diameters on the simulated impedance of small microelectrodes (32-μm square) has been studied, in order to validate the model and to characterize the microelectrode sensor response to changes in cell size and density. Keywords- Microelectrode; bioimpedance; impedance sensor; computer simulation; COMSOL. I. INTRODUCTION Many biological parameters and processes can be sensed and monitored using its impedance as marker [1-6] with the advantage of being a non-invasive and relatively cheap technique. Cell growth, changes in cell composition or changes in cell location are only some examples of processes which can be detected by microelectrode-cell impedance sensor variations. Electrical models have been reported for the electrode- cell interfaces [4][5][7], being these key for matching electrical simulations to real systems performance and hence decoding correctly the results obtained experimentally, usually known as reconstruction problem. Some of these models have been obtained by using the finite element analysis method with programs such as FEMLAB. [5]. The use of the DC mode for a sinusoidal steady state calculation is possible by assigning a complex conductivity, which works because the Poisson equation is the same form as the Laplace equation in the charge-free domain. This paper presents an alternative method for simulating electrode – cell interfaces with finite element analysis, based on COMSOL. The quasistatic mode of COMSOL is used, which also takes into account magnetic fields to calculate the electric impedance. Our work, based on previous models [5], is developed in section II. Several improvements on their model have been made both on the cellular membrane and the cell-electrode gap, are described in section III. Impedance changes on small electrodes (32- μm square) caused by different sizes of 3T3 mouse fibroblasts were simulated in section IV, in order to validate the model and characterize the microelectrode sensor response to cell growth. Finally, conclusions are highlighted in section V. II. CELL-ELECTRODE MODEL The work performed by Huang et al., was initially explored, making use of the computation advantages COMSOL provides over FEMLAB. Our objective is to compare the results in the study of the impedance changes caused by cell growth on electrodes with similar size to the cell. Cells modeled in the simulation by Huang et al. were 3T3 mouse fibroblasts, which attach closely to surfaces and which have a cell-surface separation typically of 0.15μm [8]. The cells are about 5μm in height and, from a top view, are irregularly shaped and approximately 30–50μm in extent. A circular cell 30 μm in diameter centered on a square sensing electrode that is 32μm on each side was considered. (see figure 1). The sensing electrode was surrounded by a counter electrode that has considerably greater area. 3T3 mouse fibroblasts consist of a thin (about 8 nm), poorly conducting membrane that surrounds the highly conductive interior of the cell. The capacitance of the cell membrane is approximately C mem = 1 μF/cm 2 [9]. The cell culture medium simulated by Huang et al. is highly ionic and possesses a conductivity of approximately 1.5 S/m. The cell culture medium fills the cell-electrode gap and forms an electrical double layer (Helmholtz plus diffuse layer) between the bulk of the medium and the electrode that is approximately 2 nm in thickness. Some approximations were made in ref. [5] to facilitate the resolution of the problem by FEMLAB. Only one quarter of the electrode was simulated. As the problem is characterized by a wide range of distance scales, it was difficult to solve by finite-elements techniques, so the following adjustments were made: 2010 First International Conference on Sensor Device Technologies and Applications 978-0-7695-4094-8/10 $26.00 © 2010 IEEE DOI 10.1109/SENSORDEVICES.2010.36 221 2010 First International Conference on Sensor Device Technologies and Applications 978-0-7695-4094-8/10 $26.00 © 2010 IEEE DOI 10.1109/SENSORDEVICES.2010.50 232