Automatic Generation of Analog Hardware Description Language (AHDL) Code from Cell Culture Images Alberto Yúfera 1 and Estefanía Gallego 2 1 Instituto de Microelectrónica de Sevilla (IMSE), Centro Nacional de Microelectrónica (CNM-CSIC) Universidad de Sevilla Av. Américo Vespucio s/n. 41092. Sevilla. SPAIN e-mail: yufera@imse-cnm.csic.es 2 Dto. Tecnología Electrónica, Universidad de Sevilla Av. Reina Mercedes s/n. 41022. Sevilla. SPAIN e-mail: estefania.gallego@gmail.com Abstract--This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program can be used in cell culture image processing for geographic information extraction and sensor sizing, generating cell count and Analog Hardware Description Language (AHDL) equivalent circuits useful for whole system electrical simulations. Keywords--Microelectrode; bioimpedance sensor; Analog Hardware Description Language; image processing. I. INTRODUCTION The impedance is a useful parameter for determining the properties of biological materials for several reasons: first, they are conductive [1] second, the impedance measurement represents a non-invasive technique, and third, it is a relatively cheap technique. Many biological parameters and processes can be sensed and monitored using its impedance as marker [2-5]. Impedance Spectroscopy (IS) of cell culture [6] and Electrical Impedance Tomography (EIT) in bodies [7] are examples of the impedance utility for measuring biological and medical processes and parameters. Classical real-time monitoring and imaging systems for biological samples are based on optical stimulation of samples, demanding bulky and expensive equipments. Embedded Complementary Metal-Oxide-Semiconductor (CMOS) sensors have been reported as an alternative for increasing the sensitivity to cell location and manipulation. The most popular are optical [9], capacitive [7] and impedance [8] based sensors. Despite of the high number of papers with optical sensors the last years, they still need external lamps, optical fibbers, etc, while capacitive and impedance based detection do not rely on peripheral equipment. This paper is related to a new method for impedance measurement with applications to cell culture systems. The system in fig. 1 employs a two dimensional electrode array as sensors [10,11] together with CMOS circuits for impedance measurements [12]. Microelectronic circuits must be designed to work with constraints imposed by the electrode sensors. The whole system in fig. 1 can be fully-integrated in CMOS technologies [10]. When low concentration cell cultures are carried out on top of the electrode array, depending on the position of each cell, specific electrode-cell impedance will be measured, allowing cell detection. Electrical models reported for the electrode-cell interface description [11.12] are the key for matching electrical simulations to real systems performance and hence decoding correctly the experimental results, usually known as a reconstruction problem. This kind of system can be used for real-time monitoring of cell cultures with the Electrical Cell Impedance Spectroscopy technique (ECIS), [6]. Fig. 1. (a) Simplified system set-up: circuits and 2D electrode sensor array for bio-impedance measurement. (b) Each sensor has e1 and e2 electrodes. Cell culture is done on electrode top. In this paper is presented a computer tool that aids in cell culture image processing and reconstruction, helping to the optimization of circuit design since it enables the emulation of biological loads. In the system shown in fig. 1, the tasks of to be done are: To perform a pre-processing of a cell culture image to define the areas occupied by cells. Digital Image Processing (DIP) is focused on segmentation to discriminate the total area covered by cells. To incorporate the definition of the electrode area. This is important not only from the electrode-solution-cell system modeling and characterization point of view; but because the electrode sensitivity of the impedance sensor will be dependent of its size and working frequency. The electrode-cell overlap Image Processing Theory, Tools and Applications 978-1-4244-7249-9/10/$26.00 ©2010 IEEE