On-Chip Electrochemical Impedance Spectroscopy for Biosensor Arrays Chao Yang, Daniel Rairigh, Andrew Mason Department of Electrical & Computer Engineering Michigan State University, East Lansing, United State {yangchao, rairighd, mason}@egr.msu.edu Abstract—Electrochemical impedance spectroscopy (EIS) is a powerful tool for characterizing biological materials, including lipid bilayers and many membrane proteins. However, traditional EIS methods are very slow at low frequencies, where these materials respond in biosensor applications. To enable dense arrays of biosensors based on tethered bilayer lipid membranes (tBLM), a new approach for EIS has been developed. This paper introduces a methodology and circuit that can rapidly perform EIS in the 1mHz to 100kHz frequency range. A circuit implementing this new approach has been realized in 0.5μm CMOS technology with 3.3 voltage power supply. In the sub-hertz range where membrane protein biosensor response is most critical, the circuit can measure impedance with 8 bit resolution in 20ms, three orders of magnitude faster than traditional integrator-based circuits. Though tailored for the low frequency spectrum in biosensor applications, the EIS circuit can be used to measure impedance in a wide range of sensory materials. I. INTRODUCTION Protein modified tethered bilayers lipid membranes (tBLM) [1] provide a means to measure, with high specificity and high sensitivity, unique biochemical analytes and biological phenomena. They hold great promise in many applications of biotechnology including diseases diagnosis and environmental monitoring. Electrochemical impedance spectroscopy (EIS) techniques are the best means to interrogate many tBLM-based biosensors. Currently, bench- top instruments are used to perform EIS [2,3], and no chip- scale EIS systems exist. These biosensors offer their greatest potential when used in high-density arrays of tBLMs modified with different proteins, which encourages the development of compact systems. Two constraints impede the further progress in the miniaturization of tBLM-based biosensor arrays [4]. First, routing hundreds of raw signals off the array chip introduces bandwidth challenges as well as performance-limiting noise; thus on-chip instrumentation capable of processing and reducing the raw data is necessary to fully enable these arrays. Second, the measurement speed of traditional EIS methods is not adequate to interrogate a high density array rapidly enough to ensure all important data is recorded. This paper described an on-chip EIS system targeting these constraints. In section II, the characteristics of the tBLM biosensor and its interrogation method are discussed. In section III, a new measurement scheme targeting high- density tBLM based biosensor arrays is introduced, and its circuit realization is presented in section IV. II. TBLM BASED BIOSENSORS A. Protein modified tBLM and equavalent circut model A tBLM is a synthetic lipid membrane that is tethered to the surface of a solid electrode. Proteins, including ion channels as shown in Fig. 1(a), can be embedded in the tBLM to mimic the function of a cell membrane or immobilize the protein for characterization. Only very specific analytes will cause these channels to open and allow ions to pass through them. The open/closed state of the ion channels reflects the presence of a certain analyte in the solution, and the impedance across the membrane corresponds to the analyte concentration. Thus, the protein- modified tBLM can serve as a very sensitive and selective sensor element. tBLM based biosensors modified by different proteins can be formed into an array to detect and measure a wide range of analytes efficiently. To measure a tBLM biosensor electrically, an equivalent circuit model is used as shown in Fig. 1(b). The two ends of this equivalent circuit present the solution side and solid electrode side of the tBLM biosensor. R s represents the serial resistance of the solution. C dl represents the double layer capacitance of the electrode metal-solution interface. C M is the capacitance of the lipid bilayers. R M is the resistance of the lipid bilayer, which is normally much larger than the This work was supported in part by the Engineering Research Centers Program of the National Science Foundation under Award Number EEC- 9986866. (a) (b) Figure 1. (a) Structure and (b) equivalent circuit model of a tBLM-based biosensor with an ion channel protein. 1-4244-0376-6/06/$20.00 2006 IEEE IEEE SENSORS 2006, EXCO, Daegu, Korea / October 22~25, 2006 93 1-4244-0376-6/06/$20.00 2006 IEEE