Direct Electrical Detection of Target Cells on a Microfluidic Biochip Mehdi Javanmard 1, 2 , AmirAli H. Talasaz 1, 2 , Mohsen Nemat-Gorgani 2 , Fabian Pease 1 , Mostafa Ronaghi 2 , and Ronald W. Davis 2 1 Electrical Engineering Department, Stanford, CA 94305 2 Stanford Genome Technology Center, Palo Alto, CA 94304 Abstract Pathogenic bacterial cell detection is currently performed using techniques such as culture enrichment and various plating methods, which are expensive and can take up to several days. In this study, we describe the design, fabrication, and testing of a rapid and inexpensive sensor for detection of target cells electrically in real-time. The sensor operates with the use of microelectrodes integrated in a micro-channel. As a proof of principle, we have successfully demonstrated real-time detection of target yeast cells with a concentration of 10 7 cells/ml. We have also demonstrated the selectivity of our sensors in responding to target cells while remaining irresponsive to non-target cells. We also perform theoretical modeling in order to determine the ultimate detection limit of the sensor. Based on our modeling results, proper optimization of the sensor can yield detection limits approaching the single cell level. Keywords: Electrical Biosensor, Impedance, Microfluidics, Pathogen Detection Introduction The ability to directly detect target cells at the single cell level while being inexpensive at the same time is necessary for many applications such as cancer cell detection in blood, pathogenic bacterial cell detection in food, or the testing of water quality for possible contaminations. As an example, in the case of pathogenic bacterial cell detection, currently microbiological assays involving the use of plating techniques and culture enrichment are commonly used, which can be very time consuming and expensive, taking up to several days. 1 The use of such microbiological techniques are also expensive in that it is necessary to have highly trained technicians in order to perform the assay. In an effort to automate the process and decrease the associated costs, several techniques involving fluorescent detection, surface plasmon resonance, and also electrical impedance based detection have also been proposed. Flourescence detection techniques, while highly sensitive, are disadvantageous due to the expensive cost of reagent preparation. Pathogen detection using electrical impedance based sensing techniques have also been demonstrated. 2-8 Impedance based sensors are comparatively inexpensive since they eliminate the need for fluorescence labeling. Real time detection can be achieved using flow- cytometry based methods such as the use of coulter counters. 9 Coulter counting has provided the ability to analyze the dielectric properties of a cell in real time. Single cell analysis through the miniaturization of electrodes and fluidic channels has been demonstrated. 10-15 However, through the use of Coulter counting alone, it is difficult to differentiate between two different cells which may be similar in dielectric properties and size. Here we describe an inexpensive technique which can be used for electrical (label-free format) real time detection of target cells in a solution. In this study we demonstrate the use of the described technique for detecting target cells selectively. We have demonstrated the detection selectivity of this technique using yeast cells as target cells and Concanavalin A (Con A), a glycoprotein with affinity for the sugar molecules on yeast surface, in place of antibodies. We have also performed theoretical studies for calculating the ultimate detection limit using the proposed technique and have made suggestions for improvements which can be made. We will direct future work toward further improving the detection limit. Microfluidics, BioMEMS, and Medical Microsystems VI, edited by Wanjun Wang, Claude Vauchier, Proc. of SPIE Vol. 6886, 68860B, (2008) · 0277-786X/08/$18 · doi: 10.1117/12.765611 Proc. of SPIE Vol. 6886 68860B-1 2008 SPIE Digital Library -- Subscriber Archive Copy