Kassanos, P.; (2012) Modelling, design and validation of tetrapolar impedance biosensors for lab-on-a-chip applications. Doctoral thesis , UCL (University College London).

Abstract

In the last decade the new scientific field of Lab-On-a-Chip (LOAC) systems arose. This field focuses on the miniaturization of standard and new laboratory techniques responsible for the manipulation and detection of biomolecules. This is a very diverse field with a vast number of different techniques being employed in order to develop such systems. The work carried out, focused on the detection of biomolecules. Electrochemical Impedance Spectroscopy (EIS), where the impedance is being measured as a function of frequency, has been used for the last 20 years in biosensor applications. However, it has failed to become widely available. The wider interest has been in the experimental procedure and not the instrumentation required or more importantly, the optimization of the electrode system used. Development of a customized system for the specific application and integration of such an instrument on a single microchip, would greatly aid towards the development, widespread deployment and standardization of EIS as a competitive, accurate, portable, simple to use, low cost, fast and label-free detection technique. This project, focused on the development of a tetrapolar impedance system, as tetrapolar electrode systems offer the advantage of reduced interfacial electrode polarization in contrast to bipolar and tripolar systems. For proof of principle, EIS was applied in the analysis of a biosensor developed for the detection of hCGb, a protein associated with various types of cancer. Commercially available coplanar-microband gold-electrode arrays were used in conjunction with a commercial impedance analyser in order to perform this analysis. Preliminary results indicated a clear differentiation between different biological and chemical layers and more importantly indicated hCGb detection. Thus, applicability of the tetrapolar technique for biomolecule detection was illustrated. The commercial electrode array, even though it did provide positive and promising results, was not optimized for the specific application. In order to do so, the Finite Element Method (FEM) modelling technique (Comsol Multiphysics) was employed in order to investigate the electric field properties of tetrapolar sensors. By utilizing the Geselowitz sensitivity theorem, the dependence of the sensitivity of the sensor to impedance changes on the sensor geometry was examined and understood. In order to optimize the sensor, a dedicated Matlab code employing the Conformal Mapping (CM) technique, was developed. This allowed the examination of the response of the sensitivity function over a specific region for millions of different geometries, reducing the computational and analytical time required with FEM. With 2D and 3D FEM models agreeing with the CM results and thus validating the CM analysis, a number of optimized tetrapolar sensors were generated. The optimization free parameters were the width (W) and the distance (D) between pairs of electrodes. The results also proved to be able to be scaled up and thus, a scaled-up (by 5x105) tank model of one of the optimized sensors was developed in order to experimentally prove the analysis. The first step towards a tetrapolar system is the bipolar and consequently bipolar (and thus interdigital) electrode systems were also briefly examined.

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