would be possible. I would like to thank my major professor Dr. Michael Murphy, who offered me this extraordinary opportunity to do research in the Bio-MEMS group. His vision, knowledge, experience and encouragement was vital for me to go through and finish the work. I also would like to thank Dr. Steven Soper from the Chemistry Department and Dr. Dimitri Nikitopoulos from the Mechanical Engineering, without their input and knowledge this work would not have been possible. I would like to show my appreciation to fellow students Amit Maha, for significant contribution towards the mixer development, Dr. Yun Wang, Hashimoto, Daniel Pin-Chen, Michael Mitchell who helped with experiments and made insightful suggestions. To everybody in the Muset Lab, thank you for providing a good work atmosphere that enabled a person to strive not only academically but also socially. I thank the entire staff at CAMD for given the privilege to use the facility during the fabrication of my project. I would like to express my gratitude to Chenelle, family and friends who have always been a source of strength and encouragement.

This part of our work has been aimed at designing, manufacturing and characterizing effective micro-mixers which are cheap, durable and easily integrated on a variety of bio-chips with emphasis on those performing Polymerese Chain Reactions (PCR) and Ligase Detection Reactions (LDR). A key contribution is the development of an optimization procedure for the design of passive micro-mixers utilizing high-aspect-ratio micro-channels (HARMC). The optimization procedure identifies the optimum type of mixer on the basis of the flow rate proportions of the mixture constituents and provides for two optimum designs of the selected mixer type for an aspect ratio of choice in two ways: (a) for specified mixture volume and mixer pressure drop the optimum mixer dimensions and operating condition minimize the total production time and (b) for specified mixture volume and a total production time the optimum mixer dimensions and operating condition minimize the mixer pressure drop. The simplest and easiest to manufacture layout of an optimized mixer configuration (X2JC) with two inlet ports and three layers is shown in Figure 1. The injection of compound 1 into the compound 2 main stream is performed through two side-jets in a wider channel to further reduce the pressure loss overhead followed by a contraction into the main mixing channel.

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The Ligase Detection Reaction (LDR) is a mutation detection technique used to identify point mutations in deoxyribonucleic acid (DNA). A microscale Ligase Detection Reaction (LDR) device was designed and manufactured in polycarbonate. There are at least two mixing stages involved in the LDR identification process. Various micromixers were simulated in Fluent (v5.4, Lebanon, NH) and several test geometries were selected for fabrication. Passive diffusional micromixers were made with aspect ratios from 7 to 20. The mixers were made by SU-8 lithography, LIGA, laser ablation and micromilling to characterize each fabrication method. It was found that LIGA was best for making the micromixers, but was the longest process. The micromixers were fabricated and are being tested using fluorescent dyes. For a successful reaction temperatures of 0°C, 95°C and 65°C were needed. A stationary chamber method was used with thermal cycling in which the sample held while the temperature is cycled. Finite element analysis showed uniform temperatures in the rectangular 1.5 μl chambers and that air slits can effectively separate the thermal cycle zone from the 0°C cooling zone and the mixing region. A test device was laid out and micromilled with the temperature zones. A commercial thin film heater and a thermoelectric module were used with a PID controller to obtain the required process temperatures. Heating from 65°C to 95°C took 10 seconds, while cooling from 95°C to 65°C also took 10 seconds. The residence times at the required temperatures can adapt to changes in the LDR as parameters and reactant concentrations are varied.