| Dynamic chemical signals are pervasive in biology. For example, chemical signals control biological processes in protein activation and signaling, paracrine and endocrine cell-to-cell communication, inflammatory response, and regulate many aspects of stem-cell growth and tissue differentiation. The time scales for many of these signals range from a fraction of a second to several minutes, depending on the specific system. In spite of their relevance, there are no well established techniques for analysis and separation of time-dependent signals. Conventional chemical analysis techniques such as electrophoresis and liquid chromatography can only be used for the analysis of finite, discrete and time invariant samples; hence many samples must be collected to determine the dynamic nature of a sample.;The work described in this thesis represents several significant original contributions in the field of dynamic chemical signal analysis using PDMS as a ubiquitous platform. First we designed and fabricated a new type of valve called minimum lambda Teflon seated valve (chapter 4). This new type of valve has small area of 25x25 mum2 and is suitable for large scale integration. Second, we constructed high frequency sequential segmentation micromixers (chapter 8) that can run at frequency as high as 200 Hz which reduce the mixing length less than 1 mm. To solve the problem of flow interruption in the scheme of sequential segmentation, we also developed a continuous flow tiling mixers (chapter 8) which has the same rapid mixing characteristics of the scheme of flow segmentation. Third, we developed the theory of Fourier microfluidics (chapter 8), and based on this theory, we constructed delay line filters and band-pass filters (chapter 9) that can be used for the separation of dynamic chemical signals based on their Fourier, frequency domain characteristics rather than their chemical composition. To our knowledge, we were the first to contemplate the use and advantage of Fourier microfluidics for dynamic chemical signal analysis. Fourth, we engineered novel frequency selective microfluidic filters based on nonlinear frequency mixing and synchronous modulation/demodulation (chapter 10) that can also be used for the spectral separation of dynamic chemical signals. Finally, we devised a new arbitrary chemical concentration gradient generator based on pulsed code modulation (chapter 11) and used the device to study the migration of human neutrophils under the influence of IL-8. |
