A NEW CONDUCTIVE MEMBRANE-BASED MICROFLUIDIC PLATFORM FOR ELECTROKINETIC APPLICATIONS

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Date
2017-02-09
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Johns Hopkins University
Abstract
Micro-total-analysis-system (uTAS), a technology branches from the broader concept, microfluidics, has emerged as a powerful tool for many biological and chemical applications. uTAS typically features sample-to-answer designs, minute sample assumption and short processing time, which are highly desired in point-of-care diagnostics or high-throughput chemical analysis. Despite a large number of microfluidic devices reported with the uTAS concept, most designs were detection and sensitivity focused, ignored the necessary sample preparation steps. In recent years, the increasing demand for chip automation has boosted research efforts on sample preparation. Electric force serves as one of the most applicable tools among on-chip sample processing techniques due to its portable and easy-integrating nature. To date, research has yielded a large number of designs utilizing electric field as a driving force, also known as electrokinetics, for on-chip sample processing, such as sample purification, enrichment, mixing and sorting. One biggest issue researchers countered using electric field is undesired surface reactions that may cause Faradaic reactions, electrode corrosion, and contaminations. While several microfluidic platforms have been developed to address this issue, there are still growing efforts to create new micro-design that are capable of providing sufficient electric field with improved stability, portability, and robustness. This thesis seeks to address the electrokinetic-based on-chip sample preparation issue in two aspects, continuity and flow control, which represent two main challenges of on-chip sample preparation: a limited capability to continuously process samples and lacking necessary modules for precise flow control under large extent chip integration. We first developed a new electrokinetic platform with integrated conductive membranes to effectively generate a uniform three-dimensional electric field inside microfluidic channels. The new design also has proved superiorities in avoiding surface reactions, improving portability, and reducing the fabrication cost. We then solved the continuity issue with a free flow electrophoresis device created from the platform. The free flow nature of the device allows for continuous sample throughput while adding electric field perpendicularly offers additional manipulating factors. Utilizing the newly developed free flow electrokinetic chip, we have successfully demonstrated two common on-chip sample processing functions: parallel separation and sample enrichment. On the other hand, the flow control issue is tackled by creating essential on-chip control modules under microfluidic setting. We have designed several microfluidic units with the platform to facilitate on-chip flow regulation, including micro-pumps, a sample injector, a local flow meter and a potential automatic control panel. All the flow control modules can be directly integrated into any soft lithography based sample processing modules without affecting the original designs, which significantly eases the integration difficulty. The ultimate goal of this research shall lead to a microfluidic platform that can perform essential on-chip sample pretreatments in a continuous manner and allows need-based customization. The platform shall be easily integrated with essential power functions and feedback mechanisms for automatic flow control, which offer a possibility to real highly integrated portable devices. Eventually, we can build the real uTAS by combining the platform with our real-time biosensor and turning it into a sample-to-answer uTAS. In the first chapter of this thesis, a general background correlated to my research work is provided. The introduction includes the uTAS concept and its related technologies, explains the increasing demand for on-chip sample preparation techniques, and discusses current sample process modules using electrokinetic force. It leads to Chapter 2, where I summarize the current electrokinetic-based microfluidic platforms developed to address the surface reaction issue. Then we propose the new platform along with a theoretical model to characterize this design. An extensive comparison between available designs follows to demonstrate the advantages of this new platform, including the comparison specifically focusing on surface reactions. A detailed fabrication process flow is demonstrated in the end, showing how to fabricate this new platform design using one -step photolithography. Then the thesis splits into two parallel blocks, corresponding to the two challenges of on-chip sample preparation. The continuity challenge is addressed on the first block, chapter 3, where free flow electrophoresis device is presented and followed by two demonstrations of on-chip sample pretreatment functions: mixture separation and molecule enrichment. The second block of this thesis discusses the importance of on-chip flow control and the main obstacles that current technologies struggle with. Essential modules for on-chip flow control, such as electro-osmotic pumps, fluid regulation, sample injection techniques, pressure and flow meters, will be demonstrated in chapter 4-6, respectively. In conclusion, I will summarize all my previous research work and how to sketch the big picture of on-chip sample preparation with this platform. The results shall provide guidelines and inspirations for future on-chip sample preparation research.
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Keywords
Microfluidics, Electrokinetics , Sample preparation
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