Temperature-Controlled Microchip Liquid Chromatography System

Abstract

High-performance liquid chromatography (HPLC) is one of the most important analytical tools heavily used in the fields of chemistry, biotechnology, pharmaceutics, and the food industry. The power of liquid chromatography comes from its ability to achieve molecular separation with extremely high efficiency and its great flexibility of incorporating versatile sensors for detecting a broad range of analytes. In the past decades, great efforts have been put into liquid chromatography instrumentation and methods, aiming to further improve separation efficiency, sensitivity, repeatability, throughput, and costs. The contribution of this thesis is to illustrate with real examples the great potential of MEMS microchip liquid chromatography systems with on-chip temperature control for replacing and improving the conventional desktop HPLC systems. This thesis is composed of seven chapters. Chapter 1 gives an introduction to MEMS technology and its application in making lab-on-a-chip systems. Chapter 2 describes the theoretical background and the evolution of HPLC technology. Chapter 3 demonstrates how to use state-of-the-art MEMS technology to make high-pressure microfluidic channels, which will be used for constructing microchip HPLC systems later. Chapter 4 describes a temperature-controlled microchip HPLC system that uses a temporal temperature gradient to achieve analyte elution. Separation of amino acids and low density lipoproteins was successfully demonstrated using the proposed system. Chapter 5 describes a novel embedded HPLC system, which demonstrated a record high pressure capacity (> 1000 psi) among microchip HPLC systems. High quality separation results of trace-level daunorubicin and doxorubicin were obtained using the proposed system and laser-induced fluorescence detection. A novel C4D sensor together with the RISE sensitivity enhancement method was proposed and investigated for the first time for microchip HPLC analyte detection. Chapter 6 describes the first work to pack 30 nm gold nanoparticles into the HPLC separation column as the stationary phase with the assistance of in-situ molecular self-assembly between nanoparticles and thiolated molecules. Preliminary results demonstrated the possibility of building fully filled nanoparticle HPLC columns for extremely high separation efficiency application. Chapter 7 then gives the conclusions of this thesis.