DNA detection technology has developed rapidly due to its extensive application in clinical diagnostics, bioengineering, environmental monitoring, and food science areas. Currently developed methods such as surface Plasmon resonance (SPR) methods, fluorescent dye labeled methods and electrochemical methods, usually have the problems of bulky size, high equipment cost and time-consuming algorithms, so limiting their application for in vivo detection. In this work, an intrinsic Fabry-Perot interferometric (IFPI) based DNA sensor is presented with the intrinsic advantages of small size, low cost and corrosion-tolerance. This sensor has experimentally demonstrated its high sensitivity and selectivity. In theory, DNA detection is realized by interrogating the sensor's optical cavity length variation resulting from hybridization event. First, a microgap structure based IFPI sensor is fabricated with simple etching and splicing technology. Subsequently, considering the sugar phosphate backbone of DNA, layer-by-layer electrostatic self-assembly technique is adopted to attach the single strand capture DNA to the sensor endface. When the target DNA strand binds to the single-stranded DNA successfully, the optical cavity length of sensor will be increased. Finally, by demodulating the sensor spectrum, DNA hybridization event can be judged qualitatively. This sensor can realize DNA detection without attached label, which save the experiment expense and time. Also the hybridization detection is finished within a few minutes. This quick response feature makes it more attractive in diagnose application. Since the sensitivity and specificity are the most widely used statistics to describe a diagnostic test, so these characteristics are used to evaluate this biosensor. Experimental results demonstrate that this sensor has a sensitivity of 6nmol/ml and can identify a 2 bp mismatch. Since this sensor is optical fiber based, it has robust structure and small size ( 125μm ). If extra etching process is applied to the sensor, the size can be further reduced. This promises the sensor potential application of in-cell detection. Further investigation can be focused on the nanofabrication of this DNA sensor, and this is very meaningful topic not only for diagnostic test but also in many other applications such as food industry, environment monitoring. / Master of Science

Fiber-optic Fabry-Perot interferometric (FFPI) sensors have been widely used due to their high sensitivity, ease of fabrication, miniature size, and capability for multiplexing. However, direct measurement of self-assembled thin films, receptor immobilization process or biological reaction is limited in the FFPI technique due to the difficulty of forming Fabry-Perot cavities by the thin film itself. Novel methods are needed to provide an accurate and reliable measurement for monitoring the thin-film growth in the nanometer range and under various conditions. In this work, two types of fiber-optic multicavity Fabry-Perot interferometric (MFPI) sensors with built-in temperature compensation were designed and fabricated for thin-film measurement, with applications in chemical and biological sensing. Both the tubing-based MFPI sensor and microgap MFPI sensor provide simple, yet high performance solutions for thin-film sensing. The temperature dependence of the sensing cavity is compensated by extracting the temperature information from a second multiplexed cavity. This provides the opportunity to examine the thin-film characteristics under different environment temperatures. To demonstrate the potential of this structure for practical applications, immunosensors were fabricated and tested using these structures. Self-assembled polyelectrolytes served as a precursor film for immobilization of antibodies to ensure they retain their biological activity. This not only provides a convenient method for protein immobilization but also presents the possibility of increasing the binding capacity and sensitivity by incorporating multilayers of antibodies into polyelectrolyte layers. The steady-state measurement demonstrated the surface concentration and binding ratio of the immunoreaction. Analysis of the kinetic binding profile provided a fast and effective way to measure antigen concentration. Monitoring the immunoreaction between commercially available immunoglobulin G (IgG) and anti-IgG demonstrated the feasibility of using the MFPI sensing system for immunosensing applications. / Ph. D.

DNA is the substance that encodes the genetic information that cells need to replicate and to produce proteins. The detection of DNA sequences is of great importance in a broad range of areas including genetics, pathology, criminology, pharmacogenetics, public health, food safety, civil defense, and environmental monitoring. However, the established techniques suffer from a number of problems such as the bulky size, high equipment costs, and time-consuming algorithms so that they are limited to research laboratories and cannot be applied for in-vivo situations. In our research, we developed a novel sensing scheme for DNA sequence detection, featuring sequence specificity, cost efficiency, speed, and ease of use. Without the need for labels or indicators, it may be ideal for direct in-cell application. The principle is simple. With capture DNA immobilized onto the probe by layer-by-layer selfassembly, the hybridization of a complementary strand of target DNA increases the optical thickness of the probe. Three kinds of sensors were developed. The optical fiber tip sensor has been demonstrated with good specificity and high sensitivity for target DNA quantities as small as 1.7 ng. To demonstrate the potential of this structure for practical applications, tularemia bacteria were tested. Two other micrometric structures were designed with specific advantages for different applications. The micro-fiber Bragg grating interferometer (Micro-FBGI) has the intrinsic temperature compensation capability. The micro-intrinsic Fabry-Perot interferometer (Micro-IFPI)features simple signal processing due to its simple configuration. Successful DNA immobilization and hybridization have been demonstrated onto the 25μm Micro-IFPI. Both structures have great potential for nanometric protrusion, allowing future in-cell DNA direct detection. In addition, its quick response time leads to the potential for express diagnosis. What's more, the idea of nanoscale probe has a broad impact in scanning near-field optical microscopy (SNOM), intracellular surgery in cell sensing, manipulation, and injection. / Ph. D.