Development of label-free colorimetric plasmonic biosensor for biomedical applications

The advancement in biosensor technology have allowed for detection and quantification of relevant biomarkers that are associated with a disease or a health condition, or of interest in the assessment of a patient's well-being. The high-end biosensor technology such as Biacore Surface Plasmon Resonance (SPR) system has high functionality; that is, the ability to detect multiple analyte with high sensitivity and specificity with some preparation and handling. However, the accessibility of the technology is quite low due to several barriers such as cost (initial purchase and consumables), requirement of trained personnel for operation, and a specialized facility to house and maintain the equipment. In contrast, low-end biosensor technology such as a blood glucose sensor has low functionality with the ability to detect only one analyte at relatively high concentration with minimal sample preparation and handling. Low-end biosensor technology has the advantage of high accessibility due to its low cost, user-friendliness, and portable format. Given the recent development of biosensors based on extraordinary transmission of noble metal-deposited nanohole arrays, there is an opportunity to develop biosensors that have high functionality with higher accessibility due to improvements in the ease of use, cost-effectiveness, and portability.;The work undertaken in this dissertation has been to demonstrate the potential of nanohole array sensor based biosensors for label-free detection and colorimetric sensing in biomedical applications. Chapter 1 is an overview of label-free biosensors with a focus on nanohole array-based biosensors. Chapter 2 describes the influence of the adhesion layer on the spectral property and thereby colorimetric sensing of nanohole array sensor through experimental and theoretical simulation in order to find the optimal conditions for an ideal sensor. Chapter 3 describes the integration of the nanohole array sensor with microfluidics for real-time colorimetric visualization of droplet generation as well as continuous-time monitoring of model molecule binding. This chapter also includes the theoretical derivation of the observed colorimetric sensing which will be helpful in the development of portable detectors based on this sensor. Chapter 4 consists of the characterization of surface sensitivity of the nanohole array sensor, demonstration of sensing of surface patterning and an immunoassay based on highly-relevant protein called Cytochrome P450 which is involved in drug metabolism. Chapter 5 describes an exploratory study of a dual-function nanohole array sensor that is capable of sensing refractive index changes and surface enhancing Raman signals on a single chip. Lastly, Chapter 6 describes a biodegradable sensor fabricated for surface-enhanced Raman spectroscopy.