Development of label-free colorimetric plasmonic sensor for biomedical applications (2017)

Biosensor technology is making strides due to its association with detection and quantification of a wide array of physiological profile makers, biomarkers, for the early detection of diseases. The newest technologies encompasses both qualitative as well as quantitative measurement of such markers. Colorimetric sensing, a method that enables the detection of target analytes via ‘color change’, lays the foundation of a user-friendly, economical and most of all, it’s accessibility to draw inference for the detection of notorious critical conditions such as, carcinomas, and other significant environmental monitoring. Therefore, the impact of colorimetric sensing on the clinical detection of diseases at earlier stages can be enormous, provided the gap between the accuracy of lab-equipment to point-of-care testing tools is approximated. This thesis discusses the design, fabrication and characterization of a label-free plasmonic-based colorimetric sensor on a flexible plastic substrate consisting of periodic nano cups, also referred a nano Lycurgus cups, in an array covered with metal nanoparticles on the side walls and have sub-wavelength openings to provide refractive index sensing. It is also anticipated that the colorimetric sensor can be applied to point-of-care diagnostics by utilizing proper surface functionalization techniques, which is one of the current limiting factors. \n\nChapter 1, is an overview on the existing biosensor technologies with the requirement of the next generation label free biosensor based on nanohole arrays. Chapter 2, describes the recent development of nanoscale Lycurgus cup Array (nanoLCA) with design, fabrication and characterization of the nanoplasmonic device. Chapter 3 starts with the discussion on the influence of adhesion layer on the optical properties of the nanoLCA device followed by layer by layer deposition of polyelectrolyte layers to identify the decay length of the device. Furthermore, this chapter also describes the deposition of different polymers using micro contact printing and compares the spectral results with the colorimetric properties of the device. Chapter 4 gives a demonstration of detection of drug bindings with cytochrome P450-2J2 using the nanoLCA device. Cytochrome P450-2J2 is the most common enzyme found in human heart and it is involved in drug metabolism. All bio-molecular detections are done using nanoLCA based on the shift in resonance peak wavelength with respect to change in the refractive index on the surrounding medium of the device. However, there is a constraint in using nanoLCA device to detect the lower concentration of bio-marker. Therefore, in Chapter 5, we have introduced 3D plasmonic nano cavity structure of the device in which an optical resonant cavity is combined with the plasmonic resonance in one device. This device is a modification of the previously studied nanoLCA device with additional layers, referred as multilayer nanoscale Lycurgus cup array (ML-nanoLCA device). The ML-nanoLCA device is based on a semiconductor material such as cadmium sulfide (CdS) layer, which has a high refractive index and very low extinction coefficient, sandwiched between two gold (Au) layers. This method allows intensity based bio-sensing with the help of a simple bandpass filter to allow certain wavelengths to be transmitted in the visible region at normal incidence illumination. The multilayer plasmonic substrate results in further improvement in the refractive-index sensing, DNA hybridization detection, protein-protein interaction, and detection of lower concentration of cancer biomarker, carcinoembryonic antigen (CEA) with higher sensitivity, which is discussed in chapter 6. The summary of the thesis with future outlook of the nanoplasmonic biosensor is discussed in chapter 7.