Next generation instrumentation for photonic crystal biosensors: a passage to early detection of cancer

Photonic Crystal;Enhanced Fluorescence;Protein Microarray;Cancer Biomarker

Chaudhery, Vikram

关键词: Photonic Crystal;    Enhanced Fluorescence;    Protein Microarray;    Cancer Biomarker;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/42166/Vikram_Chaudhery.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The work presented in this dissertation addresses the need for an affordable point-of-care diagnostic tool for early detection of cancer. We identified a biomarker detection approach done using photonic crystal enhanced fluorescence (PCEF) instrumentation as the best way to achieve this goal. We introduce a model for predicting enhanced fluorescence (EF) performance of a photonic crystal (PC) in the context of a given set of instrument parameters as well as insights into instrument specific device design. From this we conclude that PCEF performance is a combined effect of the PC quality-factor (Q-factor) and the instrument angle of divergence. From a practical standpoint, a higher Q-factor gives a higher fluorescence enhancement but at the cost of higher variability in the fluorescence enhancement. To combat this we introduce a new angle-scanning scheme that addresses any uniformity issues.The resulting fluorescence enhancement is recorded to be >600× on a PC with respect to glass.The PC properties are further exploited to introduce a new label-free modality that allows for selective fluorescence enhancement as well as quality control for a protein microarray, helping to identify discrepancies in binding densities of antibodies. The angle-scanning technique coupled with the new modality shows a significant reduction in the coefficient of variation by 20-99% compared to ordinary fluorescence microscopy and a lowering of the detectable biomarker concentrations. To further lower the detection limits and miniaturize the instrument size, the collimated illumination scheme was replaced by a line-focused scheme. The novel PC line-scanning method exploited the optical properties of a one-dimensional PC without significantly sacrificing the coupling efficiency. The higher power density of the approach relative to the collimated PCEF instrument resulted in improved detection limits. A compact objective-coupled design was introduced to address the size demands of an ideal point-of-care system. The biomarker detection study comparing the line-scanning instrument performance with a commercial confocal scanner showed a >10× improvement in the detectable concentrations. Finally, in order to diversify the applicability of the objective coupled system, we modified the setup to incorporate a Raman detection scheme. A PC sensor with sparse surface distribution of gold nanorods was then coated with a monolayer of 4,4’-dipyridyl. The measured Raman scattering signal showed a 7× enhancement between the on and off-resonance cases.