A Whispering Gallery Mode Microlaser Biosensor

Abstract

A biological sensor, commonly referred to simply as a biosensor, is a transducing device that allows quantitative information about specific interactions, analytes or other biological parameters to be monitored and recorded. The development of biosensors that are low-cost, reliable and simple to use stand to facilitate fundamental breakthroughs and revolutionize current medial diagnostic methods. Notably, there remains an unmet need for developing in-vivo biosensors, allowing insights to be directly gained from the precise location of biological interactions within the human body. Over the last two decades, whispering gallery modes (WGM) within microresonators have emerged as a promising technology for developing highly sensitive and selective biosensors, among many other applications. However, significant work remains to allow WGM sensors to make the transition from primarily being used within purely research environments to real-world applications. Specifically, one of the key limiting factors is the requirement of an external phase-matched coupling scheme (such as a tapered or angle polished optical fiber, prism or waveguide) to excite the WGMs, despite these devices displaying tremendous sensing performance. One way to lift this dependency on complex interrogation schemes is introduce a gain medium, such as a fluorescent dye or coating the resonator with quantum dots for example, thereby rendering it active and allowing remote excitation and collection of the WGM spectrum. Using active WGM resonators has allows the creation of novel sensing opportunities such as tagging, tracking and monitoring forces from insides living cells. Applications like these could not have been realized using external phase-matched coupling schemes. The biosensing platform presented here is based on combining WGM within active microspherical resonators with microstructured optical fibers (MOF). The MOF enables both the excitation and collection method for the WGM spectrum while simultaneously providing a robust and easy to manipulate dip sensing architecture that has the potential to address the unmet need for real time labelfree in-vivo sensing by combining with a catheter. The platform is investigated fundamentally as well as experimentally, beginning with the development of an analytical model that is able to generate the WGM spectrum of active microspherical resonators. This provides the opportunity to pinpoint the optimal choice of resonator to be used for undertaking refractive index based biosensing. Specifically by being able to extract the quality (Q) factor, a measure of the resonance linewidth, and refractive index sensitivity from the WGM spectrum, the optimal combination of resonator parameters (diameter and resonator refractive index) can be identified for optimizing the resonators sensing performance. Further, the availability, biocompatibility and cost, as well as fabrication requirements can be also considered when selecting the ideal resonator. Next, the inherently lower Q-factors observed in active resonators compared to their passive counterparts (i.e. resonators without a gain medium) is examined using a combination of theoretical, experimental and imaging methods. Through this examination process, the inherent asphericity of the resonator is identified as being the limiting factor on the Q-factor of active resonators, with its effect most notably being observed for measurements made in the far field. Experimentally, the first demonstration of this platform operating as a biosensor is presented by monitoring the well-documented specific interaction of Biotin/neutravidin in pure solutions. Including identifying ways to improve sensing performance and lower the detection limit, such as operating the resonator above its lasing threshold. Although, it is noted that in its current form, this platform is best suited for the monitoring of protein, preferably occurring in higher concentrations, until further improvements to the sensing performance can be implemented. However, the robust design coupled with its ability to provide access to previously difficult to obtain locations provides an insight into its potential future application capabilities. Finally, the extension of the platform to operating in complex samples, namely undiluted human serum, is outlined. By self-referencing the platform, through the addition of a second, almost identical resonator (only varying in its surface functionalization) into one of the remaining vacant holes on the tip of the fiber, the effects of non-specific binding as well as changes in local environmental conditions (i.e. temperature fluctuations), can be eliminated.