Tess Reynolds

A fiber-tip label-free biological sensing platform: a practical approach toward in-vivo sensing.

The platform presented here was devised to address the unmet need for real time label-free in vivo sensing by bringing together a refractive index transduction mechanism based on Whispering Gallery Modes (WGM) in dye doped microspheres and Microstructured Optical Fibers. In addition to providing remote excitation and collection of the WGM signal, the fiber provides significant practical advantages such as an easy manipulation of the microresonator and the use of this sensor in a dip sensing architecture, alleviating the need for a complex microfluidic interface. Here, we present the first demonstration of the use of this approach for biological sensing and evaluate its limitation in a sensing configuration deprived of liquid flow which is most likely to occur in an in vivo setting. We also demonstrate the ability of this sensing platform to be operated above its lasing threshold, enabling enhanced device performance.

Optimization of whispering gallery resonator design for biosensing applications

Whispering gallery modes (WGMs) within microsphere cavities enable highly sensitive label-free detection of changes in the surrounding refractive index. This detection modality is of particular interest for biosensing applications. However, the majority of biosensing work utilizing WGMs to date has been conducted with resonators made from either silica or polystyrene, while other materials remain largely uninvestigated. By considering characteristics such as the quality factor and sensitivity of the resonator, the optimal WGM sensor design can be identified for various applications. This work explores the choice of resonator refractive index and size to provide design guidelines for undertaking refractive index biosensing using WGMs.

Method for predicting whispering gallery mode spectra of spherical microresonators

A full three-dimensional Finite-Difference Time-Domain (FDTD)-based toolkit is developed to simulate the whispering gallery modes of a microsphere in the vicinity of a dipole source. This provides a guide for experiments that rely on efficient coupling to the modes of microspheres. The resultant spectra are compared to those of analytic models used in the field. In contrast to the analytic models, the FDTD method is able to collect flux from a variety of possible collection regions, such as a disk-shaped region. The customizability of the technique allows one to consider a variety of mode excitation scenarios, which are particularly useful for investigating novel properties of optical resonators, and are valuable in assessing the viability of a resonator for biosensing.

Dynamic Self-Referencing Approach to Whispering Gallery Mode Biosensing and Its Application to Measurement within Undiluted Serum

Biosensing within complex biological samples requires a sensor that can compensate for fluctuations in the signal due to changing environmental conditions and nonspecific binding events. To achieve this, we developed a novel self-referenced biosensor consisting of two almost identically sized dye-doped polystyrene microspheres placed on adjacent holes at the tip of a microstructured optical fiber (MOF). Here self-referenced biosensing is demonstrated with the detection of Neutravidin in undiluted, immunoglobulin-deprived human serum samples. The MOF allows remote excitation and collection of the whispering gallery modes (WGMs) of the microspheres while also providing a robust and easy to manipulate dip-sensing platform. By taking advantage of surface functionalization techniques, one microsphere acts as a dynamic reference, compensating for nonspecific binding events and changes in the environment (such as refractive index and temperature), while the other microsphere is functionalized to detect a specific interaction. The almost identical size allows the two spheres to have virtually identical refractive index sensitivity and surface area, while still having discernible WGM spectra. This ensures their responses to nonspecific binding and environmental changes are almost identical, whereby any specific changes, such as binding events, can be monitored via the relative movement between the two sets of WGM peaks.

Unified theory of whispering gallery multilayer microspheres with single dipole or active layer sources

The development of a fast and reliable whispering gallery mode (WGM) simulator capable of generating spectra that are comparable with experiment is an important step forward for designing microresonators. We present a new model for generating WGM spectra for multilayer microspheres, which allows for an arbitrary number of concentric dielectric layers, and any number of embedded dipole sources or uniform distributions of dipole sources to be modeled. The mode excitation methods model embedded nanoparticles, or fluorescent dye coatings, from which normalized power spectra with accurate representation of the mode coupling efficiencies can be derived. In each case, the emitted power is expressed conveniently as a function of wavelength, with minimal computational load. The model makes use of the transfer-matrix approach, incorporating improvements to its stability, resulting in a reliable, general set of formulae for calculating whispering gallery mode spectra. In the specific cases of the dielectric microsphere and the single-layer coated microsphere, our model simplifies to confirmed formulae in the literature.

Using whispering gallery mode micro lasers for biosensing within undiluted serum

Although whispering gallery mode (WGM) biosensors have shown tremendous potential, they are still yet to find practical use as biomedical diagnostic tools. This is primarily due to the nature of the interrogation mechanism itself which relies on indirect measurement of the binding of a specific biomolecule onto the sensor through the associated refractive index change. Since nonspecific binding cannot be differentiated from the specific interaction of interest, this can result in a high rate of false positive readings when the detection is performed in complex biological samples. Here we show that this inherent limitation can be solved using a relatively simple approach. This approach involves the development of a self-referenced biosensor consisting of two almost identically sized dye-doped polystyrene microspheres placed on adjacent holes at the tip of a suspended core optical fiber. Here self-referenced biosensing is demonstrated with the detection of Neutravidin in undiluted human serum samples. The fiber allows remote excitation and collection of the WGMs of the microspheres in a dip sensing setting. By taking advantage of surface functionalization techniques, one microsphere acts as a dynamic reference, compensating for nonspecific binding events, while the other microsphere is functionalized to detect the specific interaction. The almost identical size allows the two spheres to have virtually identical refractive index sensitivity and surface area. This ensures their responses to nonspecific binding and environmental changes are almost identical, whereby any specific changes such as binding events, can be monitored via the relative movement between the two sets of WGM peaks.

Optimization of whispering gallery mode sensor design for applications in biosensing

Whispering gallery modes (WGM) within microsphere cavities have demonstrated the ability to provide label-free, highly sensitive and selective detection down to a single molecule level, emerging as a promising technology for future biosensing applications. Currently however, the majority of biosensing work utilizing WGMs has been conducted in resonators made from either silica or polystyrene while other materials have been largely uninvestigated. This work looks to predict the optimal combinations of material, resonator size and excitation/coupling scheme to provide guidelines to assist in decision making when undertaking refractive index biosensing in a range of situations.

Predicting the whispering gallery mode spectra of microresonators

The whispering gallery modes (WGMs) of optical resonators have prompted intensive research efforts due to their usefulness in the field of biological sensing, and their employment in nonlinear optics. While much information is available in the literature on numerical modeling of WGMs in microspheres, it remains a challenging task to be able to predict the emitted spectra of spherical microresonators. Here, we establish a customizable Finite-Difference Time-Domain (FDTD)-based approach to investigate the WGM spectrum of microspheres. The simulations are carried out in the vicinity of a dipole source rather than a typical plane-wave beam excitation, thus providing an effective analogue of the fluorescent dye or nanoparticle coatings used in experiment. The analysis of a single dipole source at different positions on the surface or inside a microsphere, serves to assess the relative efficiency of nearby radiating TE and TM modes, characterizing the profile of the spectrum. By varying the number, positions and alignments of the dipole sources, different excitation scenarios can be compared to analytic models, and to experimental results. The energy flux is collected via a nearby disk-shaped region. The resultant spectral profile shows a dependence on the configuration of the dipole sources. The power outcoupling can then be optimized for specific modes and wavelength regions. The development of such a computational tool can aid the preparation of optical sensors prior to fabrication, by preselecting desired the optical properties of the resonator.

A demonstration of multiplex biosensing using whispering gallery mode microspheres positioned onto a microstructured optical fiber tip

Here, we show that multiplexed Whispering Gallery Modes sensing can be achieved using two dye-doped microspheres positioned onto the tip of a Microstructured Optical Fiber. By operating the dye-doped microspheres below their lasing threshold, the individual resonances of each sphere overlap and therefore cannot be distinguished. However, when excited above their lasing threshold results in a de-convoluted spectrum where the resonances belonging to the individual spheres can be determined, enabling the detection of a specific interaction in one resonator and using the second as a dynamic reference, or monitoring different specific interactions with both spheres.