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.<p> </p>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.
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.
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.
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.
Whispering Gallery Modes (WGMs) have been widely studied for the past 20 years for various applications, including
biological sensing. While the different WGM-based sensing approaches reported in the literature enable useful sensor
characteristics, at present this technology is not yet mature, mainly for practical reasons. Our work has been focused on
developing a simple, yet efficient, WGM-based sensing platform capable of being used as a dip sensor for in-vivo
We recently demonstrated that a dye-doped polymer microresonator, supporting WGMs, positioned onto the tip of a
suspended core Microstructured Optical Fiber can be used as a dip sensor. In this architecture, the resonator is located
on an air hole next to the fiber core at the fiber’s tip, enabling a significant portion of the sphere to overlap with the
guided light emerging from the fiber tip. This architecture offers significant benefits that have never been reported in
the literature in terms of radiation efficiency, compared to the standard freestanding resonators, which arise from
breaking the symmetry of the resonator. In addition to providing the remote excitation and collection of the WGMs'
signal, the fiber also allows easy manipulation of the microresonator and the use this sensor in a dip sensing
architecture, alleviating the need for a complex microfluidic interface.
Here, we present our recent results on the microstructured fiber tip WGM-based sensor, including its lasing behavior
and enhancement of the radiation efficiency as a function of the position of the resonator on the fiber tip. We also show
that this platform can be used for clinical diagnostics and applying this technology to the detection of Troponin T, an
acute myocardial infarction biomarker, down to a concentration of 7.4 pg/mL.