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

Abstract

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Mode-Splitting for Refractive Index Sensing in Fluorescent Whispering Gallery Mode Microspheres with Broken Symmetry

“…However, it comes at a significant cost in terms of refractive index sensitivity. We have previously shown that uncoated fluorescent and lasing microspheres can be used to routinely detect specific biomolecules down to few ng/mL concentrations, even in undiluted human serum [ 6 , 18 ]. Therefore, despite the significant reduction of both the refractive index sensitivity and Q-factor, we believe that such a platform would still be useful for a large range of biosensing applications where the target concentration ranges from hundreds of pg/mL to ng/mL.…”

“…The optical wave circulating along the resonator’s inner surface generates optical resonances, whose spectral positions are strongly dependent on the refractive index contrast between the resonator and its surrounding environment as well as the resonator’s shape [ 1 ]. This distinctive feature of WGMs, combined with their extremely high quality factor (Q-factor), defined as the ratio between the resonance wavelength and its full width at half maximum (FWHM), in addition to the small mode volume possible, have enabled WGM resonators to become prime candidates for highly sensitive, label-free bio-chemical sensors [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. WGM based sensing mechanisms, such as (1) resonance spectral position shifts [ 3 , 4 , 5 , 6 , 7 ], (2) linewidth broadening/Q-factor spoiling of the resonances (e.g., due to stress-induced geometry deformation [ 8 , 9 ] or dissipative interaction [ 10 , 11 , 12 ]), and (3) splitting of the two counter-propagating WGMs [ 13 , 14 ], have been extensively researched.…”

“…This distinctive feature of WGMs, combined with their extremely high quality factor (Q-factor), defined as the ratio between the resonance wavelength and its full width at half maximum (FWHM), in addition to the small mode volume possible, have enabled WGM resonators to become prime candidates for highly sensitive, label-free bio-chemical sensors [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. WGM based sensing mechanisms, such as (1) resonance spectral position shifts [ 3 , 4 , 5 , 6 , 7 ], (2) linewidth broadening/Q-factor spoiling of the resonances (e.g., due to stress-induced geometry deformation [ 8 , 9 ] or dissipative interaction [ 10 , 11 , 12 ]), and (3) splitting of the two counter-propagating WGMs [ 13 , 14 ], have been extensively researched. While unprecedented sensing performance, such as single molecule or particle detection (e.g., proteins in the range of fg/mL), has been demonstrated [ 4 , 5 , 10 , 13 , 14 ], the sensors are still complex to operate, requiring a phase-matched tapered fiber/or prism to excite and collect the WGMs.…”

Label-Free Optical Resonator-Based Biosensors

“…With respect to the system in which WGM resonators are equipped, advances such as transduction and data-processing or filtering techniques [ 21 ], dynamic referencing [ 111 ], surface functionalization [ 112 , 113 , 114 ], and the integration of microfluidics have been reported. Many WGMs are integrated into microfluidic chips to streamline testing with a small sample volume [ 104 ].…”

“…These are typically based on microbubbles, microspheres, or microdroplets. Some notable modifications were label-free surface functionalization [ 120 , 123 , 137 , 138 ], doping [ 118 , 119 ], and self-referencing [ 111 , 120 ].…”