Integration of microsphere resonators with bioassay fluidics for whispering gallery mode imaging

Abstract

Whispering gallery mode resonators are small, radially symmetric dielectrics that trap light through continuous total internal reflection. The resonant condition at which light is efficiently confined within the structure is linked with refractive index, which has led to the development of sensitive label-free sensing schemes based on whispering gallery mode resonators. One resonator design uses inexpensive high index glass microspheres that offer intrinsically superior optical characteristics, but have proven difficult to multiplex and integrate with the fluidics for sample delivery and fluid exchange necessary for assay development. Recently, we introduced a fluorescence imaging approach that enables large scale multiplexing with microsphere resonators, thus removing one obstacle for assay development. Here we report an approach for microsphere immobilization that overcomes limitations arising from their integration with fluidic delivery. The approach is an adaptation of a calcium-assisted glass bonding method originally developed for microfluidic glass chip fabrication. Microspheres bonded to glass using this technique are shown to be stable with respect to fluid flow and show no detectable loss in optical performance. Measured Q-factors, for example, remain unchanged following sphere bonding to the substrate. The stability of the immobilized resonators is further demonstrated by transferring lipid films onto the immobilized spheres using the Langmuir-Blodgett technique. Bilayers of DOPC doped with GM1 were transferred onto immobilized resonators to detect the binding of cholera toxin to GM1. Binding curves generated from shifts in the whispering gallery mode resonance result in a measured Kd of 1.5 × 10−11 with a limit of detection of 3.3 pM. These results are discussed in terms of future assay development using microsphere resonators.

Applications of Optical Microcavity Resonators in Analytical Chemistry

“…For example, microspheres resting on a surface can be interrogated via a prims (32, 64, 65). Additionally, the use of fluorescent microparticles as the microcavity itself eliminates the need for optical waveguides or fiber-optics altogether, as the fluorescence generated by a focused laser spot can be confined within the microcavity (66–68).…”

Polymer resonators sensors for detection of sphingolipid gel/fluid phase transition and melting temperature measurement

“…Experimentally, we can calculate an appropriate linear fit of such (T) laws for various resonant wavelengths  i as depicted in Fig. 4(a): then, the temperature-dependent wavelength shift (TDWS) as d i /dT, ranging between [25][26][27][28][29][30] pm/°C is quantified over the 40 nm spectral range (in wavelength) of the broadband laser source ( 0 =795nm): then, a low trend of red-shift in temperature is clearly entailed. Thus, such an approach allows us to quantify the thermal sensitivity of the DUV210 polymer applied to design MRs.…”

“…More recently, after the substantial development in telecommunications, organic materials based resonators have received intensive attention in metrology and sensing environmental applications, biology, medical and healthcare diagnostics, food quality control and security. Such photonics sensors relying on resonators have become the subject of comprehensive research with sizeable developments of enhanced sensing platforms devoted to the label-free detection of a wide variety of chemical and biochemical [14][15][16][17][18], biological agents and biomedical materials [19][20][21][22][23][24][25][26][27][28].…”

Determination of sub-diffraction-limited organelles and biomolecules using microsphere lenses in combination with fluorescence microscopy

“…Especially, microspheres formed from melts yield exquisitely smooth surfaces that provide superior optical characteristics. Moreover, such microspheres are inexpensive and are available in a range of sizes and materials [11]. Here, we present the use of high-refractive index (n p = 1.92) barium titanate glass microspheres in combination with a conventional fluorescence microscope for imaging of organelles and biomolecules in cells.…”