A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile. In vitro studies have shown good precision, good stability, sensitivity of 2.5 mumol/liter bilirubin concentration, as well as a useful working range of 2.5-100 mumol/liter bilirubin concentration. In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P < 0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Optical resonators play an ubiquitous role in modern optics. A particular class of optical resonators is constituted by spherical dielectric structures, where optical rays are total internal reflected. Due to minimal reflection losses and to potentially very low material absorption, these guided modes, known as whispering gallery modes, can confer the resonator an exceptionally high quality factor Q, leading to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. These attractive characteristics make these miniaturized optical resonators especially suited as laser cavities and resonant filters, but also as very sensitive sensors. First, a brief analysis is presented of the characteristics of microspherical resonators, of their fabrication methods, and of the light coupling techniques. Then, we attempt to overview some of the recent advances in the development of microspherical biosensors, underlining a number of important applications in the biomedical field.

Microbubble resonators combine the unique properties of whispering gallery mode resonators with the intrinsic capability of integrated microfluidics. Here an improved fabrication method of microbubble resonators is presented, based on the heating of a slightly pressurized capillary by a rotating arc discharge. Rotation of the electrodes, moved out of a fiber splicer, ensures a homogeneous distribution of the heat all over the capillary surface. The demonstrated microbubble resonators have Q factors up to 6×10(7) at 1550 nm. Microbubbles were filled with water and aqueous solutions of ethanol in order to test the refractive index sensing capabilities of such resonators, which also show a good temporal stability. The limit of detection of our microbubble resonator sensor is 10(-6) RIU.

Whispering gallery mode resonators (WGMR), as silica microspheres, have been recently proposed as an efficient tool for the realisation of optical biosensors. In this work we present a functionalization procedure based on the DNA-aptamer sequence immobilization on WGMR, able to recognize specifically thrombin or VEGF protein, preserving a high Q factor. The protein binding was optically characterized in terms of specificity in buffer solution or in 10% diluted human serum. Simulation of the protein flow was found in good agreement with experimental data. The aptasensor was also chemically regenerated and tested again, demonstrating the reusability of our system.