Accurate and reliable monitoring of blood glucose is needed for the treatment of diabetes, which has many challenges, including lack of patient compliance. Measuring tear glucose is an alternative to traditional finger-stick tests used to track blood sugar levels, but glucose sensing using tears has yet to be achieved. We report a methodology for possible tear glucose monitoring using glucose-sensitive silicone hydrogel (SiHG) contact lenses, the primary type of lenses available in today’s market. Initially, we assessed the interpenetrating polymer network, with nearly pure silicone and water regions, existing in the SiHGs using a polarity-sensitive probe Prodan. We then synthesized a glucose-sensitive fluorophore Quin-C18 with a hydrophobic side chain for localization of probe at the interfacial region. Using our glucose-sensing contact lens, we were able to measure varying concentrations of glucose in an in-vitro system. The Quin-C18 strongly bound to the lenses with insignificant leaching even after multiple rinses. The lenses displayed a similar response to glucose after three months of storage in water. This study demonstrates that it may be possible to develop a contact lens for continuous glucose monitoring in the near term, using our concept of fluorophore binding at the silicone–water interface.
In the past several years we have demonstrated the metal-enhanced fluorescence (MEF) and the significant changes
in the photophysical properties of fluorophores in the presence of metallic nanostructures and nanoparticles using
ensemble spectroscopic studies. Here, in the present study, we explored the new insights of these interactions using
single-molecule fluorescence spectroscopy. The single molecule study is expected to provide more information,
especially on the heterogeneity in the fluorescence enhancement and decrease in lifetimes associated with fluorophore-metal
interactions, which is otherwise not possible to observe using ensemble measurements. For the present study, we
considered using CdTe nanocrystals (QDots) prepared using modified Weller method as the fluorophores under
investigation. QDots having few nanometer sizes, tunable absorption and fluorescence spectral properties, and high
photo-stabilities are of important class of fluorescent probes. Because of these unique features Qdots are widely used as
probes in various fields, including biological labeling and imaging. These CdTe nanocrystals show characteristic spectral
features in solution and on the solid substrate. The CdTe nanocrystals dispersed in PVA and spin-casted on SiFs surface
show ~5-fold increase in fluorescence intensity and ~3-fold decrease in lifetimes compared to on glass substrate. The
data obtained using ensemble and single molecule spectroscopy are complimentary to each other. Additionally as
anticipated we have seen increased heterogeneity in the plasmon induced fluorescence modulations. Moreover single
molecule spectroscopic study revealed significant reduction in blinking of CdTe nanocrystals on plasmonic
nanostructures. Subsequently, we present these important findings on metal-fluorophore interactions of CdTe
nanocrystals (QDots) on plasmonic nanostructures.
Fluorescence is widely used in biological research. Future advances in biology and medicine often depend on the advances in the capabilities of fluorescence measurements. In this overview paper we describe how a combination of fluorescence, and plasmonics, and nanofabrication can fundamentally change and increase the capabilities of fluorescence technology. This change will be based on the use of surface plasmons which are collective oscillations of
free electrons in metallic surfaces and particles. Surface plasmon resonance is now used to measure bioaffinity reactions. However, the uses of surface plasmons in biology are not limited to their optical absorption or extinction. We have shown that fluorophores in the excited state can create plasmons which radiate into the far field; additionally fluorophores in the ground state can interact with and be excited by surface plasmons. These interactions suggest that the
novel optical absorption and scattering properties of metallic nanostructures can be used to control the decay rates, location and direction of fluorophore emission. We refer to this technology as plasmon-controlled fluorescence. We predict that plasmon-controlled fluorescence (PCF) will result in a new generation of probes and devices. PCF is likely to allow design of structures which enhance emission at specific wavelengths and the creation of new devices which control and transport the energy from excited fluorophores in the form of plasmons, and then convert the plasmons back to light.
We have developed a new technology for the non-invasive continuous monitoring of tear glucose using a daily use, disposable contact lens, embedded with sugar-sensing boronic acid containing fluorophores. Our findings show that our approach may be suitable for the continuous monitoring of tear glucose levels in the range 50 - 500 μM, which track blood glucose levels that are typically ≈ 5-10 fold higher. We initially tested the sensing concept with well-established, previously published, boronic acid probes and the results could conclude the used probes, with higher pKa values, are almost insensitive toward glucose within the contact lens, attributed to the low pH and polarity inside the lens. Subsequently, we have developed a range of probes based on the quinolinium backbone, having considerably lower pKa values, which enables them to be suitable to sense the physiological glucose in the acidic pH contact lens. Herein we describe the results based on our findings towards the development of glucose sensing contact lens and therefore an approach to non-invasive continuous monitoring of tear glucose using a contact lens.