Biosensors Environmental Dyes Quantum Dots Remote Detection
Mapping the electrical activity of nerve and cardiac networks in two and three dimensions is important for understanding the organization and function of these pathways. Voltage-sensitive dyes (VSDs) can report the electrical potential changes in many cells simultaneously. Effective VSDs are amphiphilic molecules that contain a water-soluble moiety and a lipophilic region. To measure rapid changes in cellular membrane potential, the sensor portions of these dye molecules associate with the hydrophobic interior of the plasma membrane where the electric field gradient is the highest. At the same time, the dyes carry polar groups to increase water solubility and facilitate the transfer of dye to the target tissues and to anchor the dye at cell surfaces. Imaging deep within tissues requires VSDs with high molar extinction coefficients at red wavelengths and near-IR emission with high quantum yields to reduce light scattering and intrinsic tissue absorption and fluorescence.

Styryl dyes are a class of fluorescent VSDs that are widely used to measure membrane potentials because of their ability to follow voltage changes on a millisecond timescale. Their structures consist of an electron-rich aminophenyl group linked to a quaternized nitrogen heterocycle by a conjugated polymethine a chain. VSDs that have high quantum yields and produce a large fractional change in fluorescence (ΔF/F) are desirable because they generate adequate signals at lower dye concentrations. VSDs carrying PEG groups of varying chain lengths (MW750–5000) to increase their water solubility were synthesized. The enhanced solubility of PEG derivatives facilitated delivery to target tissues while retaining their spectral properties and voltage sensitivity in cardiac tissues. The covalent linkage of PEGs to voltage dyes greatly simplifies protocols for probe delivery to excitable tissue.
