Cy3 carboxylic acid is a non-activated fluorescence dye. Most derivatives of non-sulfonated cyanines have low aqueous solubility except for hydrochlorides of hydrazides and amines. This Non-sulfonated reagent has limited aqueous solubility, but with good solubility in organic solvents. For biomolecule labeling, the labeling reagent has low aqueous solubility, using of organic co-solvent to dissolve this molecular is necessary for efficient reaction. First, Cyanine dye should be dissolved in organic solvent and then added to a solution of biomolecule in appropriate aqueous buffer.