Fluorescence-based sensing for crystallization and for solution characterization

Production of a specified crystal size distribution (CSD) is one of the primary goals of a crystallization process because CSD affects the cost of operation. Filtration and drying are often the limiting steps in chemical manufacturing processes and significant cost reductions can be realized by creating CSDs that have favorable filtration and drying properties. The CSD is determined by supersaturation of solution. Control of the CSD is realized by control of supersaturation which requires the accurate measurement of the supersaturation. No technique is available for the measurement of supersaturation of low solubility systems with solubility around 2wt%.; In this research, pyranine, 1-pyrene butyric acid and carminic acid were investigated as potential fluorescence probes to measure the supersaturation of low solubility systems, such as tryptophan, nicotinic acid, phenylalanine and benzoic acid, using steady state fluorescence. Pyranine was shown to be a very promising probe to be used as the sensor to measure supersaturation in solutions due to the smooth and nonlinear calibration curves which show a higher signal response at supersaturated region. In addition pyranine will not enter the crystal lattice. Pyranine is not listed as a food additive by FDA, so it cannot be added directly into food and pharmaceutical production processes. Carminic acid (CA), a FDA approved food additive, was shown to be a good sensor for phenylalanine solutions by following the fluorescence intensity change with the concentration of phenylalanine. With pyranine immobilized on a membrane, the PIR (Peak Intensity Ratio) changes with the concentration of solutes linearly. The fluorescence probe technique is a very promising technique to be used to monitor crystallization in situ.; The formation of nuclei is the beginning point of the crystallization. The nucleation of the solute must somehow depend upon the solute molecules in a supersaturated solution and also depend upon the various molecular interactions. Understanding the structure of supersaturated solutions can help us better design and control crystallization. Although lots of work has focused on this subject, no generally accepted theories are available, especially for low solubility systems, and there are no reports on supersaturated solution structure at all.; Fluorescence quenching requires the contact of fluorophores and quenchers, so the interaction of fluorophore and quenchers can provide information about the organization of solutes in solutions. Quenching curves show different trends of quenching in unsaturated and supersaturating regions which was taken as the evidence of the formation of aggregates of the solutes in supersaturated solutions. Different molecules show totally different quenching behaviors to pyranine in solution. The different quenching behaviors are the results of the different interactions of pyranine with solute molecules. The contact complex was suggested as the mechanism of the interaction between pyranine and solute molecules. The stronger quenching abilities of tryptophan and nicotinic acid are the results of formation of hydrogen bonding complex with pyranine duo to the amine in the rings. The different steady state quenching and lifetime quenching behavior of phenylalanine support strongly the contact complex assumption. The associates were suggested in tryptophan solutions and phenylalanine due to the downward quenching curves. It was shown only 73% of phenylalanine and tryptophan are accessible to fluorophores to quench the fluorescence. The excitation wavelength dependence of tryptophan maximum emission wavelength supports the exists of the associates in tryptophan solutions.