Nucleation of crystals and nano-particles from solution plays an important role in several areas of science and technology like manufacture of photonic band gap materials, formation of protein crystals for structure determination, and industrial production of pharmaceutical compounds and semiconductor materials etc. At present, limited understanding exists towards the underlying processes of particle formation from solution. My research is geared toward acquiring that fundamental understanding about the governing processes of nano particle formation and developing innovative methods and techniques to apply this knowledge in solving problems of great interest to the industry and academia.

My current research focus is on studying the particulate processes in proteins and pharmaceutical systems. The insights obtained through my studies will assist not only the practice of industrial crystallization, but also the crystallization of proteins for structure determination, and rational drug design methodology. A few specific issues that I will address in this poster are:

a). Understanding Metastability in Nucleation from Solution

While thermodynamics requires the phase transition to occur as soon as one crosses the equilibrium boundary (solubility), well known observations indicate that nucleation occurs at a relatively high supersaturation. Crystallizing solutions can sustain significant metastability. This phenomenon is often attributed to the so called unclear ‘kinetic effects'. The key questions then become, is there any limit to the metastability that a system can endure and if so what are the factors that determine such a limit? What will be the influence of ‘kinetic effects' on nucleation when one generates the supersaturation infinitesimally slow such that the system is always at equilibrium?

The above questions are addressed here by studying the nucleation behavior of various compounds under extremely slow rates of supersaturation. Such slow rates of supersaturation are achieved by crystallizing the solutions in an evaporation based micro-device. Experimental evidence to the existence of a lower boundary on the MZW is presented and this observation is explained in terms of our current understanding of kinetic / thermodynamic processes underlying nucleation. Thus, this boundary on MZW can be viewed as a ‘kinetic limit' of nucleation. We attempt to link this ‘kinetic limit' to the intermolecular interactions and suggest methods to predict nucleation behavior of compounds.

b). Influencing Polymorph Selectivity by Regulation of Diffusive Mixing in Microfluidic Devices

Rapid polymorph screening techniques that reduce the time, effort and material consumed are an essential requirement in pharmaceutical industry. Microfluidic technology offers an effective approach in developing innovative methods and techniques to address this issue. Here, a microfluidic mixer design that facilitates polymorph screening is discussed. This design effects anti-solvent crystallization utilizing the fact that mixing at the micro-scale is by diffusion only (no turbulence). Also, the rate of mixing and the composition of the liquid phase can be varied by changing the flow rates and concentrations, thus influencing the polymorph selectivity. The results of our experiments on some model systems are presented and the applicability of the concept towards the development of a high throughput microfluidic device for polymorph screening is discussed.