Graduate Students

• H. Hsi, Res. Asst., ChemE
• X. Yang, Res. Asst., ChemE
• A. Tatusko, Res. Asst., ChemE
• L. Tan, Res. Asst., ChemE

Postdoctoral Associate

• J. Chen, ChemE
• B.C. Sarma, ChemE
• S.Y. Wong, ChemE
• M. Su, ChemE
• I. Miroshnyk, ChemE

UROP

• A.S. Fried, ChemE
• A. Simi, ChemE

Support Staff

• G. Collver-Jacobson
• P. Romanow

Publications

Diao, Y., Myerson, A.S., Hatton, T.A., and Trout, B. L.  (2011).  Surface Design for Controlled Crystallization:  The Role of Surface Chemistry and Nanoscale Pores in Heterogeneous Nucleation. Langmuir (accepted).

Diao, Y., Hegelson, M.E., Myerson, A. S., Hatton, T. A.,  Doyle, P. S., and Trout, B.L.  (2011).  Controlled Nucleation from Solution Using Polymer Microgels.  Journal of the American Chemical Society 133, 3756-3759.

Lee, A.Y., Erdemir, D, Myerson, A.S. (2011).  Crystal Polymorphism in Chemical Process Development.  The Annual Review of Chemical and Biomolecular Engineering(published on web).

Chen J., Sarma B., Evans J. M.B., and Myerson A.S. (2011) Pharmaceutical Crystallization. Crystal Growth and Design, published on web.

Sarma B., Chen J., Hsi H.Y., and Myerson A.S. (2011) Solid forms of pharmaceuticals: Polymorphs, salts and cocrystals. Korean Journal of Chemical Engineering, 28, 315-322.

Kim, K, Centrone, A., Hatton, T.A., and Myerson, A.S. (2011) Polymorphism control of nanosized glycine crystals on engineered surfaces. Cryst. Eng. Comm. 13, 1127-1131.

Singh, A, Lee, I.S., Kim, K. and Myerson, A.S. (2011).  Crystal Growth on Self-assembled Monolayers.  Cryst. Eng. Comm. 13, 24-31.

Singh, A. and Myerson, A.S. (2010). Chiral Self Assembled Monolayers as Resolving Auxiliaries in the Crystallization of  Valine. Journal of Pharmaceutical Science 99, 3931-3940.

Alvarez, A. and Myerson, A.S. (2010).  Plug Flow Crystallization of Pharmaceutical Compounds.  Crystal Growth and Design 10, 2219-2228.

Kim, K, Lee, I.S., Centrone, A., Hatton, T.A. and Myerson, A.S. (2009). Formation of Nanosized Organic Molecular Crystals on Engineered Surfaces. Journal of the American Chemical Society 131, 18212-18213.

Alvarez, A., Sing, A., and Myerson, A.S. (2009). Polymorph Screening: Comparing a Semi-Automated Approach with a High Throughput Method. Crystal Growth and Design 9, 4181-4188.

Aldabaibeh, N., Jones, M., Myerson, A.S., Ulrich, J. (2009). The Solubility of Orthorhombic Lysozyme Crystals Grown at Low pH. Crystal Growth and Design 9, 3313-3317.

Erdemir, D, Lee, A.Y., and Myerson, A.S. (2009). Nucleation of Crystals From Solution: Classical and Two Step Models. Accounts of Chemical Research 42, 621-629.

Singh, A., Lee, I.S., and Myerson, A.S. (2009). Concomitant Crystallization of ROY on Patterned Substrates: Using a High Throughput Method to Improve the Chances of Crystallization of Different Polymorphs. Crystal Growth and Design 9, 1182-1185.

Konkel, J.T., and Myerson, A.S. (2008). Empirical Molecular Modeling of a Suspension Stabilization Using Polysorbate 80. Molecular Simulation 34, 1353-1357.

Lee, I.S., Evans, J.M.B., Erdemir, D., Lee, A.Y., Garetz, B.A and Myerson, A.S., (2008). Non Photochemical Laser Induced Nucleation of Hen White Lysozyme Crystals.Crystal Growth and Design 8, 4455-4461.

Sun, X., Garetz, B.A., and Myerson, A.S., (2008). Polarization Switching of Crystal Structure in the Non-Photochemical Laser Induced Nucleation of Supersaturated Aqueous L-Histidine. Crystal Growth and Design 8, 1720-1722.

Lee, I.S., Kim, K.T., Lee, A.Y. and Myerson, A.S., (2008). Concomitant Crystallization of Glycine on Patterned Substrates: The Effect of pH on the Polymorphic Outcome.Crystal Growth and Design, 8, 108-113.

Lee, I.S., Lee, A.Y., and Myerson, A.S.,  (2008).  Concomitant Polymorphism in Confined Environment:  Implication to Crystal Form Screening.  Pharmaceutical Research, 25, 960-968.

Figure 1: (a) Optical microscope image (×150) of 1600 µm2 and (b) AFM image of 4 µm2 of the 500-nm patterned SAMs on the silicon substrate. The crystals dimensions are: (A) 250 × 220 × 74 nm3, (B) 230 × 205 × 70 nm3, (C) 180 × 160 × 57 nm3, and (D) 220 × 190 × 65 nm3. (c) Raman spectra of 100 individual glycine crystals found on the patterned SAMs. All crystals were determined to be β-form ^[1] .

The formation of organic molecular nano-crystals is a topic of great interest in the pharmaceutical industry because of the potential increase in solubility of organic crystals below 1 micron and their potential use in nano-suspensions for direct injection. Direct production of nano-crystals through crystallization while controlling the crystal form (polymorph) is a difficult problem and a current active area of research. Investigators have explored methods based on the use of confinement (such as nano-wells), surface templating (such as polymers and self-assembled-monolayers (SAMs), and microfluidics ^{[1] [2] [3] [4] [5] [6] [7] [8] [9]} . Our group has developed a method to “create a confined volume” for crystallization on templated surfaces (Figure 1), which results in both a confined volume and a templating effect ^{[10] [11]} .

In our research, we fabricate both hydrophilic and hydrophobic thiol SAMs on gold surfaces. With the use of photolithography or electron beam lithography, desired patterns of hydrophilic and hydrophobic SAMs can be generated, allowing the formation of small droplets of solution on the hydrophilic surfaces.  By controlling the solution conditions through cooling evaporation or vapor diffusion of an anti-solvent, we can control the supersaturation profile and thus induce nucleation and growth of crystalline solids.

Our current work employs patterns of SAMs allowing the formation of droplets as small as 100 nm in diameter. Using these droplets, we are probing issues related to nucleation and polymorphism in a number of different systems to better understand the fundamentals of nucleation and polymorphism.

1. C. Price, A. Grzesiak, and A. Matzger, “Crystalline polymorph selection and discovery with polymer heteronuclei,” J. Am. Chem. Soc., vol. 127, pp. 5512-5517, 2005.
2. P. Carter and M. Ward, “Directing polymorph selectivity during nucleation of anthranilic acid on molecular substrates,” J. Am. Chem. Soc., vol. 116, pp. 769-770, 1994.
3. R. Hiremath, J. Basile, S. Varney, and J. Swift, “Controlling molecular crystal polymorphism with self-assembled monolayer templates,” J. Am. Chem. Soc., vol. 127, pp. 18321-18327, 2005.
4. V. Genota, S. Desportesb, C. Croushorea, J. Lefevrea, R. Pansua, J. Delairea, P. von Rohr , “Synthesis of organic nanoparticles in a 3D flow focusing microreactor,” Chemical Engineering Journal, vol. 161, pp. 234-239, 2010.
5. C. Hansen, S. Classen, J. Berger, and S. Quake, “A microfluidic device for kinetic optimization of protein crystallization and in situ structure determination,” Journal of the American Chemical Society, vol. 128, pp. 3142-3143, 2006.
6. C. Hansen, E. Skordalakes, J. Berger, and S. Quake, “A robust and scalable microfluidic metering method that allows protein crystal Growth by Free Interface Diffusion,” Proc. National Academy of Sciences of the United States of America, vol. 99, pp. 16531-16536, 2002.
7. C. Jackson and G. McKenna, “Vitrification and crystallization of organic ;iquids confined to nanoscale pores,” Chem. Mater., vol. 8, pp. 2128-2137, 1996.
8. L. Wang, M. Lee, J. Barton, L. Hughes, and T. Odom, “Shape-control of protein crystals in patterned microwells,” J. Am. Chem. Soc., vol. 130, pp. 2142-2143, 2008.
9. E. You, R. Ahn, M. Lee, M. Raja, T. O’Halloran, and T.  Odom, “Size control of arsenic trioxide nanocrystals grown in manowells,” J. Am. Chem. Soc., vol. 131, pp. 10863-10865, 2009.
10. K. Kim, I. Lee, A. Centrone, T. Hatton, and A. Myerson, “Formation of nanosized organic molecular crystals on engineered surfaces,” J. Am. Chem. Soc., vol. 131, pp. 18212-18213, 2009.
11. K. Kim, A. Centrone, A. Hatton, and A. Myerson, “Polymorphism control of nanosized glycine crystals on engineered surfaces,” Cryst. Eng. Comm., vol. 13, pp. 1127-1131, 2011.