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Updated: Jan 3, 2026

Optimizing the Growth of Endothiapepsin Crystals for Serial Crystallography Experiments
Published on: February 4, 2021
In Situ Crystal Growth Rate Distributions of Active Pharmaceutical Ingredients
Sreya Sarkar1, Zhengtian Song1, Scott R Griffin1
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
Abstract:
Single-particle tracking of crystal growth performed in situ enables substantial improvements in the signal-to-noise ratio (SNR) for recovered crystal nucleation and growth rates by nonlinear optical microscopy. Second harmonic generation (SHG) is exquisitely sensitive to noncentrosymmetric crystals, including those produced by many homochiral active pharmaceutical ingredients (APIs). Accelerated stability testing at elevated temperatures and relative humidity informs design of pharmaceutical formulations. In the present work, we demonstrate reduction in the Poisson noise associated with the finite number of particles present in a given field of view through continuous monitoring during stability testing. Single-particle tracking enables recovery of crystal growth rates of individual crystallites and enables unambiguous direct detection of nucleation events. Collectively, these capabilities provide significant improvements in the signal-to-noise for nucleation and crystal growth measurements, corresponding to approximately an order of magnitude reduction in anticipated measurement time for recovery of kinetics parameters.
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