(324f) Principles for Designing Effective Modifiers of Calcium Oxalate Monohydrate Crystallization and Dissolution

The role of (macro)molecular additives as crystal growth modifiers plays a significant role in the regulation of pathological diseases, such as kidney stones, which is becoming increasingly more prevalent worldwide. Kidney stones are precipitates of inorganic and organic constituents formed either in the kidneys, urethra, or bladder in the human body. The most common inorganic constituent is calcium oxalate monohydrate (COM) crystals, which accounts for approximately 80% of all human stones.¹ Research on COM crystallization over the past two decades has revealed unique mechanisms by which modifiers either inhibit or promote crystal nucleation and growth.^2-4 Here, we will present a comprehensive analysis of COM growth modification, which we extend to studies of dissolution in an effort to elucidate general trends in modifier – crystal interactions that facilitate the addition or removal of solute. Our studies probe events at both macroscopic and microscopic length scales. We screened a library of diverse modifiers using a combination of bulk crystallization assays and a microfluidic platform that enables the in situ analysis of COM crystal growth and dissolution at macroscopic scale. For select modifiers, we performed in situ atomic force microscopy (AFM) measurements to probe detailed mechanisms of surface nucleation, growth, and dissolution. Our findings identified highly efficient modifiers capable of suppressing growth as well as enhancing dissolution under different environments. These collective results have the potential to aid the design of new therapies for the pathological crystallization of kidney stones.