From Heterogeneity to Homogeneity: Protein Deposition and Salt Crystallization in Drying Colloidal Drops

Morphological analysis on the desiccation pattern from plasma drops has received increasing research attention due to its wide engineering applications in medical diagnostic screening. However, most previous studies focused on the internal drop flow rather than the actual distribution of nonvolatile materials in plasma drops, thus limiting their diagnostic relevance. To address this research gap, we developed a simulation model to explore the distribution of bovine serum albumin (BSA) particles and NaCl during drop desiccation. Different from previous simulation work, a nonuniform evaporation rate is implemented at the drop-air interface; also, aggregation between BSA particles and BSA adsorption onto substrate surfaces are both considered, subject to varying ionic strength in a moving medium. This comprehensive framework aims to overcome key oversimplifications in traditional models, such as the assumed uniform evaporation flux and the neglect of interparticle aggregation under varying ionic strength. Consequently, this approach provides new findings beyond prior observations, such as millisecond-scale BSA adsorption kinetics and the formation of a quantifiable and heterogeneous protein band near the drop periphery. Specifically, our model provides numerical forecasts to key BSA adsorption metrics under physiological conditions, including adsorption layer thickness and surface coverage, which are challenging to quantify experimentally. Also, rapid millisecond-scale adsorption kinetics is predicted, which is sensitive to the initial ionic strength. Concentration curves of BSA particles result from the interplay between inward sol-gel interface movement and interparticle aggregation, leading to a heterogeneous area with a highly nonuniform BSA distribution at the drop periphery, while a more homogeneous distribution is observed near the center. The extent of heterogeneity can be tuned by relative humidity, aggregation number between BSA particles, and the initial ionic strength. Simulations also provide the precise position of NaCl crystallization initiated near the drop center, and a conservative threshold concentration of 10 mM, below which crystallization is suppressed in a BSA saline drop.