Accelerating nanodrug development in continuous flow systems using informed prediction models based on low-cost surrogate nanoparticles

Streaming-potential-mediated transport of viscoelastic fluids has attracted research attention owing to its applications in electrokinetic energy conversion and microfluidic transport. Existing analytical and semi-analytical models in published literature provide valuable physical insights, but require repeated numerical evaluations for exploring large design spaces and identifying the optimal operating conditions. In this work, a surrogate-assisted framework is developed for rapid design optimization of pressure-driven electrokinetic transport of simplified Phan-Thien-Tanner fluids in a slit microchannel. A high-fidelity numerical database is generated over a broad range of governing dimensionless parameters, which includes the zeta potential, the Debye parameter, the Dukhin number, and the viscoelastic parameter. A Machine Learning surrogate model is subsequently trained to accurately approximate the nonlinear relationship between the governing parameters and the streaming potential, while the volumetric flow rate and hydroelectric energy conversion efficiency were calculated from closed form equation by using the streaming potential predicted by the surrogate. This is coupled with a multi-objective optimization strategy to identify operating conditions that simultaneously maximize energy conversion efficiency and volumetric flow rate. The proposed methodology can significantly accelerate parametric exploration compared with repeated numerical simulations across different parameters and provides practical design guidelines for electrokinetic microfluidic devices. The study demonstrates the potential of combining computational fluid mechanics with data-driven surrogate modeling for efficient engineering design and optimization.

The simulation of fluid flows is computationally expensive due to the complexity of its governing partial differential equations. Machine learning models offer a potential surrogate, enabling learning from simulations and significantly faster predictions of flow fields. However, these models require large training datasets, which introduces a trade-off between dataset generation cost and predictive accuracy. In this work, we investigate the relationship between the size of the training-set and accuracy of the prediction when learning steady flow fields in an industrial-scale stirred vessel. A data set of steady flows is generated using Reynolds Averaged Navier Stokes (RANS) simulations in a range of realistic operating conditions, including impeller speeds and liquid heights. We train implicit neural representations of flow fields and compare purely data-driven and constrained variants. Model performance is evaluated using global mean squared error (MSE), qualitative spatial comparisons of predicted and reference flow fields, and tracer transport simulations. We find that the prediction error decreases monotonically with increasing training data, but also that it exhibits clear diminishing returns beyond moderate dataset sizes. Physics-based constraints significantly improve accuracy and reduce variability across training runs in low-data regimes, and they lead to more stable tracer-transport behavior. Furthermore, reasonable interpolation can be achieved over different impeller speeds and liquid heights. However, these benefits come with an increase in the complexity of training, and their relative advantage diminishes as the training set grows.

Lipid nanoparticles (LNPs) are efficient delivery systems for negatively charged nucleic acids. Their multi-component architecture yields a core-shell structure. Small-angle X-ray scattering (SAXS) is an important characterization technique for LNPs, but recovering internal structure and size distribution from SAXS is an inverse problem with non-unique solutions. Realistic models are often too expensive for systematic exploration. We introduce a machine-learning-accelerated, differentiable framework for SAXS analysis of heterogeneous, polydisperse LNPs. The forward model combines a core-shell particle with a Gaussian random-field interior, a neural surrogate for the monodisperse SAXS map, and a differentiable layer integrating over particle-size distributions. The surrogate reduces prediction cost by four orders of magnitude, while differentiability enables large-scale multi-start fitting and ensemble identifiability analysis. Applied to synthetic and experimental MC3 LNP data, the framework shows that near-identical SAXS fits can arise from distinct parameter modes, with the experimental fits dominated by a trade-off between size-distribution and interior-structure parameters.