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Srimanta Santra

Publications and source records attributed to Srimanta Santra.

2 recordsLinked to original sources

Fast Risk Certification of Candidate Trajectories under Uncertain Time-Varying Constraints

This paper studies the certification of a fixed candidate trajectory on a finite certification grid under parametric uncertainty. For each constraint-time pair, we define a scalar measure of constraint violation and aggregate the resulting pointwise chance constraints into a worst-case Value-at-Risk (VaR) margin. The goal is not to generate a new trajectory, but to assess online whether a trajectory produced by a planner or predictive controller is sufficiently safe on the certification grid. Direct evaluation requires repeated uncertainty propagation and is often too expensive for computationally demanding models. We therefore adopt an offline-online scheme: offline, a surrogate of the constraint violation map along the candidate trajectory is constructed using polynomial chaos expansion (PCE) when the uncertainty law is known, or kernel regression when only sampled input-output data are available; online, the surrogate is sampled to evaluate conservative VaR bounds at low computational cost. On the theoretical side, we derive a finite-sample upper bound for the grid-based VaR margin using empirical quantiles, the Dvoretzky-Kiefer-Wolfowitz (DKW) inequality, and a union bound over all constraint-time pairs, without assuming a parametric family for the underlying violation distribution. We also show how a uniform surrogate error bound transfers to the certified VaR margin. The approach is illustrated on a crystallization population balance model, where the surrogate-based risk estimates track direct Monte Carlo results while substantially reducing online evaluation time.

eess.SY

Mechanistic Modeling of Lipid Nanoparticle Formation for the Delivery of Nucleic Acid Therapeutics

Nucleic acids such as mRNA have emerged as a promising therapeutic modality with the capability of addressing a wide range of diseases. Lipid nanoparticles (LNPs) as a delivery platform for nucleic acids were used in the COVID-19 vaccines and have received much attention. While modern manufacturing processes which involve rapidly mixing an organic stream containing the lipids with an aqueous stream containing the nucleic acids are conceptually straightforward, detailed understanding of LNP formation and structure is still limited and scale-up can be challenging. Mathematical and computational methods are a promising avenue for deepening scientific understanding of the LNP formation process and facilitating improved process development and control. This article describes strategies for the mechanistic modeling of LNP formation, starting with strategies to estimate and predict important physicochemical properties of the various species such as diffusivities and solubilities. Subsequently, a framework is outlined for constructing mechanistic models of reactor- and particle-scale processes. Insights gained from the various models are mapped back to product quality attributes and process insights. Lastly, the use of the models to guide development of advanced process control and optimization strategies is discussed.

cond-mat.soft