arXiv subjects

Alexander Mitsos

Publications and source records attributed to Alexander Mitsos.

At least 37 records · Page 2Linked to original sources

arXiv2025

Molecular Machine Learning in Chemical Process Design

We present a perspective on molecular machine learning (ML) in the field of chemical process engineering. Recently, molecular ML has demonstrated great potential in (i) providing highly accurate predictions for properties of pure components and their mixtures, and (ii) exploring the chemical space for new molecular structures. We review current state-of-the-art molecular ML models and discuss research directions that promise further advancements. This includes ML methods, such as graph neural networks and transformers, which can be further advanced through the incorporation of physicochemical knowledge in a hybrid or physics-informed fashion. Then, we consider leveraging molecular ML at the chemical process scale, which is highly desirable yet rather unexplored. We discuss how molecular ML can be integrated into process design and optimization formulations, promising to accelerate the identification of novel molecules and processes. To this end, it will be essential to create molecule and process design benchmarks and practically validate proposed candidates, possibly in collaboration with the chemical industry.

physics.chem-ph↗

arXiv2025

Accelerating Deterministic Global Optimization via GPU-parallel Interval Arithmetic

Spatial Branch and Bound (B&B) algorithms are widely used for solving nonconvex problems to global optimality, yet they remain computationally expensive. Though some works have been carried out to speed up B&B via CPU parallelization, GPU parallelization is much less explored. In this work, we investigate the design of a spatial B&B algorithm that involves an interval-based GPU-parallel lower bounding solver: The domain of each B&B node is temporarily partitioned into numerous subdomains, then massive GPU parallelism is leveraged to compute interval bounds of the objective function and constraints on each subdomain, using the Mean Value Form. The resulting bounds are tighter than those achieved via regular interval arithmetic without partitioning, but they remain fast to compute. We implement the method into our open-source solver MAiNGO via CUDA in two manners: wrapping all GPU tasks within one kernel function, or distributing the GPU tasks onto a CUDA graph. Numerical experiments show that using more subdomains leads to significantly tighter lower bounds and thus less B&B iterations. Regarding wall clock time, the proposed spatial B&B framework achieves a speedup of three orders of magnitude compared to applying interval arithmetic on the CPU without domain partitioning. Among the two implementations, the one developed with CUDA graph enables higher efficiency. Moreover, in some case studies, the proposed method delivers competitive or better performance compared to MAiNGO's default solver which is based on McCormick relaxations. These results highlight the potential of GPU-accelerated bounding techniques to accelerate B&B algorithms.

math.OC↗

arXiv2025

Simultaneous Design of Microbe and Bioreactor

When developing a biotechnological process, the microorganism is first designed, e.g., using metabolic engineering. Then, the optimum fermentation parameters are determined on a laboratory scale, and lastly, they are transferred to the bioreactor scale. However, this step-by-step approach is costly and time-consuming and may result in suboptimal configurations. Herein, we present the bilevel optimization formulation SimulKnockReactor, which connects bioreactor design with microbial strain design, an extension of our previous formulation, SimulKnock (Ziegler et al., 2024, AIChE J.). At the upper (bioreactor) level, we minimize investment and operation costs for agitation, aeration, and pH control by determining the size and operating conditions of a continuous stirred-tank reactor - without selecting specific devices like the stirrer type. The lower (cellular) level is based on flux balance analysis and implements optimal reaction knockouts predicted by the upper level. Our results with a core and a genome-scale metabolic model of Escherichia coli show that the substrate is the largest cost factor. Our simultaneous approach outperforms a sequential approach using OptKnock. Namely, the knockouts proposed by OptKnock cannot guarantee the required production capacity in all cases considered. In the case that both approaches deliver feasible results, the total annual costs are the same or lower with SimulKnockReactor, highlighting the advantage of combining cellular and bioreactor levels. This work is a further step towards a fully integrated bioprocess design.

math.OC↗

arXiv2025

Robust Energy System Design via Semi-infinite Programming

Time-series information needs to be incorporated into energy system optimization to account for the uncertainty of renewable energy sources. Typically, time-series aggregation methods are used to reduce historical data to a few representative scenarios but they may neglect extreme scenarios, which disproportionally drive the costs in energy system design. We propose the robust energy system design (RESD) approach based on semi-infinite programming and use an adaptive discretization-based algorithm to identify worst-case scenarios during optimization. The RESD approach can guarantee robust designs for problems with nonconvex operational behavior, which current methods cannot achieve. The RESD approach is demonstrated by designing an energy supply system for the island of La Palma. To improve computational performance, principal component analysis is used to reduce the dimensionality of the uncertainty space. The robustness and costs of the approximated problem with significantly reduced dimensionality approximate the full-dimensional solution closely. Even with strong dimensionality reduction, the RESD approach is computationally intense and thus limited to small problems.

math.OC↗

arXiv2025

Sample-Efficient Reinforcement Learning of Koopman eNMPC

Reinforcement learning (RL) can be used to tune data-driven (economic) nonlinear model predictive controllers ((e)NMPCs) for optimal performance in a specific control task by optimizing the dynamic model or parameters in the policy's objective function or constraints, such as state bounds. However, the sample efficiency of RL is crucial, and to improve it, we combine a model-based RL algorithm with our published method that turns Koopman (e)NMPCs into automatically differentiable policies. We apply our approach to an eNMPC case study of a continuous stirred-tank reactor (CSTR) model from the literature. The approach outperforms benchmark methods, i.e., data-driven eNMPCs using models based on system identification without further RL tuning of the resulting policy, and neural network controllers trained with model-based RL, by achieving superior control performance and higher sample efficiency. Furthermore, utilizing partial prior knowledge about the system dynamics via physics-informed learning further increases sample efficiency.

cs.LG↗

arXiv2025

GraphXForm: Graph transformer for computer-aided molecular design

Generative deep learning has become pivotal in molecular design for drug discovery, materials science, and chemical engineering. A widely used paradigm is to pretrain neural networks on string representations of molecules and fine-tune them using reinforcement learning on specific objectives. However, string-based models face challenges in ensuring chemical validity and enforcing structural constraints like the presence of specific substructures. We propose to instead combine graph-based molecular representations, which can naturally ensure chemical validity, with transformer architectures, which are highly expressive and capable of modeling long-range dependencies between atoms. Our approach iteratively modifies a molecular graph by adding atoms and bonds, which ensures chemical validity and facilitates the incorporation of structural constraints. We present GraphXForm, a decoder-only graph transformer architecture, which is pretrained on existing compounds and then fine-tuned using a new training algorithm that combines elements of the deep cross-entropy method and self-improvement learning. We evaluate GraphXForm on various drug design tasks, demonstrating superior objective scores compared to state-of-the-art molecular design approaches. Furthermore, we apply GraphXForm to two solvent design tasks for liquid-liquid extraction, again outperforming alternative methods while flexibly enforcing structural constraints or initiating design from existing molecular structures.

cs.LG↗

arXiv2025

Task-optimal data-driven surrogate models for eNMPC via differentiable simulation and optimization

Mechanistic dynamic process models may be too computationally expensive to be usable as part of a real-time capable predictive controller. We present a method for end-to-end learning of Koopman surrogate models for optimal performance in a specific control task. In contrast to previous contributions that employ standard reinforcement learning (RL) algorithms, we use a training algorithm that exploits the differentiability of environments based on mechanistic simulation models to aid the policy optimization. We evaluate the performance of our method by comparing it to that of other training algorithms on an existing economic nonlinear model predictive control (eNMPC) case study of a continuous stirred-tank reactor (CSTR) model. Compared to the benchmark methods, our method produces similar economic performance while eliminating constraint violations. Thus, for this case study, our method outperforms the others and offers a promising path toward more performant controllers that employ dynamic surrogate models.

cs.LG↗

arXiv2025

Optimizing Flexibility in Power Systems by Maximizing the Region of Manageable Uncertainties

Motivated by the increasing need to hedge against load and generation uncertainty in the operation of power grids, we propose flexibility maximization during operation. We consider flexibility explicitly as the amount of uncertainty that can be handled while still ensuring nominal grid operation in the worst-case. We apply the proposed flexibility optimization in the context of a DC flow approximation. By using a corresponding parameterization, we can find the maximal range of uncertainty and a range for the manageable power transfer between two parts of a network subject to uncertainty. We formulate the corresponding optimization problem as an (existence-constrained) semi-infinite optimization problem and specialize an existing algorithm for its solution.

math.OC↗

arXiv2024

Predicting the Temperature-Dependent CMC of Surfactant Mixtures with Graph Neural Networks

Surfactants are key ingredients in foaming and cleansing products across various industries such as personal and home care, industrial cleaning, and more, with the critical micelle concentration (CMC) being of major interest. Predictive models for CMC of pure surfactants have been developed based on recent ML methods, however, in practice surfactant mixtures are typically used due to to performance, environmental, and cost reasons. This requires accounting for synergistic/antagonistic interactions between surfactants; however, predictive ML models for a wide spectrum of mixtures are missing so far. Herein, we develop a graph neural network (GNN) framework for surfactant mixtures to predict the temperature-dependent CMC. We collect data for 108 surfactant binary mixtures, to which we add data for pure species from our previous work [Brozos et al. (2024), J. Chem. Theory Comput.]. We then develop and train GNNs and evaluate their accuracy across different prediction test scenarios for binary mixtures relevant to practical applications. The final GNN models demonstrate very high predictive performance when interpolating between different mixture compositions and for new binary mixtures with known species. Extrapolation to binary surfactant mixtures where either one or both surfactant species are not seen before, yields accurate results for the majority of surfactant systems. We further find superior accuracy of the GNN over a semi-empirical model based on activity coefficients, which has been widely used to date. We then explore if GNN models trained solely on binary mixture and pure species data can also accurately predict the CMCs of ternary mixtures. Finally, we experimentally measure the CMC of 4 commercial surfactants that contain up to four species and industrial relevant mixtures and find a very good agreement between measured and predicted CMC values.

physics.chem-ph↗

arXiv2024

Physics-Informed Neural Networks for Dynamic Process Operations with Limited Physical Knowledge and Data

In chemical engineering, process data are expensive to acquire, and complex phenomena are difficult to fully model. We explore the use of physics-informed neural networks (PINNs) for modeling dynamic processes with incomplete mechanistic semi-explicit differential-algebraic equation systems and scarce process data. In particular, we focus on estimating states for which neither direct observational data nor constitutive equations are available. We propose an easy-to-apply heuristic to assess whether estimation of such states may be possible. As numerical examples, we consider a continuously stirred tank reactor and a liquid-liquid separator. We find that PINNs can infer immeasurable states with reasonable accuracy, even if respective constitutive equations are unknown. We thus show that PINNs are capable of modeling processes when relatively few experimental data and only partially known mechanistic descriptions are available, and conclude that they constitute a promising avenue that warrants further investigation.

cs.LG↗

arXiv2024

End-to-End Reinforcement Learning of Koopman Models for Economic Nonlinear Model Predictive Control

(Economic) nonlinear model predictive control ((e)NMPC) requires dynamic models that are sufficiently accurate and computationally tractable. Data-driven surrogate models for mechanistic models can reduce the computational burden of (e)NMPC; however, such models are typically trained by system identification for maximum prediction accuracy on simulation samples and perform suboptimally in (e)NMPC. We present a method for end-to-end reinforcement learning of Koopman surrogate models for optimal performance as part of (e)NMPC. We apply our method to two applications derived from an established nonlinear continuous stirred-tank reactor model. The controller performance is compared to that of (e)NMPCs utilizing models trained using system identification, and model-free neural network controllers trained using reinforcement learning. We show that the end-to-end trained models outperform those trained using system identification in (e)NMPC, and that, in contrast to the neural network controllers, the (e)NMPC controllers can react to changes in the control setting without retraining.

cs.LG↗

arXiv2024

Thermodynamics-Consistent Graph Neural Networks

We propose excess Gibbs free energy graph neural networks (GE-GNNs) for predicting composition-dependent activity coefficients of binary mixtures. The GE-GNN architecture ensures thermodynamic consistency by predicting the molar excess Gibbs free energy and using thermodynamic relations to obtain activity coefficients. As these are differential, automatic differentiation is applied to learn the activity coefficients in an end-to-end manner. Since the architecture is based on fundamental thermodynamics, we do not require additional loss terms to learn thermodynamic consistency. As the output is a fundamental property, we neither impose thermodynamic modeling limitations and assumptions. We demonstrate high accuracy and thermodynamic consistency of the activity coefficient predictions.

cond-mat.dis-nn↗

arXiv2024

Nonlinear Manifold Learning Determines Microgel Size from Raman Spectroscopy

Polymer particle size constitutes a crucial characteristic of product quality in polymerization. Raman spectroscopy is an established and reliable process analytical technology for in-line concentration monitoring. Recent approaches and some theoretical considerations show a correlation between Raman signals and particle sizes but do not determine polymer size from Raman spectroscopic measurements accurately and reliably. With this in mind, we propose three alternative machine learning workflows to perform this task, all involving diffusion maps, a nonlinear manifold learning technique for dimensionality reduction: (i) directly from diffusion maps, (ii) alternating diffusion maps, and (iii) conformal autoencoder neural networks. We apply the workflows to a data set of Raman spectra with associated size measured via dynamic light scattering of 47 microgel (cross-linked polymer) samples in a diameter range of 208nm to 483 nm. The conformal autoencoders substantially outperform state-of-the-art methods and results for the first time in a promising prediction of polymer size from Raman spectra.

cs.LG↗

arXiv2024

Optimal design of a local renewable electricity supply system for power-intensive production processes with demand response

This work studies synergies arising from combining industrial demand response and local renewable electricity supply. To this end, we optimize the design of a local electricity generation and storage system with an integrated demand response scheduling of a continuous power-intensive production process in a multi-stage problem. We optimize both total annualized cost and global warming impact and consider local photovoltaic and wind electricity generation, an electric battery, and electricity trading on day-ahead and intraday market. We find that installing a battery can reduce emissions and enable large trading volumes on the electricity markets, but significantly increases cost. Economically and ecologically-optimal operation of the process and battery are driven primarily by the electricity price and grid emission factor, respectively, rather than locally generated electricity. A parameter study reveals that cost savings from the local system and flexibilizing the process behave almost additively.

math.OC↗

arXiv2024

Predicting the Temperature Dependence of Surfactant CMCs Using Graph Neural Networks

The critical micelle concentration (CMC) of surfactant molecules is an essential property for surfactant applications in industry. Recently, classical QSPR and Graph Neural Networks (GNNs), a deep learning technique, have been successfully applied to predict the CMC of surfactants at room temperature. However, these models have not yet considered the temperature dependency of the CMC, which is highly relevant for practical applications. We herein develop a GNN model for temperature-dependent CMC prediction of surfactants. We collect about 1400 data points from public sources for all surfactant classes, i.e., ionic, nonionic, and zwitterionic, at multiple temperatures. We test the predictive quality of the model for following scenarios: i) when CMC data for surfactants are present in the training of the model in at least one different temperature, and ii) CMC data for surfactants are not present in the training, i.e., generalizing to unseen surfactants. In both test scenarios, our model exhibits a high predictive performance of R$^2 \geq $ 0.94 on test data. We also find that the model performance varies by surfactant class. Finally, we evaluate the model for sugar-based surfactants with complex molecular structures, as these represent a more sustainable alternative to synthetic surfactants and are therefore of great interest for future applications in the personal and home care industries.

physics.chem-ph↗

arXiv2024

Simultaneous design of fermentation and microbe

Constraint-based optimization of microbial strains and model-based bioprocess design have been used extensively to enhance yields in biotechnological processes. However, strain and process optimization are usually carried out in sequential steps, causing underperformance of the biotechnological process when scaling up to industrial fermentation conditions. Herein, we propose the optimization formulation SimulKnock that combines the optimization of a fermentation process with metabolic network design in a bilevel optimization program. The upper level maximizes space-time yield and includes mass balances of a continuous fermentation, while the lower level is based on flux balance analysis. SimulKnock predicts optimal gene deletions and finds the optimal trade-off between growth rate and product yield. Results of a case study with a genome-scale metabolic model of E. coli indicate higher space-time yields than a sequential approach using OptKnock for almost all target products considered. By leveraging SimulKnock, we reduce the gap between strain and process optimization.

math.OC↗

arXiv2024

Data-driven Nonlinear Model Reduction using Koopman Theory: Integrated Control Form and NMPC Case Study

We use Koopman theory for data-driven model reduction of nonlinear dynamical systems with controls. We propose generic model structures combining delay-coordinate encoding of measurements and full-state decoding to integrate reduced Koopman modeling and state estimation. We present a deep-learning approach to train the proposed models. A case study demonstrates that our approach provides accurate control models and enables real-time capable nonlinear model predictive control of a high-purity cryogenic distillation column.

eess.SY↗

arXiv2024

Graph Neural Networks for Surfactant Multi-Property Prediction

Surfactants are of high importance in different industrial sectors such as cosmetics, detergents, oil recovery and drug delivery systems. Therefore, many quantitative structure-property relationship (QSPR) models have been developed for surfactants. Each predictive model typically focuses on one surfactant class, mostly nonionics. Graph Neural Networks (GNNs) have exhibited a great predictive performance for property prediction of ionic liquids, polymers and drugs in general. Specifically for surfactants, GNNs can successfully predict critical micelle concentration (CMC), a key surfactant property associated with micellization. A key factor in the predictive ability of QSPR and GNN models is the data available for training. Based on extensive literature search, we create the largest available CMC database with 429 molecules and the first large data collection for surface excess concentration ($Γ$$_{m}$), another surfactant property associated with foaming, with 164 molecules. Then, we develop GNN models to predict the CMC and $Γ$$_{m}$ and we explore different learning approaches, i.e., single- and multi-task learning, as well as different training strategies, namely ensemble and transfer learning. We find that a multi-task GNN with ensemble learning trained on all $Γ$$_{m}$ and CMC data performs best. Finally, we test the ability of our CMC model to generalize on industrial grade pure component surfactants. The GNN yields highly accurate predictions for CMC, showing great potential for future industrial applications.

physics.chem-ph↗