Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2511.22893

Switching-time bioprocess control with pulse-width-modulated optogenetics

Sebastián Espinel-Ríos
View original source ↗Read source document ↗Export metadata ↓

Abstract

Biotechnology can benefit from dynamic control to improve production efficiency. In this context, optogenetics enables modulation of gene expression using light as an external input, allowing fine-tuning of protein levels to unlock dynamic metabolic control and regulation of cell growth. Optogenetic systems can be actuated by light intensity. However, relying solely on intensity-driven control (i.e., signal amplitude) may fail to properly tune optogenetic bioprocesses when the dose-response relationship (i.e., light intensity versus gene-expression strength) is steep. In these cases, tunability is effectively constrained to either fully active or fully repressed gene expression, with little intermediate regulation. Pulse-width modulation can alleviate this issue by alternating between fully ON and OFF light intensity within forcing periods, thereby smoothing the average response and enhancing process controllability. Optimizing pulse-width-modulated optogenetics entails a switching-time optimal control problem with a binary input over multiple forcing periods. While this can be formulated as a mixed-integer optimization problem on a refined control grid with monotonic input constraints, the number of decision variables can grow rapidly with increasing control-grid resolution within forcing periods and with the total number of forcing periods, complicating the task. Here, we propose an alternative solution based on reinforcement learning. We parametrize control actions via the duty cycle, a continuous proxy variable that encodes the ON-to-OFF switching time within each forcing period, thereby respecting the intrinsic binary nature of the light intensity while avoiding fine-grid binary decision variables.

Explore related subjects

eess.SYcs.AIcs.SY

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sebastián Espinel-Ríos. 2026-05-07. Switching-time bioprocess control with pulse-width-modulated optogenetics. https://arxiv.org/abs/2511.22893

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Constrained Feedback Control of Nonlinear Systems via Approximate HJB and Control Barrier Functions

This paper presents a two-stage framework for constrained feedback control of input-affine nonlinear systems. Offline, an approximate value function for the unconstrained problem is computed, for example using Hamilton--Jacobi--Bellman (HJB)-based policy iteration. Online, the proposed quadratic program (QP) minimizes the pre-Hamiltonian evaluated using the approximate value-function gradient subject to safety constraints enforced by control barrier functions (CBFs). This architecture decouples performance optimization from constraint enforcement, allowing constraints to be modified without recomputing the value function. As in CBF-QP architectures based on control Lyapunov functions (CLFs), safety is enforced as a hard constraint; however, the performance objective targets approximate optimality rather than a prescribed Lyapunov decay. Numerical results on a linear 2-state hovercraft and a nonlinear 9-state spacecraft attitude-control problem show agreement with the constrained open-loop optimal control problem (OCP) benchmark in the linear case, and performance close to the OCP benchmark, improving on CLF-based controllers, in the nonlinear case.

eess.SY↗
arXiv2026

Rao-Blackwellized Stein Gradient Descent for Joint State-Parameter Estimation

We present a filtering framework for online joint state estimation and parameter identification in nonlinear, time-varying systems. The algorithm uses a Rao-Blackwellization technique to infer joint state-parameter posteriors efficiently. In particular, conditional state distributions are computed analytically via Kalman filtering, while model parameters, including the measurement-noise covariance, are approximated using particle-based Stein Variational Gradient Descent (SVGD), enabling stable real-time inference. To handle parameters subject to physical constraints, we further introduce constrained variants that enforce them through an alternating direction method of multipliers (ADMM) splitting of the SVGD update, including nonlinear equality constraints that standard particle filters cannot readily handle. We derive a stability bound that relates the approximation error in the parameter posterior to the resulting error in the marginal state distribution. Performance of the proposed filters is validated on three case studies: a fed-batch bioreactor with Haldane kinetics and a damped pendulum, both under physical constraints, and a neural-network-augmented dynamic system. The examples cover parameter estimation under inequality and equality constraints and online neural-network training within a dynamical model.

eess.SY↗
arXiv2026

Firing Rate Neural Network Implementations of Model Predictive Control

Human and animal brains perform planning to enable complex movements and behaviors, a process that can be effectively described using model predictive control (MPC). How could the brain physically implement MPC? In this work, we translate model predictive controllers into firing rate neural networks, offering insights into the nonlinear neural dynamics that underpin planning. We propose a constructive method; no training is required. This is done first applying the projected gradient method to the dual problem to derive a baseline neural network implementation. We then use factorization and contraction analysis to systematically generate alternative network architectures; in other words, we systematically generate hypotheses for how planning is done in the brain via neural dynamics. Finally, we present numerical simulations to study different neural networks performing MPC to balance an inverted pendulum on a cart (i.e., balancing a stick on a hand), including one example in which imposing sparse connectivity (a property observed in brain networks) does not degrade control performance.

eess.SY↗