A Molecular Communication Scheme to Estimate the State of Biochemical Processes on a Lab-on-a-Chip

International audienceA key application of advanced spectroscopy methods is to estimate equilibrium states of biochemical processes in situ and in vivo. Nevertheless, an often present difficulty is the requirement that the biochemical process and its environment (such as the substrate) satisfy special conditions. One means of resolving this issue is to communicate information about the equilibrium states of the biochemical process to another location, supported via microfluidic channles within a lab-on-a-chip. In this paper, we develop a signaling strategy and estimation algorithms for equilibrium states of a biochemical process. For a toggle-switch circuit model important in cellular differentiation studies, we study via simulation the tradeoff between the rate of obtaining spectroscopy measurements and the estimation error, providing insights into requirements of spectroscopy devices for high-throughput biological assays. CCS CONCEPTS • Applied computing → Health care information systems; • Computing methodologies → Model verification and validation; Mixture modeling

Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population.The authors declare no competing interests. We thank Dr. Nigel J. Savery at the University of Bristol for useful discussions around the subject of GRNs and for his help in developing the original ABM model. We also wish to thank Dr Gianfranco Fiore at the University of Bristol and the anonymous reviewers for reading the revised manuscript carefully and providing insightful comments that led to a consistent revision of the original manuscript. P.M. was supported by EPSRC Grant EP/E501214/1 and K.T.-A. by EPSRC Grant EP/I018638/1. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. This work was carried out using the computational facilities of the Advanced Computing Research Centre, University of Bristol, http://www.bris.ac.uk/acrc/

Analysis Of Rhythm Generation In The Caenorhabditis Elegans Motor Circuit

Understanding the neuronal control of movement has been a central goal of neuroscience for decades. In many organisms, chains of neural oscillators underlie the generation of coordinated rhythmic movements. However, the sheer complexity of spinal locomotor circuits has made understanding the mechanisms underlying rhythmic locomotion in vertebrates challenging. The roundworm C. elegans generates rhythmic undulatory movements that resemble those of swimming vertebrates, but using only a few hundred neurons. The relative simplicity of this organism has allowed a complete synaptic map of the nervous system to be developed. Moreover, C. elegans has a three-day life cycle and is amenable to a powerful battery of genetic techniques that allow the molecular basis of circuit functions to be probed much more rapidly than is possible in more complex organisms. Because of these advantages, C. elegans offers the possibility of understanding the network, cellular, and molecular principles of rhythmic locomotion in deeper detail than has been possible in any other model organism. However, it is currently unclear where in the C. elegans motor circuit rhythms are generated, and whether there exists more than one rhythm generator. I used optogenetic and lesioning experiments to probe the nature of rhythm generation in the locomotor circuit. I found that rhythmic activity in different parts of the body can be decoupled by both methods, implying that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, I localized at least two rhythmic sources to a network of cholinergic motor neurons that are distributed along the body. Moreover, I used rhythmic optogenetic manipulations to show that imposed rhythmic signals in any portion of the motor circuit can entrain oscillatory activity in the rest of the body, suggesting bidirectional coupling within the motor circuit. This organization, in which distributed oscillating circuits exist along the body but are closely linked by bidirectional coupling, is found in wide range of vertebrate and invertebrate animals. My results show that the functional architecture of the C. elegans motor circuit is highly analogous to that of much more complex organisms

Molecular Communication for Equilibrium State Estimation in Biochemical Processes on a Lab-on-a-Chip

International audienceA basic problem in molecular biology is to estimate equilibrium states of biochemical processes. To this end, advanced spectroscopy methods have been developed in order to estimate chemical concentrations in situ or in vivo. However, such spectroscopy methods can require special conditions that do not allow direct observation of the biochemical process. A natural means of resolving this problem is to transmit chemical signals to another location within a lab-on-a-chip device; that is, employing molecular communication in order to perform spectroscopy in a different location. In this paper, we develop such a signaling strategy and estimation algorithms for equilibrium states of a biochemical process. In two biologically-inspired models, we then study via simulation the tradeoff between the rate of obtaining spectroscopy measurements and the estimation error, providing insights into requirements of spectroscopy devices for highthroughput biological assays

Design of a Customized multipurpose nano-enabled implantable system for in-vivo theranostics

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device