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With conventional silicon-based computing approaching its physical and efficiency limits, biocomputing emerges as a promising alternative. This approach utilises biomaterials such as DNA and neurons as an interesting alternative to data processing and storage. This study explores the potential of neuronal biocomputing to rival silicon-based systems. We explore neuronal logic gates and sequential circuits that mimic conventional computer architectures. Through mathematical modelling, optimisation, and computer simulation, we demonstrate the operational capabilities of neuronal sequential circuits. These circuits include a neuronal NAND gate, SR Latch flip-flop, and D flip-flop memory units. Our approach involves manipulating neuron communication, synaptic conductance, spike buffers, neuron types, and specific neuronal network topology designs. The experiments demonstrate the practicality of encoding binary information using patterns of neuronal activity and overcoming synchronization difficulties with neuronal buffers and inhibition strategies. Our results confirm the effectiveness and scalability of neuronal logic circuits, showing that they maintain a stable metabolic burden even in complex data storage configurations. Our study not only demonstrates the concept of embodied biocomputing by manipulating neuronal properties for digital signal processing but also establishes the foundation for cutting-edge biocomputing technologies. Our designs open up possibilities for using neurons as energy-efficient computing solutions. These solutions have the potential to become an alternate to silicon-based systems by providing a carbon-neutral, biologically feasible alternative.

With many advancements in in silico biology in recent years, the paramount challenge is to translate the accumulated knowledge into exciting industry partnerships and clinical applications. Achieving models that characterize the link of molecular interactions to the activity and structure of a whole organ are termed multiscale biophysics. Historically, the pharmaceutical industry has worked well with in silico models by leveraging their prediction capabilities for drug testing. However, the needed higher fidelity and higher resolution of models for efficient prediction of pharmacological phenomenon dictates that in silico approaches must account for the verifiable multiscale biophysical phenomena, as a spatial and temporal dimension variation for different processes and models. The collection of different multiscale models for different tissues and organs can compose digital twin solutions towards becoming a service for researchers, clinicians, and drug developers. Our paper has two main goals: 1) To clarify to what extent detailed single- and multiscale modeling has been accomplished thus far, we provide a review on this topic focusing on the biophysics of epithelial, cardiac, and brain tissues; 2) To discuss the present and future role of multiscale biophysics in in silico pharmacology as a digital twin solution by defining a roadmap from simple biophysical models to powerful prediction tools. Digital twins have the potential to pave the way for extensive clinical and pharmaceutical usage of multiscale models and our paper shows the basic fundamentals and opportunities towards their accurate development enabling the quantum leaps of future precise and personalized medical software., Comment: 30 pages, 10 figures, 1 table

Biocomputing technologies exploit biological communication mechanisms involving cell-cell signal propagation to perform computations. Researchers recently worked toward realising logic gates made by neurons to develop novel devices such as organic neuroprostheses or brain implants made by cells, herein termed living implants. Several challenges arise from this approach, mainly associated with the stochastic nature and noise of neuronal communication. Since astrocytes play a crucial role in the regulation of neurons activity, there is a possibility whereby astrocytes can be engineered to control synapses favouring reliable biocomputing. This work proposes a mathematical model of neuronal logic gates involving neurons and astrocytes, realising OR and AND gating. We use a shallow coupling of both the Izhikevich and Postnov models to characterise gating responses with spike pattern variability and astrocyte synaptic regulation. Logic operation error ratio and accuracy assess the AND and OR gates' performances at different synaptic Gaussian noise levels. Our results demonstrate that the astrocyte regulating activity can effectively be used as a denoising mechanism, paving the way for highly reliable biocomputing implementations., Comment: Added references, Corrected typos, Reformulated some sentences and added some clearer explanations

The recent COVID-19 pandemic has driven researchers from different spectrum to develop novel solutions that can improve detection and understanding of SARS-CoV-2 virus. In this article we propose the use of Intelligent Reflector Surface (IRS) emitting terahertz signals to detect airborne respiratory aerosol cloud that are secreted from people. Our proposed approach makes use of future IRS infrastructure to extend beyond communication functionality by adding environmental scanning for aerosol clouds. Simulations have also been conducted to analyze the accuracy of aerosol cloud detection based on a signal scanning and path optimization algorithm. Utilizing IRS for detecting respiratory aerosol cloud can lead to new added value of telecommunication infrastructures for sensor monitoring data that can be used for public health., Comment: 7 pages, 6 figures. This work has been submitted to the IEEE for possible publication

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations' molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications., Comment: 11 pages, 6 figures

The COVID-19 pandemic has shaken the world unprecedentedly, where it has affected the vast global population both socially and economically. The pandemic has also opened our eyes to the many threats that novel virus infections can pose for humanity. While numerous unknowns are being investigated in terms of the distributed damage that the virus can do to the human body, recent studies have also shown that the infection can lead to lifelong sequelae that could affect other parts of the body, and one example is the brain. As part of this work, we investigate how viral infection can affect the brain by modelling and simulating a neuron's behaviour under demyelination that is affected by the cytokine storm. We quantify the effects of cytokine-induced demyelination on the propagation of action potential signals within a neuron. We used information and communication theory analysis on the signal propagated through the axonal pathway under different intensity levels of demyelination to analyse these effects. Our simulations demonstrate that virus-induced degeneration can play a role in the signal power and spiking rate and the probability of releasing neurotransmitters and compromising the propagation and processing of information between the neurons. We also propose a transfer function that models these attenuation effects that degenerates the action potential, where this model has the potential to be used as a framework for the analysis of virus-induced neurodegeneration that can pave the way to improved understanding of virus-induced demyelination.

Hundreds of millions of people worldwide are affected by viral infections each year, and yet, several of them neither have vaccines nor effective treatment during and post-infection. This challenge has been highlighted by the COVID-19 pandemic, showing how viruses can quickly spread and how they can impact society as a whole. Novel techniques that bring in different disciplines must emerge to provide forward-looking strategies to combat viral infections, as well as possible future pandemics. In the past decade, an interdisciplinary area involving bioengineering, nanotechnology and information and communication technology (ICT) has been developing, known as Molecular Communications. This new emerging area uses elements of classical communication systems and maps it to molecular signalling and communication found inside and outside the body, where the aim is to develop new tools that can serve future medicine. In this paper, we provide an extensive and detailed discussion on how Molecular Communications can be integrated into the research on viral infectious diseases modelling, and how possible treatment and vaccines can be developed considering molecules as information carriers. We provide a literature review on the existing models of Molecular Communications for viral infection (in-body and out-body), a deep analysis on their effects on the host and subsequent communication process for other systems within the body (e.g., immune response), sources of experimental data on known viral infections and how it can be used by the Molecular Communications community, as well as open issues and future directions. Since the development of therapeutics/vaccines needs an interdisciplinary approach centred around ICT, we are confident that Molecular Communications can play a central role here by providing a detail characterisation and manipulation of the propagation of molecules in different media., Comment: Submitted for journal publication

While metasurface based intelligent reflecting surfaces (IRS) are an important emerging technology for future generations of wireless connectivity in its own right, the plans for the mass deployment of these surfaces motivate the question of their integration with other new and emerging technologies that would require mass proliferation. This question of integration and the vision of future communication systems as an invaluable component for public health motivated our new concept of Intelligent Reflector-Viral Detectors (IR-VD). In this novel scheme, we propose deployment of intelligent reflectors with strips of receptor-based viral detectors placed between the reflective surface tiles. Our proposed approach encodes information of the virus by flicking the angle of the reflected beams, using time variations between the beam deviations to represent the messages. This information includes the presence of the virus, its location and load size. The paper presents simulation to demonstrate the encoding process based on varying quantity of virus that have bound onto the IR-VD., Comment: This work has been submitted to the IEEE for possible publication

Brain-Computer Interfaces (BCI) arose as systems that merge computing systems with the human brain to facilitate recording, stimulation, and inhibition of neural activity. Over the years, the development of BCI technologies has shifted towards miniaturization of devices that can be seamlessly embedded into the brain and can target single neuron or small population sensing and control. We present a motivating example highlighting vulnerabilities of two promising micron-scale BCI technologies, demonstrating the lack of security and privacy principles in existing solutions. This situation opens the door to a novel family of cyberattacks, called neuronal cyberattacks, affecting neuronal signaling. This paper defines the first two neural cyberattacks, Neuronal Flooding (FLO) and Neuronal Scanning (SCA), where each threat can affect the natural activity of neurons. This work implements these attacks in a neuronal simulator to determine their impact over the spontaneous neuronal behavior, defining three metrics: number of spikes, percentage of shifts, and dispersion of spikes. Several experiments demonstrate that both cyberattacks produce a reduction of spikes compared to spontaneous behavior, generating a rise in temporal shifts and a dispersion increase. Mainly, SCA presents a higher impact than FLO in the metrics focused on the number of spikes and dispersion, where FLO is slightly more damaging, considering the percentage of shifts. Nevertheless, the intrinsic behavior of each attack generates a differentiation on how they alter neuronal signaling. FLO is adequate to generate an immediate impact on the neuronal activity, whereas SCA presents higher effectiveness for damages to the neural signaling in the long-term.

This paper proposes the use of Eukaryotic cells, namely astrocytes, to develop logic gates. The logic gates are achieved by manipulating the threshold of Ca$^{2+}$ ion flows between the cells, based on the input signals. Through wet-lab experiments that engineer the astrocytes cells with pcDNA3.1-hGPR17 genes, we show that both AND and OR gates can be implemented by controlling Ca$^{2+}$ signals that flow through the population. A reinforced learning platform is also presented in the paper to optimize two main parameters, which are the Ca$^{2+}$ activation threshold and time slot of input signals $T_b$ into the gate. This design platform caters for any size and connectivity of the cell population, by taking into consideration the delay and noise produced from the signalling between the cells, in order to fine-tune the activation threshold and input signal time slot parameters. To validate the effectiveness of the reinforced learning platform, a Ca$^{2+}$ Signalling-based Molecular Communications Simulator was used to simulate the signalling between the astrocyte cells. The results from the simulation showed that an optimum value for both the Ca$^{2+}$ activation threshold and time slot of input signals $T_b$ is required to achieve optimal computation accuracy, where up to 90\% accuracy for both the AND and OR gates can be achieved with the right combination of values. The reinforced learning platform for the engineered astrocytes to create digital logic gates can be used for future Neural-Molecular Computing chip, which can revolutionize brain implants that are constructed from engineered biological cells., Comment: Submitted to journal publication

This paper presents the first comprehensive tutorial on a promising research field located at the frontier of two well-established domains: Neurosciences and wireless communications, motivated by the ongoing efforts to define how the sixth generation of mobile networks (6G) will be. In particular, this tutorial first provides a novel integrative approach that bridges the gap between these two, seemingly disparate fields. Then, we present the state-of-the-art and key challenges of these two topics. In particular, we propose a novel systematization that divides the contributions into two groups, one focused on what neurosciences will offer to 6G in terms of new applications and systems architecture (Neurosciences for Wireless), and the other focused on how wireless communication theory and 6G systems can provide new ways to study the brain (Wireless for Neurosciences). For the first group, we concretely explain how current scientific understanding of the brain would enable new application for 6G within the context of a new type of service that we dub braintype communications and that has more stringent requirements than human- and machine-type communication. In this regard, we expose the key requirements of brain-type communication services and we discuss how future wireless networks can be equipped to deal with such services. Meanwhile, for the second group, we thoroughly explore modern communication system paradigms, including Internet of Bio-nano Things and chaosbased communications, in addition to highlighting how complex systems tools can help bridging 6G and neuroscience applications. Brain-controlled vehicles are then presented as our case study. All in all, this tutorial is expected to provide a largely missing articulation between these two emerging fields while delineating concrete ways to move forward in such an interdisciplinary endeavor.

Classification of biological neuron types and networks poses challenges to the full understanding of the brain's organisation and functioning. In this paper, we develop a novel objective classification model of biological neuronal types and networks based on the communication metrics of neurons. This presents advantages against the existing approaches since the mutual information or the delay between neurons obtained from spike trains are more abundant data compare to conventional morphological data. We firstly designed two open-access supporting computational platforms of various neuronal circuits from the Blue Brain Project realistic models, named Neurpy and Neurgen. Then we investigate how the concept of network tomography could be achieved with cortical neuronal circuits for morphological, topological and electrical classification of neurons. We extract the simulated data to many different classifiers (including SVM, Decision Trees, Random Forest, and Artificial Neuron Networks) classifying the specific cell type (and sub-group types) achieving accuracies of up to 70\%. Inference of biological network structures using network tomography reached up to 65\% of accuracy. We also analysed recall, precision and F1score of the classification of five layers, 25 cell m-types, and 14 cell e-types. Our research not only contributes to existing classification efforts but sets the road-map for future usage of cellular-scaled brain-machine interfaces for in-vivo objective classification of neurons as a sensing mechanism of the brain's structure.

With the advancement of synthetic biology, several new tools have been conceptualized over the years as alternative treatments for current medical procedures. Most of those applications are applied to various chronic diseases. This work investigates how synthetically engineered neurons can operate as digital logic gates that can be used towards bio-computing for the brain. We quantify the accuracy of logic gates under high firing rates amid a network of neurons and by how much it can smooth out uncontrolled neuronal firings. To test the efficacy of our method, simulations composed of computational models of neurons connected in a structure that represents a logic gate are performed. The simulations demonstrated the accuracy of performing the correct logic operation, and how specific properties such as the firing rate can play an important role in the accuracy. As part of the analysis, the Mean squared error is used to quantify the quality of our proposed model and predicting the accurate operation of a gate based on different sampling frequencies. As an application, the logic gates were used to trap epileptic seizures in a neuronal network, where the results demonstrated the effectiveness of reducing the firing rate. Our proposed system has the potential for computing numerous neurological conditions of the brain., Comment: Submitted for journal publication

BCIs have significantly improved the patients' quality of life by restoring damaged hearing, sight, and movement capabilities. After evolving their application scenarios, the current trend of BCI is to enable new innovative brain-to-brain and brain-to-the-Internet communication paradigms. This technological advancement generates opportunities for attackers since users' personal information and physical integrity could be under tremendous risk. This work presents the existing versions of the BCI life-cycle and homogenizes them in a new approach that overcomes current limitations. After that, we offer a qualitative characterization of the security attacks affecting each phase of the BCI cycle to analyze their impacts and countermeasures documented in the literature. Finally, we reflect on lessons learned, highlighting research trends and future challenges concerning security on BCIs.

The Internet of Bio-Nano-Things is a new paradigm that can bring novel remotely controlled actuation and sensing techniques inside the human body. Towards precise bionano sensing techniques in the brain, we investigate the challenges of modelling spatial distribution of astrocyte networks in developing a mathematical framework that lay the groundwork for future early-detection techniques of neurodegenerative disease. In this paper, we investigate the effect of the $\beta$-amyloid plaques in astrocytes with the Alzheimer's disease. We developed a computation model of healthy and Alzheimer's diseases astrocytes networks from the state of the art models and results that account for the intracellular pathways, IP$_3$ dynamics, gap junctions, voltage-gated calcium channels and astrocytes volumes. We also implemented different types of astrocytes network topologies including shortcut networks, regular degree networks, Erd\"os R\'enyi networks and link radius networks. A proposed multi-scale stochastic computational model captures the relationship between the intracellular and intercellular scales. Lastly, we designed and evaluated a single-hop communication system with frequency modulation using metrics such as propagation extend, molecular delay and channel gain. The results show that the more unstable but at the same time lower level oscillations of Alzheimer's astrocyte networks can create a multi-scale effect on communication between astrocytes with increased molecular delay and lower channel gain compared to healthy astrocytes, with an elevated impact on Erd\"os R\'enyi networks and link radius networks topologies., Comment: Submitted to journal publication

In recent years, numerous research efforts have been dedicated towards developing efficient implantable devices for brain stimulation. However, there are limitations and challenges with the current technologies. Firstly, the stimulation of neurons currently is possible through implantable electrodes but limited to a population of neurons. Secondly, a major hurdle lies in developing miniature devices that can last for a lifetime in the patient's brain. In parallel, Optogenetics has emerged proposing the stimulation of neurons using light by means of optical fibers inserted through the skull. Many challenges are thus introduced in terms of suitability to patient's lifestyle and biocompatibility. We have recently proposed the concept of wireless optogenetic nanonetworking devices (WiOptND), addressing these long-term deployment problems, and at the same time targeting single neuron stimulation [1]. The WiOptND is equipped with a miniature LED that is able to stimulate a genetically engineered neuron while harvesting energy from ultrasonic vibrations. This paper investigates how light propagates in the brain tissue, and based on the power required to emit sufficient intensity for stimulation, an energy harvesting circuitry is designed. A number of charging protocols are also proposed to maximize energy efficiency while ensuring minimum number of neural spike misfirings. These protocols include the Charge and Fire, the Predictive Sliding Detection Window, and its variant Markov-Chain based Time-Delay Patterns. Simulation results show the drop of stimulation ratio for 25% and more stable trend in its efficiency ratio are exhibited on Markov-Chain based Time-Delay Patterns compared to Change and Fire. The results show the feasibility of utilizing WiOptND for long-term implants, and a new direction towards precise stimulation of neurons in the cortical columns of the brain.