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The internet of Bio-Nano things
Abstract and Figures
The Internet of Things (IoT) has become an important research topic in the last decade, where things refer to interconnected machines and objects with embedded computing capabilities employed to extend the Internet to many application domains. While research and development continue for general IoT devices, there are many application domains where very tiny, concealable, and non-intrusive Things are needed. The properties of recently studied nanomaterials, such as graphene, have inspired the concept of Internet of NanoThings (IoNT), based on the interconnection of nanoscale devices. Despite being an enabler for many applications, the artificial nature of IoNT devices can be detrimental where the deployment of NanoThings could result in unwanted effects on health or pollution. The novel paradigm of the Internet of Bio-Nano Things (IoBNT) is introduced in this paper by stemming from synthetic biology and nanotechnology tools that allow the engineering of biological embedded computing devices. Based on biological cells, and their functionalities in the biochemical domain, Bio-NanoThings promise to enable applications such as intra-body sensing and actuation networks, and environmental control of toxic agents and pollution. The IoBNT stands as a paradigm-shifting concept for communication and network engineering, where novel challenges are faced to develop efficient and safe techniques for the exchange of information, interaction, and networking within the biochemical domain, while enabling an interface to the electrical domain of the Internet.
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... In biomedical applications, the IoBNTs [6], [29] and bodycentric communication [30]- [32] leverage THz nanocommunication for non-invasive, real-time monitoring and targeted therapeutic interventions [5]. For example, in [6], authors demonstrated that an organ monitoring sensor could transmit internal body signals through the IoBNT to health-monitoring applications. ...
... This study also introduced a nanosystem capable of molecular communication, using indium gallium zinc oxide (IGZO) enzymes to detect and report variations in glucose concentrations. However, several challenges remain in practically implementing these bio-nanonetworks [29]. Another emerging area is body-centric THz communication, which includes both on-and in-body networks [30]. ...
The advent of groundbreaking nanomaterials like graphene, renowned for their exceptional electrical properties, has ignited significant interest in nanocommunication. The potential to develop graphene-based plasmonic nanoantenna arrays and transceivers, combined with the capability of transmitting nanocommunication pulses at terahertz (THz) frequencies—bridging the THz gap in the electromagnetic spectrum—has been particularly compelling. Over the past decade, research in nanocommunication has led to remarkable advancements, particularly in the physical and link layers. These developments have paved the way for integrating fully operational nanonetworks into beyond 6G (B6G) wireless systems. Given the anticipated data rates in the terabits per second range for nanonetwork applications, continuous efforts are being made to develop new modulation and multiple access (MA) schemes. This survey paper explores the most advanced modulation and MA strategies tailored for B6G nanosystems operating in the THz band. Unlike previous surveys, our focus is on the physical layer, emphasizing rate-division and time-hopping strategies, including pulse position and pulse amplitude modulation techniques. We begin with an introduction to the foundational aspects of nanocommunication as an integral part of B6G nanosystems, followed by a detailed examination of various modulation schemes and their applicability to MA in nanonetworks. The paper concludes with a comparative analysis of these approaches regarding link capacity and a discussion of key open issues and future research directions for the design of electromagnetic nanocommunication systems.
... Details of how the data-based receive filter g D C (t n ), referred to as smoothed correlation filter (SCF), and the blind receive filter g B C (t n ), referred to as blind correlation filter (BCF), are obtained, respectively, are provided in Section IV-C. 4 Note that detecting the end of transmission is not needed, as we assume fixed-length messages. 5 In particular, we user (t n ) ∈ {1 − r (t n ), r (t n +1 ) − r (t n )}, as explained in detail in the next paragraph. ...
We present a fluid-based experimental molecular communication (MC) testbed which uses media modulation. Motivated by the natural human cardiovascular system, the testbed operates in a closed-loop tube system. The proposed system is designed to be biocompatible, resource-efficient, and controllable from outside the tube. As signaling molecule, the testbed employs the green fluorescent protein variant "Dreiklang" (GFPD). GFPDs can be reversibly switched via light of different wavelengths between a bright fluorescent state and a less fluorescent state. GFPDs in solution are filled into the testbed prior to the start of information transmission and remain there for an entire experiment. For information transmission, an optical transmitter (TX) and an optical eraser (EX), which are located outside the tube, are used to write and erase the information encoded in the state of the GFPDs, respectively. At the receiver (RX), the state of the GFPDs is read out by fluorescence detection. In our testbed, due to the closed-loop setup, we observe new forms of inter-symbol interferences (ISI), which do not occur in short experiments and open-loop systems. For the testbed, we developed a communication scheme, which includes blind transmission start detection, symbol-by-symbol synchronization, and adaptive threshold detection. We comprehensively analyze our MC experiments using different performance metrics. Moreover, we experimentally demonstrate the error-free transmission of 5370 bit at a data rate of 36 using 8-ary modulation and the error-free binary transmission of around 90000 bit at a data rate of 12 . For the latter experiment, data was transmitted for a period of 125 hours. All signals recorded and parts of the evaluation code are publicly available on Zenodo and Github, respectively.
... Compared to other communication methods, MC exhibits better biocompatibility, higher energy efficiency, and greater robustness within physiological conditions. Therefore, it has become one of the most promising methods for enabling nanonetworks and the Internet of Bio-Nano Things (IoBNT) [1]. Novel applications can be realized through MC, which has the potential to revolutionize our understanding of disease mechanisms by actively linking information and communication technology (ICT) with other biotechnologies, such as smart drug delivery, artificial organs, and lab-on-a-chip systems [2]. ...
Molecular communication (MC) is an emerging paradigm that takes inspiration from biological processes, enabling communication at the nanoscale and facilitating the development of the Internet of Bio-Nano Things (IoBNT). Traditional models of MC often rely on idealized assumptions that overlook practical challenges related to noise and signal behavior. This paper proposes and evaluates the first physical MC ion transmitter (ITX) using an ion exchange membrane. The circuit network model is used to simulate ion transport and analyze both transient and steady-state behavior. This analysis includes the effects of noise sources such as thermal and shot noise on signal integrity and SNR. The main contributions of this paper are to demonstrate how a practical MC ITX can produce a realistic waveform and to highlight future research challenges associated with a physical membrane-based ITX.
... The artificiality of nanoelectronics may have unfavorable health consequences. To overcome this issue, the notion of an internet of bio-nano things (IoBNT) has been proposed [25]. IoBNT was developed by fusing nanotechnology, IoNT, and synthetic biology to control, change, reengineer, and reuse biological cells in IoT-enabled computing devices [26]. ...
The Internet of Nano Things (IoNT) is a relatively new addition to the Internet of Things (IoT). The IoNT refers to the connectivity of nanodevices and nanosensors, and next-generation standards based on the IoT have been established to connect many nanomachines with current communications systems via the Internet. In communication networks, nanoscale applications provide a new edge. Because of the novel features resulting from nanotechnology's benefits, IoNT opened the door to a slew of new applications in a range of fields. This study provides an overview of the IoNT technique, including its implementation, objectives, general implications, and most significant problems, as well as the differences between IoT and IoNT. The architecture of the IoNT in smart health care, as well as the most essential technologies used in nano communication networks, have been recognized, along with an assessment of each technology's merits.
Molecular Communications (MC), transferring information via chemical signals, holds promise for transformative healthcare applications within the Internet of Bio-Nano Things (IoBNT) framework. Despite promising advances toward practical MC systems, progress has been constrained by experimental testbeds that are costly, difficult to customize, and require labor-intensive fabrication. Here, we address these challenges by introducing a low-cost (\<$1 hour), and highly customizable microfluidic testbed that integrates hydrodynamic gating and screen-printed potentiometric sensors. This platform enables precise spatiotemporal control over chemical signals and supports reconfigurable channel architectures along with on-demand sensor functionalization. As a proof of concept, we demonstrate a pH-based MC system combining a polyaniline (PANI)-functionalized sensor for real-time signal detection with a programmable hydrodynamic gating architecture, patterned in a double-sided adhesive tape, as the transmitter. By dynamically mixing phosphate-buffered saline (PBS) with an acidic solution (pH 3), the testbed reliably generates pH-encoded pulses. Experimental results confirm robust control over pulse amplitude and pulse width, enabling the simulation of end-to-end MC scenarios with 4-ary concentration shift keying (CSK) modulation. By combining affordability and rapid prototyping without compromising customizability, this platform is poised to accelerate the translation of MC concepts into practical IoBNT applications.
The Internet of bio-nano things (IoBNT), envisioned as a revolutionary healthcare paradigm, shows promise for epidemic control. This article explores the potential for using molecular communication (MC) to address the challenges in constructing the IoBNT for epidemic prevention, specifically focusing on modeling viral transmission, detecting the virus/infected individuals, and identifying virus mutations. First, the MC channels in macroscale and microscale scenarios are discussed to match viral transmission in both scales separately. In addition, the detection methods for these two scales are studied, along with the localization mechanism designed for the virus/infected individuals. Moreover, an identification strategy is proposed to determine potential virus mutations, which is validated through simulation using the ORF3a protein as a benchmark. Finally, open research issues are discussed. In summary, this article aims to analyze viral transmission through MC, and combat viral spread using signal processing techniques within MC.
Particulate Drug Delivery Systems (PDDS) are therapeutic methods that use nanoparticles to achieve their healing effects at the exact time, concentration level of drug nanoparticles, and location in the body, while minimizing the effects on other healthy locations. The Molecular Communication (MC) paradigm, where the transmitted message is the drug injection process, the channel is the cardiovascular system, and the received message is the drug reception process, has been investigated as a tool to study nanoscale biological and medical systems in recent years. In this paper, the various noise effects that cause uncertainty in the cardiovascular system are analyzed, modeled, and evaluated from the information theory perspective. Analytical MC noises are presented to include all end-to-end noise effects, from the drug injection, to the absorption of drug nanoparticles by the diseased cells, in the presence of a time-varying and turbulent blood flow. The PDDS capacity is derived analytically including all these noise effects and the constraints on the drug injection. The proposed MC noise is validated by using the kinetic Monte-Carlo simulation technique. Analytical expressions of the noise and the capacity are derived, and MC is presented as a framework for the optimization of particulate drug delivery systems (PDDS).
Molecular communications is a new paradigm that enables nanomachines to communicate within a biological environment. One form of molecular communications is calcium (Ca) signaling, which occurs naturally in living biological cells. Ca signaling enables cells in a tightly packed tissue structure to communicate at short ranges with neighboring cells. The achievable mutual information of Ca signaling between tissue embedded nanomachines is investigated in this paper, focusing in particular on the impact that the deformation of the tissue structure has on the communication channel. Based on this analysis, a number of transmission protocols are proposed; nanomachines can utilize these to communicate using Ca signaling. These protocols are static time-slot configuration, dynamic time-slot configuration, dynamic time-slot configuration with silent communication, and improved dynamic time-slot configuration with silent communication (IDTC-SC). The results of a simulation study show that IDTC-SC provides the maximum data rate when tissues experience frequent deformation.
The goal of a Drug Delivery System (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions.Molecular Communication (MC) is used as an abstraction of the propagation of drug particles in the body. MC is a new paradigm in communication research where the exchange of information is achieved through the propagation of molecules. Here, the transmitter is the drug injection, the receiver is the drug delivery and the channel is realized by the transport of drug particles, thus enabling the analysis and design of a particulate DDS using communication tools. This is achieved by modeling the MC channel as two separate contributions, namely, the cardiovascular network model and the drug propagation network. The cardiovascular network model allows to analytically compute the blood velocity profile in every location of the cardiovascular system given the flow input by the heart. The drug propagation network model allows the analytical expression of the drug delivery rate at the targeted site given the drug injection rate. Numerical results are also presented to assess the flexibility and accuracy of the developed model. The study of novel optimization techniques for a more effective and less invasive drug delivery will be aided by this model, while paving the way for novel communication techniques for Intra-Body communication Networks (IBN).
Background
Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies.
Results
We conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants.
Conclusions
The set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential.
Molecular communication (MC) is a promising bio-inspired paradigm for the interconnection of autonomous nanotechnology-enabled devices, or nanomachines, into nanonetworks. MC realizes the exchange of information through the transmission, propagation, and reception of molecules, and it is proposed as a feasible solution for nanonetworks. This idea is motivated by the observation of nature, where MC is successfully adopted by cells for intracellular and intercellular communication. MC-based nanonetworks have the potential to be the enabling technology for a wide range of applications, mostly in the biomedical, but also in the industrial and surveillance fields. The focus of this article is on the most fundamental type of MC, i.e., diffusion-based MC, where the propagation of information-bearing molecules between a transmitter and a receiver is realized through free diffusion in a fluid. The objectives of the research presented in this article are to analyze an MC link from the point of view of communication engineering and information theory, and to provide solutions to the modeling and design of MC-based nanonetworks. First, a deterministic model is realized to study each component, as well as the overall diffusion-based- MC link, in terms of gain and delay. Second, the noise sources affecting a diffusion-based-MC link are identified and statistically modeled. Third, upper/lower bounds to the capacity are derived to evaluate the information-theoretic performance of diffusion-based MC. Fourth, an analysis of the interference produced by multiple diffusion-based MC links in a nanonetwork is provided. This research provides fundamental results that establish a basis for the modeling, design, and realization of future MC-based nanonetworks, as novel technologies and tools are being developed.
Recent advances in synthetic biology, in particular towards the engineering of DNA-based circuits, are providing tools to program man-designed functions within biological cells, thus paving the way for the realization of biological nanoscale devices, known as nanomachines. By stemming from the way biological cells communicate in the nature, Molecular Communication (MC), i.e., the exchange of information through the emission, propagation, and reception of molecules, has been identified as the key paradigm to interconnect these biological nanomachines into nanoscale networks, or nanonetwork. The design of MC nanonetworks built upon biological circuits is particularly interesting since cells possess many of the elements required to realize this type of communication, thus enabling the design of cooperative functions in the biological environment. In this paper, a systems-theoretic modeling is realized by analyzing a minimal subset of biological circuit elements necessary to be included in an MC nanonetwork design where the message-bearing molecules are propagated via free diffusion between two cells. The obtained system-theoretic models stem from the biochemical processes underlying cell-to-cell MC, and are analytically characterized by their transfer functions, attenuation and delay experienced by an information signal exchanged by the communicating cells. Numerical results are presented to evaluate the obtained analytical expressions as functions of realistic biological parameters.
Artificial cellular systems are minimal systems that mimic certain properties of natural cells, including signaling pathways, membranes, and metabolic pathways. These artificial cells (or protocells) can be constructed following a synthetic biology approach by assembling biomembranes, synthetic gene circuits, and cell‐free expression systems. As artificial cells are built from bottom‐up using minimal and a defined number of components, they are more amenable to predictive mathematical modeling and engineered controls when compared with natural cells. Indeed, artificial cells have been implemented as drug delivery machineries and in situ protein expression systems. Furthermore, artificial cells have been used as biomimetic systems to unveil new insights into functions of natural cells, which are otherwise difficult to investigate owing to their inherent complexity. It is our vision that the development of artificial cells would bring forth parallel advancements in synthetic biology, cell‐free systems, and in vitro systems biology.
This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
This article presents a branch of research where the use of molecules to encode and transmit information among nanoscale devices (nanomachines) is investigated as a bio-inspired viable solution to realize nano-communication networks. Unlike traditional technologies, molecular communication is a radically new paradigm, which demands novel solutions, including the identification of naturally existing molecular communication mechanisms, the establishment of the foundations of a molecular information theory, or the development of architectures and networking protocols for nanomachines. The tight connection of this cutting edge engineering research field with biology will ultimately enable both the bio-inspired study of molecular nanonetwork architectures and their realization with tools already available in nature. The testbed described in this article, which is based on a microfluidic device hosting intercommunicating populations of genetically engineered bacteria, is a clear example of this research direction.
This paper reviews recent developments in the design and application of two types of optical nanosensor, those based on: (1) localized surface plasmon resonance (LSPR) spectroscopy and (2) surface-enhanced Raman scattering (SERS). The performance of these sensors is discussed in the context of biological and chemical sensing. The first section addresses the LSPR sensors. Arrays of nanotriangles were evaluated and characterized using realistic protein/ligand interactions. Isolated, single nanoparticles were used for chemosensing and performed comparably to the nanoparticle array sensors. In particular, we highlight the effect of nanoparticle morphology on sensing response. The second section details the use of SERS sensors using metal film over nanosphere (MFON) surfaces. The high SERS enhancements and long-term stability of MFONs were exploited in order to develop SERS-based sensors for two important target molecules: a Bacillus anthracis biomarker and glucose in a serum protein mixture.