A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Multicellular organisms create complex patterned structures from identical, unreliable components. Learning how to engineer such robust behavior is important to both an improved understanding of computer science and to a better understanding of the natural developmental process. Earlier work by our colleagues and ourselves on amorphous computing demonstrates in simulation how one might build complex patterned behavior in this way. This work reports on our first efforts to engineer microbial cells to exhibit this kind of multicellular pattern directed behavior. We describe a specific natural system, the Lux operon of Vibrio fischeri, which exhibits density dependent behavior using a well characterized set of genetic components. We have isolated, sequenced, and used these components to engineer intercellular communication mechanisms between living bacterial cells. In combination with digitally controlled intracellular genetic circuits, we believe this work allows us to begin the more difficult process of using these communication mechanisms to perform directed engineering of multicellular structures, using techniques such as chemical diffusion dependent behavior. These same techniques form an essential part of our toolkit for engineering with life, and are widely applicable in the field of microbial robotics, with potential applications in medicine, environmental monitoring and control, engineered crop cultivation, and molecular scale fabrication. <s> BIB001 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> To understand complex biological systems requires the integration of experimental and computational research — in other words a systems biology approach. Computational biology, through pragmatic modelling and theoretical exploration, provides a powerful foundation from which to address critical scientific questions head-on. The reviews in this Insight cover many different aspects of this energetic field, although all, in one way or another, illuminate the functioning of modular circuits, including their robustness, design and manipulation. Computational systems biology addresses questions fundamental to our understanding of life, yet progress here will lead to practical innovations in medicine, drug discovery and engineering. <s> BIB002 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Author(s): Requicha, Ari | Abstract: Nanorobotics encompasses the design, fabrication, and programming of robots with overall dimensions below a few micrometers, and the programmable assembly of nanoscale objects. Nanorobots are quintessential nanoelectromechanical systems (NEMS) and raise all the important issues that must be addressed in NEMS design: sensing, actuation, control, communications, power, and interfacing across spatial scales and between the organic/inorganic and biotic/abiotic realms. Nanorobots are expected to have revolutionary applications in such areas as environmental monitoring and health care.This paper begins by discussing nanorobot construction, which is still at an embryonic stage. The emphasis is on nanomachines, an area which has seen a spate of rapid progress over the last few years. Nanoactuators will be essential components of future NEMS.The paper's focus then changes to nanoassembly by manipulation with scanning probe microscopes (SPMs), which is a relatively well established process for prototyping nanosystems. Prototyping of nanodevices and systems is important for design validation, parameter optimization and sensitivity studies. Nanomanipulation also has applications in repair and modification of nanostructures built by other means. High-throughput SPM manipulation may be achieved by using multitip arrays.Experimental results are presented which show that interactive SPM manipulation can be used to accurately and reliably position molecular-sized components. These can then be linked by chemical or physical means to form subassemblies, which in turn can be further manipulated. Applications in building wires, single-electron transistors, and nanowaveguides are presented. <s> BIB003 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> The authors present a new approach using genetic algorithms, neural networks, and nanorobotics concepts applied to the problem of control design for nanoassembly automation and its application in medicine. As a practical approach to validate the proposed design, we have elaborated and simulated a virtual environment focused on control automation for nanorobotics teams that exhibit collective behavior. This collective behavior is a suitable way to perform a large range of tasks and positional assembly manipulation in a complex three-dimensional workspace. We emphasize the application of such techniques as a feasible approach for the investigation of nanorobotics system design in nanomedicine. Theoretical and practical analyses of control modeling is one important aspect that will enable rapid development in the emerging field of nanotechnology. <s> BIB004 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Molecular communication is a new communication paradigm using molecules as a communication carrier. In molecular communication, information is encoded onto molecules at senders and the molecules propagate to receivers in a controlled manner. The receivers, upon receiving the molecules, decode the encoded information and react biochemically. Molecular communication provides means to deliver molecules to destinations and allows biological and artificially-created components to communicate with each other. This paper describes a design of a molecular communication system that has potentialities to enable future health care applications. <s> BIB005 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Recent years have seen considerable progress in the development of microfabricated systems for use in the chemical and biological sciences. Much development has been driven by a need to perform rapid measurements on small sample volumes. However, at a more primary level, interest in miniaturized analytical systems has been stimulated by the fact that physical processes can be more easily controlled and harnessed when instrumental dimensions are reduced to the micrometre scale. Such systems define new operational paradigms and provide predictions about how molecular synthesis might be revolutionized in the fields of high-throughput synthesis and chemical production. <s> BIB006 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Advances in technology have allowed chemical sampling with high spatial resolution and the manipulation and measurement of individual molecules. Adaptation of these approaches to lab-on-a-chip formats is providing a new class of research tools for the investigation of biochemistry and life processes. <s> BIB007 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world. <s> BIB008 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> The developing world does not have access to many of the best medical diagnostic technologies; they were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive, but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world. <s> BIB009 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Miniaturizing in chip technology, optics, micro mechanics, medicine, gene and biotechnology requires highly precise positioning techniques. The motivation for the new manipulation technology is the desire to enter the micro- and nanoworld not only by viewing but also acting, altering micro- and nanosized objects. A new era on medicine are expected to happen in the coming years. Due to the advances in the field of nanotechnology, nanodevice manufacturing has been growing gradually. From such achievements in nanotechnology and recent results in biotechnology and genetics, the first operating biological nanorobots are expected to appear in the coming 5 years and more complex diamondoid based nanorobots will become available in about 10 years. In terms of time, it means a very near better future with significant improvements in medicine. <s> BIB010 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development. <s> BIB011 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> This work presents chemical communication techniques for nanorobots foraging in fluid environments relevant for medical applications. Unlike larger robots, viscous forces and rapid diffusion dominate their behaviors. Examples range from modified microorganisms to nanorobots using ongoing developments in molecular computation, sensors and motors. The nanorobots use an innovative methodology to achieve decentralized control for a distributed collective action in the combat of cancer. A communication approach is described in the context of recognize a single tumor cell in a small venule as a target for medical treatment. Thus, a higher gradient of signal intensity of E-cadherin is used as chemical parameter identification in guiding nanorobots to identify malignant tissues. A nanorobot can effectively use chemical communication to improve intervention time to identify tumor cells. <s> BIB012 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> In this paper we present how nanoelectronics should advance medicine, providing details on the teleoperated techniques and equipment design methodology necessary for the effective development of nanorobots. The platform architecture describes how to use a nanorobot for intracranial prognosis, and shows how it should be integrated for medical instrumentation. Furthermore, the current study establishes proteomics, nanobioelectronics, and electromagnetics as the basis to advance medical nanorobotics. To illustrate the proposed approach, the nanorobots must search for protein overexpression signals in order to recognize initial stages of aneurysm. An advanced nanomechatromics simulator, using a three-dimensional task-based environment, is implemented to provide an effective tool for device prototyping and medical instrumentation analysis. Thus, based on clinical data and nanobioelectronics, the proposed model offers details about how a nanorobot should help with the early detection of cerebral aneurysm. <s> BIB013 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Although nanorobots may play critical roles for many applications in the human body such as targeting tumoral lesions for therapeutic purposes, miniaturization of the power source with an effective onboard controllable propulsion and steering system have prevented the implementation of such mobile robots. Here, we show that the flagellated nanomotors combined with the nanometer-sized magnetosomes of a single Magnetotactic Bacterium (MTB) can be used as an effective integrated propulsion and steering system for devices such as nanorobots designed for targeting locations only accessible through the smallest capillaries in humans while being visible for tracking and monitoring purposes using modern medical imaging modalities such as Magnetic Resonance Imaging (MRI). Through directional and magnetic field intensities, the displacement speeds, directions, and behaviors of swarms of these bacterial actuators can be controlled from an external computer. <s> BIB014 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties. <s> BIB015 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Since the pioneering vision of Feynman in his now famous lecture ‘There’s Plenty of Room at the Bottom’ first delivered at an American Physical Society meeting at Caltech in December 1959 [1], film and scientific exploration at the nanoscale have been lending each other imagery and targets to achieve. It took only 5 years from Feynman’s lecture for a fellow resident of Los Angeles, Harry Kleiner, to complete the script for the film ‘The Fantastic Voyage’ that was released in 1965 to popularize ‘miniaturization for medicine’ like no scientist could ever do. The inspirational power of miniaturizing matter to navigate throughout the human body and reach the brain to remove aneurysm-causing blood clots depicted in the film, even transcended into the art world thanks to Salvador Dali and his painting ‘Le Voyage Fantastique’ portraying the voyage in to the human subconscious, a result of the painter’s direct involvement in the production of the film (Figure 1). Today, 45 years after this first cinematography-originated use of nanotechnology for medicine, numerous scientists, thinkers, film makers and authors have been describing how this powerful technology can assist us to explore the nanoscale of the human body. However, one question still persists. Where do fantasy, imagination and science fiction stop and where does ‘real’ science and medicine start? The answer is that even though dramatic developments in technology and engineering at the nanoscale have occurred in the last decade, we are still at a state of infancy regarding the capability to design, manufacture, control and navigate nanorobots (nanomachines, nanobots, nanoids, nanites and nanonites or however else described) and purposefully use them for diagnosis or therapy. Some of the most critical challenges are discussed below. <s> BIB016 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Toward the intelligent control of internal and external environments, we present an idea of the sequence design for the network formation of DNA-based nanorobots. We already developed a DNA nanomachine that has the potential ability of producing a functional molecule called “aptamer” when bacterial two-component signal transduction systems are detected. Here we have succeeded in demonstrating the network formation based on the sticky-end programming of DNA modules. By combining the aptamer transcription function with the network formation ability, we can implement various missions in DNA nanomacines. The network design is essential to keep the appropriate density, configurations and functions to carry out target missions. We expect that the network of DNA nanorobots make a contribution to realize the effective regulation of microorganisms to promote environmental preservation and health maintenance. <s> BIB017 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> a b s t r a c t To realize molecular nanonetworks, the foundations of molecular information theory should be established through identification of the existing molecular communication mechanisms, and architectures and networking techniques for nanomachines should be developed, which demand novel engineering efforts. Luckily, these engineering skills and technology have been prepared for us by the natural evolution in the last several billions of years. Indeed, the human body is a massive nanoscale molecular communications network as it is composed of billions of interacting nanomachines, i.e., cells. Intra-body biological systems are closely linked to each other and communicate primarily through molecular transactions. Thus, vital activities inside the human body are regulated by everlasting communication performance and operations of intra-body molecular nanonetworks. However, natural intra-body molecular nanonetworks are yet to be explored with the elegant tools of information and communication theories. In this paper, first, the elementary models for significant intra-body molecular communication channels, i.e., nanoscale neuro-spike communication channel, action potential-based cardiomyocyte molecular communication channel, and hormonal molecular communication channel, are introduced. Next, molecular nanonetworks belonging to multi-terminal extensions of channel models, i.e., nervous, cardiovascular molecular, and endocrine nanonetworks are discussed. Furthermore, heterogeneous communication network of intra-body molecular nanonetworks together with five senses, i.e., nanosensory networks, is explored from the perspectives of communication and network theories. Moreover, open research challenges, such as extension of molecular channel models to multi-terminal cases, and developing a communication theory perspective to understand the physiology and to capture potential communication failures of intra-body biological systems, are provided. Our objectives are to learn from the elegant molecular communication mechanisms inside us for engineering practical communication techniques for emerging nanonetworks, as well as to pave the way for the advancement of revolutionary diagnosis and treatment techniques inspired from information and communication technologies, which is promising for future nanomedicine and bio-inspired molecular communication applications. <s> BIB018 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Potential Applications <s> Self-assembled barrel-like DNA nanostructures carrying active payloads and pre-programmed with logic operations to reconfigure in response to cell-surface cues can trigger a variety of intracellular functions. <s> BIB019
There are many potential applications for molecular communication at microscales, such as medical application  , BIB005 , control and detection of chemical reactions BIB006 , computational biology BIB002 ,  , better understanding of biology BIB018 , environmental control and preservation BIB017 , and communication among nanorobots BIB003 . Among all these applications, the main driving force for engineering molecular communication is the medical field  . In application such as lab-on-a-chip devices BIB007 , cell on chips devices BIB008 , point-of-care diagnostic chips BIB009 , and targeted drug delivery BIB015 , communication among different components of the systems is at the focus. Another driving force behind molecular communication is recent advancements in the field of nanotechnology, which is making nanoscale devices such as nanorobots [100] a reality. Limited by their size, nanorobots can perform only simple tasks. To accomplish complex goals nanorobots must be able to communicate BIB016 . Communicating nanorobots can be used for biomedical engineering applications, where nanorobots inside the body provide significant improvements in diagnosis and treatment of disease BIB010 ,  , BIB011 . In BIB012 ,  it is shown that communicating nanorobots can be much more effective at targeted drug delivery than uncommunicative nanorobots. In BIB013 nanorobots are proposed for detection of brain aneurysm. Nanorobots can also be used for transporting molecular payloads to cells  , and altering the cell's behavior BIB019 . Ongoing development of nanoscale electronics, sensors and motors has further advanced the field of nanorobots BIB004 . For example, programmable bacteria BIB001 can create computation capability for nanodevices. Moreover, different techniques can be employed to power nanorobots  . For example, flagellated magnetotactic bacteria along with magnetic resonance imaging (MRI) can be used as medical nanorobots. Tracking and controlling of swarms of these bacterias are demonstrated in BIB014 .