COMMUNICATIONS SS TANDARD · otechnology. Second, the application of commu-nication engineering to design Bio-NanoThings telecommuni- cations is detailed, while the chal-lenges to

32

INTRODUCTIONThe Internet of Things (IoT) defines a cyberphysical paradigm, where all types of real-worldphysical elements (sensors, actuators, personalelectronic devices, or home appliances, amongothers) are connected, and are able toautonomously interact with each other. This newform of seamless connectivity is the enabler formany applications such as machine to machinecommunication, real time monitoring of industri-al processes, smart cities, smart grids for energymanagement, intelligent transportation, environ-mental monitoring, infrastructure management,medical and healthcare systems, building andhome automation, and large scale deployments.The Internet of Things became a focus for

ABSTRACTThe Internet of Things (IoT) has become an

important research topic in the last decade,where things refer to interconnected machinesand objects with embedded computing capabili-ties employed to extend the Internet to manyapplication domains. While research and devel-opment continue for general IoT devices, thereare many application domains where very tiny,concealable, and non-intrusive Things are need-ed. The properties of recentlystudied nanomaterials, such asgraphene, have inspired the con-cept of Internet of NanoThings(IoNT), based on the intercon-nection of nanoscale devices. Despite being anenabler for many applications, the artificialnature of IoNT devices can be detrimental wherethe deployment of NanoThings could result inunwanted effects on health or pollution. Thenovel paradigm of the Internet of Bio-NanoThings (IoBNT) is introduced in this paper bystemming from synthetic biology and nanotech-nology tools that allow the engineering of bio-logical embedded computing devices. Based onbiological cells, and their functionalities in thebiochemical domain, Bio-NanoThings promiseto enable applications such as intra-body sensingand actuation networks, and environmental con-trol of toxic agents and pollution. The IoBNTstands as a paradigm-shifting concept for com-munication and network engineering, wherenovel challenges are faced to develop efficientand safe techniques for the exchange of informa-tion, interaction, and networking within the bio-chemical domain, while enabling an interface tothe electrical domain of the Internet.

research and development in the last 15 years. Alarge amount of investments for Internet ofThings was and is still being made by govern-ment agencies and industry worldwide.

Recently, the concept of IoT has been revisedin light of novel research advances made in thefield of nanotechnology and communicationengineering, which enable the development ofnetworks of embedded computing devices, basedon nanomaterials such as graphene or metama-terials, having scales ranging from one to a fewhundred nanometers, called nanothings. TheInternet of NanoThings (IoNT), introduced forthe first time in [1], is proposed as the basis ofnumerous future applications, such as in the mil-itary, healthcare, and security fields, where thenanothings, thanks to their limited size, can beeasily concealed, implanted, and scattered in theenvironment, where they can cooperatively performsensing, actuation, processing, and networking.

While nanothings can push the engineering ofdevices and systems to unprecedented environ-ments and scales, similarly to other devices, theyhave an artificial nature, since they are based onsynthesized materials, electronic circuits, and

interact through electromagnetic(EM) communications [1].These characteristics can bedetrimental for some applicationenvironments, such as inside the

body or in natural ecosystems, where the deploy-ment of nanothings and their EM radiationcould result in unwanted effects on health orpollution.

A novel research direction in the engineeringof nanoscale devices and systems is being pur-sued in the field of biology, by combining nan-otechnology with tools from synthetic biology tocontrol, reuse, modify, and reengineer biologicalcells [2]. By stemming from an analogy betweena biological cell and a typical IoT embeddedcomputing device, a cell can be effectively uti-lized as a substrate to realize a so-called Bio-NanoThing, through the control, reuse, andreengineering of biological cells’ functionalities,such as sensing, actuation, processing, and com-munication. Since cells are based on biologicalmolecules and biochemical reactions, rather thanelectronics, the concept of Internet of Bio-Nan-oThing (IoBNT), introduced in this article, isexpected to be paradigm shifting for many relat-ed disciplines, such as communication and net-work engineering, which is the focus of thisarticle. The execution of DNA-based instruc-tions, the biochemical processing of data, thetransformation of chemical energy, and theexchange of information through the transmis-sion and reception of molecules, termed molecu-lar communication (MC) [3], are at the basis ofa plethora of applications that will be enabled bythe IoBNT, such as:• Intra-body sensing and actuation, where

Bio-NanoThings inside the human bodywould collaboratively collect health-relatedinformation, transmit it to an externalhealthcare provider through the Internet,and execute commands from the same pro-vider such as synthesis and release of drugs.

• Intra-body connectivity control, where Bio-NanoThings would repair or prevent fail-

THE INTERNET OF BIO-NANOTHINGSThe 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 ofinformation, interaction, and networking within the biochemical domain, while enabling an

interface to the electrical domain of the Internet.

I. F. Akyildiz, M. Pierobon, S. Balasubramaniam, and Y. Koucheryavy

Hormones

Bacteriacommun

olecularotors

Calciumsignali

COMMUNICATIONSTANDA RDS S

I. F. Akyildiz is with theGeorgia Institute of Tech-nology and Tampere Uni-versity of Technology.

S. Balasubramaniam andY. Koucheryavy are withTampere University ofTechnology.

M. Pierobon is with theUniversity of Nebraska.

IEEE Communications Magazine — Communications Standards Supplement • March 20150163-6804/15/$25.00 © 2015 IEEE

BALASUBRAMANIAM_LAYOUT_Layout 3/4/15 11:46 AM Page 32

IEEE Communications Magazine — Communications Standards Supplement • March 2015 33

ures in the communications between ourinternal organs, such as those based on theendocrine and the nervous systems, whichare at the basis of many diseases.

• Environmental control and cleaning, whereBio-NanoThings deployed in the environ-ment, such as a natural ecosystem, wouldcheck for toxic and pollutant agents, andcollaboratively transform these agentsthrough bioremediation, e.g. bacteriaemployed to clean oil spills.This article is organized as follows. First, Bio-

Nano-Things are defined in light of the toolsavailable today from synthetic biology and nan-otechnology. Second, the application of commu-nication engineering to design Bio-NanoThingstelecommuni- cations is detailed, while the chal-lenges to engineer Bio-NanoThings networksand Internet connections are discussed. Third,we describe further research challenges for therealization of IoBNT. Finally, we conclude thearticle.

BIO-NANOTHINGSWithin the scope of the IoBNT, Bio-NanoThingsare defined as uniquely identifiable basic struc-tural and functional units that operate and inter-act within the biological environment. Stemmingfrom biological cells, and enabled by syntheticbiology and nanotechnology, Bio-NanoThingsare expected to perform tasks and functionalitiestypical of the embedded computing devices inthe IoT, such as sensing, processing, actuation,and interaction with each other.

BIOLOGICAL CELLS AS THE SUBSTRATES OF BIO-NANOTHINGSA biological cell is the basic unit of life, consist-ing of a membrane that encloses a mixture ofhighly specialized molecules, with defined chem-ical composition and function, which may also beorganized into functional structures [4]. A map-ping between the components of a typical IoTembedded computing device, and the elementsof a cell, becomes apparent if we compare elec-trons’ propagation in semiconductors to func-tionally similar, although much more complex,biochemical reactions. In this context, as illus-trated in Fig. 1, some examples are as follows.

The control unit, which contains the embeddedsoftware of the device, would correspond to thegenetic instructions densely packed into thecells’ DNA molecules, which encode proteinstructures, the cell’s “data units,” and regulatorysequences, similar to the software conditionalexpressions. The memory unit, which containsthe values of the embedded system data, wouldcorrespond to the chemical content of the cyto-plasm, i.e. the interior of the cell, comprised ofmolecules synthesized by the cell as a result ofDNA instructions, and other molecules or struc-tures, e.g. vesicles, exchanged with the externalenvironment. The processing unit, which exe-cutes the software instructions and managesmemory and peripherals, would correspond tothe molecular machinery that, from the DNAmolecules, through the so-called transcriptionand translation, generates protein moleculeswith instruction-dependent types and concentra-tions. The power unit, which supplies the energyto maintain the electrical currents in the embed-ded system’s circuits, would correspond to thereservoir in the cell of the Adenosine TriPhos-phate (ATP) molecule, which is synthesized bythe cell from energy supplied from the externalenvironment in various forms, and provides theenergy necessary for the cell’s biochemical reac-tions to take place. The transceivers, whichallow the embedded systems to exchange infor-mation, would correspond to the specific chainsof chemical reactions, i.e. signaling pathways,through which cells exchange information-bear-ing molecules. Sensing and actuation, whichallow embedded systems to acquire data andinteract with the environment, would correspondto the capability of a cell to chemically recognizeexternal molecules or physical stimuli, e.g. lightor mechanical stress, and to change the chemicalcharacteristics of the environment or mechani-cally interact through moving elements, such asflagella, pili, or cilia.

ENABLING TECHNOLOGIES AND CHALLENGESThe discipline of synthetic biology is providingtools to control, reuse, modify, and reengineerthe cells’ structure and function, and it is expect-ed to enable engineers to effectively use the bio-

Figure 1. Elements of a biological cell and components of a typical IoT device.

Control unit

ProcessorCytoplasm

Mitochondria

Gap junctionChemicalreceptors

Flagella/Pili/Cilia

Biologicalcell

Nucleus Ribosomes

IoTcomputing

device

Memory

Battery

Actuator

Sensors

Transceiver

Stemming from biolog-ical cells, and enabled

by synthetic biologyand nanotechnology,Bio-NanoThings areexpected to perform

tasks and functionali-ties typical of the

embedded computingdevices in the IoT, such as sensing,

processing, actuation,and interaction with

each other.


logical cells as programmable substrates to real-ize Bio-NanoThings as biological embeddedcomputing devices [2]. DNA sequencing andsynthesis technologies, enabling the reading andwriting of genetic code information in the DNAmolecules of biological cells, are giving engineersan increasingly open access to the set of struc-tural and functional instructions at the basis oflife. In particular, the engineering of syntheticbiological circuits [5] through genetic codemanipulation has enabled the programming ofspecifically designed functions to be executed bycells. A biological circuit is a set of genes thatencode proteins and regulatory sequences, whichlink together the protein synthesis by mecha-nisms of mutual activation and repression. Thefunctions today successfully developed via bio-logical circuits range from AND and OR logicgates, to various types of tunable oscillators, tog-gle switches, and counters. The development ofdatabases with characterized standard biologicalcircuit parts with known functions and behaviors,e.g. BioBricks, and tools to combine them intomore complex designs [6], are pushing syntheticbiology to a future development similar to thatexperienced by integrated electrical circuit designin electronics. As a consequence, engineers willbe soon able to gain full access to the functional-ities of the aforementioned cells’ elements, andreuse cells and their features, without requiringan in-depth knowledge of biotechnology.

One of the latest frontiers in synthetic biologyis the development of artificial cells, enabled,among others, by tools from nanotechnology.Artificial cells have minimal functionalities andstructural components compared to natural cells,and are assembled bottom-up by encapsulatingthe necessary elements into either biological orfully synthetic enclosing membranes [7]. Artifi-cial cells can therefore contain genetic informa-tion, the related molecular machineries for theirtranscription, translation, and replication, and allthe required specialized molecules and struc-tures. Artificial cells are expected to enable amore agile and controllable use of synthetic bio-logical circuits by removing all the additionalcomplexity of natural cells that are not necessaryto perform the designed functions. Although stillin its infancy, this technology has been success-fully applied, e.g. for drug delivery, gene thera-py, and artificial blood cell production, and it isexpected to deliver ideal substrates for syntheticbiology with a more predictable behavior.

Although very promising, the aforementionedtechnologies have to provide solutions to majorresearch challenges in biotechnology and engi-neering before being considered as reliable toolsfor the realization of Bio-NanoThings. Focusing onthe engineering design viewpoint, a major chal-lenge is to develop reliable mathematical andphysical models, and computer simulation envi-ronments, able to capture the peculiar character-istics of the biological processes underlyingengineered cells, such as intrinsic non-linearphenomena and processes with noisy outcomes.Moreover, engineered cells, similar to naturalcells, reproduce and mutate, i.e. tend to random-ly change parts of their genetic programs, andselectively evolve, i.e. tend to maintain the bestmutations for their survival while reproducing,

adding possible problems but also new degreesof freedom to the biological device designer.Another challenge that needs to be considered isrelated to bioethics and security, since auto-nomously evolving engineered organisms couldpose a threat to the natural ecosystems, andeven become new pathogens. The recent devel-opment of “kill” switches into biological circuits,able to stop cell reproduction or trigger celldestruction upon an external command, is onlypartially addressing these problems.

BIO-NANOTHINGS COMMUNICATIONSAt the basis of the IoBNT concept there is theneed for Bio-NanoThings to communicate witheach other, and interact on the basis of theexchanged information. Since Bio-NanoThingsstem from the engineering of biological cells, asdetailed above, the natural environment is themain inspiration for studying communicationtechniques for IoBNT.

MOLECULAR COMMUNICATION IN NATUREIn nature, the exchange of information betweencells is based on the synthesis, transformation,emission, propagation, and reception of moleculesthrough biochemical and physical processes. Thisinformation exchange, recently classified intelecommunications engineering as MC [1],enables cells’ interactions and coordination ofuni-cellular and multi-cellular organisms, popula-tions, and multi-species consortia, and partici-pates in most of the major cellular functionalitiessuch as cell growth and proliferation.

MC in cells is based on the aforementionedsignaling pathways, which are chains of chemicalreactions that process information signals modu-lated into chemical characteristics, such asmolecule concentration, type, and energy state,and propagate them from a source, or transmit-ter, to a destination or receiver [4]. Cell signal-ing pathways can be classified on the basis of thedistance between source and destination intointracrine (source and destination are within thesame cell), juxtracrine (source and destination arecells in contact with each other), paracrine (sourceand destination are in the vicinity of each other,but not in contact), or endocrine (source anddestination are distant from each other).

An example of intracrine communication isgiven by the intracellular transport of moleculesor molecule structures operated by cytoskeletalmolecular motors. Molecular motors are intra-cellular specialized proteins able to convert theaforementioned ATP molecules into mechanicalenergy. The cytoskeletal molecular motors areable to bind to a particular cargo, such as vesiclesenclosing sets of molecules, or whole cellorganelles, attach to the microfilament structuresthat compose the cell’s skeleton, and crawl alongthem transporting the cargo from the nucleus tothe membrane of the cell and vice versa.

The exchange of molecules, such as calciumions Ca2+, between two cells connected by com-municating junctions in their membrane, is anexample of juxtacrine communication. Severalexamples in nature, such as the signaling duringa cardiac contraction happening between muscu-lar cells, or myocytes, show how a small quantity

IEEE Communications Magazine — Communications Standards Supplement • March 201534

At the basis of theIoBNT concept there isthe need for Bio-Nan-oThings to communi-cate with each other,and interact on the

basis of the exchangedinformation. Since Bio-NanoThings stem fromthe engineering of bio-logical cells, the natu-ral environment is the

main inspiration forstudying communica-

tion techniques for IoBNT.



of molecules can flow by diffusion betweenneighboring cells, and be responsible for syn-chronizing coordinated actions.

Bacteria show several means of communica-tion in nature, such as the paracrine communi-cation underlying the emission of signalingmolecules called autoinducers by members of apopulation. In this process, called bacterial quo-rum sensing, the autoinducers diffuse within theintercellular space and, upon reception, allowthe bacteria to estimate the population density,and have a correlated response, such as the pro-duction of specific types of proteins. Bacteriacan also exchange specific DNA molecules, i.e.plasmids, via direct contact, through a processcalled conjugation, and carry the plasmids toother distant bacteria within the intercellularspace by swimming according to chemical trails,with a process called chemotaxis.

In multicellular organisms, an example ofendocrine communication is realized throughsignaling molecules called hormones that areemitted from cells composing glands, propagatethrough the circulatory system, and are receivedby the cells of distant organs, where they elicitspecific responses, such as increased cell growthand reproduction.

CHALLENGES IN ENGINEERINGMOLECULAR COMMUNICATION FOR IOBNT

Within the IoBNT, Bio-NanoThings are expectedto interact with each other by exchanging varioustypes of information, e.g. synchronization signals,values of sensed chemical/physical parameters,results of logical operations, and sets of instruc-tions and commands. The engineering of thecommunication techniques to support these inter-actions in the biological environment has to stemfrom solutions found in nature, such as thosedescribed above. One of the major challenges isto understand how these natural solutions can becontrolled, modified, or reengineered for thetransmission of information that can be differentfrom the natural. By stemming from the afore-mentioned tools that are being developed in syn-thetic biology and nanotechnology, engineershave recently started to analyze several differentpossibilities to realize MC systems, either bygenetically reprogramming cells’ behaviors withintheir natural communications [8], or by develop-ing totally new artificial communication systemsby assembling natural biological components [9].

Examples of MC systems that have been envi-sioned so far can be classified on the basis of thedistance range that they are expected to coverfrom transmission to reception. For example, thecontrol of juxtracrine communications throughthe genetic programming of biological cells canenable the engineering of networks where Bio-NanoThings are in contact with each other, e.g.when organized in a tissue or biofilm [10]. ThisMC technique, usually referred to the aforemen-tioned Ca2+ exchange, shown in Fig. 2a, coversdistances proportional to the thickness of cellmembranes, and it can be considered as veryshort range (tens to hundreds of nm) MC. Theaforementioned cytoskeletal molecular motorscan be considered for the realization of MC inthe short range (nm-mm) [11], as shown in Fig.

2b, to cover intracrine Bio-NanoThings commu-nications. Communication engineers have alsocombined models of the bacterial conjugationand chemotaxis processes described above totheoretically study a possible artificial MC sys-tem, which can be considered, according to theknown chemotaxis characteristics, as coveringthe medium range (mm-mm) [9]. In particular,the information is represented into DNAmolecules, i.e. plasmids, which are loaded at thetransmitter location into bacteria and extractedfrom the same bacteria at the receiver through aconjugation process. These bacteria are able toswim by chemotaxis toward the receiver, by fol-lowing the receiver’s release of specific molecules,i.e. chemoattractants, as shown in Fig. 2c. Anexample of long range (mm-m) MC system hasbeen envisioned by stemming from the hormonalcommunication within the human endocrine sys-tem [12], as shown in Fig. 2d.

From the telecommunications engineeringperspective, one of the main challenges stands inmapping MC into the classical elements of anengineered communication system, and in theuse of tools from systems and information theorywith the final goals of modeling and analyzingthe main telecommunication characteristics andperformance, such as range, delay (latency),capacity, throughput, and bit error rate [13]. Theknowledge of these characteristics will thenallow for the comparison and classification ofpossible different techniques to realize MC fordifferent IoBNT application scenarios, and theoptimization of their design and realization.

Examples of the aforementioned mapping areshown in Fig. 3, where the main processesinvolved in each MC system described above aredivided into communication elements as follows.Encoding and decoding are related to how theinformation to be transmitted is represented intoone or more molecule characteristics, such assets of particular molecule types and numbers(molecular motors and hormonal communica-tion), composition of biological macromolecules,such as DNA plasmids (bacteria conjugation-chemotaxis), or released molecule concentration(Ca2+ exchange). Transmission and receptioninvolve the chemical and physical processes toinitiate the propagation of molecules, e.g. theencapsulation into vesicles for molecular motortransportation, the release of molecules in afluid, such as the blood stream, or through ajunction between two adjacent cells, or therelease of bacteria upon the presence of chemoat-tractant molecules in the environment. Finally,the propagation is concerned with the mobiliza-tion of the information-bearing molecules fromthe location of the transmitter to the receiver,such as through molecular motor crawling alongmicrofilament structures, diffusion throughmembrane junctions, diffusion and advection inthe blood stream, and bacterial chemotaxistoward the chemoattractant source (receiver).

While a great amount of the literature withinthe MC field has been devoted to the modelingand analysis of the aforementioned systemsthrough simplifying assumptions, which increasethe mathematical tractability of the underlyingphysical and chemical phenomena, there is still along way to go for a communication engineer to

Within the IoBNT, Bio-NanoThings areexpected to interactwith each other byexchanging various

types of information,e.g., synchronization

signals, values ofsensed chemical/phys-

ical parameters,results of logical oper-ations, sets of instruc-tions and commands.


fully understand how to design realistic MC sys-tems for IoBNT communications. The mainchallenges are given by the conversion of thesesimplified models to more realistic scenarios.For example, the free diffusion models consid-ered so far in MC engineering for the propaga-tion and reaction of molecules in the intra-cellular environment, e.g. in Ca2+ communica-tion, have to be revised to include more realisticphenomena, such as the effect of high concen-trations of macromolecules, e.g. proteins, calledmacromolecular crowding. Another example isgiven by the endocrine propagation, so far con-sidered for a small subset of well-defined bloodvessels, where models should take into accountnot only the whole average physiology of thehuman cardiovascular system, but also that thespecific characteristics of each individual canresult in very different propagation dynamics.Also, the models of bacteria chemotaxis used sofar in MC engineering are only based on thebehavior and properties of single bacteria andin-vitro environments, where in fact more realis-tic environments, such as within the humanbody, and the fact that bacteria can replicate andproliferate dynamically and interact within multi-species consortia, should be taken into account.Other challenges for the development of reliableanalytical tools for MC engineering are given bythe non-linear nature of many biochemical phe-

nomena, and the presence of very different noisesources, such as genetic mutations, compared toclassical systems.

BIO-NANOTHING NETWORKS AND THE INTERNETWithin the IoBNT, Bio-NanoThings are expect-ed to not only communicate with each other, butalso interact into networks, which will ultimatelyinterface with the Internet. To this end, the defi-nition of network architectures and protocols ontop of the aforementioned MC systems is anessential step for IoBNT development. A furtherchallenge for the IoBNT is the interconnectionof heterogeneous networks, i.e. composed of dif-ferent types of Bio-NanoThings and based ondifferent MC systems. Finally, the realization ofinterfaces between the electrical domain of theInternet and the biochemical domain of theIoBNT networks will be the ultimate frontier tocreate a seamless interconnection betweentoday’s cyber-world and the biological environ-ment. In Fig. 4 we show a possible scenariowhere a complete IoBNT, composed of severalnetworks based on different MC systems, isdeployed inside the human body, and interfacesthrough a personal electrical device connected tothe Internet to deliver intra-body status parame-ters (and receive commands and instructions) to(from) a healthcare provider.


Figure 2. Examples of molecular communication,: a) Ca2+ communication; b) molecular motors; c) bacteria conjugation-chemotaxis;and d) hormonal communication.

Node

Molecularrail

Molecularmotor

nm - µm

(b)

(a)

(d)(c)

Chemotaxis

mm - m

HormonesTxTx

Conjugation Conjugation

Tx

Rx

Rx

RxGap junctions

Calcium

Tissue

Blood

nm - mm

10 - 100nm

~10um



CHALLENGES FOR REALIZING BIO-NANOTHING NETWORKS

While the engineering of computer networks is awell-established field, where several differentsolutions have been provided for many differenttechnologies and application scenarios, thedesign of networks within the biological environ-ment, and based on the MC paradigm as thephysical medium, poses new challenges to thenetworking community. For example, molecularinformation generally does not follow predictableand definite propagation directions, as otherwisedone by electromagnetic signals in classical com-munications [13]. The diffusion of molecules, thebacterial chemotaxis, and the filaments support-ing molecular motors, tend to cover random pat-terns between source and destination. This andother peculiarities, such as the non-linear natureof many biochemical phenomena, make it partic-ularly challenging to utilize classical techniquesfor regulating Bio-NanoThings access to sharedmedia, such as fluids, addressing Bio-NanoTh-ings, and designing information routing mecha-nisms, which are important basic aspects ofcomputer networks.

As done for the MC systems, one possiblesolution will be to model, analyze, and reuse themechanisms of interactions of multiple cells in

nature, such as in bacteria populations [14] andmultispecies consortia, or within the tissues ofmulti-cellular organisms, to relay the IoBNTinformation.

In this direction, a solution for the intercon-nection of heterogeneous Bio-NanoThing net-works, based on different MC systems, might aswell come from the natural way our body man-ages and fuses several types of information tomaintain a stable, healthy status, or homeostasis [4].These intra-body processes allow heterogeneouscommunications to occur at various scales, trans-lating from intracrine communications within acell, to juxtacrine communication within tissues,to endocrine communications between differentorgans. For example, the cells of the pituitarygland perform this type of translation by releas-ing hormones to body organs to control severalprocesses, such as growth, blood pressure, tem-perature, and sleeping patterns, as a result of thereception of other hormones from the cells ofthe adjacent hypothalamic tissue. Biological cir-cuits based on these processes could effectivelyprovide a set of genetic instructions that mimicthe classical gateways between different subnetson the Internet. Figure 5a illustrates a generalexample of an artificial cell that translates theinformation encoded into molecules emitted

Figure 3. Mapping of classical communication theory to bio-nanothings communication, including: a) veryshort range — Ca2+ signaling: a) short range — molecular motors; c) medium range — bacteriachemotaxis and conjugation; and d) long range — hormonal communication.

Encoding Transmission

Classical blocks of communication theory

Molecular communication blocks

Propagation Reception Decoding

ModulateCa2+

concentration

Emitmodulated Ca2+

concentration

Ca2+

propagatesvia molecule

diffusion

Absorb andsense

incoming Ca2+

molecules

Interpretreceived

information

Very short range - Ca2+ communication

Insertinformationmolecules

into vesicles

Attach vesiclesto molecular

motors

Molecularmotors travel

alongmolecular

rails

Detachvesiclesfrom

molecularmotors

Extractinformationfrom vesiclesand interpret

Short range - molecular motors

Modulateproduction of

molecules

Release moleculesinto the

circulatorysystem

Moleculespropagateaccording

to the bloodflow

Senseincomingmolecules

withchemicalreceptors

Interpretreceived

information

Long range - hormonal communication

Encodeinformation

into DNAplasmids and

insert intobacteria

DNA plasmidsextracted from

the bacteriaand information

is interpreted

Bacteria swim following the receiver’srelease of chemoattractants

Medium range - bacterial chemotaxis and conjugation

Within the IoBNT, Bio-NanoThings are

expected to not onlycommunicate witheach other, but also

interact into networks,which will ultimately

interface with theInternet. To this end,the definition of net-work architectures

and protocols on top ofMC systems is anessential step for

IoBNT development.


from engineered bacteria into hormones thatcan be secreted into the circulatory system. Inthis design, receptors would intercept the incom-ing molecules that, through a cascade of chemi-cal reactions, would activate a biological circuit,which in turn would synthesize proteins able totrigger the necessary chemical reactions to pro-duce the hormones.

CHALLENGES FOR BIO-CYBER INTERFACESA bio-cyber interface is here defined as the setof processes necessary to translate informationfrom the biochemical domain of Bio-NanoThingnetworks to the Internet cyber-domain, which isbased on electrical circuits and electromagneticcommunications, and vice versa.

One of the main challenges for the realiza-tion of these interfaces stands in the engineeringof chemical and physical processes able to accu-rately read the molecule characteristics whereinformation is encoded, and translate them intothe modulation of electromagnetic parameters.A possible solution in this direction might comefrom novel chemical and biological sensorsenabled by nanotechnology, which promiseunprecedented sensing capabilities [15]. Thesesensors are in general composed of materialscharacterized by electrical or electromagneticproperties that can be altered by the presence ofdeterminate molecules or molecule complexes,such as biological receptors bound to molecules,and accordingly modulate the current in an elec-trical circuit. The major problems for using thissensing technology for IoBNT applications standin their currently high latency, low selectivity,lack of standardized response, and, more impor-tantly, unknown biocompatibility, which is con-sidered next.

Biocompatibility, intended here as the prop-erty of an engineered system of limiting itsaction on the biological environment exclusivelyto its intended function, without any unwantedalteration of biological parameters, is another

challenge for the deployment of bio-cyber inter-faces, especially for intra-body IoBNT applica-tions as shown in Fig. 4. Given the limited sizeof the aforementioned nanosensors, and currentpromising research results in electromagnetic(EM) nanocommunications, we envision the pos-sibility to develop bio-cyber interfaces by encap-sulating biological nanosensors and EM nano-communication units within the aforementionedartificial cells, as shown in Fig. 5b. In this design,the biological nanosensor would be responsiblefor interfacing chemical and electrical domains,the EM nano-communication unit would wire-lessly communicate with electrical devices out-side of the biological environment, and theartificial cell would assure biocompatibility.However, a challenge lies in the ability to pro-duce sufficient power for the wireless transmitterto emit electromagnetic waves that can propa-gate through the artificial cell membrane. At thesame time, approaches are also required to har-vest energy for the transmitter unit from withinthe cell. Another alternative is to push the elec-trical/EM domain at the physical interfacebetween the biological environment and theexternal world, such as the skin for intra-bodyIoBNT applications. In this direction, electronictattoos, similar to those based on radio frequen-cy identification (RFID) technology, which allowusers to authenticate devices within close range,could incorporate a bio-cyber interface able tosense biochemical information from cells onthe epidermis, sweat glands, or nervous termina-tions, and communicate it wirelessly to nearbyexternal electronic devices.

FURTHER CHALLENGESWe now briefly mention some further challengesto be faced for the IoBNT development.

The IoBNT enabling technologies discussedin this article could pose serious security threatsif handled with malicious intent. A new type of


Figure 4. Network architecture for the Internet of Bio-NanoThings for Intra-body applications.

HormonesInternet

Healthcareprovider

Bio-cyberinterface

Bacteriacommunication

Molecularmotors

Calciumsignaling

A bio-cyber interfaceis here defined as theset of processes nec-

essary to translateinformation from the

biochemical domain ofBio-NanoThing net-

works to the Internetcyber-domain, whichis based on electricalcircuits and electro-

magnetic communica-tions, and vice versa.



terrorism, which we term as bio-cyber terrorism,could effectively take advantage of the numerouspossibilities offered by the IoBNT to control andinteract with the biological environment. Forexample, Bio-NanoThings could be used toaccess the human body, and either steal personalhealth-related information, or even create newdiseases. Moreover, new types of viruses couldbe created to hack into already deployed IoBNTs.Research within the IoBNT field should neces-sarily address these problems by combining thesecurity assurance methods applied to today’scomputer networks with security solutions devel-oped through evolution by nature, such as thehuman immune system.

The realization of localization and trackingtechniques within the IoBNT, in a similar way asrealized in wireless sensor networks (WSNs),could enable important applications related, forexample, to the monitoring of disease locationsin the body or identification of the location anddistribution of toxic agents in an environment.One solution could come from the engineeringof chemotaxis in Bio-NanoThings, based on theaforementioned capability of bacteria to localizeand track sources of particular types ofmolecules, which could be, for example, biomark-ers released by cancerous or infected cells.

In line with the vision of “all-Things connect-ed,” an ultimate goal is to interconnect theparadigms of IoBNT and IoNT to the IoT. Achallenge of incorporating nanoscale devices isthe large quantity of information that willemerge, taking the challenges of managing “Big-Data” to a new level. Besides the increase in thequantity of data, new services will need to bedesigned to semantically map between differenttypes of data that IoBNT and IoNT will feed to

the IoT. New service discovery solutions will alsobe required to search deep into the biologicalenvironments and interact with engineered bio-logical entities to actuate or collect information.

CONCLUSIONWhile the Internet of Things (IoT) is enablingthe pervasive connectivity of real-world physicalelements among themselves and to the Internet,the Internet of NanoThings proposes to push thelimits of this concept to nanotechnology-enablednanoscale devices, which can be easily con-cealed, implanted, and scattered in the environ-ment. In this article we introduced the furtherconcept of Internet of Bio-NanoThings, wheresynthetic biology and nanotechnology are com-bined to develop Things based on the control,reuse, modification, and reengineering of biolog-ical cells. This article outlined the challengesthat will be faced to realize these Things and,more importantly, to enable their communica-tion and networking, with paradigm-shiftingtechniques for the fields of communication andnetwork engineering. We believe that the IoBNTresearch field, while still in its infancy, will resultin a game-changer technology for the society oftomorrow.

ACKNOWLEDGEMENTThe authors would like to thank Josep MiquelJornet, Ozan Bicen, and Bige Unluturk for theirconstructive comments.

This work is supported by the Academy ofFinland FiDiPro (Finnish Distinguished Profes-sor) program, for the project “Nanocommunica-tion Networks,” 2012–2016, and the FinnishAcademy Research Fellow program under Pro-

Figure 5. Application of artificial cells for the bio-nanothings networking: a) artificial cells for translatingmultiple molecule types; b) EM-nano transmitter and nanosensor embedded into an artificial cell forbio-cyber interface; and c) electronic tattoo for bio-cyber interface.

Artificial cell

Bacteria

Biomembrane

Outgoinghormones

Receptors

EM nanotransmitter

Biologicalnanosensor

Electronictattoo Engineered cell

(a)

(b) (c)

Expressionsystem

Biological gene circuit

Incomingautoinducers

Research within theIoBNT should neces-sarily address these

problems by combin-ing the security assur-ance methods appliedto today’ s electrical

networks with securitysolutions developedthrough evolution bynature, such as the

human immune system.


ject no. 284531, as well as the US National Sci-ence Foundation through the grants CNS-1110947 and MCB-1449014.

REFERENCES[1] I. F. Akyildiz and J. M. Jornet, “The Internet of Nano-Things,” IEEE Wireless

Commun., vol. 17, no. 6, Dec.2010, pp. 58–63.[2] L. J. Kahl and D. Endy, “A Survey of Enabling Technologies in Synthetic Biolo-

gy,” J. Biological Engineering, vol. 7, no. 1, May 2013, p. 13. [3] I. F. Akyildiz, F. Brunetti, and C. Blazquez, “Nanonetworks: A New Communi-

cation Paradigm,” Computer Networks, vol. 52, no. 12, Aug. 2008, pp.2260–79.

[4] D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry, W. H. Free-man, 2005, pp. 425–29.

[5] C. J. Myers, Engineering Genetic Circuits, Chapman & Hall/CRC, Mathemati-cal and Computational Biology Series, 2009.

[6] D. Baker et al., Engineering Life: Building A Fab for Biology, Scientific Ameri-can, vol. 294, no. 6, June 2006, pp. 44–51.

[7] F. Wu and C. Tan, “The Engineering of artificial Cellular Nanosystems UsingSynthetic Biology Approaches,” WIREs Nanomedicine and Nanobiotech, vol.6, no. 4, July/Aug. 2014.

[8] M. Pierobon,“A Systems-Theoretic Model of a Biological Circuit for MolecularCommunication in Nanonetworks,” Nano Communication Networks (Elsevi-er), vol. 5, no. 1–2, Mar.–June 2014, pp. 25–34.

[9] M. Gregori and I. F. Akyildiz, “A New NanoNetwork Architecture using Flagel-lated Bacteria and Catalytic Nanomotors,” IEEE JSAC, vol. 28, no. 4, May2010, pp. 612–19.

[10] M. Barros et al., “Transmission Protocols for Calcium-Signaling-basedMolecular Communications in Deformable Cellular Tissue,” IEEE Trans.Nanotechnology, vol. 13, no. 4, May 2014, pp. 779–88.

[11] M. J. Moore, T. Suda, and K. Oiwa, “Molecular Communication: ModelingNoise Effects on Information Rate,” IEEE Trans. Nanobioscience, vol. 8, no.2, June 2009, pp. 169–80.

[12] Y. Chahibi et al., “A Molecular Communication System Model for ParticulateDrug Delivery Systems,” IEEE Trans. Biomedical Engineering, vol. 60, no. 12,2013, pp. 3468–83.

[13] M. Pierobon and I. F. Akyildiz, “Fundamentals of Diffusion-Based MolecularCommunication in Nanonetworks,” Now Publishers Inc , ISBN-10:1601988168, ISBN-13: 978- 1601988164, Apr. 2014, 164 pages.

[14] I. F. Akyildiz et al., “MoNaCo: Fundamentals of Molecular Nano-Communica-tion Networks,” IEEE Wireless Commun. Mag., vol. 19, no. 5, Oct. 2012, pp.12–18.

[15] C. R. Yonzon et al., “Towards Advanced Chemical and Biological Nanosen-sors – An Overview,” Talanta, vol. 67, no. 3, Sept. 2005, pp. 438–48.

BIOGRAPHIESI. F. AKYILDIZ ([email protected]) is Ken Byers Chair Professor in Telecommuni-cations with the School of Electrical and Computer Engineering, Georgia Insti-tute of Technology, Atlanta, the Director of the Broadband Wireless Networking(BWN) Laboratory and the Chair of the Telecommunication Group at GeorgiaTech. Since 2013 he has been a FiDiPro Professor (Finland Distinguished Profes-sor Program (FiDiPro) supported by the Academy of Finland) in the Departmentof Electronics and Communications Engineering at Tampere University of Tech-nology, Finland. He is an IEEE Fellow (1996) and an ACM Fellow (1997). He hasreceived numerous awards from IEEE and ACM. His current research interestsare in nanonetworks, TeraHertz band communication networks, 5G cellular sys-tems, and wireless sensor networks.

M. PIEROBON ([email protected]) received the Ph.D. degree in electrical and com-puter engineering from the Georgia Institute of Technology, Atlanta, GA, in2013, and his M.S. degree in telecommunication engineering from the Politecni-co di Milano, Milan, Italy, in 2005. Currently he is an assistant professor with theDepartment of Computer Science & Engineering at the University of Nebraska-Lincoln. He is an editor of the IEEE Transactions on Communications. He is amember of IEEE, ACM, and ACS. His current research interests are in molecularcommunication theory for nanonetworks, communication engineering appliedto intelligent drug delivery systems, and telecommunication engineering appliedto cell-to-cell communications.

S. BALASUBRAMANIAM ([email protected]) received his bachelor (electrical andelectronic engineering) and Ph.D. degrees from the University of Queenslandin 1998 and 2005, respectively, and the master’s (computer and communica-tion engineering) degree in 1999 from Queensland University of Technology.He is currently a senior research fellow at the Nano Communication Centre,Department of Electronic and Communication Engineering, Tampere Universityof Technology (TUT), Finland. He was the TPC co-chair for ACM NANOCOM2014 and IEEE MoNaCom 2011. He is currently an editor for IEEE Internet ofThings and Elsevier’s Nano Communication Networks. His current researchinterests include bio-inspired communication networks and molecular commu-nication.

Y. KOUCHERYAVY ([email protected]) is a full professor and lab director inthe Department of Electronics and Communications Engineering at the Tam-pere University of Technology (TUT), Finland. He received his Ph.D. degree(2004) from the TUT. He is the author of numerous publications in the field ofadvanced wired and wireless networking and communications. His currentresearch interests include various aspects of heterogeneous wireless commu-nication networks and systems, the Internet of Things and its standardization,and nano communications. He is an associate technical editor of IEEE Communi-cations Magazine and an editor of IEEE Communications Surveys and Tutorials.


We believe that theIoBNT research field,while still being at its

infancy, will result in agame-changer

technology for thesociety of tomorrow.


Documents

COMMUNICATIONS SS TANDARD · otechnology. Second, the application of commu-nication engineering to design Bio-NanoThings telecommuni- cations is detailed, while the chal-lenges to