Nano Survey

Computer Networks 52 (2008) 2260–2279
Contents lists available at ScienceDirect
Computer Networks
journal homepage: www.elsevier.com/locate/comnet
Nanonetworks: A new communication paradigm

Ian F. Akyildiz a,*, Fernando Brunetti b,1, Cristina Blázquez c,2
a
Broadband Wireless Networking (BWN) Laboratory, School of Electrical and Computer Engineering, Georgia Institute of Technology,
250 14th Street, Atlanta, GA 30332, USA
b
Bioengineering Group, Institute of Industrial Automation, Spanish Research Council (CSIC), Madrid, Spain
c
Departament d’Arquitectura de Computadors Universitat Politècnica de Catalunya, Barcelona, Spain
a r t i c l e i n f o a b s t r a c t
Article history: Nanotechnologies promise new solutions for several applications in biomedical, industrial
Received 1 February 2008 and military fields. At nano-scale, a nano-machine can be considered as the most basic func-
Received in revised form 1 April 2008 tional unit. Nano-machines are tiny components consisting of an arranged set of molecules,
Accepted 15 May 2008
which are able to perform very simple tasks. Nanonetworks. i.e., the interconnection of
Available online 6 April 2008
nano-machines are expected to expand the capabilities of single nano-machines by allow-
ing them to cooperate and share information. Traditional communication technologies are
not suitable for nanonetworks mainly due to the size and power consumption of transceiv-
Keywords:
Nanonetworks
ers, receivers and other components. The use of molecules, instead of electromagnetic or
Nanocommunication acoustic waves, to encode and transmit the information represents a new communication
Molecular communication paradigm that demands novel solutions such as molecular transceivers, channel models
or protocols for nanonetworks. In this paper, first the state-of-the-art in nano-machines,
including architectural aspects, expected features of future nano-machines, and current
developments are presented for a better understanding of nanonetwork scenarios. More-
over, nanonetworks features and components are explained and compared with traditional
communication networks. Also some interesting and important applications for nanonet-
works are highlighted to motivate the communication needs between the nano-machines.
Furthermore, nanonetworks for short-range communication based on calcium signaling
and molecular motors as well as for long-range communication based on pheromones are
explained in detail. Finally, open research challenges, such as the development of network
components, molecular communication theory, and the development of new architectures
and protocols, are presented which need to be solved in order to pave the way for the devel-
opment and deployment of nanonetworks within the next couple of decades.
Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction lieved humans would create increasingly tinier and pow-

erful devices in the future. The term ‘‘nanotechnology”
The concepts in nanotechnology was first pointed out was first defined by [59] 15 years later as: ‘‘Nanotechnol-
by the 1965 nobel laureate physicist Richard Feynman in ogy mainly consists of the processing of, separation, con-
his famous speech entitled ‘‘There’s Plenty of Room at the solidation, and deformation of materials by one atom or
Bottom” in December 1959. The main focus of his speech by one molecule”. In the 1980s, the basic idea of this def-
was about the field of miniaturization and how he be- inition was explored in much more depth by [26] who
took the Feynman concept of a billion tiny factories and
added the idea that they could replicate themselves, via
* Corresponding author. Tel.: +1 404 894 5141; fax: +1 404 894 7883. computer control instead of control by a human operator.
E-mail addresses: [email protected] (I.F. Akyildiz), [email protected].
es (F. Brunetti), [email protected] (C. Blázquez).
Activity surrounding nanotechnology began to slowly in-
1
This work was conducted during his stay at BWN Lab in 2007–2008. crease and the advancements really began to accelerate
2
This work was conducted during her stay at BWN Lab in 2007–2008. in the early 2000s.
1389-1286/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.comnet.2008.04.001
I.F. Akyildiz et al. / Computer Networks 52 (2008) 2260–2279 2261
Nanotechnology enables the miniaturization and fabri- areas, where transmitters and receivers can be remotely
cation of devices in a scale ranging from 1 to 100 nanome- located as long as the transmitted molecules reach the
ters. At this scale, a nano-machine can be considered as the intended receiver.
most basic functional unit. Nano-machines are tiny com-
ponents consisting of an arranged set of molecules which In the recent literature, the term ‘‘nanonetworks” re-
are able to perform very simple computation, sensing fers to electronic components and their interconnection
and/or actuation tasks [57]. Nano-machines can be further within a single chip on a nano-scale [12]. This concept
used as building blocks for the development of more com- is also known as Network on Chip (NoC). This term is
plex systems such as nano-robots and computing devices also referred to as the network-like interconnection of
such as nano-processors, nano-memory or nano-clocks. nanomaterials as well, e.g., carbon nanotubes arrays
Nano-machines can be interconnected to execute collab- [38,15]. In this paper, we use the term ‘‘nanonetworks”
orative tasks in a distributed manner. Resulting nanonet- strictly for the interconnection of nano-machines based
works are envisaged to expand the capabilities and on molecular communication.
applications of single nano-machines in the following ways: This paper follows the bio-inspired approach to explore,
from a telecommunication point of view, the potential of
Nano-machines such as chemical sensors, nano-valves, molecular communication for nanonetworks. First, in Sec-
nano-switches, or molecular elevators [4], cannot exe- tion 2, we present the nano-machines including the state-
cute complex tasks by themselves. The exchange of of-the-art in research and current approaches for their
information and commands between networked nano- development. In Section 4, we explain nanonetwork fea-
machines will allow them to work in a cooperative tures and their advantages and disadvantages over tradi-
and synchronous manner to perform more complex tional communication networks. In Section 3, we explain
tasks such as in-body drug delivery or disease potential applications of nanonetworks. We explore exist-
treatments. ing biological models and techniques for molecular com-
The workspace of a single nano-machine is extremely munication for short and long-ranges in Sections 5–7,
limited. Nanonetworks will allow dense deployments respectively. Finally, we outline open research issues and
of interconnected nano-machines. Thus, larger applica- contrast them with traditional communication network
tion scenarios will be enabled, such as monitoring and challenges in Section 8. We conclude the paper in Section
control of chemical agents in ambient air. 9.
In some application scenarios, nano-machines will be
deployed over large areas, ranging from meters to kilo-
meters. In these scenarios, the control of a specific 2. Overview of Nano-machines
nano-machine is extremely difficult due to its small size.
Nanonetworks will enable the interaction with remote A nano-machine is defined as ‘‘an artificial eutactic
nano-machines by means of broadcasting and multihop mechanical device that relies on nanometer-scale compo-
communication mechanisms. nents” [24]. Also the term ‘‘molecular machine” is defined
as ‘‘a mechanical device that performs a useful function using
Communication between nano-machines can be real- components of nanometer-scale and defined molecular struc-
ized through nanomechanical, acoustic, electromagnetic ture; includes both artificial nano-machines and naturally
and chemical or molecular communication means [31]. occurring devices found in biological systems”.
Nanomechanical communication is defined as the trans- In general terms, we define a nano-machine as ‘‘a de-
mission of information through mechanical contact vice, consisting of nano-scale components, able to perform a
between the transmitter and the receiver. In acoustic com- specific task at nano-level, such as communicating, comput-
munication, the transmitted message is encoded using ing, data storing, sensing and/or actuation”. The tasks per-
acoustic energy, i.e., pressure variations. Electromagnetic formed by one nano-machine are very simple and
communication is based on the modulation of electromag- restricted to its close environment due to its low complex-
netic waves to transmit information. Molecular communica- ity and small size.
tion can be formally defined as the use of molecules as There are three different approaches for the develop-
messages between transmitters and receivers. ment of nano-machines as depicted in Fig. 1. In the top-
Molecular communication is the most promising ap- down approach, nano-machines are developed by means
proach for nano-networking based on the following of downscaling current microelectronic and micro-elec-
advantages: tro-mechanical technologies without atomic level control.
In the bottom-up approach, the design of nano-machines
Due to the size and principles of traditional acoustic is realized from molecular components, which assemble
transducers and radiofrequency transceivers, their inte- themselves chemically by principles of molecular recogni-
gration at molecular or nano-scale is not feasible [31]. tion arranging molecule by molecule. Recently, a third ap-
By contrast, molecular transceivers are intrinsically con- proach called bio-hybrid is proposed for the development
ceived at nano-scale. These are nano-machines which of nano-machines [63]. This approach is based on the use
are able to emit and receive molecules. of existing biological nano-machines, such as molecular
In nanomechanical communication, transmitters and motors, as components or models for the development of
receivers need to be in direct contact. This is not a new nano-machines. In Fig. 1, different systems are
restriction for molecular communication over large mapped according to their origin, biological or man-made
2262 I.F. Akyildiz et al. / Computer Networks 52 (2008) 2260–2279
Humans Insects Cell

Cells organells
Nature Bio-hybrid
Bacteria
Molecules
Robots Micro-robots Nano-robots NANOMACHINES
Top-down
Man-made
Bottom-up
Computers Micro-electonics Nano-electronics
MEMS NEMS
m mm μm nm
Scale
Fig. 1. Approaches for the development of nano-machines.
systems, and to their size, ranging from nanometers to me- and molecular shuttles [6], are based on self-assembly
ters. In the future, nano-machines will be obtained follow- molecular properties [7].
ing any of these three approaches. However, the existence
of successful biological nano-machines, which are highly 2.1.3. Bio-hybrid approach
optimized in terms of architecture, power consumption Several biological structures found in living organisms
and communication, motivate their use as models or build- can be considered as nano-machines. Most of these bio-
ing blocks for new developments. logical nano-machines can be found in cells. Biological
nano-machines in cells include: nano-biosensors, nano-
2.1. Development of nano-machines actuators, biological data storing components, tools and
control units [25]. Expected features of future nano-
2.1.1. Top-down approach machines are already present in a living cell, which can
Recently, newest manufacturing processes, such as the be defined as a self-replicating collection of nano-machines
45 nm lithographic process, have made the integration of [63]. Several biological nano-machines are interconnected
nano-scale electronic components in a single device possi- in order to perform more complex tasks such as cell
ble [39]. The top-down approach is focused on the develop- division. The resulting nanonetwork is based on molecular
ment of nano-scale objects by downscaling current signaling. This communication technique is also used for
existing micro-scale level device components. To achieve inter-cell communication allowing multiple cells to coop-
this goal, advanced manufacturing techniques, such as elec- erate to achieve a common objective such as the control
tron beam lithography [61] and micro-contact printing [42], of hormonal activities or immune system responses in
are used. Resulting devices keep the architecture of pre- humans.
existing micro-scale components such as microelectronic The bio-hybrid approach proposes the use of these bio-
devices and micro-electro-mechanical systems (MEMS). logical nano-machines as models to develop new nano-
Nano-machines, such as nano-electromechanical sys- machines or to use them as building blocks integrating
tems (NEMS) components, are being developed using this them into more complex systems such as nano-robots. Fol-
approach [19,34,45]. However, the fabrication and assem- lowing this approach, the use of a biological nano-motor to
bly of these nano-machines is still at an early stage. So power a nano-device has been reported in [56]. Another
far, only simple mechanical structures, such as nano-gears example in line with this approach is the use of bacteria
[66], can be created following this approach. as controlled propulsion mechanisms for the transport of
micro-scale objects [10].
2.1.2. Bottom-up approach
In the bottom-up approach, nano-machines are devel- 2.2. Expected features of nano-machines
oped using individual molecules as the building blocks.
Recently, many nano-machines, such as molecular The main constraint in the development of nano-ma-
differential gears and pumps [51], have been theoretically chines is the lack of tools which are able to handle and
designed using a discrete number of molecules. Manufac- assemble molecular structures in a precise way. However,
turing technologies able to assemble nano-machines mol- given the rapid advances in manufacturing technologies,
ecule by molecule do not exist, but once they do; nano- efficient fabrication of more complex nano-machines will
machines could be efficiently created by the precise and be possible in the near future. They are expected to include
controlled arrangement of molecules. This process is called most of the functionalities of existing devices at micro-
molecular manufacturing [24]. scale. In addition, nano-machines will present novel fea-
Molecular manufacturing could be developed from cur- tures enabled by molecular properties of the materials that
rent technologies in couple decades if adequate resources can be exploited at nano-scale. The most important and ex-
are invested. Current development of nano-machines using pected features of future nano-machines can be described
this bottom-up approach, such as molecular switches [5] as follows:
Nano-machines will be intrinsically self-contained. This external elements, and then assemble them to repli-
means that each nano-machine will contain a set of cate the nano-machine. This unit is provided with all
instructions or code to realize the intended task. These the instructions needed to realize this task.
instructions or sequence of operations can be embedded (4) Power unit. This unit is aimed at powering all the
in the molecular structure of nano-machines, or can be components of the nano-machine. The unit will be
read from another molecular structure in which the able to scavenge energy from external sources such
instruction set is stored. as light, temperature and store it for a later distribu-
Self-assembly is defined as the process in which several tion and consumption.
disordered elements form an organized structure with- (5) Sensor and actuators. Similar to the communication
out external intervention, as a result of local interactions unit, these components act as an interface between
between them. At nano-level, self-assembly is naturally the environment and the nano-machine. Several sen-
driven by molecular affinities between two different ele- sors and/or actuators can be included in a nano-
ments. Self-assembly will leverage the development of machine, e.g., temperature sensors, chemical sensors,
nano-machines and will allow them to interact with clamps, pumps, motor or locomotion mechanisms.
external molecules in an autonomous way.
Self-replication is defined as the process in which a Currently such complex nano-machines cannot be built.
device makes a copy of itself using external elements. However, there exist systems found in the nature, such as
This potential process will enable the creation of large living cells, with similar architectures. According to the
number of nano-machines to realize macroscopic tasks bio-hybrid approach these biological models, i.e., the cells,
in an inexpensive way [43]. Similar to the first feature, can be used to learn and understand the principles govern-
self-replication implies that the nano-machine contains ing the operation of nano-machines and their interactions.
the instructions to create a copy of itself. This knowledge is expected to contribute to the develop-
Locomotion is the ability to move from one place to ment of new bio-inspired nano-machines and systems for
another. Nano-machines are aimed to accomplish spe- specific purposes. In Fig. 2, we show a component mapping
cific tasks, which are usually described by a spatial-tem-
poral actuation. This means that a nano-machine should
be located in the right place at the right time to accom-
Microrobot node
plish the task. However, no single nano-machine is able
to move towards a previously identified target. More
complex systems could use embedded nano-sensors Sensors Actuators
4 5
and nano-propellers to detect and follow specific traces
of the target. Locomotion will enable the use of nano-
machines in applications where mobile actors are Processing and Control
Unit Location
needed, e.g., nano-robots for disease treatments [18]. Transceiver 1 System
Communication between nano-machines is needed to 3 Storage Unit
2
allow them to realize more complex tasks in a coopera-
tive manner. At this level, as explained in Section 1, the
most promising technique is based on molecular com- Power Unit 6
munication. Further advances in nano-sensors and Energy Scavenger 7
nano-actuators are expected to enable the integration
of molecular transceivers into nano-machines.
Nanonetwork
2.3. Nano-machine architecture node
Gap
(Cell inspired) 1 Junctions
A nano-machine could consist of one or more compo- Nucleus
3
nents, resulting in different levels of complexity, which
Receptors
could be from simple molecular switches to nano-robots ADN
[18]. The most complete nano-machines will include the 2 4

following architecture components: Mitochondrion
Vacuoles
6
(1) Control unit. It is aimed at executing the instructions 7
to perform the intended tasks. To achieve this goal, it
can control all the other components of the nano-
machine. The control unit could include a storage
unit, in which the information of the nano-machine
is saved. Flagellum
(2) Communication unit. It consists of a transceiver able 5
to transmit and receive messages at nano-level,
e.g., molecules.
(3) Reproduction unit. The function of this unit is to fab- Fig. 2. Functional architecture mapping between nano-machines of a
ricate each component of the nano-machine using micro or nano-robot, and nano-machines found in cells.
between a generic architecture of a nano-machine and a els inspire and encourage the use of nanotechnologies to
living cell, including its biological nano-machines. Similar interact with organs and tissues. The advantages provided
to the architecture of a nano-machine, a cell contains the by nanonetworks are clearly in terms of size, biocompati-
following components: bility and biostability, enabled by the control of system
components at molecular level. These are some of the
(1) Control unit. The nucleus can be considered as the envisaged applications:
control unit of the cell. It contains all the instruc-
tions to realize the intended cell functions. Immune system support. The immune system is com-
(2) Communication. The gap junctions and hormonal and posed by several nano-machines that protect organism
pheromonal receptors, located on the cell mem- against diseases. These nano-machines are a collection
brane, act as molecular transceivers for inter-cell of nano, micro and macro systems, including sensors
communication. and actuators, acting in a coordinated way to identify
(3) Reproduction. Several nano-machines are involved in and control foreign and pathogen elements. Nano-
the reproduction process of the cell such as the cen- machines can be used to help the detection and elimina-
trosome and some molecular motors. The code of tion procedures. They could realize tasks of localization
the nano-machine is stored in molecular sequences, and response to malicious agents and cells, such as can-
which are duplicated before the cell division. Each cer cells [20,32], resulting in a less aggressive and inva-
resulting cell will contain a copy of the original sive treatments compared to the existing ones.
DNA sequence. Bio-hybrid implants. These are aimed at supporting or
(4) Power unit. Cells can include different nano- replacing components such as organs, nervous tracks
machines for power generation. One of them is the or lost tissues [24,30]. Nanonetworks can provide
mitochondrion that generates most of the chemical friendly interfaces between the implant and the envi-
substances, which are used as energy in many cellu- ronment. Restoration of central nervous system tracks
lar processes. Another interesting nano-machine is is a possible application of bio-hybrid implants.
the chloroplast, which converts sunlight into chemi- Drug delivery systems. These are another specific type of
cal fuel. implants. For instance, these systems could help to com-
(5) Sensors and actuators. Cells can include several sen- pensate metabolism diseases such as diabetes. In this
sors and actuators such as the Transient Receptor sense, nano-sensors and smart glucose reservoirs or pro-
Potential channels for tastes and the flagellum of ducers can work in a cooperative manner to support reg-
the bacteria for locomotion. The chloroplast of the ulating mechanisms [29]. Drug delivery systems could
plants can also be considered as an actuator since also help to mitigate the effects of neurodegenerative
it transforms water to oxygen that is later released diseases by delivering neurotransmitters or specific
to the environment. drugs [64].
Health monitoring. Oxygen and cholesterol level, hor-
A bio-hybrid approach cannot only be used to develop monal disorders, and early diagnosis are some examples
novel nano-machines, but also to understand their interac- of possible applications that can take advantage of in-
tions in larger systems such as cells. These interactions, body nano-sensor networks [22,30]. The information
exclusively enabled by molecular communication tech- retrieved by these systems must be accessible by rele-
niques, are essential since this is the only way to explore vant actors. Thus, nanonetworks must provide the
their capabilities to achieve more complex tasks in a coop- proper level of connectivity to deliver the sensed
erative manner. information.
In this paper, we expand the bio-hybrid approach be- Genetic engineering. Manipulation and modification of
yond the models for novel nano-machines in order to study nano-structures such as molecular sequences and genes
and develop molecular communication techniques for can be achieved by nano-machines. The use of nanonet-
their interconnection. works will allow expanding the potential applications in
genetic engineering.
3. Nanonetworks applications
3.2. Industrial and consumer goods applications
The potential applications of nanonetworks are unlim-
ited. We classify them in four groups: biomedical, environ- Nanonetworks will be used not only the intra-body but
mental, industrial and military applications. However, also in industries. Nanonetworks can help with the devel-
since nanotechnologies have a key role in the manufactur- opment of new materials, manufacturing processes and
ing process of several devices, nanonetworks could be used quality control procedures. More specifically, these appli-
extensively in many other fields such as consumer elec- cations have already been proposed:
tronics, life style and home appliances among others.
Food and water quality control. Similar to health monitor-
3.1. Biomedical applications ing applications, food and fluids quality control can take
advantage of nanonetworks. Nano-sensor networks can
The most direct applications of nano-machines and help detecting small bacteria and toxic components that
nanonetworks are in the biomedical field. Biological mod- can affect to the product quality and cannot be detected
using traditional sensing technologies [3]. Advanced process in the garbage dumps. Nanonetworks can help
self-powered nano-sensor networks can be used to detect the biodegradation process by sensing and tagging dif-
very small amount of chemical or biological agents ferent materials that can be later located and processed
installed in water supplies across the country. by smart nano-actuators.
Functionalized materials and fabrics. Nanonetworks can Animals and biodiversity control. Nanonetworks can be
be included in advanced fabrics and materials to get also used in natural environments to control several
new and improved functionalities. Antimicrobial and species. For instance, as seen in nature, nanonetworks
stain-repeller textiles are being developed using nano- using pheromones as messages can trigger certain
functionalized materials [60]. For instance, nano-actua- behaviors on animals. As a result it is possible to interact
tors can help to improve the airflow in smart fabrics. with those animals and also to control their presence in
These nano-actuators can communicate to nano-sensors particular areas.
to control the proper reaction based on the external Air pollution control. Similar to the quality control appli-
conditions. cations, air can be monitored using nanonetworks.
Moreover, nano-filters can be developed to improve
the air quality by removing harmful substances con-
3.3. Military applications tained in it [35].
Nanotechnologies can also have several applications in 4. Communication among nano-machines

the military field. While in the applications pointed out be-
fore, the range covered by nanonetworks is short, in mili- Among all of the expected features of future nano-ma-
tary field the deployment range of nanonetworks can be chines, the communication capabilities are also very
widely variable depending on the application. Battlefield important. This is the only feature that enables them to
monitoring and actuation demand a dense deployment of work in a synchronous, supervised and cooperative man-
nanonetworks over large areas, while systems aimed at ner to pursuit a common objective.
monitoring soldier performance are deployed in smaller Nano-machines communication can include the two
areas, i.e., human body. Among the military applications, following bidirectional scenarios:
we can mention:
(1) Communication between a nano-machine and a lar-
Nuclear, biological and chemical (NBC) defenses. This is a ger system such as electronic micro-devices, and
classic application for large area deployment. Nanonet- (2) Communication between two or more nano-
works can be deployed over the battlefield or targeted machines.
areas to detect aggressive chemical and biological
agents and coordinate the defensive response [55]. The Different communication technologies, such as electro-
overall system can be compounded of nano-sensors magnetic, acoustic, nanomechanical or molecular; have
and nano-actuators, which would detect and control been proposed for each scenario in [31].
the hostile agents. Nano-sensor networks could also be Communication based on electromagnetic waves is the
deployed into cargo containers to detect the unautho- most common technique to interconnect microelectronic
rized entrance of chemical, biological or radiological devices. These waves can propagate with minimal losses
materials. along wires or through air. However, given the size of
Nano-functionalized equipments. These applications are nano-machines, wiring a large quantity of them is unfeasi-
similar to those found in consumer goods field, but it ble. As an alternative, wireless solutions could be used. To
is focused on military equipment. Advanced camouflage establish a bidirectional wireless communication, a radio-
as well as army uniforms can take advantage of nanon- frequency transceiver should be integrated in the nano-
etworks. For instance, equipments can be manufactured machine. Nano-scale antennas could be developed for very
using advanced materials containing nanonetworks that high frequency communication. However, due to the size
self-regulate the temperature underneath soldiers and current complexity of the transceivers, they still can-
clothes [27] and even detect whether the soldier has not be easily integrated into nano-machines. In addition,
been injured. if the integration were possible, the output power of the
nano-transceiver would not be enough to establish a bidi-
rectional communication channel [31]. As a consequence,
3.4. Environmental applications electromagnetic communication could be used to transmit
information from a micro-device to a nano-machine, but
Since nanoneworks are inspired in biological systems not from nano-machines to micro-devices, nor among
found in nature, they can also be applied in environmental nano-machines.
fields achieving several goals that could not be solved with At nano-level, acoustic communication is mainly based
current technologies. Some environmental applications on the transmission of ultrasonic waves. Similar to the
are: communication based on electromagnetic waves, the
acoustic communication implies the integration of ultra-
Biodegradation. There is an existing and growing prob- sonic transducers in the nano-machines. These transducers
lem with garbage handling around the world. In this should be capable to sense the rapid variations of pressure
line, nanonetworks could help with the biodegradation produced by ultrasonic waves and to emit acoustic signals
accordingly. Again, the size of these transducers represents The reduced size of nano-machines and the resulting
the major barrier in their integration in the nano- nanonetwork components can be an advantage in many
machines. applications where the dimension of the involved sys-
In nanomechanical communication, the information is tems is critic. For instance, in the biomedical field,
transmitted through hard junctions between linked de- nano-machines can be used for intra-body applications
vices at nano-level. The main drawback of this type of com- allowing nanonetworks to lead to nano-invasive and
munication is that a physical contact between the more selective treatments.
transmitter and the receiver is required. Moreover, this Biocompatibility is defined as the quality of a device to
coupling should be precise enough to guarantee that the operate accordingly in biological environments without
desired mechanical transceivers are aligned correctly. This affecting them negatively. In some biomedical applica-
communication technique is not suitable in many applications, many electronic devices have to cope with hostile
tion scenarios where nano-machines are deployed over environments as well as many organisms reject
large areas without any direct contact between them. In implants and drugs. Nanotechnologies can be used to
addition, without precise navigation systems in nano-ma- enhance the compatibility between nano-machines
chines, their positioning for a correct nanomechanical and natural organs or tissues by means of more friendly
communication is a major barrier. materials and interfaces. For instance, bio-hybrid nano-
Molecular communication is defined as the transmission machines compound by biological elements can interact
and reception of information encoded in molecules. Molec- with natural processes without any side effect. In addi-
ular communication is a new and interdisciplinary field tion, nano-machines and molecular messages may also
that spans nano, bio and communication technologies be programmed to deactivate after completing the
[46]. Unlike previous communication techniques, the inte- nanonetwork task preventing removal procedures.
gration process of molecular transceivers in nano-ma- Nanotechnologies, allow the control of materials at
chines is more feasible due to the size and natural molecular level. Using these materials, we can design
domain of molecular transceivers, i.e., nano-scale frame- nanonetworks nodes according to specific environmen-
work. These transceivers are nano-machines which are tal conditions improving the biocompatibility of the
able to react to specific molecules, and to release others system.
as a response to an internal command. Chemical reactions are highly efficient in terms of energy
Molecular communication can be used to interconnect consumption [47]. These reactions will power the nanon-
multiple nano-machines, resulting in nanonetworks as de- etworks nodes and processes. Chemical reactions can
fined in Section 1. Nanonetworks expand the capabilities of also represent complex computation and decision pro-
single nano-machines in the following terms: cesses, which in traditional communication could mean
multiple operations.
More complex objectives can be achieved if multiple
nano-machines cooperate. Nanonetworks enable this
cooperation by providing mechanisms to exchange 4.1. Nanonetworks versus Traditional communication
information between different nano-machines such as networks
molecular motors or nano-switches.
Single nano-machines can only perform tasks at nano- Nanonetworks are not a simple extension of traditional
level, and therefore their workspace is very limited. communication networks at the nano-scale. They are a
However, if a large number of nano-machines are inter- complete new communication paradigm, in which most
connected, they can pursuit macro-scale objectives, and of the communication processes are inspired by biological
work over larger areas, such as treatment of cancer systems found in nature. Nanonetworks have the following
tumors or air pollution monitoring. differences with traditional communication networks:
If multiple nano-machines are deployed over large
areas, the interaction with a specific nano-machine is In nanonetworks, the message is encoded using molecules;
extremely difficult due to its small size. This interaction while in traditional communication networks, the infor-
includes procedures such as nano-machines activation/ mation is encoded in electromagnetic, acoustic or opti-
deactivation, configuration of parameters, data acquisi- cal signals. Two different and complementary coding
tion or actuation commands. Nanonetworks will techniques can be considered to represent the informa-
enable this interaction by providing the infrastructure tion in nanonetworks. The first one uses temporal
and mechanism to broadcast the information over sequences to encode the information, such as the tem-
these areas. In addition, two nano-machines could poral concentration of specific molecules in the med-
interact indirectly by using other nano-machines as ium. According to the level of the concentration, i.e.,
repeaters. the number of molecules per volume, the receptor
decodes the received message. For instance, this tech-
Besides expanding capabilities of single nano-machines, nique is used by the Central Nervous System to propa-
nanonetworks represent a potential solution for some gate the neural impulses. This technique can be
applications where available communication networks considered similar to those used in traditional networks
and micro-devices are not suitable. Compared to current where time-varying sequences transport the informa-
communication network technologies, nanonetworks have tion. The second technique, hereinafter called molecular
the following advantages: encoding, uses internal parameters of the molecules to
encode the information such as the chemical structure, ing communication networks knowledge is not suitable for
relative positioning of molecular elements or polariza- nanonetworks due to their particular features. Nanonet-
tion [46]. In this case, the receiver must be able to detect works require innovative networking solutions according
these specific molecules to decode the information. This to the characteristics of the network components and the
technique is similar to the use of encrypted packets in molecular communication processes.
communication networks, in which only the intended
receiver is capable to read the information. In nature, 4.2. Nanonetwork components
molecular encoding is used in pheromonal communica-
tion, where only members of the transmitter specie can The first models of nanonetworks are based on those
decode the transmitted message. used in Information and Communication Technologies
The propagation speed of signals used in traditional com- (ICT) for telecommunication networks. In Fig. 3, we show
munication networks, such as electromagnetic or acous- the general concepts of nanonetworks versus existing tele-
tic waves, is much faster than the propagation of communication systems. Nanonetworks components are
molecular messages. In nanonetworks, the information, functionally similar to those found in traditional networks.
i.e., molecules, has to be physically transported from In nanonetworks, we can identify five different compo-
the transmitter to the receiver. In addition, molecules nents: the transmitter node, the receiver node, the mes-
can be subject to random diffusion processes and envi- sages, the carrier, and the medium. Each of these
ronmental conditions, such as temperature, which can components affects the overall communication process,
affect the propagation of the molecular messages. which includes the following steps as Fig. 3b depicts:
In traditional communication networks, noise is
described as an undesired signal overlapped with the (1) The transmitter encodes the message onto
signals transporting the information. In nanonetworks, molecules.
according to the coding techniques, two different types (2) The transmitter inserts the message into the med-
of noise can affect the messages. First, as occurs in tradi- ium by releasing the molecules to the environment
tional communication systems, noise can be overlapped or attaching them to molecular carriers.
with molecular signals such as concentration level of (3) The message propagates from the transmitter to the
molecules. This means that another source emits the receiver.
same molecules used to encode the message, therefore (4) The receiver detects the message.
they affect the concentration sensed by the receiver. In (5) The receiver decodes the molecular message into
nanonetworks, noise can also be understood as an unde- useful information such as reaction, data storing,
sired reaction occurring between information molecules actuation commands, etc.
and other molecules present in the environment. These
reactions can modify the structure of the information
molecules and therefore the receiver would not be able 4.2.1. Transmitters and receivers
to detect the transmitted message. The transmitter role is played by a nano-machine such
Text, voice and video are usually transmitted over as a modified living cell, a biomedical implant, or a nano-
traditional communication networks. By contrast, in robot. In most of traditional communication networks,
nanonetworks, since the message is a molecule, the the nodes encode the information by modulating electro-
transmitted information is more related to phenomena, magnetic signals. In nanonetworks the nodes encode the
chemical states and processes [11]. information by modifying molecules by means of chemical
In nanonetworks, most of the processes are chemically reactions. Nano-machines also play the receiver role. The
driven resulting in low power consumption. In tradi- receiver should be able to extract the message from the
tional communication networks the communication medium. Since nano-machines are very simple, and the
processes consume electrical power that is obtained message is basically a molecule, handling this message
from batteries or from external sources such as electro- could not be a trivial task. The message contains useful
magnetic induction. information that is going to be used by the receiver. At
molecular level, this can mean to forward the message,
We summarize nanonetworks and traditional commu- to store it, or to react to it. Nanonetwork nodes transmit
nication network features in Table 1 [37]. Most of the exist- and receive molecules. These molecules are a finite source.
Table 1
Main differences between traditional communication networks and nanonetworks enabled by molecular communication [37]
Communication Traditional Molecular

Communication carrier Electromagnetic waves Molecules
Signal type Electronic and optical (Electromagnetic) Chemical
Propagation speed Light (3 108 m/s) Extremely low
Medium conditions Wired: Almost immune Affect communication
Wireless: Affect communication
Noise Electromagnetic fields and signals Particles and molecules in medium
Encoded information Voice, text and video Phenomena, chemical states or processes
Other features High energy consumption Low energy consumption
a
RX
Propagation
speed (Light)
RX
TX
Electromagnetic
waves
b RX
Nano-machine
Matter
TX (Molecules) Noise
Nano-machine
Encoder
Sensitive to
obstacles
Low propagation Decoder

speed RX
(Random process) Nano-machine
Fig. 3. Overview of (a) traditional communication systems and (b) nanonetworks: energy transmission vs. molecular transmission.
This has two consequences. First, the transmitter nano-ma- This molecule can be compounded by a sequence of hydro-
chines should be able to obtain, from an external source, gen and flour atoms, resulting in a binary sequence able to
raw molecules and store them for a later use as messages. store digital data [9].
Second, the receiver nano-machines should be able to buf-
fer a limited number of molecules, and also include release 4.2.3. Carrier
mechanisms to empty this molecular buffer to be ready for In classical communication paradigm, a carrier is used to
the next messages. transport the message. The carrier is used because of its sig-
nal feature advantages, especially in terms of propagation.
4.2.2. Message In traditional computer networks, the carriers also allow
In traditional computer networks, the information is creating multiple communication channels. In nanonet-
represented using a binary system and the transmitted works, the carriers are particular molecules which are able
message is usually a set of bits. In molecular communica- to transport chemosignals or molecular structures contain-
tion, the message is a molecule. This molecular message ing the information. The aim of the molecular carriers is to
will have three important characteristics [31]. First, it will enhance the propagation features of single information
present a predefined external structure that will allow an molecules, to create more reliable communication by pro-
easy recognition at the receiver. Second, it will be inactive. tecting molecules from external noise sources, and finally
This means that molecular messages will not be prone to to enable the creation of multiple independent channels
react to other molecules in the medium. Finally, molecular using the same medium. The use of molecules as informa-
messages should easily be eliminated without any side ef- tion carriers in molecular communication was observed in
fect once they are decoded at the receiver nano-machine. biological systems. According to these observations, two
In [37], some molecular features such as polarity, motion, potential types of carriers have been identified: the molecu-
magnetization, and structures, are suggested for informa- lar motors and the calcium ions [50]. Molecular motors, e.g.,
tion coding. A potential candidate for molecular messaging kinesin, dynein and myosin, are proteins that can generate
is the partially fluorinated polyethylene proposed in [24]. movements using chemical energy. These protein motors
can transport a data packet, i.e., molecule, from the trans- day. The ability to move molecules makes molecular mo-
mitter to the receiver as described in [49]. The second type tors a feasible way to transport information packets, i.e.,
of carrier consists of calcium ions (Ca2+). The transmitter can molecules, from the transmitter to the receiver nano-ma-
modulate the concentration of these ions in amplitude and chine. As an additional advantage, molecular motors and
frequency to encode the information [17]. microtubules can be used as a bio-hybrid communication
interface between man-made nano-machines and biologi-
4.2.4. Medium cal structures. For instance, nano-machines could use this
Wireless communication networks have been devel- communication interface to interact with cell organelles
oped for almost every type of media found in nature such to achieve specific tasks, such as drug delivery.
as airborne, waterborne, and underground. Many wireless The deployment of the microtubules, i.e., network infra-
transmission technologies have also been applied success- structure, to support the movement of the molecular mo-
fully to communicate with implantable devices. The propa- tors is a key issue. Two different solutions could be used
gation of typical network signals, such as acoustic, optical for the deployment of the network infrastructure. The first
or electromagnetic, can be affected by the medium condi- one is based on natural mechanisms found in cells, in
tions. In molecular communication, the medium can be which microtubules can be developed by means of molec-
wet or dry, e.g., in-body or environmental monitoring nan- ular self-assembly [62]. The second solution is based on the
onetworks, and the propagation is even more dependent on development of lithographic tracks of molecular motors to
the medium conditions. The speed of the medium, which is interconnect nano-machines. These tracks, which are made
faster than the propagation speed of the molecules, can af- of molecular motors attached to a surface, can move struc-
fect the communication between nano-machines. In addi- tures similar to the microtubules from one point to another
tion, physical obstacles on the signal pathway can impede [36]. In this solution, the information molecule is not at-
the propagation of the molecules, which can go through so- tached to the molecular motor but to the microtubule or
lid objects. These radical changes oblige the review of many a structure with similar characteristics [48].
common communication concepts such radiation, range, as The concept behind these two solutions is the same. In
well as the development of new propagation models. both solutions, the movement created by molecular mo-
tors is used to transport the information molecules. Fur-
ther description of this molecular communication
5. Short-range communication using molecular motors technique will consider the scenario according to the first
solution. The scenario is assumed to include system com-
First nanonetworks models are inspired by molecular ponents such as pre-deployed microtubules between
communication schemes observed in biological systems. nano-machines and traveling molecular motors. These
Biological nanonetworks are used for intra-cell, inter-cell components, shown in Fig. 4, should present specific fea-
and intra-specie communication. Intra-cell and inter-cell tures to support all of the communication processes be-
communication are referred as short-range techniques tween the nano-machines.
due to the size of living cells and their internal compo-
nents. Thus, in the framework of nanonetworks, we classify 5.1. Communication features
as short-range the communication process that takes place
in a range from nm to few mm. Complementarily, we clas- Molecular communication enabled by molecular mo-
sify as long-range communication, the interconnection of tors takes place in aqueous medium. The environment
two nano-machines in a range of mm to km as occurs in should include the necessary components at biologically
pheromonal communication. appropriate conditions [28], such as temperature, humid-
Most of the intra-cell communications are based on ity, medium viscosity and pH. Due to the organic and
molecular motors. Molecular motors, e.g., dynein, are pro- chemical nature of the involved nano-machines and infor-
teins or protein complexes that transform chemical energy mation packets, the nanonetwork is highly sensitive to
into mechanical work at a nano-scale [16]. Their use as these conditions and the communication process can be
information shuttles or communication carriers for nano- negatively affected by sudden variations of the environ-
machines within a short-range has been widely proposed mental conditions.
[21,46,54]. These molecular motors can be found in In molecular communication based on molecular mo-
eukaryotic cells in living organisms. tors, the communication process includes one transmitter
Inside the cells, molecular motors are aimed at trans- and only one receiver. When the communication process
porting essential particles among organelles during differ- occurs, the information molecule is altered and the en-
ent stages of the cell life cycle. They travel or move along coded information is lost. Therefore the molecule informa-
molecular rails called microtubules. These microtubules tion restricts the communication process to one receiver.
are widely deployed setting a complete railway network The outcome is similar to a point-to-point physical com-
for intra-cell substance transportation. The microtubules munication link in traditional communication networks.
go from the centrosome, i.e., cell organelle, outwards the To implement more complex communication schemes
cell membrane resembling a star topology in communica- including multihoping techniques, the receiver nano-ma-
tion networks. chines should be able to amplify, decode and redirect the
Specific molecular motors able to carry other molecules information.
use these intracellular molecular rails. Depending on the On the transmitter side, the information molecules
cargo, molecular motors move at a speed up to 400 mm/ are loaded on molecular motors, which transport the
Molecular rail
TX
Encoder Molecular motor
RX
Decoder
De de
Fig. 4. System components in molecular motors communication systems.
information along the microtubules to the receiver. Encoding. This task involves the generation of the infor-
The packets can be encapsulated in vesicles. A vesicle is a mation molecules. When an external stimulus is applied
fluid or an air-filled cavity that can store or digest cellular to transmitter nano-machines, they generate these
products [1]. The objective if this encapsulation of the information molecules. The encoding process consists
information is twofold [48]. First, it allows enhancing of selecting the right molecules that represent the infor-
the compatibility between the information molecule and mation or the reaction to be invoked at the receiver.
the molecular motor, enabling the use of diverse types Thus, it is possible to control the reaction at the receiver
of molecules as information packets. Second, the by selecting the proper stimulus applied to the transmit-
encapsulation protects the information molecules avoiding ter nano-machine.
them to react with antagonistic receptors present in the Transmission. This is a key task in this scenario and fur-
medium. ther research is needed to establish the process to attach
The network infrastructure should be deployed prior the information packet to carrier molecules in an accu-
to the beginning of the communication process. Several rate way. The feasibility of this process is based on
microtubules could be deployed to interconnect one ligand-receptor binding process [41]. A ligand molecule,
node, i.e., nano-machine, with many others. Depending usually a protein, can bind to another larger molecule
on the nanonetwork infrastructure, a transmitter nano- referred as receptor according to the affinity between
machine will be able to use unicasting or multicasting them. In chemical terms, affinity is defined as the trend
mechanisms. To implement the first mechanism, the of dissimilar elements to form chemical compounds
transmitter should be able to select a specific molecular based on their electronic properties. The transmitter
rail to transmit the information molecule to the intended nano-machine should guarantee the high affinity
receiver. To achieve a multicast transmission, the trans- between the information molecules and the molecular
mitter could release several molecules, containing each motors. If this affinity exists, the information molecule
one the same data, which are self-assembled onto molec- can bind to the molecular motors to start the propaga-
ular motors traveling on different molecular rails and tion process. Encapsulation techniques can be used to
hence different destinations. The propagation of molecu- ensure the affinity between the information molecule
lar motors along a microtubule is unidirectional. The and the molecular motors. Vesicles are biological cap-
polarity of the microtubule indicates the movement sules with high affinity with molecular motors, there-
direction of specific molecular motors, e.g., kinesin moves fore, they can be used as standard interfaces between
towards the (+) end of the microtubule, and dynein to- different information molecules and molecular motors.
wards the ( ) end. Thus, bidirectional communication Other biological process such as cell fission, reproduc-
links can be obtained using different molecular motors tion or pore formation could also be used to release
or a pair of opposite microtubules between two nano- information packet to the medium [48].
machines. Propagation. This part of the process refers to the move-
ment of the information molecules through the medium.
5.2. Communication process using molecular motors Microtubules or molecular rails interconnecting nano-
machines restrict the movement to themselves. As a
Molecular motors are used to carry vesicles containing result, molecules move in the direction of these rails
information molecules that are transmitted from the trans- instead of diffusing or moving randomly through the
mitter to the receiver. To facilitate the reception, the trans- medium. In this scenario, the propagation is similar to
mitter uses protein tags that bind to specific receptors on propagation of electrical signals through conducting
receiver nano-machines. Once the infrastructure is de- materials. The difference lies on the propagation speed,
ployed between the transmitter and receiver nano-ma- which will depend on the information molecule, the
chines, the process includes the following tasks [46]: molecular motors and the molecular rail. The natural
domain for molecular motors is intra-cell communica- Second, we could use a set of messengers, i.e., chemical
tion. However, new advances in biomolecular science agents, to obtain different signal transduction and decod-
can enable inter-cell and bio-hybrid scenarios, as ing results. The combination of different messengers could
reported in [36]. lead to different results and could be used to adapt the
Reception. It is the process in which molecular motors propagation parameters to a specific environment. The li-
containing information molecules arrive at the receiver gand-receptor binding principle is one of the most impor-
nano-machine. The information molecules are detached tant processes participating in the information transfer
from the molecular motors. This is achieved thanks to among messengers. This process consists in the bounding
the affinity between the protein tags or the molecular of two molecules resulting in a local reaction, which in turn
encapsulation and receptors at the receiver. A receiver can trigger other processes.
can have several reception properties in order to detach If cells are deployed separately in the chemosignal
different information molecules from the molecular pathway, as it is shown in Fig. 5b, the information mole-
rails. Similar to the transmission, the extraction of cule, i.e., the ligand, binds to a molecular receptor located
information from a vesicle can also be done through on the external membrane of the cell. This binding gener-
different cellular processes such as fusion or pore forma- ates an inner cell signal, which can be decoded by cell com-
tion [58]. ponents. In this case, the ligand is considered as the first
Decoding. The receiver nano-machine invokes the messenger while the inner signal molecules are considered
desired reaction according to the received information as second messengers of the chemosignal pathway. First
molecule. These biological reactions depend on the messengers are molecules that transport the information
information molecule sent by the transmitter nano- outside the cell. Complementarily, second messengers
machine. A nano-machine can be equipped with several transport the information inside the cells. Membrane
receptors. Each receptor would be able to react to a spe- receptors convert the first messenger signals into second
cific information molecule. The decoding can be highly messenger signals by chemical reactions.
associated to these specific receptors. For instance, each When cells are located next to each other, as it is shown
receptor can be mapped to a specific action of the in Fig. 5a, they can be connected through gap junctions.
receiver nano-machine. Another option is to decode These biological gates allow different molecules and ions
the information molecules inside the nano-machines. to pass freely between cells [1]. In this deployment sce-
In this case the nano-machine could have one receptor nario, the signal travels along cells using second messen-
and the different messages should use a common inter- gers, such IP3 and without the intervention of first
face such as vesicles. As we can see, molecular motors messengers. The IP3 is a messenger that provokes the re-
just provide a means to transport the information from lease of calcium ions by cell organelles. Thus, the diffusion
one point to another. Nano-machines will have to of IP3 through gap junctions propagates a Ca2+ wave along
include all the mechanisms to support traditional net- the interconnected cells.
work tasks such as message coding/decoding, multi- Several cellular components participate in the flux reg-
hopping and routing. ulation of Ca2+ that makes signal propagation possible. The
storage of Ca2+ inside the cell is enabled by certain proteins
6. Short-range communication using calcium signaling of the cytoplasm and organelles such as the endoplasmatic
reticulum that can act as Ca2+ buffers or reservoirs. Extra-
Inter-cell communication based on calcium signaling is cellular mechanisms, such as ion channel located on the
one of the most well-known molecular communication cell membrane, are also involved in this process in order
techniques. It is responsible for many coordinated cellular to maintain this finite resource.
tasks such as fertilization, contraction or secretion [11]. Calcium signaling provides a mean to interconnect
Calcium signaling is used in two different deployment sce- neighboring cells. Unlike communication based on molec-
narios. It can be used to exchange information among cells ular motors and molecular rails, as explained in Section 5,
physically located one next to each or among cells de- calcium signaling provides more flexible transmission
ployed separately without any physical contact. Depending schemes. Using calcium signaling, all the surrounding
on the scenario, the propagation of the chemosignals in- nano-machines can receive a message sent by a unique
cludes different messengers such as ATP substance, cal- transmitter. This communication technique is similar to
cium ions (Ca2+) or inositol 1,4,5-triphosphate (IP3) broadcast networks in which all the transceivers located
among others. in the transmission range of the transmitter can sense
The description of the sequential propagation of the the electromagnetic signal.
chemosignals driven by different messengers is known as
the chemosignal pathway. One messenger transports the 6.1. Communication features
information until certain point of the pathway where the
information is transferred to another messenger. The infor- Calcium signaling can be used for short-range commu-
mation transfer from one messenger to another continues nication among several nano-machines [50]. Similar to
until the information reaches its destination. This multi- natural models, nano-machines should be near each other.
messenger propagation scheme presents two advantages. Similar to the natural models, the propagation of the
First, the signal can be amplified at different levels of the information can be performed in two different
chemosignal pathway. The amplification is usually done schemes depending on the deployment of the nano-
when the information is transferred among messengers. machines:
TX
Encoder RX
Calcium Decoder
Signalin Gap
Junctio
TX
Encoder RX
Diffusion
Calcium Process
Decoder
Signaling
Fig. 5. Signal propagation in calcium signaling communication systems by (a) gap junctions signal forwarding and (b) by diffusion.
Direct access. If nano-machines are physically con- These two propagation schemes enable the formation of
nected, Ca2+ signals travel from one nano-machine to networks supporting multicast or broadcasting transmis-
the next one through the gates, as shown in Fig. 5a. sion mechanisms. The overall communication system
These gates should work similarly to the gap junctions could work as follows: transmitter and receiver nano-ma-
allowing the flux of ions and molecules from one chines are connected to each other through a signaling net-
nano-machine to the interior of another nano- work consisting of interconnected nodes, which propagate
machine. the information using Ca2+ signals.
Indirect access. If the nano-machines are not in direct Due to the close interaction between nano-machines,
contact, the transmitter nano-machine should be able the propagation of the information is not affected by the
to release the information molecules to the medium natural speed of the medium. However, the channel is
as first messenger in the chemosignal pathway. Infor- not expected to be noiseless. Ca2+ can bind easily to
mation molecules will move through the medium fol- charged particles that can be found in the network
lowing a diffusion process. They will generate a medium. A nanonetwork could use several different mes-
calcium signal inside the receiver nano-machine. sengers to design the chemosignal pathway according to
Transmitters can encode the information varying the the working conditions. Nanonetworks should also be
concentration of first messengers as shown in aware of potential communication process running in the
Fig. 5b. Biological systems encode the information on environment. One of the potential drawbacks on using cal-
frequency and amplitude of concentration changes, cium signaling is the interference that can be caused in
usually referred to as Ca2+ oscillation and Ca2+ spikes biological process such as muscle contractions or
[11]. neurosignals.
6.2. Communication process within calcium signaling access, the propagation of first messengers containing
the information can be described by using diffusion or
For a better description of the communication process, Brownian motion models. When these information mol-
we use two different network scenarios as shown in ecules bind to the receptors of the receiver nano-
Fig. 5a and b, respectively. The direct access scenario con- machines, they are translated into Ca2+ internal signals.
tains one transmitter nano-machine and many other cells The indirect access is much more sensitive to the med-
or similar nano-machines that are able to propagate the ium conditions than the direct access. Transmitter
signal, i.e., the message. These components are physically nano-machines should consider the medium conditions
located one next to each other and they are interconnected such as wind, flow, temperature and noise to ensure that
through functional gates or gap junctions. The receiver the information molecules will arrive to the intended
nano-machine, to which the message is addressed, can be receiver.
any of these nano-machines members of the network. Reception. When using direct reception, receiver nano-
The indirect access scenario includes nano-machines that machine establishes gap junctions with the neighboring
are deployed separately and where the signals propagate cells and perceives the Ca2+ concentration from inside of
along the medium where the nano-machine are deployed. these cells. Once the message is received, receiver nano-
In these two scenarios, the communication process machine can stop the IP3 propagation by closing the
based on calcium signaling includes the following steps: gates or gap junctions connecting with other nano-
machines. In the case of indirect reception, the receptor
Encoding. This task refers to the generation of the infor- plays the most import role. They have to translate the
mation molecules. If neighboring nano-machines are information molecule into internal Ca2+ signals. A
used for the propagation of the signal as occurs in direct nano-machine could be equipped with several receptors
access scenario, the transmitter nano-machine encodes capable to detect different information molecules. This
the information using Ca2+. The information is precisely can be used to establish several parallel communication
encoded in amplitude and frequency of the function channels among different nano-machines.
describing the concentration of Ca2+ signal. These Decoding. The receiver nano-machine reacts to the inter-
encoding methods are known as amplitude modulation nal Ca2+ concentration. The concentration depends on
(AM) and frequency modulation (FM). In the indirect the influx of IP3 and Ca2+ that arrives to the receiver or
access case, the transmitter should encode the informa- on the bindings occurred between information mole-
tion in the molecule to be used as a first messenger. The cules and nano-machines receptors. The Ca2+ signal
first messengers could also be encoded using AM and can be encoded in amplitude and frequency enabling
FM techniques. An external stimulus can be used to start the activation of different processes. The basic difference
the generation encoding process. For instance, it has between the receiver and those nano-machines or cells
been reported that some mechanical stimulus applied participating in the signal propagation is that the recei-
to cells provoke the generation of IP3 substance inside ver can decode the message, while other nano-machines
the cell. The presence of IP3 unleashes the release of just receive the signal and forward it. Since calcium sig-
Ca2+. naling can be considered as a broadcast scheme, multi-
Transmission. This task involves the signaling initiation. ple receivers can decode the same message.
In direct access scheme, transmitter nano-machines
stimulate neighboring cells and consequently the signal- 7. Long-range communication using pheromones
ing process starts. The signaling generates the initiation
of propagation of Ca2+ waves. IP3, which was generated Long-range communication is referred to as the com-
previously in the transmitter nano-machine, starts flow- munication process in which the distance between trans-
ing into neighboring cells through the gates or gap junc- mitter and receiver nano-machines ranges from
tions. Thus, neighboring nano-machines would release millimeters up to kilometers. Control and communication
more Ca2+ driven by the presence on IP3 substance. In of nano-machines in long-range communication can be
the indirect access case, transmitters may initiate sig- useful in many applications, such as the military field or
naling by releasing substances to the environment. Sim- environmental monitoring.
ilar processes to cell fission or pore formation could be Nanonetworks in long-range communication scenario
used by nano-machines to release the information mol- are also inspired in biological systems found in nature.
ecules to the medium. Ants, butterflies, bees and many mammals use molecular
Signal propagation. When nano-machines use direct messages, i.e., pheromones, to communicate with mem-
access, IP3 transmitted to neighboring cells or nano- bers of the same species. Pheromones can be defined as
machines induces the release of Ca2+ from the IP3-sensi- molecular compounds containing information that can
tive Ca2+ stores. The diffusion of the IP3 substance con- only be decoded by specific receivers and can invoke cer-
tinues to new neighboring nano-machines inducing tain reactions in them. Pheromonal communication is used
again the release of Ca2+ on these nano-machines. This to build complex networks including micro and macro-
chain reaction provokes an increase of the Ca2+ concen- scale mobile actors. For instance, in ants colony, the com-
tration and as a result, the Ca2+ wave propagates across munication between members is based on pheromones
the networked nodes affected by IP3. This propagation and a whole set of social behavior primitives is encoded
can be controlled varying the permeability of the gates in these nano-messages. Another example is the long-dis-
or gap junctions. When nano-machines use indirect tance communication between butterflies using phero-
mones where molecular messages can reach the range of a machines, i.e., animals, can be considered as macro-sys-
few kilometers [65]. tems. However, the communication is still based on
nano-transceivers and nano-messages and therefore is in
7.1. Communication features line with the definition of nanonetworks. In these biologi-
cal systems, complex neural networks and hormonal sys-
Communication using pheromones is similar to the tems act as the interface among these macro entities, e.g.,
short-range techniques described in Section 5 and 6. The brain, and the nano communication system.
communication is based on the release of molecules that
can be detected by a receiver. In long-range nanonetworks 7.2. Long-range pheromonal communication process
the channel cannot be modeled as a deterministic neither a
physical link between transmitter and receiver. Thus, con- The communication process includes five tasks similar
cepts like diffusion, flows and molecules concentration in to those found in short-range communication techniques.
the medium play a key role in the communication process. Currently, there are still no artificial nano-machines capa-
Regarding the medium, molecular communication using ble of executing the tasks described in this section but they
pheromones can be used in dry [14] and wet [40] environ- are expected to be available in the near future. The objec-
ments. Once the molecules are released to the medium, tive of the following description is to identify the existing
they can be affected by several factors, such as antagonist biological communication processes and to map them into
agents, medium flow and temperature, and dispersion. All those communication processes found in traditional com-
those factors can be considered as sources of noise, similar munication networks. This knowledge mapping can help
to those found in traditional communication channels, and to understand the biological communication mechanisms
they can compromise the transmission reliability. and to develop solutions for future nano-machines.
A key feature in long-range communication using pher-
omones is the coding system. While in traditional commu- Encoding. This process includes the selection of the spe-
nication networks the message is encoded using a binary cific pheromones or appropriate molecules to transmit
system, the information in long-range nanonetworks is en- the information and produce the reaction at the
coded on the molecule itself. Since messages consist of mol- intended receiver. On the biological systems found in
ecules, there is a huge quantity of possible combinations nature, animals release specific pheromones to invoke
that can be used to transmit data. Moreover, messages certain reactions at the receivers. For instance, the
can be compounded by several different molecules allow- female Douglas-fir beetle releases pheromones to attract
ing even more combinations to encode the information. the male to the host tree. When the male detects these
The reception of the transmitted molecules is realized pheromones, it transmits an acoustic signal to stop the
by molecular receptors located on the receiver, as depicted sexual pheromones production and also releases Doug-
in Fig. 6. This phenomenon is based on the ligand-receptor las-fir anti-odors to avoid the detection of the host by
binding process as occurs within calcium signaling trig- other males. Another example of coding through mole-
gered by first messengers. A ligand is a molecule that inter- cules can be found in colonies of bees. Honeybees use
acts with a protein, by specifically binding to this one. In up to 15 known glands in their molecular communica-
molecular communication using pheromones, the receptor tion process. The released message is not a single com-
proteins can be considered as the receiver nano-machine ponent but rather a complex molecular structure
antenna or transducer, which transforms energy contained compound by different chemicals. Different pheromones
in the message into a reaction at the receiver. can be used as sexual, alarm, marking, attraction or
Nanonetworks based on pheromonal communication aggregation and orientation messages.
are good examples of scalable molecular communication Transmission. This process consists of releasing the
systems. In biological communication systems based on selected pheromones during the encoding process to
pheromones, the information is encoded on molecules at the medium. Since pheromones can be released to
nano-scale, although the transmitter and receiver nano- the medium through physiological fluids, molecular
micro
Micro-system Micro-system
Scale Receptors
Encoder
nano
TX RX
Nano-machine Nano-machine
Pheromones
(the message)
Fig. 6. Conceptual diagram of a pheromonal communication. Biological models provide a useful example of molecular communication scalability.
messages can be in liquids or gases. The transmission of these technologies leverages the continuous development
information is defined as a voluntary action of the trans- of new tools, such as simulators [18], scanning probe
mitter. It is important to emphasize the voluntary char- microscopes [44], or lithography machines able to pattern
acter of the transmission, otherwise it is not considered nano-metric structures.
as a communication message. For instance, odors can Over the last years, novel molecular manufacturing
contain information and can trigger specific behaviors techniques are enabling the development of more ad-
at the receivers, but usually they are not transmitted vanced nano-machines. Using nanonetworks, these nano-
voluntarily and therefore they cannot be considered as machines can be interconnected to realize more complex
an example for nanonetwork communication. tasks in a coordinated and complementary manner. First
Propagation. The propagation of pheromones, from the developments in nanonetworks are inspired by biological
transmitter to the receiver nano-machine, can be mod- systems based on molecular communication.
eled using diffusion processes where each molecule is Recently, two molecular communication schemes have
subjected to Brownian motion. The diffusion of mole- been proposed based on natural models. These schemes
cules or propagation is very sensitive to environmental are based on inter and intra-cell molecular communication
conditions such as temperature, viscosity and pressure. techniques [57]. Additionally, in this paper we propose a
Antagonist molecules present in the medium can also third communication scheme based on pheromones. These
affect the propagation negatively by modifying the infor- three communication schemes are examples for short or
mation molecules before they reach the destination. In long-range molecular communication observed in nature.
biology, the reception of pheromonal messages is stud- They are proposed as basic models for the development
ied by measuring the concentration level of pheromones of future nanonetworks.
near the intended receiver [13]. These communication Nanonetworks are not only related to the molecular
models based on concentration level and diffusion mod- communication techniques, but also to nano-machines,
els, can help to determine some parameters, such as the which are able to communicate at this level. The nanonet-
sensitivity needed in the receptor to detect the molecular works development roadmap includes several stages, in
messages. The model can also help to develop channel- which an interdisciplinary scientific approach is needed
multiplexing mechanisms and to assess the channel to address all the posted research challenges.
capacity according to the propagation characteristics.
Reception. Once the information message reaches the 8.1. Development of nano-machines, testbeds and simulation
receiver, it can use receptor proteins to detach the mol- tools
ecule from the carrier. These receptors can be located on
the physical surface of the receiver. Receptors are pro- One of the first phases in the nanonetworks roadmap is
teins with a high molecular affinity to pheromonal mes- aimed at developing nano-machines including molecular
sages, so that they can bind to them. The ligand-receptor transceivers. Latest efforts on nanotechnologies enabled
binding process also depends on the environmental con- the creation of functional nano-structures that introduce
ditions. Special structures can be included in nano- switching, memory, and light-emitting behaviors [8].
machines for this task, e.g., the vomeronasal organ that These are still very simple but they will lead to more com-
acts as the receiver for pheromonal communication in plex nano-machines, which will be capable of performing
most mammals [14]. This biological organ is a blind- specific communication processes. Future nano-machines
ended mucus-filled tube, located in the nasal septum are expected to operate autonomously, and also to include
[23]. The vomeronasal sensory neurons (VSNs) trans- self-assembly, self-replication, locomotion and communi-
form these received molecules into bioelectric signals cation capabilities as described in Section 4.
that are transmitted to the brain and later decoded into Despite the current existence of simulation tools for
a specific reaction. molecular assembly, and biological and genetic systems,
Decoding. This process is referred to the interpretation of there is none for nanonetworks up to now. Simulation
the information transmitted or the reaction invoked by tools should allow the use of different nanonetwork topol-
the received message. For instance, in some insects the ogies and molecular communication schemes such as cal-
reception organs includes many different receptors that cium signaling or networks based on molecular motors. It
can be sensitive to different molecules or messages. The should also include the medium parameters that affect
molecular receptor of the fruit fly is its antennae and the the propagation of the information molecules, and allow
maxillary palps that include 1300 olfactory receptor the selection of different carriers to transport the
neurons (ORNs). These ORNs, which are connected to information.
the brain, can decode 40 different odors. The decoding Simple nano-machines or molecular transducers can be
system is embedded in the reception organs and can considered for the development of first nanonetworks
be expressed as spatial-temporal activation patterns of testbeds for molecular communication solutions. This is
the receptors. the case of robotic micro-noses, which could be used to
measure concentration level of certain molecules in the
environment [33], and therefore act as molecular receiv-
8. Research challenges in nanonetworks ers. Using molecular releasers as transmitters, and sys-
tems like the robotic noses, developments in signal
The interest in nanotechnologies is growing while more modulation, channel models, and medium access could
applications are being proposed. The potential impact of be tested.
8.2. Theoretical approach: basis for a new communication described using a particle diffusion model. Uncontrolled
paradigm medium conditions such as rain, obstacles, wind or tide,
can also affect the communication pathway. Prior to the
A typical communication process includes the following development of communication mechanisms or protocols,
phases: it is important to develop, analyze and understand the
channel model and the molecular signal propagation fea-
The encoding phase in which the transmitter forms the tures. Brownian motion models were successfully used to
information molecule. describe the free movement of particles in fluids [53].
The transmission or release of these molecules to the Using similar models, the communication based on
environment. diffusion of pheromones in ant colonies has been described
The propagation of the information molecules trough in [13]. These models can help to develop the channel and
the medium. propagation models for nanonetworks. Transmitter and re-
The reception of the information molecules. ceiver binding features can be added to these propagation
The decoding of the received information molecules. models to assess the molecular channel capacity [2].
Similar models, but including molecular propagation prin-
First nanonetworks are based on many biological com- ciples, can be used to explore more complex encoding
munication processes. However, the communication tasks techniques for molecular transmissions, such as AM and
occurring among these biological components are still FM. If molecular motors are used as carriers, the propaga-
not completely understood. tion is restricted to the nanonetwork infrastructure and
When talking about nanonetworks, the first questions therefore the communication process can be considered
that arise are regarding the information encoding and later to be more deterministic. The signal propagation speed
decoding. Based on the three bio-inspired communication using this physical channel as well as the reliability of
schemes presented in Sections 5–7, we can identify two the transmission using molecular rails still need to be
different methods to encode the information in molecular measured.
communication. The first method encodes the information
in the information molecule itself, e.g., structure or polar- 8.3. Knowledge transfer: architectures and protocols
ity. Depending on the molecular structure the message will
bind only to specific receptors, resulting in a channel de- Once the basic nanonetwork components are built, the
fined by these information molecules and proper receptors. transmission is controlled and the propagation is under-
Thus, the communication system could use different mol- stood, advanced networking knowledge can be applied to
ecules and receptors to encode the information as spa- design and realize more complex nanonetworks. The
tial-temporal activation patterns of the receptors, e.g., development of the nanonetworks can be done using a lay-
decoding of odors in fruit flies. The second method encodes ered architecture including medium access protocols, rout-
the information in the fluctuations of the concentration of ing schemes and application interfaces.
ions, similar to amplitude and frequency modulation A medium access control (MAC) protocol is needed to
methods used in traditional telecommunication systems. define and apply mechanisms to ensure a fair use of
How nano-machines decode these different fluctuations transmission channel. In biological molecular communi-
is still uncertain although the activation of some cellular cations, most of the channel access schemes are based
processes according to these variations has already been on code division. In nanonetworks, many molecular cod-
proven [11]. ing schemes could be used to transmit the information
The transmission and reception of information mole- while these molecules do not interfere with each other
cules is more related to the nano-machines, more specifi- and do not affect the medium, e.g., changing the viscos-
cally with the molecular transceiver. There are many ity. An example of biological channel access based on dif-
open questions regarding the transmission and reception ferent codes can be found in pheromonal communication.
such as (i) how to acquire new molecules and modify them In this example, each communication channel uses differ-
to encode the information, (ii) how to manage the received ent information molecules that can only be decoded by
molecules, and (iii) how to control the binding processes to intended receivers, resulting in multiple communication
release the information molecules to the medium. In [52], channels over the same medium, one per species. An-
models for flux and concentration detectors are presented. other medium access technique used by biological sys-
Such models demonstrate the dependence of the binding tems is based on the modulation in frequency (FM) and
process on the medium conditions. This kind of models amplitude (AM) of the molecular signal. According to
can help to understand the interaction between the recep- these last techniques, the communication channels
tors and the information signal, and to assess some trans- among nano-machines can be established using different
ceivers features such as the molecule release rate or the frequencies or signal amplitudes. Each frequency and
sensitivity of the receptor. amplitude channel can be decoded by specific nano-
The propagation of the communication signals in nan- machines.
onetworks is totally different than in classical communica- For more complex networks, an addressing scheme is
tion networks. Nanonetworks use molecules instead of needed. The packet should include the information about
electromagnetic or acoustic waves. The propagation of its origin and destination to allow bidirectional and multi-
these molecules, which is subject to different medium hop communications. How to include this information in
parameters such as viscosity, temperature or pH, can be an information molecule is still an open issue. However,
according to natural models of nanonetworks, the informa- sors, actuators and devices at nano-scale, if they are not
tion is usually encoded and broadcast without including a able to communicate to cooperate to perform more com-
specific address of the transmitter nano-machine. In bio- plex tasks. This need for a communication network will
logical nanonetworks it is assumed that only the autho- be more plausible with the increased complexity of devel-
rized transmitters can have access to the channel and oped nano-devices.
send the encoded message. When this message arrives at Molecular communication seems to provide efficient
the receptor, it reacts according to the molecular informa- mechanisms for networking of nano-machines. It repre-
tion ignoring its origin. Thus, these nanonetworks can be sents a complete new communication paradigm in which
considered as data centric networks. This behavior can be the information is encoded into molecules. In this paper
observed in pheromonal communication, or in living cell the term ‘‘nanonetwork” was defined as the interconnec-
networks using calcium signaling. In these examples, the tion of multiple nano-machines using molecular communi-
reactions at the receiver are triggered by the molecular sig- cation. Nanonetworks demand innovative solutions to
nal itself, which does not contain any specific data about create reliable molecular communication channels among
the origin. This principle is also the basis for drugs delivery nano-machines. First developments are bio-inspired by
and the use of supplementary hormones in healthcare. By existing biological nanonetworks. At nano-level, many
contrast, the destination address is crucial in data centric components and communication process has been studied
networks. Nano-machines participating in the propagation from a biological or chemical point of view.
pathway should be able to route a packet towards the right Despite being a novel communication paradigm that re-
receptor based on the destination address. Addressing and quires an interdisciplinary approach, information and com-
routing schemes are not trivial, and solutions will be devel- munication technologies (ICT) are called to be a key
oped according to the level of complexity of nano-ma- contributor for the evolution of the nanonetworks. Net-
chines participating in the propagation of the molecular work architectures, channel models, nano-machines and
signals. In natural models encoded signals are broadcast transceivers architectures, medium access control and
in a medium where the intended receivers are located. This routing protocols are some of the contributions that are ex-
simple mechanism is used to reach the intended receivers pected from the ICT field.
of the network.
Nanonetworks are developed for a specific purpose or Acknowledgement
application. The objectives are described in a main control-
ler or are distributed in the internal code of the participat- The authors would like to thank Eylem Ekici, Mehmet C.
ing nano-machines. All the interfacing aspects between the Vuran, Linda Jiang Xie, Tommaso Melodia, and Dario
controller of a nano-machine, in which the application Pompili for their valuable comments.
tasks are described, and the nanonetwork must be ex-
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Ian F. Akyildiz (M’86-SM’89-F’96) received Faculty Achievement Award from School of ECE, Georgia Tech. He has been
the B.S., M.S., and Ph.D. degrees in Computer a Fellow of the Association for Computing Machinery (ACM) since 1996.
Engineering from the University of Erlangen-
Nuernberg, Germany, in 1978, 1981 and 1984,
respectively. Fernando Brunetti was born in Asunción,
Currently, he is the Ken Byers Distinguished Paraguay. In 2004, he received his Electrical
Chair Professor with the School of Electrical Engineering diploma from the Universidad
and Computer Engineering, Georgia Institute Católica de Asunción, in Paraguay. In 2005, he
of Technology, Atlanta, and Director of received a second M.S. degree from the School
Broadband Wireless Networking Laboratory. of Informatics of the Universidad Politécnica
He is an Editor-in-Chief of Computer de Madrid (UPM), Spain. Currently, he is
Networks Journal (Elsevier) as well as the affiliated to the Bioengineering Group of the
founding Editor-in-Chief of the AdHoc Net- Industrial Automation Institute, Spanish
work Journal (Elsevier) and the Physical Communication Journal (Else- Research Council (CSIC) and is a Ph.D. candi-
vier). His current research interests are nanonetworks, cognitive radio date in the School of Telecommunications
networks, wireless mesh networks and next generation sensor networks. Engineering of the UPM. He has been a visit-
He received the ‘‘Don Federico Santa Maria Medal” for his services to the ing researcher at the Broadband Wireless
Universidad of Federico Santa Maria, in 1986. From 1989 to 1998, he Networking Laboratory, Georgia Institute of Technology, Atlanta, from
served as a National Lecturer for ACM and received the ACM Outstanding October 2007 to March 2008. His current research interests are nanon-
Distinguished Lecturer Award in 1994. He received the 1997 IEEE Leonard etworks, body area networks, and inertial sensing.
G. Abraham Prize Award (IEEE Communications Society) for his paper
entitled ‘‘Multimedia Group Synchronization Protocols for Integrated
Services Architectures” published in the IEEE Journal of Selected Areas in Cristina Blázquez was born in Barcelona
Communications (JSAC) in January 1996. He received the 2002 IEEE Harry (Spain) in 1983. She is pursuing her M.S.
M. Goode Memorial Award (IEEE Computer Society) with the citation ‘‘for degree in Telecommunication Engineering
significant and pioneering contributions to advanced architectures and from the ETSETB-Telecom Barcelona, Univer-
protocols for gíreles and satellite networking”. He received the 2003 IEEE sitat Politècnica de Catalunya (UPC), Spain.
Best Tutorial Award (IEEE Communication Society) for his paper entitled From August 2007 she is working at the
‘‘A Survey on Sensor Networks,” published in IEEE Communications Broadband Wireless Networking Laboratory,
Magazine, in August 2002. He also received the 2003 ACM Sigmobile School of Electrical and Computer Engineering
Outstanding Contribution Award with the citation ‘‘for pioneering con- in Georgia Institute of Technology, Atlanta.
tributions in the area of mobility and resource management for gı´reles
communication networks”. He received the 2004 Georgia Tech Faculty
Research Author Award for his ‘‘outstanding record of publications of
papers between 1999 and 2003”. He also received the 2005 Distinguished

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Nano Survey

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Computer Networks 52 (2008) 2260–2279

Contents lists available at ScienceDirect

Nanonetworks: A new communication paradigm

1. Introduction lieved humans would create increasingly tinier and pow-

Humans Insects Cell

Fig. 1. Approaches for the development of nano-machines.

[18]. The most complete nano-machines will include the 2 4

Nanotechnologies can also have several applications in 4. Communication among nano-machines

Communication Traditional Molecular

Low propagation Decoder

Encoder Molecular motor

Fig. 4. System components in molecular motors communication systems.

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