A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications

Abstract

With the huge advancement of nanotechnology over the past years, the devices are shrinking into micro-scale, even nano-scale. Additionally, the Internet of nano-things (IoNTs) are generally regarded as the ultimate formation of the current sensor networks and the development of nanonetworks would be of great help to its fulfilment, which would be ubiquitous with numerous applications in all domains of life. However, the communication between the devices in such nanonetworks is still an open problem. Body-centric nanonetworks are believed to play an essential role in the practical application of IoNTs. BCNNs are also considered as domain specific like wireless sensor networks and always deployed on purpose to support a particular application. In these networks, electromagnetic and molecular communications are widely considered as two main promising paradigms and both follow their own development process. In this survey, the recent developments of these two paradigms are first illustrated in the aspects of applications, network structures, modulation techniques, coding techniques and security to then investigate the potential of hybrid communication paradigms. Meanwhile, the enabling technologies have been presented to apprehend the state-of-art with the discussion on the possibility of the hybrid technologies. Additionally, the inter-connectivity of electromagnetic and molecular body-centric nanonetworks is discussed. Afterwards, the related security issues of the proposed networks are discussed. Finally, the challenges and open research directions are presented.

Full text

1
A Comprehensive Survey on Hybrid
Communication for Internet of Nano-Things in
Context of Body-Centric Communications
Ke Yang, Dadi Bi, Yansha Deng, Rui Zhang, M. Mahboob Ur Rahman, Najah Abu Ali, Muhammad Ali Imran,
Josep M. Jornet, Qammer H. Abbasi, and Akram Alomainy
Abstract—With the huge advancement of nanotechnology over
the past years, the devices are shrinking into micro-scale, even
nano-scale. Additionally, the Internet of nano-things (IoNTs) are
generally regarded as the ultimate formation of the current
sensor networks and the development of nanonetworks would
be of great help to its fulfilment, which would be ubiquitous
with numerous applications in all domains of life. However, the
communication between the devices in such nanonetworks is
still an open problem. Body-centric nanonetworks are believed
to play an essential role in the practical application of IoNTs.
BCNNs are also considered as domain specific like wireless sensor
networks and always deployed on purpose to support a particular
application. In these networks, electromagnetic and molecular
communications are widely considered as two main promising
paradigms and both follow their own development process. In
this survey, the recent developments of these two paradigms are
first illustrated in the aspects of applications, network structures,
modulation techniques, coding techniques and security to then
investigate the potential of hybrid communication paradigms.
Meanwhile, the enabling technologies have been presented to
apprehend the state-of-art with the discussion on the possibility
of the hybrid technologies. Additionally, the inter-connectivity
of electromagnetic and molecular body-centric nanonetworks is
discussed. Afterwards, the related security issues of the proposed
networks are discussed. Finally, the challenges and open research
directions are presented.
Index Terms—Nano-communication, nano-technology, tera-
hertz, molecular communication, hybrid networks.
(Ke Yang and Dadi Bi are both first authors.) (Corresponding author:
Yansha Deng.)
K. Yang is with the School of Marine Science and Technology,
Northwestern Polytechnical University, Xi’an, 710072, China (e-mail:
k.yang@nwpu.edu.cn).
D. Bi and Y. Deng are with the Department of Engineering,
King’s College London, London, WC2R 2LS, U.K. (e-mail:{dadi.bi, yan-
sha.deng}@kcl.ac.uk).
R. Zhang is with the Department of Information and Electronic, Beijing In-
stitute of Technology, Beijing, 100081, China (e-mail: rui.zhang@bit.edu.cn).
M. M. U. Rahman is with the Department of Electrical Engineering,
Information Technology University, Lahore 54000, Pakistan (e-mail: mah-
boob.rahman@itu.edu.pk).
N. A. Ali is with the College of Information Technology, United Arab
Emirates University, Al Ain, 15551, United Arab Emirates (e-mail: na-
jah@uaeu.ac.ae).
M. A. Imran and Q. H. Abbasi are with the Department of Electronics and
Nanoscale Engineering, University of Glasgow, Glasgow, G12 8QQ, U.K.
(e-mail: {muhammad.Imran, qammer.abbasi}@glasgow.ac.uk).
J. M. Jornet is with the Department of Electrical and Computer Engi-
neering, Northeastern University, Boston, MA 02120, USA (e-mail: jmjor-
net@northeastern.edu).
A. Alomainy is with the School of Electronic Engineering and Computer
Science, Queen Mary University of London, London, E1 4NS, U.K (e-mail:
a.alomainy@qmul.ac.uk).
I. INTROD UC TION TO NAN ON ET WORKS
In upcoming years, the advancement in nanotechnology is
expected to accelerate the development of integrated devices
with the size ranging from one to a few hundred nano-
meters [1], [2]. With the aim of shrinking traditional ma-
chines and creating nano-devices with new functionality, nano-
technologies have produced some novel nano-materials and
nano-particles with novel behaviours and properties which
are not observed at the microscopic level. The links and
connectivity between nano-devices distributed through collab-
orative effort lead to the vision of nanonetworks, after the
concept of nano-machine is proposed. The limited capabilities
of nano-machines in terms of processing power, complexity
and range of operations can be expanded by this collaborative
communication. It is changing the paradigm from the Internet
of Things (IoT) to Internet of Nano-Things (IoNTs) [3] which
shares the same development path as the nanonetworks.
Communication between nano-machines in IoNTs can be
set up through nano-mechanical, acoustic, chemical, electro-
magnetic (EM) and molecular communication approaches [1].
Unfortunately, traditional communication technologies are not
suitable mainly due to the limitations, such as size, complexity
and energy consumption of transmitters, receivers and other
components at nano-scale [4]; thus, novel and suitable com-
munication techniques from physical layer to higher layers are
required to develop for each paradigm.
The molecular and EM communication schemes are en-
visioned as two most promising paradigms and numerous
researches have been done in these two paradigms. This
review focuses on molecular and EM approaches and presents
their backgrounds, applications, recent developments and chal-
lenges. We mainly present a comprehensive survey on the
researches that have already been done to enable the com-
munication in nanonetworks. Moreover, several aspects of the
integration of nanonetworks have been identified. We propose
to implement a hybrid communication taking advantage of
both paradigms to enhance the communication performance
and aim to broaden and realize more applications. The feasi-
bility of the novel hybrid communication is discussed based on
the requirements and enabling technologies from both micro
and macro perspectives, and the open challenges are explored
as a source if inspiration towards future developments of this
inter-connectivity.
This paper provides a structured and comprehensive review
arXiv:submit/2972834 [eess.SY] 16 Dec 2019

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on the recent literature on Body-Centric nanonetworks, an
effectual foundation of IoNTs. The main contributions of this
survey are summarized as follows.
•The various applications are classified and summarized.
•The latest advancement in physical, link, MAC, network
and application layers have been comprehensively re-
viewed in addition to security changes.
•The hybrid communication scheme by collaboratively
employing EM-based nano-communication and molecu-
lar communication together is introduced.
•Open issues and challenges for such hybrid networks are
introduced.
The rest of the paper is organized as follows. Section II
presents an overview of various communication paradigms,
numerous applications and standardization. Section III dis-
cusses the general requirements and performance metrics of
the envisioned body-centric nanonetworks, while Section IV
illustrates the enabling and concomitant technologies which
would help the development of nanonetworks from EM and
bio perspective, respectively. The architecture of the network
and performance of EM and molecular communication is
discussed in Section V and Section VI, respectively. The
connectivity of both communication methods are discussed
in Section VII. In Section VIII, the researches related to the
security issues are discussed. In the end, the challenges and
open problems are discussed with a brief conclusion.
II. ANOVERVIEW OF NANONETWORKS
According to Feynman, there is plenty of room at the bottom
[5]. Based on such statement and the considerable develop-
ment of nano-technology, Prof. Metin Sitti has proposed that
in the near future the network would go down to the nano-
scale if the nano robots and molecular machine are adopted
as its elements [6]. Thus, the concept of nano-networks was
proposed. However, the connection between nano-devices in
such networks would be a challenge, leading to the study on
nano-communication [7], [8]. Therefore, nano-communication
can be defined as the communication between nano-devices
where the communication principles should be novel and
modified to meet the demands in the nano-world. To make it
clearer, four requirements are summarized in IEEE P1906.1 [9]
in the aspects of components, system structure, communication
principles and etc.,
A. Nano-communication paradigms
To make the network work well, the communication be-
tween the nano-devices needs to be linked. In [8], nano-
communication is studied in two scenarios: (1) Communi-
cation between the nano-devices to the micro/macro-system,
and (2) Communication between nano-devices. Furthermore,
molecular, electromagnetic, acoustic, nano-mechanical com-
munication can be modified to nano-networks [10], summa-
rized in our previous work in [11]. Based on the burgeoning
of the nanotechnology, a fresh model of mechanical commu-
nication, i.e. touch communication (TouchCom), was also pro-
posed in [12], where bunches of nano-robots were adopted to
play as the message carriers. In TouchCom, transient microbots
(a) Scheme of the procedure
(b) Capture of the movie showing how the vital health information was
shown
Fig. 1: Health monitoring system described at the film of The
Circle (from 34:35 to 35:55)
(TMs) [13]–[15] were used to carry the drug particles and they
are controlled and guided by the external macro-unit (MAU)
[16], [17]. These TMs would stay in the body for some time
whose pathway is the channel and the operations of loading
and unloading of drugs can be treated as the transmitting and
receiving process. The channel model of TouchCom could be
described by the propagation delay, loss of the signal strength
in the aspects of the angular/delay spectra [12]. A simulation
tool was also introduced to characterize the action of the nano-
robots in the blood vessel [17].
B. Applications of nanonetworks
Nano-communication spans a wide area such as military,
ubiquitous health care, sport, entertainment and many other
areas, detailed description of which has been summarized and
classified in [8], shown in Table I. The main characteristic
in all applications is to improve people’s life quality and
nanonetworks are generally believed as the perfect candidate
for bio-medical fields due to bio-compatibility, bio-stability
and its dimension. Generally, the applications are classified
into two general categories, medical and non-medical as below.
1) Medical Applications: There are many biomedical appli-
cation in literature, e.g, intraocular pressure (IOP) for vision
[6] and nano robotos for cancer cells in [52]. Moreover,
nanonetworks will monitor the body status in real time and
some nano-devices can be used as tissue substitutes, i.e., bio-
hybrid implants. In the following, we present two interesting

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TABLE I: Summaries of the pictured applications [6], [8]
Biomedical [18] Environmental Industrial Military
•Active Visual Imaging for Disease Diagnosis
[19] [20] [21] [22] [23]
Health Monitor •Mobile Sensing for Disease Diagnosis
[24] [25] [26] [27] Bio-Degradation [28] Product Quality Control [29] Nuclear, Biological and Chemical Defences [30]
•Tissue Engineering
[31] [32] [33]
•Bio-Hybrid Implant
[34] [35]
•Targeted Therapy/Drug Delivery
[36] [37] [38] [39] [40]
•Cell Manipulation
[41] [19] [42] [43] [44]
Therapy
•Minimally Invasive Surgery
[45] [46] [47]
Bio-Control [48] [49] [50] Intelligent Office [51] Nano-Fictionalized Equipment [10]
Location of James
Status of SmartBlood
Health Status of James
Fig. 2: Injection of SmartBlood James Bond at the file of 007:
Spectre (from 25:12 to 25:37)
examples that come from movies, which shows the limitless
possibilities of nano network medical applications.
a) Health-Monitoring: In the movie The Circle, an ex-
ample of the health-monitor system which is installed in the
body of the lead actress May has been displayed. The whole
system consists of two parts: digestible nano-sensors and a
wristband. At first, the doctor asked May to drink a bag of
green solution with the nano-sensors in and then gave her a
wristband which should be worn all the time, shown in Fig. 1a.
The medium band would sync up with the sensors May has
swallowed while both equipments would collect data of the
heart rate, blood pressure, cholesterol, sleep duration, sleep
quality, digestive efficiency, and so on. The capture of the
movie in Fig. 1b shows the related information on the wall.
Through the wristband, all the data can be stored anywhere
May wants. Also, all the data would be shared with the related
people, like the doctor or the nutritionist.
b) Real-Time Detection: In the movie of 007: Spectre,
a technology called Smart Blood was illustrated, which is a
bunch of nano-machines/micro-chips capable of tracking Mr.
Bond’s movement in the field. They were injected into Bond’s
blood system, and the institute would monitor Bond’s vital
signs from anywhere on the planet, shown in Fig. 2. It is not
just a scientific idea in the movie because several researchers
are working on various kinds of injectable substances that can
identify cancer cells. The folks at Seattle-based Blaze Bio-
science are among the pioneers.
c) Drug Delivery: It is believed that the nanonetworks
can not only sense the information but also make some actions
when needed. The most trustworthy application would go for
real-time glucose control. The nano-sensors spreading in blood
vessels can monitor the glucose level; at the same time, the
nano-machines could release the insulin to regulate the glucose
level (shown in Fig. 3). With such technologies, people with
diabetes would not need to needle themselves and inject the
medicine in public which would cause the embarrassment and
infection if the operation is not correct. Also, the signal can
also be sent to related people through wearable devices or
smart phones to let them help the patients build a healthy
habit.
Fig. 3: Nanonetwork for drug delivery
2) Non-Medical Applications:
a) Entertainment (VR/AR): Currently, the realization of
the visual/augmented reality requires the help of external
devices like smartphones, shown in Fig. 4a which is bulky
and not convenient. If the nano-devices are spreading over
the eyes, near the retina, they would help people see things
as required. At the same time, the nano-machines spreading
over the body would excite different parts of human to make
the experience real. Take the Pokemon shown in Fig. 4b as an
example, the nano-machines in the eyes would help people see
the monster in real world. If you want to catch the monster,
all you need to do is just throwing you arm and the sensors in
the arm would capture this action and judge if it is the right
path and strength to capture the monster. If the monster fight,
such as the shock generated by Pikachu, the nano-machines
on the skin would cause some itches or aches to you. It is
widely thought that such new technologies would cause radical
changes to the current game experiences and would also help
people gain the experiences they never have.

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(a) current technology for visual/augmented reality
(b) Envisioned scenario for future visual/augmented reality
Fig. 4: Nanonetwork for entertainment
Fig. 5: Network architecture of the e-office [51]
b) E-Environment: The illustration of the e-office is
shown in Fig. 5. Every elements spreading over the office
or the internal components are nano devices permanently
connecting to the Internet. Thus, the locations and statuses
of all belongings can be tracked effortlessly. Furthermore, by
analysing all the information collected by nanonetworks of the
office, actuators can make the working environment pleasant
and intelligent.
c) Agriculture/Industry Monitoring: Fig. 6 shows an
example of using nanonetworks for crop-monitor [53]. Since
the plants would release typical chemical compound which
would be used to analyse the environment conditions and
plant growth condition. The structure of such monitor network
is described in [53], shown in Fig. 6a. It is said that such
systems can not only monitor growth status of the plants but
also analyse the underground soil and air conditions which can
be used as a chemical defence system.
C. Standardization of nanonetworks
To make nanonetworks function well, the IEEE has built a
standard development project: IEEE P1906.1/Draft 1.0 Rec-
(a) Network architecture
(b) Details of the nodes distribution
Fig. 6: nanonetworks for plant monitoring [53]
ommended Practice for Nano-scale and Molecular Commu-
nication Framework [9], leading by S.F. Bush. The initial
ballot was done on Jan. 2 2015 and then materials related
to SBML (Systems Biology Markup Language) was added
to make the draft complete in August, which was approved
by IEEE RevCom later in 2015. Currently, IEEE 1906.1.1 -
Standard Data Model for Nano-scale Communication Systems
is proposed to define a network management and configuration
data model for nanonetworks, written in YANG Model (Yet
Another Next Generation).
The IEEE P1906.1/Draft 1.0 specifies a framework for net-
works rather than protocols or layering. The standard defines
the framework through the use of the term, “component”, to
limit any alluding to layering or a protocol stack. The provided
services by the components remain an integral part of the
process for the framework. As such, protocols are necessary to
manage this process. The nano-scale communication network
is comprised of five fundamental components necessary for
the deployment of the network: the message carrier, motion,
field, perturbation, and specificity.
1) The Message Carrier may take the form of a particle or
a wave and is defined as the physical entity that carries
a message.
2) The Motion Component provides force that enables the
message carrier to move. Motion provides the necessary
potential to transport information through a communi-
cation channel.
3) The Field Component guides the message carrier. For
example, an internal implementation includes swarm
motion or flocking behavior while external implemen-
tations may include non-turbulent fluid flow, EM field,
a chemical gradient released to guide the movement of
bacteria, or molecular motors guided by micro-tubules.
4) Perturbation provides the service of varying Message
Carriers as needed to represent a signal. It functions like
modulation in telecommunications. Perturbation can be

5
Fig. 7: Message Carrier: CNT radio [54]
achieved via varying signals based on the number of
received message carriers, controlled dense vs. sparse
concentrations of molecules, simple on vs. sparse con-
centrations of molecules, simple on vs. off flow of
signal molecules. It uses different types of message
carriers, modifying the conformation of molecules to
represent multiple states for the component that provides
controlled change to create a signal.
5) Specificity provides the function of reception of a mes-
sage carrier by a target. It is analogous to addressing
in classical communication systems. Specificity can be
seen in the shape of a molecule or its affinity to a target,
such as complementary DNA for hybridization.
The framework also defines the relationships and how each
component is interfaced in relation to the other components.
This will allow for a broader and more encompassing defini-
tion for networking when compared to the classical networking
protocol stack and OSI layering system. Table II and III
show the function of nanonetworks components and map the
relationship between the IEEE P1906.1 framework and the
classical networking protocol stack, respectively.
An instant of the framework in an active network may in-
clude the message carrier component that transports a message,
as shown in Figs. 7 and 8 [54]. The specificity component
provides message addressing, which aids in message delivery
to the correct receiver. The perturbation component aids in
signal formation by applying necessary variations to motion
or concentration that lead to the recognition by the required
target or receiver. Finally, the message is moved across the
network physically through motion, and the field acts as a
directional vector of motion that guides the message towards
the target or receiver..
Other elements of a nanonetwork are also defined by the
framework, such as the nanonetworks interface to micro/macro
classical networks and the relay; details are given in Sec.
VII) to micro/macro classical networks and the relay, but did
not discuss the required number of interfaces to the classical
networks or the number of components required for accurate
detection of an event or performing a specific function such as
drug delivery. These issues are left for academia and industry
to provide innovative solutions.
Fig. 8: Message carrier in molecular communication [54]
III. REQUIREMENTS AND PERFORMANCE METRICS OF
BODY-CENTRIC NANONETWORKS
A. EM-Based Body-Centric Nanonetworks
1) Achievable Information Rates: The maximum achiev-
able information rate, I Rmax(sy m), with the unit of bit/symbol
based on a specific modulation scheme in a communication
system has been defined as [55]:
I Rmax(sym)=max
x{H(X)−H(X|Y)},(1)
where X and Y denote the message sent by the transmitter
and its noisy version at the receiver, respectively. Here, H(X)
represents the entropy of message X, while H(X|Y) is the
conditional entropy of X given Y. Represent the transmitted
information over the asymmetric THz band channel without
coding as a discrete binary random variable, x0and x1; then,
H(X) is given as [56]:
H(X)=−
1
Õ
m=0{pX(xm) · log2PX(xm)},(2)
where pX(xm)indicates the probability of transmitted symbol
x0named as silence and x1named as pulse. Assuming Addi-
tive Coloured Gaussian Noise (ACGN) [57] at the receiver, and
a Binary Asymmetric Channel (BAC) with Y being a discrete
random variable, the information rate (in bits/second) is given
as [58]:
I Rmax(sec)=B
βI Rmax(sym),(3)
where B represents the bandwidth of channel. βis the ratio of
the symbol interval Tsand the pulse length Tp. And the rate
of the symbols transmitted is defined as R=1
/Ts=1
(βTp).
Note that the requirements on the transceiver can be greatly
relaxed by reducing the single-user rate to increase β. Fig.
9 studies the trade-off between the information rate and the
transmission distance, for three different human body tissues
(with an EM channel of bandwidth 1 THz [59].
2) Bit Error Rate: Since EM waves propagate through
the frequency-dependent materials inside the human body, the
operating frequency has an important effect on the communi-
cation channel. [60] shows that the scattering from cells is the
major phenomenon affecting the propagation of EM waves at

6
TABLE II: An example of nanoscale communication network components [IEEE P1906.1].
Layer name Explanation Example (molecular) Example (nanotube/terahertz)
Specificity Correctly detect true ver-
sus false messages Shape or affinity of molecule to a particular target
complementary DNA for hybridization, etc.Antenna aperture, resonant fre-
quency, impedance match
Perturbation Vary concentration or
motion as needed for
signal (shockwave)
Dense versus sparse concentrations of molecules,
on versus off flow of signal molecules or motors,
conformational changes in molecules, etc.
Amplitude, frequency, or phase
modulation
Field Organized flow direction Flowing liquid applied EM field, motors attached
to microtubules, concentration gradient of chemical
molecules, swarm motion, etc.
Omni or directed with multiple
CNTs
Motion Potential communica-
tion channel in the wild
(semi-random)
Molecules diffusing through liquid, unattached
molecular motors, Brownian motion, self-propelled
motion, etc.
Wave propagation and phase ve-
locity
Message Carrier Mass and energy Molecule chain, etc. EM wave
TABLE III: An example of OSI to nanoscale communication network mapping [IEEE P1906.1].
OSI model IEEE 1906 component mapping Explanation
Application No 1906 component
Presentation No 1906 component
Session No 1906 component
Transport No 1906 component
Network Field Field may enable Message Carrier transport across multiple nodes
Data Link Specificity Motion, enhanced by Field and Specificity, enable Message Carrier to reach next-hop node
Physical Message Carrier Motion Perturbation Perturbation creates the signal transported by the Message Carrier using Motion
Fig. 9: The trade-off between Information rate and transmis-
sion distance for three different human tissues [59].
optical frequencies inside the human body. [61] does the error
analysis (at the physical layer and link layer) of an EM system
operating in THz band.
3) Symbol Error Rate: [62] studies different types of
modulators capable of setting the amplitude or phase of the
THz wave. A meta-material-based modulator was employed
to control the phase of THz wave in [63]. [64] proposes
and validates an analytic model for the plasmonic phase
modulator that starts from the dynamic complex conductivity
of graphene. By applying the model, the symbol error rate
performance of the plasmonic modulator is studied when
it is utilized to implement an M-array phase shift keying
modulation.
B. MC-Based Body-Centric Nanonetworks
1) Achievable Information Rates: The discussion of the
performance limits of the MC-based nanonetworks in terms of
achievable information rates was first initiated by [65]. Later,
Eckford computed the mutual information (i.e., the maximum
achievable information rate) for an MC channel whereby the
information was encoded into the release time of molecules
[66], and by a set of distinct molecules [67]. In a followup
work, Eckford also provided tractable lower and upper bounds
on information rate of one-dimensional MC system [68]. In
another work [69], Kadloor et. al. considered an MC system
inside a blood vessel and introduced a drift component into
the MC channel to take into account the blood flow, and
computed the information rate for the case when pulse-position
modulation is used by the emitter. Last but not the least, [70]
reported an important finding whereby it was proved that the
noise in the one-dimensional MC channel with positive drift
velocity is additive with inverse Gaussian (IG) distribution.
Below, we summarize the information rates achieved by
some very prominent MC channels.
•Timing Channel: In a timing channel, the point transmitter
encodes a message in the release time of a molecule, and
once a molecule reaches the receiver, it is fully absorbed,
thus the first arrival time determines the actual arrival
time of the molecule. For a single molecule released at
time X, its actual arrival time Ywill be expressed as [70],
[71]
Y=X+NT,(4)
where NTis the first arrival time at the receiver boundary.
For the positive drift v>0,NTfollows AIGN distribu-
tion IG( l
v,2l2
D) with the communication distance land
diffusion coefficient D. Based on
C=max
fX(x):E[X]≤mI(X,Y),(5)

7
[70] bounded from above and below the capacity of
additive IG noise channel with a constraint on the mean
of the transmitted message X. Extended from [70], the
authors in [71] studied the capacity of the same additive
IG noise channel under either an average- and a peak-
delay constraint or a peak-delay constraint, and the au-
thors in [72] revisited the capacity bounds of diffusion-
based timing channel (without drift) with finite particle’s
time.
•Concentration-encoded Channel: In this channel, concen-
tration of molecules is varied to convey information [73]–
[76]. The authors in [73] studied the mutual information
of a more specific molecular communication system with
ligand-binding receptors, where the molecules can bind
or unbind from the receiver, but without taking into
account the diffusion propagation and channel memory.
The authors in [74] modeled and measured the informa-
tion rate of various molecular communication systems
with diffusion, connected, or hybrid-aster propagation
approaches, and noise-free, all-noise, exponential decay,
and receiver removal noise model. The achievable rates
of the diffusion-based MC channel, under two different
coding schemes were studied in [75].
[76] considered concentration encoding at the emitter, a
diffusion-based MC channel with memory and noise at
the receiver, and derived the closed-form expression for
the channel capacity. To account for memory, the bounds
on capacity of the conventional memoryless Poisson
channel was extended to that of the Linear Time Invarient-
Poisson channel of diffusion-based single-hop networks
[77]. However, the reception process has not been treated
in [76], [77].
•Biological System: In [78] and [79], the capacities of
an inter-cellular signal transduction channel and bacterial
communication were studied by modelling the ligand-
reception processes as a discrete-time Markov model, and
a Binomial Channel for a bacterial colony, respectively.
The capacity analysis of molecular communication chan-
nel in a drug delivery system [80] and cell metabolism
[81] were studied using COMSOL Multiphysics and
KBase (Department of Energy Systems Biology Knowl-
edgebase) software application suite, respectively. More
detailed literature review on information theoretic study
of molecular commmunication can be found in [82].
2) Bit Error Rate: During each slot, the receiver will
receive the molecules due to the current slot as well as from
the previous slots (due to brownian motion of molecules).
This phenomenon is known as inter-symbol interference (ISI).
As the main bottleneck of bit error performance of molecular
communication system, the ISI is first characterized in [83],
and increasing attention has been focused on the bit error rate
performance characterization from then on.
•Single-Hop System with the Passive Receiver: Initial MC
works have focused on a passive (spherical) receiver that
just counts the number of received molecules in its close
vicinity without interacting with them. The bit error rate
of the MC system with a passive receiver under ISI and
no ISI was studied in [84] where the receiver implements
the optimal maximum a-posteriori probability (MAP)
rule. To improve the BER performance of the MC
systems, [85] introduced a new family of ISI-free coding
with fairly low decoding complexity. While, [86] did the
MAP based, maximum likelihood (ML) based, linear
equalizer/minimum mean-square error (MMSE) based,
and a decision-feedback equalizer (DFE) based sequence
detection. [87] introduced the enzyme reactions to the
diffusion, derived the average BER, and verified it via
the realistic particle-based simulation. All these works
point to the undesirable effect of ISI on the performance
of an MC system with a passive receiver.
•Single-Hop System with the Active Receiver: In a real
biological system, the receiver actually consists of
receptors that react to some specific molecules (e.g.,
peptides or calcium ions). Thus, research efforts have
shifted to the simulation and modelling of the active
receivers, such as the fully absorbing receiver [88], the
reversible absorbing receiver [89], and the ligand-binding
receiver [90]. [88] derived a simple expression for the
channel impulse response of an MC system with an fully
absorbing receiver, and validated it by the particle-based
simulation simulator (MUCIN). [89] and [90] derived the
analytical expressions for the expected received signal
and the average BER for an MC system with reversible
absorbing receiver, and for an MC system with the
ligand-binding receiver, respectively. The expressions
obtained were then verified by particle-based simulation
algorithms.
•Multi-Hop System and Large-scale System: The average
BER of the multi-hop decode-and-forward relay and
amplify-and-forward relay MC systems were derived and
simulated in [91] and [92] to extend the transmission
range and improve the reliability of MC systems.
Using the three-dimensional stochastic geometry, the
average BER with large number of transmitters perfrom
joint transmission to the fully absorbing receiver were
analyzed and simulated via particle-based simulation and
Pseudo-Random simulation in [93], which provided an
analytical model of BER evaluation for large-scale MC
system with all kinds of active receivers.
•Experimental System: The BER performance of the
FÜ
orster Resonance Energy Transfer (FRET) nanoscale
MIMO communication channel has been tested and ex-
amined in [94], which was shown to provide acceptable
reliability with BER about 5.7×10−5bit−1for nanonet-
works up to 150 kbps transmission rates.
3) Symbol Error Rate: The symbol error rate (SER) of
molecular communication system was first mentioned in [95],
then the SERs of an MC system with absorbing receiver
under the binary concentration keying (BCSK), the quadrature
CSK (QCSK), the binary molecular frequency shift keying
(BMFSK), and the quadrature MFSK (QMFSK) were simu-

8
lated in [96] using MUCIN simulator. In [97], the SER of
diffusion-based MC system with receiver having periodically
ON and OFF receptors and analog filter for computing the
logarithm of the MAP ratio was studied.
4) Energy Cost: [98] develops an energy model for the MC
system whereby the energy costs in the messenger molecule
synthesizing process, the secretory vesicle production process,
the secretory vesicle carrying process, and the molecule re-
leasing process were defined based on molecular cell biology.
The energy model of vesicle-based active transport MC system
was described in [99], where the energy costs of the vesicle
synthesis, the intranode transportation, the DNA hybridization,
the vesicle anchoring, loading, unloading, and the micro-tubule
motion were defined. In [100], [101], a detailed mathematical
model for the molecule synthesis cost in MC system with
the absorbing receiver was provided to examine the energy
efficiency of different relay schemes. In [102], the energy costs
in the encoding and synthesizing plasmid, the plasmid trans-
portation, the carrier bacterial transportation, the decapsulation
and decoding were defined and examined within bacterial relay
MC networks.
IV. ENABLING AND CONCOMITANT TECHNOLOGIES
A. EM Aspects
1) Nano-Devices: Advances in nanotechnology have par-
alleled developments in Internet and sensing technology. The
development routine is summarised in Fig. 10. At the same
time, due to the general belief that graphene/CNT would be the
future star of the nano-technology world since its appearance,
more attentions has been put on such novel materials and great
advances have been achieved. Antenna, as the basic element
in communication system, is firstly fully investigated with nu-
merous papers on the design of the antenna made of graphene
or CNT in the last five years. First, the possibility of the
applications of graphene and CNT was investigated [103] and
the wave performance on a graphene sheet was also studied
in [104]. Then, various antennas like graphene patch antenna
with different shapes [105]–[107], CNT dipole antenna [103],
[108], [109], and so on were proposed. Furthermore, a nano-
antenna with the shape of log-periodic tooth made of graphene
was proposed in [110] and a novel graphene-based nano-
antenna, which exploits the behaviour of Surface Plasmon
Polariton waves in semi-finite sized Graphene Nanoribons
(GNRs) was proposed in [111]. Recently, a beam reconfig-
urable multiple input multiple output (MIMO) antenna system
based on graphene nano-patch antenna is proposed in [112],
whose radiation pattern can be steered dynamically, leading
to different channel state matrices. Meanwhile, the design of
the sensors made of graphene is also introduced. Reference
[113] introduces a graphene-based wearable sensor which can
be used to detect airborne chemicals and its concentration
level like acetone (an indicator of diabetes) or nitric oxide and
oxygen (a bio-marker for high blood pressure, anemia, or lung
disease). Later, the sensor made of graphene is designed with
higher accuracy to detect HIV-related DNA hybridization at
picomolar concentrations, which is a charge detector fabricated
of graphene capable of detecting extremely low concentration
Fig. 10: Development routine of the micro/nano-devices [116]
of charges close to its surface [114]. A Stochastic Reso-
nance based (SR-based) electronic device, consisting of single-
walled carbon nanotubes (SWNTs) and phosphomolybdic acid
(PMo12) molecules, has been developed at Osaka University
to apply in bio-inspired sensor [115]. It is believed by the
authors that by using such devices neural networks capable of
spontaneous fluctuation can be developed.
2) Internet-of-Things: Internet-of-Things (IoT) refers to a
network of devices with Internet connectivity to communicate
directly without human-intervention in order to provide smart
services to users [117]. The Internet-of-Things shares the
same development route with nanonetworks, and it is believed
that the ultimate goal is to emerge both technologies to
form the Internet-of-Nano-Things (IoNT) [118]. It is generally
believed that the achievements in IoT can also be applied
to nanonetworks with minor modification. In IoT, the num-
ber of sensors/devices could achieve as high as tons [117],
many challenges related to addressing and identification of
the connected devices would appear, same as nanonetworks.
Furthermore, huge amount of data would be produced by such
high numbers of sensors which requires high bandwidth and
real-time access. Furthermore, implementation of IoT is com-
plex, as it includes cooperation among massive, distributed,
autonomous and heterogeneous components at various levels
of granularity and abstraction [119]. Applications in health
[120], smart security, and smart cities found their way to the
market and realize the potential benefits of this technology
[121]. In addition, many other applications of IoT can be
enumerated such as agriculture, industry, natural resources
(water, forests, etc.) monitoring, transport system design, and
military applications [122].
Network densification is considered as an enabler for the
successful diffusion of IoT services and application in the
society. In reality, millions of simultaneous connections would
be built in IoT, involving a variety of devices, connected
homes, smart grids and smart transportation systems [122].
The concept of cloud and fog computing is introduced to offer
large storage, high computation and networking capabilities
[123]. Also, a high level design of cloud assisted, intelligent,
software agent-based IoT architecture is proposed in [119].

9
Besides of the concept of IoNT, Social Internet of Things
(SIoT) is also proposed recently [124]. To advocate a common
standard, IoT Global Standards (IoT-GSI) are proposed by
ITU-T [125].
3) Bio-Tissue Characterization: Characterization of chan-
nel medium is an essential part to investigate the channel;
therefore, it is important to obtain the parameters of bio-
tissues if the body-centric communication is under study.
Usually, the electromagnetic parameters, i.e., permittivity 
and permiability µ, are used to describe medium in microwave
and RF frequency; while at optical frequency, the material is
usually described by refractive index (or index of refraction).
The techniques such as resonant cavity perturbation method,
Transmission-Reflection-Method (TRM), and THz Time Do-
main Spectroscopy system have been applied to obtain the di-
electric property of human tissues [126]. In [127], the database
of the parameters for human tissues (skin, muscle blood bone
and etc.) from 10 Hz to 100 GHz are illustrated, mainly on
the basis of Gabriel’s work [128]–[130]. THZ TDS system is
fully studied by E. Pickwell [131]–[134] and has been applied
to measure the dielectric parameters of bio-tissues like livers
[135], human colonic tissues [136], human breast tissues [137],
etc.. Both basal cell carcinoma and normal skin are measured
by C.Bao to investigate the possibility of the detection of skin
cancer at early stage [138] based on the work of parameter
extraction of skin with global optimization method [139].
And also, the model of human breast tissue in THz band is
studied in [140]. Recently, the performance of DED samples
and collagen have been investigated in [141], [142] and the
corresponding model has been studied as well to investigate
the possibility of adoption of collagen and DED sample as
the phantom during the measurement [126]. More work needs
to be done to build the database and the appropriate phantom
should be sought to use in the measurement setup.
B. Molecular Aspects
1) Molecular Test-beds: Until now, one fundamental chal-
lenge in the application of molecular communication is that
we still do not have well studied nano-size biological friendly
molecular communication transceivers, despite the existing
research efforts in designing and building MC test-beds [94],
[143]–[148], and in engineering biological MC systems [149],
[150].
•Macroscale MC Test-beds: The first macro-scale
experimental test-bed for molecular communication was
shown in [143], where the text messages were converted
to binary sequence, and transmitted via alcohol particles
based on a time-slotted on-off-keying modulation. In
this tabletop MC test-bed the messages transmission and
detection were realized via the alcohol spray and the
alcohol metal-oxide sensor, and the message generation
and interpretation were electronically controlled via
the Arduino micro-controllers. They shown that a
transmission data rate of 0.3 bit/s with the bit error
rates of 0.01 to 0.03 can be achieved using this
single-input-single-output (SISO) tabletop MC test-bed.
Later on, this SISO test-bed was duplicated to form
a multiple-input-multiple-output (MIMO) tabletop MC
test-bed with multiple sprays and sensors in [144], which
achieved 1.7 times higher transmission data rates than
that of the SISO test-bed.
•Nanoscale MC Test-bed: The first nanoscale molecular
communication based on the F Ü
orster Resonance Energy
Transfer (FRET) was implemented and tested in [94],
where the information was encoded on the energy states
of fluorescent molecules, and the energy states were
exchanged via FRET.
•Microfludic MC Test-beds: In [145], the genetically
engineered Escherichia coli (E. coli) bacteria population
housed in micrometer sized chambers were used as MC
transceivers connected via microfluidic pathways, and the
message molecule (N-(3-Oxyhexanoyl)-L-homoserine
lactone, or C6-HSL) generation and detection were
realized via the LuxI enzyme catalyzes and the LuxR
receptor protein with fluorescent light based on On-Off
Keying (OOK). To improve the achievable data rates of
this testbed with OOK, the time-elapse communication
(TEC) was proposed by encoding the information in
the time interval between two consecutive pulses, which
shown an order of magnitude data-rate improvement.
In [146], the Hydrodynamic Controlled microfluidic
Network (HCN) fabricated in poly(dimethylsiloxane)
(PDMS) polymer was proposed, where the information
was encoded and decoded based on the distance between
consecutive droplets, and droplets carrying information
were controlled and transported in HCN to realize
molecular communication. The maximum information
rate of HCN was analyzed, the noise effect in HCN was
simulated using OpenFOAM, and a HCN prototype was
fabricated in poly(dimethylsiloxane) (PDMS) polymer.
Inspired by the biological circuits in synthetic biology,
a chemical circuits based on a series of faster chemical
reactions were designed to achieve the transformation
of the timing varying information molecules flow from
the digital signal to the analog signal inside a designed
microfluidic devices in [147]. This work provides a novel
research direction for performing signal processing using
chemical circuits inside microfluidic device, and also
an alternative method for proof-of-concept analogues of
biological circuits with potentially higher speed.
2) Molecular Experiments:
•In Vivo Nervous System Experiment: The first controlled
information transfer through an in vivo nervous system
was demonstrated in [148]. Modulated signals were
transmitted into nervous systems of earthworms from
anterior end, and propagated through earthworms’ nerve
cord. Although the network of neurons, i.e., the channel
response, were considered as a black-box, the authors
found the received signals can be decoded as the number
of average nerve spikes per input pulse counted in the
posterior end. In addition, the MC system was optimized

10
in terms of frequency, amplitude, and modulation
scheme, and the authors showed that the data rate can
reach 52.6646 bps with a 7.2×10−4bit error rate when
employing a 4FSK modulation and square shaped pulse.
•Biological MC Experiments: The first engineered intercel-
lular MC experiment between living bacterial cells was
reported in [149], where the plasmid pSND-1 was the
sender constructed to produce the autoinducer chemical
(VAI) via the LuxI gene expression inside E. coli. Then,
the VAI (information messenger) migrates through the
cell membranes and medium to interact with the LuxR
gene of the receiver-plasmid pRCV-3 inside E. coli, and
produces Green fluorescent protein (GFP) for information
decoding.
Using the protein engineering and synthetic biology, a
simple MC based on baterial quorum sensing (QS) was
engineered in [150], where a multidomain fusion pro-
tein with QS molecular signal generation capability was
fabricated as the sender, and an E. coli was engineered
as the receiver to receive and report this QS signal.
These research demonstrated the great potential of bio-
fabrication of MC devices.
V. ARCHITECTURE OF EM AND MOLECULAR
BODY-CENTRIC NA NO NE TWORKS
Generally, it is believed that both EM and MC should share
the same network architecture, but will have minor differences
according to various specific applications.
1) Network Deployment: Aligned with the IEEE P1906.1
framework, the authors of [151] provided an overview of the
nanonetworks and is divided in to nano-routers, nano-nodes,
gateway and nano-micro interfaces. The work proposed in
[152] attempts to investigate the ideal number of devices,
optimal edge length relative to horizontal length of a general
human body organ. The proposed scheme assumes nano-
sensors are distributed in a 3-dimensional space in the nanonet-
works according to a homogeneous spatial Poisson process as
shown in Fig. 11. Authors represent the network deployment
as cylindrical 3D hexagonal pole, claiming that the cylindrical
shape is closer to the shape of human body organs. They
assume that they can put as many nano-sensors as possible
and there is only one active nano-sensor in each hexagonal
cell. They proposed a scheme for each sensor duty cycle with
the assumption that only one sensor is active in each cell. A
cell is defined as the smallest living unit of an organ. The
ideal number of nano-sensors is calculated using an equation
derived by the authors. The equation describes the diameter
of the cylinder, the width of the organ in relation to the edge
length of the cylinder. The work of [152] is considered a step
forward in realizing the nano-sensors deployment; however,
the authors assume that all the nano-sensors may recognize
other neighbouring nano-sensors. The authors also assume that
network deployment also includes routeing nodes; however,
they did not state how to calculate the number of routers or
micro-interfaces and the positioning technique for these nodes.
Emre et. al. [153] debates that the first step in network
design and deployment is highly tied to the parameters of
Fig. 11: Cylindrical shape 3D hexagonal pole.
the nano-antenna, hence nano-antenna design is a critical
component of the network design. The reason behind this
is their observation that there is a clear trade-off between
the number of different tasks the nanonetworks can execute
and the reliable communication over the network. Hence,
the authors proposed a network of nano-devices that are
able to carry out binary tasks and proved that it is possible
to construct multi-hop nanonetworks using simple individual
nodes activated simultaneously over a shared medium without
a significant detriment in reliability. The number of nodes
depends on the number of complex tasks for the nanonetworks.
The authors did not provide a mechanism describing the
process of choosing the appropriate number of nano-nodes or
interfaces. Additionally, the authors did not provide an analysis
of the nano-router or interfaces as they did for nano-sensors.
Dressler and Fischer [154] discussed the requirements and
challenges of designing the gateway or the interface between
the nanonetwork and the macro/micro network to bridge the
gap of the gateway or interface void. They stated that multiple
gateways are required in IoNT deployment such that each
one of them is associated with one or more nanonetworks.
They also suggested that a gateway should operate at the
application layer and recognize the right nanonetwork to
receive a message. They also suggested that the gateway being
equipped with one or more nano communication interface
should contain the molecular and terahertz interface. As a
molecular network may prove to be a significant challenge,
a reasonable approach might be to make the gateway an
implantable micro device that uses electromagnetic wireless
communication to interface the molecular network to the
Internet. While the study in [154] discussed the requirement
and challenges of gateway deployment, they did not provide
any solution. Similar to [154], the study presented in [155]
discussed the challenges and requirements for the gateway
deployment. The study concluded that the gateway will be an
implantable device equipped to enable communication with the
molecular interface as well as the EM nanonetworks. However,
the study remarked that the high ratio of nano-sensors to
gateways could lead to swift energy depletion if gateways
process information from every nano-sensor. They suggested

11
to thereby distribute the sink architecture and develop a two-
layered hierarchy consisting of gateways and nanonetworks.
The aforementioned research attempts to address the net-
work deployment, however, the proposed schemes provide
partial solutions to the network deployment; some focused on
nano-sensor deployment, while others discussed the require-
ments and challenges of gateway deployment. However, no
all-encompassing solution has been provided in literature yet.
Additionally, deployment that achieves essential goals such
as survivability, reliability, accuracy or latency intolerance
remains an unexplored area of research in nanonetworks
deployment.
2) Network Mobility: Nano sensors (NS) are dynamic com-
ponents in their applications whereby they are forced to move
and each move is dictated by their environment. Environmental
NS will move according to wind direction and force, which in
turns will act to adjust their controller association, location and
link quality. Comparatively, the motion of blood monitoring
NS will be influenced by its surroundings, whereby speed
and turbidity of blood flow and vessel thickness will affect
NS link communication quality, velocity and location. This
effect is highly pronounced in nanonetworks when compared
to traditional sensor networks due to the unique nature of
the NS and the used modulation used in nanonetwork com-
munication. Nanonetworks communicate using TS-OOK. This
requires nodes to be highly synchronized, an aspect that can
be significantly affected by changes in NS mobility. TS-OOK
synchronizes transmissions between sender and receiver by
requiring the receiver to listen to transmissions on fixed time
intervals, thereby ensuring that transmitted bits are received.
Distance between the receiver and sender has the largest
impact on this process and deciding the time intervals at which
the receiver should listen. This distance may change due to NS
movement and might result in missing a transmission. The
work in [156] studied the effect of NS movements on the
communication link. The authors studied the pulse time-shift,
which is defined by the authors as the distance in time between
the actual arrival of the signal and its estimated arrival (in
case of no movement), taking into account the Doppler effect,
information reduction, and error rate increase. The authors
concluded that the doppler effect can be negligible; however,
the pulse time-shift can introduce inter-symbol interference
(ISI), and the NS movement influences the maximum infor-
mation rate and the attainable error rate. The work presented
in [156] provides a good insight on the effect of mobility in
nanosensors networks. However, the assumption of the authors
that the transmitter is static while the receiver is mobile, and
NSs are moving with the speed of light may limit the scope
of the results and their adaptability into applications.
Even though the mobility of NSs may pause a major
challenge on practical deployment of nanosensors, this area
is still severely under-researched. References [157] remarked
that there is an eminent need to come up with mobility
perdition models; a reactive response to NS movement is no
longer satisfactory. The authors of [158] proposed a movement
control method for nanonetworks which is self-organised.
The algorithm uses the localization of a particle and its
neighbouring paticles to optimise the location of particles
and enhance movement positions fo NS through the use of
particle swarm optimisation. The proposed algorithm cannot
be considered a general mobility model for nanosensors be-
cause the algorithm is proposed for homogeneous networks,
which is not the norm of a nanonetwork; they are expected
to consist of heterogeneous devices with diverse capabilities.
Additionally, the model is designed based on the unit disk
coverage thereby inheriting the advantages and disadvantages
of using this method. In [159], the authors proposed a scheme
for the hand-off of mobile sensors to the most appropriate
nano-controller to conserve energy consumption and reduce
the unsuccessful transmission rates. The authors presented a
TDMA-based MAC protocol simple fuzzy logic system to
control the mobility procedure. They used locally available
metrics at each nano-node consisting of the distance of mo-
bile nano-node from nano-controller, traffic load and residual
energy of nano-controller, which are considered as fuzzy input
variables to control the hand-off decision procedure. The scope
of the offered solution is limited by the assumption of constant
velocity of the nanosensors and the unit disk transmission
similarly to the other proposed schemes. Additionally, the
practicality of the system deployment is highly dependent
of the trade-off between accuracy and complexity of the
algorithm. Hence, the problem of NSs mobility modeling still
stands as an urgent area of research for practical deployment
of nanonetworkss.
VI. COMMUNICATION AND NETWORKING OF EM AND
MOLECULAR BODY-CENTRIC NAN ON ET WORKS
A. EM-Based Body-Centric Nanonetworks
1) Physical Layer and MAC Layer:
a) Path Loss Model: Studies on THz channel modelling
of nano-communication is conducted in [160]–[162], based
on the researches of the one in the air [163]–[166]. From the
above studies, it can be concluded that there are three parts
in the path loss of the THz wave inside human tissues: the
spread path loss PLs pr , the absorption path loss PLab s and
the scattering path loss PLsc a:
PLtot al [dB]=P Ls pr (f,r)[dB]+P La bs (f,r)[dB]+P Ls ca (f,r),
(6)
where fis the frequency while rstands for the path length.
The spread path loss, caused by the expansion of the wave
in the medium, is defined as
PLspr (f,r)=4πr
λg2
=(4πnrf r
c)2,(7)
where λg=λo/nrrepresents the wavelength in medium with
free-space wavelength λo, and rstands for the transmission
distance of the wave. Generally, the electromagnetic power
is considered to travel spherically. 4πr2denotes the isotropic
expansion term and 4π(nrf
c)2is the frequency dependent
receiver antenna aperture term.
The absorption path loss represents the attenuation absorbed
by the molecular of the medium. It is assumed that part of the
energy would convert into internal kinetic energy to excite the

12
molecules in the medium. By reversing the the transmittance
of the medium τ(f,d), we can obtain the absorption loss:
PLabs =1
τ(f,r)=eα(f)r,(8)
where αis the absorption coefficient while ris the distance.
The scattering path loss accounts for the loss of the signals
caused by the deflection of the beam because of the non-
uniformity’s of the environment. Take human as an example,
there are tons of molecules, cells, organs with various shapes
and EM properties. The effects are dependent not only on the
size, shape and EM properties of the particles but also on the
wavelength of the transmitting signal. In [167], the detailed
phenomenon was discussed and it can be written as
PLsc a(f,r)=e−µs c a r,(9)
where µsc a refers to the scattering coefficient and ris the
travelling distance.
In [167], the effects of all three path loss have been fully
discussed for the in-body nano-communication. It is stated that
the scattering path loss is almost negligible compared with the
absorption path loss at the THz band.
b) Noise model: The molecular absorption noise is the
main element of the noises at Terahertz band, which is
introduced by the molecular vibration, partially re-radiated the
energy absorbed from the EM waves [164]. Therefore, such
noises are dependent on the transmitted signal. In [168], noise
model was investigated while in [169] noise of the human
tissues was studied.
The total molecular absorption noise p.s.d. SNcan consid-
ered as the summation of the atmospheric noise SN0, the self-
induced noise SN1and others originating from other sources
like devices SNo :
SN(r,f)=SN0(r,f)+SN1(r,f)+SNo,(10)
SN0(f)=lim
r→∞ kBT0(1−e−α(f)r)( c
√4πf0)2,(11)
SN1(r,f)=S(f)(1−e−α(f)r)( c
4πf r )2,(12)
where rrefers to the propagation distance, fstands for the
frequency of the EM wave, kBis the Boltzmann constant,
T0is the reference temperature of the medium, α(f)is the
absorption coefficient, cis the speed of light in vacuum,
f0is the design centre frequency, and Sis the p.s.d of the
transmitted signal.
The atmosphere can be seen as an effective black body
radiatior in the homogeneously absorbing medium; thus, the
absorbing atmosphere with any temperature would produce the
atmospheric noise [170]. Such atmospheric noise is called as
the background noise, independent on the transmitted signal.
However, the noise model of Eq. (11) only describes a special
case for THz wave in air. Without loss of the generality,
the term kBT0should be replaced with the Planck’s law,
which describes the general radiation of the black body [170].
Therefore, the molecular absorption noise contains three main
contributors: the background noise SN b(r,f), the self-induced
noise SN s (r,f)and other noise SNo (r,f):
SN(r,f)=SN b(r,f)+SN s (r,f)+SN o (r,f).(13)
The detailed discussions were conducted in [169], and it
is found that the molecular absorption noise would be the
essential part of the contributors to the noise at the receiver.
Meanwhile, p.s.d of human tissues on the sef-induced noise
and background noise are investigated as well, where the
following trends were observed:
•The background noise p.s.d stay steady for all three tissue
types because of the slight difference of refractive index.
•The induced noise p.s.d change slowly with frequency,
different from the fierce fluctuations of THz communica-
tion in air [164].
•The self-induced noise p.s.d is way bigger than the
background noise for all three human tissues, leading
to the conclusion that the background noise could be
neglected in vivo.
c) Modulation Technique: Because the limitation of the
size, nano-devices are power-limited; thus, it is not possible to
adopt the traditional modulation techniques which would cause
energy. Based on such situations, the modulation of carrier-less
pulse based modulation is investigated in [171]. And a pulse
modulation technique, , named TS-OOK, is studied in [172]
and improved in [173] to fully exploit the potential of the
nano-devices made of graphene. So far, TS-OOK is the most
promising communication scheme for resource-constrained
nanonetworks.
To investigate the collision between symbols in body-centric
nano-communication, reference [169] investigated the feasibil-
ity of TS-OOK as a communication scheme at THz band for
the in-body communication of nanonetwork where not only
the noise but also the interference is investigated. It shows that
the received signal power is closely related to the transmitted
signal power; thus we need to choose the transmitted power
carefully to make the difference of the received power with
the silence pulse large enough to make the detection accurate.
In [174], TS-OOK is introduced and femto-second pulse
is used as the communication signal between nano-devices
[28]. Reference [173] analysed this pulse-based modulation
where the transmitted pulse length is 100 f s. Meanwhile,
the channel access scheme of nano networks at THz band
was proposed and analyzed. In the paper, interference-free
scenario and multi-user scenario were both discussed. In the
end, the model was evaluated by COMSOL Multi-physics
[175]. The results showed that such modulation schemes were
suitable for nanonetworks and by choosing suitable parameters
the rates would go from a few Gbps to a few Tbps. Later,
Rate Division Time-Spread On-Off Keying (RD TS-OOK)
is studied in [176] and the PHysical Layer Aware MAC
protocol for Electromagnetic nanonetworks in the Terahertz
Band (PHLAME) is first proposed. The proposal of these two
concept is to support the extremely high density of nano-
devices in nanonetworks and enable the network throughput to
go up to tens of Gbps. In 2013, the critical packet transmission
ratio (CTR) was derived in [177] to introduce an energy and
spectrum aware MAC protocol which can make nano-sensors
transmit with high speed with little energy consumption.
d) Coding Technique: Due to the simple structure, nano-
nodes only have limited power storage. Thus, to save the
transmitted energy, numerous coding methods were discussed.

13
Fixed-length codewords with a constant weight can be used
not only reduce the power consumption, but also to reduce
the interference [178]. Kocaoglu et al. [179], [180] proposed
a fixed-length coding methods later to keep the Hamming
distance of codewords which would make the Average Code
Weight (ACW) lowest. The performance study of the fixed-
length code at the aspects on ACW and code length was
conducted in [181]. Based on this research, variable-length
low weight codes for OOK modulation was investigated in
[182] which would lower the transmission energy while keep
the desired throughput.
2) Network Layer:
•Addressing The IEEE 1906 standard defines the speci-
ficity as the technique that enables a reception of a
message carrier by a target and maps it to an address in
classical communication systems. However, it does not
provide any discussion on how to generate, manage, or
assign specificity component to nanonodes in molecular
or EM nanonetworks. Individualized network addresses
and conventional addressing are not feasible nor practical
due to the nano-scale of the nanonetworks. Therefore,
the use of cluster-based addressing is advantageous over
node-base addressing. It provides the ability to address
a group of nodes with a specific function in monitoring
health or in a specific biological organ [183]. Addition-
ally, addressing may be safely assumed to be required in
inbound direction within the nanonetworks to inform a
cluster or a nanonetwork performing a specific function
(application) on its next action. However, in outbound
direction, no addressing is necessary since the outbound
device is the sink of communication of the nanonetworks;
whenever a gateway receives a message from inside, it
will simply forward it to that device [154]. Hence, con-
ventional addressing is not necessary for nanonetworks.
It may be sufficient to reach a destination just to know
the right direction, since it may be the only possible
option as discussed above or any member of cluster in
that direction is a suitable destination. Addressing in its
conventional meaning may not be needed. For example,
broadcasting a message in nanonetworks may be a solu-
tion for data dissemination because of the low possibility
of collision in THz band due to the wide bandwidth and
transmission time. A receiver overhearing the message
decides if the message is of interest. This method can
be naturally implemented in molecular nanonetworks.
Direct connectivity between nanodevices is another ex-
ample, where a guided communication can be provided
via antenna aperture, resonant frequency, or impedance
match in EM nanonetworks and shape or affinity of
molecule to a particular target, complementary DNA for
hybridization, etc in molecular networks. In literature,
several authors in the context of proposing routing or
MAC protocols for EM nanonetworks assumed that the
nanonodes are assigned addresses without discussing how
(for e.g [184], [185]). Few studies discuss nanonetwork
addressing. Stelzner et.al. [186] proposed an addressing
scheme that is based on the function of the nanosensor
and its location rather than focussing on individual nodes.
The authors proposed employing known protocols like
IPv6 or overhead-reduced variants like 6LoWPAN for the
control station and gateways. In the proposed scheme, it is
irrelevant which specific sensor detects an event or which
node executes a service as long as the right function is
performed at the right location. However, this scheme is
challenged when exact and specific quantities are required
such as the case in releasing a certain amount of a
drug. Addressing a partial number of nodes based on the
required quantity with the lack of individual addressing
of node continues to be an open area of research.
•Routing One of the most fundamental concerns for Body-
Centric nanonetworkss is accurate routing in order to
transmit signal promptly and precisely. Some challenges
affect the routing protocol, including energy, complexity,
latency and throughput. Thinking of the limited resource-
equipped nano-sensors, one of the most important re-
quirement is to reduce the energy consumption. There
have been a few attempts towards achieving energy effi-
ciency in such networks by multi-hop networking [187]–
[189].
A routing framework for WNSNs is proposed to guar-
antee the perpetual operation while increase the overall
network throughput [187]. The framework uses a hier-
archical cluster-based architecture. The choice between
direct and multi-hop transmission is determined based on
the probability of energy savings through the transmission
process. It is concluded that multi-hop performs better
for varying distance. However, only two hop counts are
considered which requires more hops consideration in
the performance evaluation. Besides, it mainly focuses
on WNSNs and does not solve the requirements and
constraints of BCNN. The primary task of network-
ing protocol is forwarding, which is sending packets
to the next-hop along its path to the destination. In
traditional wireless sensor networks (WSN), multi-hop
forwarding schemes including the nearest hop forward-
ing, the longest hop forwarding and the random for-
warding schemes as well as the single-hop end-to-end
transmission are utilised. For long range THz wireless
nano-sensor networks (WNSN) with absorption-defined
windows, in order to overcome the frequency-selective
feature, a channel-aware forwarding scheme is proposed
in [188]. The selection of the next hop is a trade-off
between minmising the transmission distance and the hop
count. Nevertheless, all the relay nodes are assumed to
have sufficient energy and computation capacity which
is impractical. Moreover, authors in [189], [190] propose
a geographic routing protocol. User-selected nodes are
used as anchor-points at the setup phase, and all nodes
measure their distances from these anchors to obtain
address. The routing then employs the appropriate subset
of anchors which is selected by the sender of a packet.
However, the proposed scheme is based on fixed topology
neglecting the mobility and dynamic of nano-nodes. A
flood-based data dissemination scheme is introduced in
[191]. This scheme classifies each node as infrastructure
or network user after processing the reception quality.

14
Only infrastructure nodes can act as re-transmitters, while
the remaining nodes revert to receiving-only mode. This
approach improves the energy efficiency by avoiding
the unconditional broadcast and reliving the serious re-
dundancy and collisions. Nonetheless, this dynamically-
forming infrastructure requires topology-dependent op-
timisation and digital signal processing capabilities of
nano-nodes.
BCNN routing protocols design provides a challenge with
no real solutions despite the growing research tackling
this area. Two kinds of energy-harvesting protocol stacks
that regulate the communication among nano-devices are
proposed in [192]. The greedy energy-harvesting scheme
simply delivers the packet to the node with the higher
energy level, while the optimal energy-harvesting scheme
selects the node that can maximise the overall energy
level within each cluster. Both schemes shown better
performance compared with the traditional flooding-based
scheme. However, the optimal routing strategy cannot
be easily employed because of its high computational
capacity requirement. Besides, the transmission distance
is not taken into consideration, which makes the selection
of relay path inappropriate only based on the energy
level. Recently, a cognitive routing named enhanced
energy-efficient approach is proposed for IoNT [193].
An analytic-hierarchy process is implemented as the
reasoning element to make the cognitive decision based
on observing the dynamically changing topology of the
network.
3) Transport Layer: IEEE P1906.1 standard in mapping the
nanonetwork to the conventional layering system ignored the
transport layer as shown in Table II. Reliable transmission
is a requirement for practical implementation of nanonet-
works. Due to the peculiar characteristics of the nanonetworks,
researchers agree that reliability at the MAC layer or the
transport layer is sufficient but not necessary in both. Hence,
the IEEE P1906.1 framework assumes the existence of the
MAC layer and the absence of the transport layer. Piro et. al.
[185] implemented two types of MAC protocols, transparent
MAC and Smart MAC, in designing their nano simulator.
Transparent MAC pushes packets from the network layer to
the physical interface without any processing at the MAC
layer. Smart MAC enqueues a packet in reception to discover
the neighboring nodes before sending the packet through
a handshaking procedure. For transparent MAC, researches
assume that the reliability service is shifted to the transport
layer, thereby advocating for the existence of transport layer.
The authors of [194] proposed adapting the Optimized Ex-
change Protocol (OEP) protocol, which is part of the IEEE
11073-20601 standard [195] and is particularly important in
telemedicine to provide access points to services from the
application layer to the transport layer. The OEP protocol is
flexible and lightweight, which makes it suitable for imple-
mentation in constraint processing power and storage nano
devices. However, the authors did not propose any technique
on how to adapt or implement the OEP protocol for nanonet-
works. Tairin et. al. [196] proposed an acknowledgement-
based UDP protocol to improve the packet delivery ratio in
a nanonetwork. The proposed protocol utilizes timeout timer
in UDP to double check whether the packet gets delivered
to the destination. The authors evaluated the performance
of the protocol via simulation and found that the proposed
protocol improved the delivery ratio of packets but introduced
additional delay to the network. Few proposals addressed
transport layer protocol design. This area remains unexplored
in academia and industrial research. The interaction of con-
gestion avoidance and reliability between the MAC layer and
the transport layer along with the trade-off of induced delay
and energy consumption is yet to be explored.
B. MC-Based Body-Centric Nanonetworks
1) Propagation Channel Model:
•In the free-diffusion channel, the information molecules
(such as hormones, pheromones, DNA) move in the fluid
medium via Brownian motion. In this case, the propaga-
tion is often assumed to follow the Wiener process, and
the propagation model can be mathematically described
using Fick’s second law [197]:
∂C
∂t=D∇2C,(14)
where the diffusion coefficient Dis governed by the
Einstein relation as [198]
D=kBT
6πηrm
,(15)
where Tis temperature in kelvin, ηis the viscosity of
the fluid environment, rmis the radius of information
molecule, and kBis the Boltmann constant. This Einstein
relation may lose accuracy in most realistic scenarios,
and the diffusion coefficient of which is usually obtained
via experiment [198].
•In the diffusion with drift channel, the propagation model
in a 3D environment can be mathematically expressed as
[197, Ch. 4]
∂C
∂t=D∇2C−vx
∂C
∂x−vy
∂C
∂y−vz
∂C
∂z,(16)
where vx,vy, and vzare the constant drift velocities in
the +x,+y, and +zdirections, respectively.
Different from the EM wave propagation model,
the molecular propagation has the advantages of not
sufferring from the diffraction loss under the shadow of
objects, and not restricting by the cut-off frequency in
pipe, aperture, and mesh environments [199].
2) Noise Model:
•The inherent noise is usually contributed by the random
arrival of emitted molecules at the previous bit intervals.
In the timing channel, the noise NTis the first arrival
time at the receiver boundary given as [70]
NT∼IG(l
v
,2l2
D),(17)

15
with the communication distance land diffusion coeffi-
cient Dfor the positive drift v>0.
In the concentration-encoded channel, the number of left
over molecules belonging to the previous bit to the current
bit duration follows the binomial distributions, and the
noise at the nbth bit interval due to previous (nb−1)bit
intervals is described as [89], [98]
Nnb∼
nb−1
Õ
i=1
Binomi al (N,F(d,(nb−i)Tb,(nb−i+1)Tb)),
(18)
where Nis the number of transmit molecules at the start
of the first bit interval, nbis the number bit intervals,
Tbis the length of one bit interval, dis the distance
between the transmitter and the receiver, and F(·,·,·)is
the fraction number of molecules counted at the receiver.
•The external noise usually includes the biochemical
noise, the thermal noise, the physical noise, the
sampling noise, and the counting noise. The biochemical
noise is the biochemically interaction between the
information molecules/bio-nanomachines and the
surrouding molecules and environment. The thermal
noise is the varied activity levels of the thermally
activated processes or stochastic thermal motion due
to the changing surrounding temperature, and the
physical noise is the physical force on the molecules
movement due to the viscosity of fluid environment
[200]. The counting noise arises when measuring the
molecular concentration at the receiver location, and it
is due to the randomness in the molecules movement
and to the discreteness of the molecules, whereas the
sampling noise arises when modulating the molecular
concentration at the emission of molecules, and is due
to the discreteness of the molecules and the unwanted
perturbation at the emission process [201].
3) Modulation Techniques: Different from the modula-
tion in radio frequency (RF) wireless communication sys-
tems where the information is modulated on the amplitude,
frequency, and phase of the radio waves, the molecular
communication transmitters modulate the information on the
type/structure, the emitting time, and the number of releasing
molecules.
•In the timing channel, the information was modulated
on the emitting time of molecules as in [68]–[71].
•In the concentration-encoded channel, two types of mod-
ulation schemes for binary MC system was first described
in [202], which are the ON-OFF modulation and the
Multilevel amplitude modulation (M-AM). In the ON-
OFF modulation scheme, the concentration of informa-
tion molecules during the bit interval is Qto represent
bit-1, and the concentration of information molecules
during the bit interval is 0 to represent bit-0. In the M-
AM scheme, the concentration of information molecules
is continuous sinusoidal wave, where the amplitude and
the frequency can be encoded. The Concentration shift
keying (CSK) was proposed for modulating the number
of information molecules, and Molecule Shift Keying
(MoSK) was proposed for modulating on different types
of information molecules [75].
Due to the constraints in the accurate time arrival of
molecules in random walks, and the limited types of
molecules in MC system, the Binary CSK modulation
based on the number of releasing molecules have been
widely applied [75], [88], [89], [93], [96], [203], [204],
where the molecules concentration is considered as the
signal amplitude. In more detail, in the Binary CSK,
the transmitter emits N1molecules at the start of the bit
interval to represent the bit-1 transmission, and emits N2
molecules at the start of the bit interval to represent the
bit-0 transmission. In most works, N1can be set as zero
to reduce the energy consumption and make the received
signal more distinguishable. The hybrid modulation based
on the number as well as the types of releasing moleules
were proposed and studied in [205], [206].
4) Reception Model: For the same single point transmitter
located at −→
rrelative to the center of a receiver with radius rr,
the received number of molecules will be different depending
on the types of receivers.
•For the passive receiver, the local point concentration at
the center of the passive receiver at time tdue to a single
pulse emission by the transmitter occurring at t=0is
given as [207, Eq. (4.28)]
CΩrr,t−→
r=1
(4πDt)3/2exp −−→
r
2
4Dt ,(19)
where −→
r=[x,y,z], and [x,y,z]are the coordinates along
the three axes.
•For the fully absorbing receiver with spherical symmetry,
the reception process can be described as [208, Eq. (3.64)]
D∂CFA (r,t|r0)
∂rr=r+
r
=kCFA (rr,t|r0),k→ ∞ (20)
where kis the absorption rate (in length×time−1). The
molecule distribution function of the fully absorbing
receiver at time tdue to a single pulse emission by the
transmitter occurring at t=0is presented as
CFA (r,t|r0)=1
4πrr0
1
√4πDt e−(r−r0)2
4Dt −e−(r+r0−2rr)2
4Dt ,
(21)
•For the reversible adsorption receiver with spherical
symmetry, the boundary condition of the information
molecules at its surface is [209, Eq. (4)]
D∂(C(r,t|r0))
∂rr=r+
r
=k1C(rr,t|r0)−k−1Ca(t|r0),
(22)
where k1is the adsorption rate (length×time−1) and k−1is
the desorption rate (time−1), and its molecule distribution
function was derived in [210, Eq. (8)].

16
•For the ligand binding receiver with spherical symmetry,
the boundary condition of the information molecules at
its surface is
4πr2
rD∂C(r,t|r0)
∂rr=rr
=kfC(r,t|r0)−kb[1−S(t|r0)],
(23)
where S(t|r0)is the probability that the information
molecules released at distance r0given as
S(t|r0)=1−∫t
0
4πr2
rD∂C(r, τ|r0)
∂rr=rr
dτ, (24)
and its molecule distribution function was derived in [211,
Eq. (23)].
5) Coding Techniques: Similar to traditional wireless com-
munication systems, many coding schemes have been studied
for molecular paradigm to improve transmission reliability.
Hamming codes were used as the error control coding (ECC)
for DMC in [212], where the coding gain can achieve 1.7dB
with transmission distance being 1µm. Meanwhile, the authors
modelled the energy consumption of coding and decoding to
show that the proposed coding scheme is energy inefficient
at shorter transmission distances. In their subsequent work,
the minimum energy codes (MECs) were investigated and
outperformed the Hamming codes in bit error rate and energy
consumption [213]. Moreover, the authors of [214] compared
and evaluated the Hamming codes, Euclidean geometry low
density parity check (EG-LDPC) and cyclic Reed-Muller (C-
RM) codes. In order to mitigate the inter-symbol-interference
(ISI) caused by the overlap of two consecutive symbols for
DMC, Reed Solomon (RS) codes were investigated in [215].
Compared with the Hamming codes capable of correcting one
bit error, the RS codes are highly effective against burst and
random errors. The results showed that the bit error probability
(BEP) increases as either the number of molecules per bit
increases or the codeword minimum distance decreases.
Besides these frequently used wireless communication
codes, new coding schemes were developed to tailor MC
channel characteristics, such as the coding based on molecular
coding (MoCo) distance function [216] and the ISI-free code
for DMC channels with a drift [85]. Further to these, the au-
thors of [217] considered coding implementation and designed
a parity check analog decoder using biological components.
The decoding process depends on the computation of a-
posteriori log-likelihood ratio involving L-value and box-plus
calculation. The calculations are completed with the help
of chemical reactions and the gene regulation mechanism
whose input-output relation can be described by Hill function.
Through carefully choosing the parameters in Hill function,
the Hill function is able to approximate some mathematical
operations, such as the hyperbolic operation and logarithmic
operation, and finally leads to the successfully bits decoding.
More details on coding schemes for MC could refer to [218],
[219].
(a) The proposed scheme in [220]
(b) The proposed scheme in [221].
Fig. 12: Two nanonetworks schemes that adopt electromag-
netic paradigm as their in-body and body-area communication
method.
VII. INTERCONNECTIVITY OF EM AND MOLECULAR
BODY-CENTRIC NA NO NE TWORKS
A. Requirements and Opportunities
Besides the five components discussed in Sec. II-C, the
IEEE P1906.1 framework also defined the element of the
interface between the In-Body Network and the Body-Area
Network which is an important part for the application im-
plementation of nanonetworks, especially for medical-related
applications. However, as the goal of the standard is to
highlight the minimum required components and their corre-
sponding functions necessary to deploy a nanonetwork, which
communication paradigm is adopted inside the human body
and outside people, and what is the interface to transmit
healthy parameters from nano-nodes inside human body to
outside devices are not specified.
Some groups specified the communication paradigm with
corresponding interface either using EM paradigm or MC
paradigm. The authors of [220] proposed a network deploy-
ment tailored for coronary heart disease monitoring, which
is shown in Fig 12a. The network consists of two ma-
jor components: Nanodevice-embedded Drug Eluting Stents
(nanoDESs) and Nano-macro Interface (NM). The nanoDESs
are deployed to occluded regions of coronary arteries and
responsible for measuring the arterial constriction, commu-
nicating relevant information, and controlling the release of
any required drugs. NanoDESs use THz band to communicate
with an interface which is inserted in the intercostal space of
the rib cage of a Coronary Heart Disease (CHD) patient and
acts as a gateway between the nanonetworks and the macro-
world. Another example that chooses THz communication is
presented in [221]. It proposed a nanoscale communication
network consisting of nanonodes circulating in bloodstream
and a nanorouter implanted between epidermis and dermis in
hand skin, illustrated in Fig. 12b. The nanonodes in blood

17
vessels collect healthy parameters and exchange data with
the nanorouter using THz band only when they approach the
nanorouter. In this way, the relatively short distance between
nanonodes and the nanorouter minimizes the negative impact
of path loss. Subsequently, the nanorouter transmits the re-
ceived information also in THz band to a gateway wristband
that relays the healthy data to external devices or the Internet
via traditional communication methods.
As for MC paradigm, authors in [222] implemented ar-
tificially synthesized materials (ARTs) as an interface. In
their wet laboratory experiments, the ART contains pHrodo
molecules which are a kind of fluorescent dyes that are
almost non-fluorescent under neutral solutions while fluores-
cent in acidic solutions. Therefore, conducting fluorescence
microscopy observations and measuring fluorescent intensity
can tell us the information inside our body.
Apparently, all the above schemes can enable the connection
between the In-Body Network and the Body-Area Network
using electromagnetic paradigm or molecular paradigm, but
there are some factors making them less practical. First,
the nanonodes in [221] and nanoDESs in [220] are non-
biological and may intervene other physiological activities, as
the nanonodes need to be injected into blood vessels or enter
the human body through drinking a solution containing them,
and the nanoDESs are even required to be surgically placed
into body. Moreover, the injection or insertion of numerous
nanonodes into the human body may not be accepted by
the public, and some countries have published national laws
to strictly regulate the production and marketing of such
devices [154]. Meanwhile, how to recycle these nanonodes
is also a problem. Second, with regard to the method in
[222], the need of externally devices, fluorescent microscope,
makes the method too complicated to implement for ordinary
being. Furthermore, the fluorescent intensity information has
to be transformed to electromagnetic form for the following
transmission to the Internet.
The nanoscale is the natural domain of molecules, proteins,
DNA, organelles, and major components of cells [2], [223].
[224] investigated three kinds of possible signaling particles
and discussed their corresponding biological building blocks
to serve as transmitters and receivers for MC. A physiological
process that happens naturally is the neurotransmitters trans-
mission between presynaptic part and postsynaptic terminal,
which is depicted in Fig. 13. In response to an excitation
of a nerve fiber, the generated action potential moves along
the presynaptic part and triggers the release of neurotransmit-
ters (signaling particles) contained in vesicles. The released
information molecules diffuse in the environment, and they
can bind to the ion channel located at the membrane of
postsynaptic terminal. Then, the binded ion channel becomes
permeable to some ions, which the ion influx finally leads
to a depolarization of the cell membrane that propagates
subsequently as a new action potential along the cell [224],
[225]. Undoubtedly, the neurotransmitter delivery establishes
a MC link and is much more biological, biocompatible, and
less invasive than nanonetworks systems consisting of nanon-
odes and using electromagnetic paradigm, since spontaneously
existed molecular paradigms eliminate the risk of injection or
(a) Transmission process of signaling particles
(b) Detection process of signaling particles
Fig. 13: The transmission and detection of neurotransmitters.
The red molecules are signaling neurotransmitters enclosed
by roundshaped vesicles, and the green molecules are ion
molecules who can result in a depolarization of the cell
membrane [224].
intake of nano devices. In other words, the molecular paradigm
makes up for the drawback of [220], [221].
Moreover, the implementation in [148] further demonstrates
the feasibility of that some physiological processes can be
interpreted as MC systems. In MC, the information is generally
modulated by molecules’ concentration, while the information
is usually transmitted outside the human body via electromag-
netic waves, so a chemical concentration/electromagnetic wave
convertor or interface is needed. Fortunately, some nanonodes
with chemical nanosensors being embedded on the CNTs or
GNRs are able to take this responsibility [226]–[228]. The
mechanism is that some specific type of molecules can be
absorbed on the top of CNTs and GNRs, thus resulting in a
locally change in the number of electrons moving through the
carbon lattice and generating an electrical signal [2]. So far,
the discussed advantages brougth by MC and electromagnetic
communication provide the opportunity and open a door to

18
Healthcare Provider
Internet
Molecular Communication
Teraherz Communication
Bacteria
Virus
Nanomachine
Implantable
Device
Terahertz
Antenna
Microgateway
Nanosensor
Nano-node
Implantable nano-device
Nano-micro interface
Nano-link
Micro-link
Fig. 14: The sketch of the proposed nano communication network.
propose a hybrid communication for nanonetworks systems.
B. Hybrid nanonetworks Communication and Enabling Tech-
nologies
Based on the opportunities offered by molecular paradigm
and electromagnetic paradigm, we propose a hybrid communi-
cation that combines molecuar paradigm and electromagnetic
paradigm for nanonetworks systems, which is shown in Fig.
14.
In the proposed hybrid communication network, the MC is
utilized in the human body because it shows a superiority over
other communication schemes in terms of biocompatibility and
noninvasiveness. The blue nano-node in Fig. 14 refers to a MC
system, and MC systems are grouped to constitute a molecular
nanonetwork who is only responsible for a certain area. The
molecular nanonetworks are either made up of multiple MC
transmitters and receivers or a MC transmitter, MC receiver,
and multiple transceivers that play the role of relaying. A
biological transmitter first collects health parameters, and then
modulates and transmits the collected information among the
molecular nanonetworks. In order to successfully delivery the
information to the outside of the human body, a graphene
based nano-device is implanted into the human body. This de-
vice is mainly made up of a chemical nanosensor, a transceiver,
and the battery. The embedded chemical nanosensor is capable
of detecting the concentration information coming from the
molecular nanonetworks, and converts it to an electrical signal.
The THz electromagnetic signal is further transmitted to a
nano-micro interface. This interface can either be a dermal
display device [229] or a gateway to connect with the Internet.
The nano-micro interface is usually equipped with two kinds
of antennas: THz antenna and micro/macro antenna. The
proposed hybrid communication architecture not only tries its
best to avoid using non-biological nanonodes inside the body
but also makes in-body healthy parameters easily be detected
outside.
There are several enabling technologies to enhance the
feasibility of the proposed hybrid communication. First, the
molecular nanonetworks have been well studied (see Sec.
III-B2) [91], [92], [230], [231]. Different relaying or multi-
hop schemes have been proposed and their performance are
theoretically and numerically analysed, which demonstrate
the effectiveness of communication distance extension and
communication reliability improvement. Then, the in-vivo THz
communication including the channel modelling, modulation
methods, and channel capacity has been studied (see Sec.
VI-A1) [161], [169], [232]. The conducted research not only
helps us understand the impact of human tissue on signal prop-
agation but also assists researchers to estimate the received
signal level which is a key indicator for the further information
transmission.
C. Challenges and Open Issues
The integration of molecular paradigm and electromagnetic
paradigm will boost the application of medical monitoring.
However, this combination also imposes some challenges.
The first concern comes from MC. As the existing biological
system descried in Sec. VII-A, the signal delivery process
involves the subjects of electrochemistry, neuroscience, and bi-
ology. Hence, the highly interdisciplinary technical knowledge
and tools required to analyse puts forward higher requirements
for researchers. At the same time, although [224] presents
some possible MC systems occurring in the human body,
biological transmitters and receivers are still required to be

19
modified to be tailored to various application needs. Given
the synthetic MC is in its infancy, the design, analysis,
and implementation of synthetic MC also inherently require
a multidisciplinary approach [224]. Another concern is the
choice of signaling particles. We hope the signaling particle is
a kind of neutral or intermediate substance. It should be easily
detectable, non-toxic to the human body, and cannot intervene
other biological processes. Meanwhile, the selected signaling
molecular is supposed to be reversible, which means it can
be recycled and used for repeated transmission. The finding
of an ideal candidate needs a further study of various human
physiological processes.
From the THz communication perspective, the obtained
channel parameters may not fit everyone because channel
characteristics for intra-body nanonetworks may vary with
health conditions and from person to person [233]. Thereby,
further investigation of channel modelling is needed.
VIII. SECURITY IN NANONETWORKS: PROGRESS & OPE N
ISSUES
The fundamental goals of security schemes are to ensure
confidentiality, integrity, and availability of the data exchanged
between the legitimate nano nodes. This section summarizes
the works which have attempted to address/raise the security
challenges faced by (EM/MC based) nano networks, and
provides authors’ vision about the nature of the open security
issues and their potential solutions. But, before we outline
our vision of the security in nano networks, it is imperative to
quickly review and summarize the main ingredients of security
in traditional wireless networks.
A. Security in traditional wireless networks
In traditional wireless networks, communication between le-
gitimate nodes is prone to active and passive attacks by adver-
saries, due to the broadcast nature of the wireless medium. The
literature have considered various kinds of attacks, e.g., imper-
sonation attack, Sybil attack, Replay attack, Sinkhole attack,
jamming, man-in-the-middle attack, denial of service attack,
eavesdropping attacks, selfish/malicious relays in cooperative
communication systems etc., and their potential (cryptogra-
phy based) solutions. More recently, researchers have started
to develop various security solutions at physical layer by
exploiting the unique characteristics of the physical/wireless
medium. Some of the most significant problems in physi-
cal layer security include intrusion detection/authentication,
shared secret key generation, secrecy capacity maximization
(for a wiretap channel), artificial noise generation, design of
friendly jammers (in a cooperative communication system) etc.
Keeping this context in mind, we evaluate the answer to the
following question: do the aforementioned security solutions
hold for the nano-scale communication? The answer is in
negation for MC based nano networks because information
exchange by using molecules instead of EM waves as carriers
is a different regime altogether. On the other hand, we find that
for EM based nano networks, operating at THz frequencies,
some of the aforementioned concepts (if not the solutions) are
still meaningful.
TABLE IV: Potential security attacks at each layer [240].
Layer Type of Attack
Molecular Transport Layer Unfairness, Desynchronization
Molecular Network Layer Exhaustion of packets storage.
Flooding attacks
Molecular Link Layer Collision, Unfairness
Signaling sublayer Jamming, Misuse of Replication
functionality
Bio-nanomachine sublayer Jamming, Tampering
B. Security in EM based Nano networks
As explained earlier, EM based nano-scale communication
at THz frequencies is a relatively new phenomena which
has garnered much interest recently only because the device
fabrication techniques are now approaching to the level of
miniaturization needed to fabricate nano transmitters and
receivers (e.g., graphene based nano antennae etc.). This
implies that the EM based nano-scale communication, being
an extremely short-ranged communication regime, is still at
risk of passive and active attacks by adversaries in the close
vicinity. Nevertheless, due to THz band communication being
in its infancy, not much works are available in the open
literature which investigate the security issues faced by THz
systems. On the contrary, THz waves have a long-standing
history of being used for imaging, sensing etc. for security
purposes [234]. However, THz based imaging systems are not
the focus of this survey article.
The survey articles [235], [236] review some of the fun-
damental security mechanisms for THz systems and conclude
that the traditional crypto based mechanisms could be ported to
THz systems, but they need to be light weighted due to limited
processing capabilities of the THz devices. The so-called
BANA protocol proposed by Shi et. al. in [237] addresses
the security needs of the micro-macro link of a body area
network. In [238], the authors consider a scenario where an on-
body nano device communicates with inside-body nano device,
while a malicious node attempts to send malicious/harmful
data to the inside-body node. To this end, the authors utilize the
measured pathloss as the fingerprint of transmit nano device
to do the authentication at the physical layer. [239] presents
the device layout which consists of a micro-ring transceiver
and a graphene based panda ring-resonator. The molecules are
trapped in a whispering gallery mode, the polarized light is
transceived and this device which could be used as a molecular
RFID system.
C. Security in Molecular based Nanonetworks
For MC networks, the traditional crypto based methods
need to be replaced by the so-called biochemical crypto
techniques whereby attacks as well as countermeasures are
all defined by the chemical reactions between the molecules
[236], [235]. Various bio-inspired approaches are proposed in
[240] to secure MC systems and different attacks are classified
according to the (five) different layers of MC system in Table
IV. From the table, we can see that besides the classical attacks
numerous other novel attacks are possible.
Two kinds of attacks are discussed in [241], which are
blackhole attack where malicious bionano things attract

20
the other bionano things towards itself (by emitting chemo-
attractants) preventing them from their task of localization,
and sentry attacks where malicious bionano things in the
vicinity of the target cells emit chemo-repellents not letting the
legitimate bionano things reach their target. Reference [242]
and [243] consider the situations that eavesdropper appears and
causes troubles; furthermore, the solutions are also discussed
and evaluated. Additionally, in vesicle based molecular trans-
port, vesicles act like keys in MC networks and thus inherently
help the cause of secure communication. Recently, researchers
from cryptography have extensively work on DNA inspired
cryptography [244] [245] [246] [247], the crux of which is
that DNA computing is a computationally hard problem of
biological origin, just as Heisenberg’s uncertainty principle is
a hard problem of physics origin; thus, this could be applied
to cryptography purposes.
D. Security in Hybrid nano-scale communication
The proposed hybrid nano-scale communication systems
could either switch between EM/MC mode from one leg to
another, or, from one time-slot to another. For the former
scenario, the aforementioned details of the security challenges
and potential solutions hold as is (as the nano network under
consideration will be either MC based or EM based at a
given leg and will be secured accordingly). For the latter
scenario, authors envision that one could develop a systematic
approach that optimally switches between MC mode or EM
mode depending upon the security requirement of a given
application and/or extent of hostility (or trustworthiness) of
the environment nano network is operating inside.
IX. CONCLUSION AND RECOMMENDATIONS
With the development of the novel manufacturing tech-
niques, the size of the sensors or machines can be made as
small as micro scale, even smaller to nano-level; however, the
realization of the nanonetworks is still very challenging. It is
generally believed that it is hard to fulfill the ultimate goal only
by one individual communication method; thus, the hybrid
communication method should be fully studied, and it is
believed that the hybrid communication is firstly studied in this
survey. By combining the EM and molecular communication,
the drawback of short communication distance for EM and
huge latency for molecular communication can be solved
simultaneously. However, how to combine both paradigms
seamlessly still need effort. In this survey, the connectivity
of EM and molecular methods is investigated, and it shows
promising potential; however, it is far from achievement. First,
the interfaces for both methods are difficult to design because
of the different information throughput; thus, how to design
an interface which can balance both network throughput is of
great interest. Second, there is no uniform simulation platform
for the hybrid communication because of the different network
realization pattern. Even for different molecular methods, there
are different analytic models. Because of the diversity, it is
hard to unify all the communication methods. Third, how to
deal with the conflict of the nano-devices is also important
because of the different latency of both paradigms. It is be-
lieved that the performance of the channel would change with
the composition of the medium; however, the communication
process of the molecular method would change the channel
composition. Therefore, it would be of great importance to
study the effect of the molecular communication on the EM
channel.
Besides the challenges and the corresponding future work
presented above, there are still other research directions which
can be summarised as follows:
A. Investigations of the Novel Materials
From the previous experiences, the discovery of a novel
material would make the development of the engineering
leaping forward by a huge gap. Taking the investigation of
graphene for an example, the study of its characteristics
solidates the concept of nano EM communication with the
application of THz technology, which sets up the foundation of
the current work. Recently, the study on the Pervoskite enables
the design of the Terahertz Antenna which brings a bright
future of the short-range body-centric communication [248].
It is generally believed by the author that the researches on the
bio-materials would rocket the development of the truly nano-
devices, enabling the realization of nanonetworks. Also the
new material would enable the transfer from different signal
types which would make the conversion between different
communication methods possible. Additionally, we all believe
that the more discoveries on the bio-materials, the closer the
nanonetworks comes into reality.
B. Integration Techniques of Diverse Communication Methods
Currently, every communication methods seems well-
developed in their own fields; however, the transformation
between each others is still at its initial stage, especially for
the nano-devices. In the survey, such problems are discussed
in Section VII but only in the shallow phase. The researches
on the interfaces between the different communication meth-
ods should be deeply investigated which are apparently not
sufficient right now, not only from the material perspective
but also on the devices level. The same problems occur for
the interfaces of macro-and-micro scenarios. It is believed
that if such problems are tackled, the major problems in
nanonetworks would be solved.
C. Development of the Generalized Platform
The ultimate goal would be the integration of all com-
munication methods in nanonetworks. However, the studies
on the communication methods are independent with each
other. Moreover, the interactions between two methods are
missing. For example, the emission of the molecules would
change the channel environment for EM ones. And at the
same time, it is clear from the previous studies that the
refined models are necessary like the nerve system and skin.
Therefore, the platform to simulate the interaction between the
environment and the devices should be further studied to make
sure the whole network act normal. Although in IEEE P1906.1,

21
different schemes are studied according to EM standard based
on NS-3 Platform; but the general platforms to simulate hybrid
communication with every part under considerations are still
absent and not well studied.
D. Introduction of Big Data Analysis Techniques
The integration of big data techniques with the nanonet-
works would be a hot topic because of the nature of nanonet-
works that numerous stakeholders are involved in data gen-
eration and management. From the perspective of the data
analysts, the study is still missing. First, the standardization
of the data-format and protocols should be set up while a
unified data schema should be put forward and adopted by the
whole network investigators. Most importantly, new powerful
analytic tools should be developed because the amount of the
data we will face would go up hugely.
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