AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 42
W I R E L E S S N A N O S C A L E C O M M U N I C AT I O N S
ENABLING COMMUNICATION AND COOPERATION IN
BIO-NANOSENSOR NETWORKS: TOWARD
INNOVATIVE HEALTHCARE SOLUTIONS
NAZIM AGOULMINE, UNIVERSITY OF EVRY VAL D’ESSONNE
KIHYUN KIM, SUNGHO KIM, TAIUK RIM, JEONG-SOO LEE, AND
M. MEYYAPPAN, POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY
AND NASA AMES RESEARCH CENTER
ABSTRACT
Bio-nanosensors and communication at the
nanoscale are a promising paradigm and tech-
nology for the development of a new class of e-
health solutions. While recent communication
Relay technologies such as mobile and wireless com-
bined with medical sensors have allowed new
Drug molecule
c release successful eHealth applications, another level of
innovation is required to deliver scalable and
cost-effective solutions via developing devices
that operate and communicate directly inside the
body. This work presents the application of
nanotechnology for the development of minia-
turized bio-nanosensors that are able to commu-
Receiver B nicate and exchange information about sensed
molecules or chemical compound concentration
The authors present and therefore draw a global response in the case
of health anomalies. Two communication tech-
the application of niques are reviewed: electromagnetic wireless
communication in the terahertz band and molec-
nanotechnology for ular communication. The characteristics of these
two modes of communication are highlighted,
the development of and a general architecture for bio-nanosensors is
miniaturized bio- proposed along with examples of cooperation
schemes. An implementation of the bio-nanosen-
nanosensors which sor part of the nanomachine is presented along
with some experimental results of sensing
are able to communi- biomolecules. Finally, a general example of coor-
dination among bio-nanomachines using both
cate and exchange communication technologies is presented, and
challenges in terms of communication protocols,
information about data transmission, and coordination among
sensed molecules or nanomachines are discussed.
chemical compound INTRODUCTION
concentration. Recently, telemedicine and e-health activities
have produced a large number of successful
applications in health care delivery through dif-
ferent communication technologies. Mobile,
42 1536-1284/12/$25.00 © 2012 IEEE
wireless, and fixed communication networks
have pushed the deployment of new e-health
services, being a very useful and real testbed for
the R&D activities applied to communication-
based services. Additionally, the use of nano and
micro devices (within personal and body area
networks) and the new wireless standards
demand innovative, efficient, interoperable, and
scalable solutions for the deployment of e-health
systems in a massive and affordable manner,
with clear societal benefits. This study reveals
that the current services are too expensive, inad-
equate, and cannot respond to the growing
demands in spite of currently available advanced
technologies.
Non-intrusive, non-invasive, and continuous
health monitoring solutions are key elements of
the envisioned ubiquitous health or U-Health in
the future. In order to reduce the cost of health
care in an era characterized by an aging society
and the emergence of new diseases, diagnostic
tools have to evolve from the stethoscope and
blood sampling to networked bio-nanosensors
capable of communicating at the level of cells;
we call such networks bio-nanosensor networks
(B2Ns). These bio-nanosensors, equipped with
communication capabilities, will certainly revolu-
tionize medical practice, allowing the extraction
of important information from a very specific
part of the human body and communicating it to
doctors. With their communication capabilities,
these bio-nanosensors could also provide imme-
diate response to anomalies detected in the
human body. While traditional diagnostic tools
still offer information that is nothing more than
a “snapshot in time,” the golden opportunity
afforded by B2Ns lies in their ability to monitor
a patient’s physical and biochemical parameters
continuously, directly, in vivo, and under natural
physiological status. B2Ns can even provide con-
tinuous and sustainable responses such as deliv-
IEEE Wireless Communications • October 2012
AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 43
ering drugs at the right time and with high accu-
racy and quality [2]. The effective combination
of information and communications technologies
(ICTs) with emerging areas such as nanotechnol-
ogy (NT) and biotechnology (BT) offers a new
opportunity for pushing this progress forward
while dramatically reducing the cost of future U-
Health solutions. The cost of the whole health
care system could decrease significantly, which is
very important for many countries where the
aging population and the population with chron-
ic diseases are increasing drastically. This work is
undertaken in the framework of a global picture
called “Future eHealth,” and these technologies
should be integrated with other solutions such as
computation services (localization, fall detection,
etc.) in U-Health smart homes. These character-
istics are especially important for medical appli-
cations, since a heavy burden on the hospital will
be eased radically by introducing innovative,
highly efficient, and cost-effective solutions [15].
In this article, we describe how nanotechnolo-
gies combined with existing or novel communica-
tion techniques, wireless or molecular, can help
to design B2Ns that can be used to develop
innovative healthcare solutions. Nanoscale
devices open up amazing opportunities in health
care. Indeed, these systems can be introduced
into the human body and could intervene very
closely with organs and cells. Inspired directly by
natural biological interactions [4], nanodevices
intervening at the molecular level will allow
novel healthcare solutions to be developed that
could be not only more efficient but also cost
effective because of the possibility of large-scale
production.
This article is divided into three parts. The
first part introduces the concept of bio-nanosen-
sor networks, the second part describes some
implementation work with bio-nanosensors, and
the last part is a discussion about the use of
wireless or molecular communication protocols
to achieve cooperation among nanomachines to
address medical problems.
BIO-NANOSENSOR NETWORKS
Nanotechnology is a multidisciplinary field that
requires competencies from several fields such
as chemistry, physics, molecular biology, material
science, computer science, and engineering.
Applications of nanotechnology are today
impacting numerous aspects of our society such
as computing, communications, manufacturing,
energy, healthcare, transportation, and security.
With this technology, it is possible to build
devices on the nanometer scale. The basic unit
function may be called a nanomachine (NM),
which can perform simple tasks of computation,
sensing, and actuation (e.g., detection of
molecules, generation of motion, or performing
chemical reactions) in a close environment. With
communication capabilities, these can form a
network of NMs with enhanced capabilities. At
the simplest level, it can be a sensor network
with sensing being the only function.
With communication capabilities, NMs can
exchange information and collaborate together
to provide enhanced functionalities and/or cover
a larger area of applications. However, commu-
IEEE Wireless Communications • October 2012
nication is very difficult at the nanoscale level
due to the lack of biocompatibility of many
Applications of nan-
nanodevices and the signal propagation proper- otechnology are
ties of body tissues. The solutions that are inves-
tigated today are either nanomechanical via today impacting
mechanical contacts, electromagnetic, chemical,
or molecular. In the nanomechanical approach, numerous aspects of
communication between the transmitter and the
receiver is pursued through mechanical contacts; our society such as
more specifically, it is through hard junctions
between a transmitting NM and a receiving NM;
computing, commu-
but this limits the range of communication to a nications, manufac-
few nanometers. In the case of nano electromag-
netic wireless communication, the aim is to use turing, energy,
electromagnetic signals, and send and receive
them using nanoscale antennas, nanotransmit- healthcare, trans-
ters, and nanoreceivers. Indeed, using existing
wireless technology to communicate in vivo will portation, security,
not be acceptable for many reasons such as bulk-
iness of the devices and potential radiation dam-
etc. With this tech-
age. However, materials such as graphene and nology, it is possible
carbon nanotubes (CNTs) have opened opportu-
nities for developing nanoscale batteries, anten- to build devices in
nas, electronics, and nano electron mechanical
systems (NEMSs) that are necessary to consti- the nanometer
tute the communication chain [1]. Molecular
communication is another innovative approach scale range.
aiming to use specific molecules to encode and
transmit information [5]. The transmitting
nanomachine uses natural or artificial molecules,
or even bacteria or a virus to carry the message
to the receiving nanomachines [6]. In the
Molecules Concentration Approach (MCA), the
emitter changes the concentration of the emitted
molecules to encode information, while in DNA
Based Communications (DBC), the emitter
introduces a fragment of DNA representing the
information to transmit directly in the bacteria
or virus. In the MCA, molecules move from the
emitter to the receptor via a random diffusion
process [12] while in DBC, bacteria and viruses
are attracted by specific attractors in the
receivers [7].
While all these solutions are possible, there is
increasing complexity in implementing them.
The community today has much expertise in
wireless communications that could be used in
designing nano wireless protocols and systems.
However, despite the availability of strong theo-
retical models and practical knowledge, imple-
mentation on the nanoscale is very challenging
due to the lack of understanding of energy and
propagation issues at this scale. Nevertheless,
coverage range with this technology could be the
greatest challenge. Molecular communication is
another option that is specifically adequate
because this mechanism is already successfully
used in natural systems. Hence, the logic to
implement may be simpler than DBC; however,
the communication range is only in the range of
a few centimeters. There is actually no consen-
sus about the best approach to follow, and dif-
ferent research teams pursue research in
numerous directions. To summarize these differ-
ent techniques, we present in Table 1 a compari-
son of various approaches.
In this work, we aim to address the two main
approaches, nano wireless communication and
molecular communication, and discuss in the fol-
lowing sections how nanomachines implement-
43
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Approach Range in body Rate Biocompatibility Energy
Nano wireless 1 cm to 1 m ~kb/s Medium to low High
Nano acoustic 1 cm to 10 cm ~kb/s Low High
Molecular 1 nm to 1 cm ~b/h High to medium Very low
Nanomechanic 1 mm to 1 nm ~b/s Medium to low Very low
Bacteria-based 1 mm to 1 cm ~b/s High to medium Very low
Table 1. Comparison between different communication modes at the
nanoscale.
ing one of these techniques could communicate
with each other to coordinate their actions in the
face of a health anomaly.
DIFFUSION OF INFORMATION AND
COORDINATION OF ACTIONS
As previously stated, the aim is to deploy several
NMs that communicate in order to achieve col-
lectively and in a distributed manner a coordi-
nated task such as global sensing or globally
actuating the environment in space and time.
The interconnection and communication of
functional components at the nanoscale is
defined here by the term nano networks. We
consider in this work two types of communica-
tions, nano wireless communication and molecu-
lar communication.
Nano wireless communication aims at allow-
ing NMs to communicate using electromagnetic
waves similar to existing wireless technologies.
However, existing technology cannot be used at
the nano scale due to the requirements in terms
of size of the devices, required energy, and also
the frequency band. Recent works have shown
that it was possible to design nano-antennas of
a few hundred nanometers operating in the ter-
ahertz band. Some experimental antennas have
already been implemented using graphene or
carbon nanotubes (CNTs) [1], but further work
is needed to identify the exact operating fre-
quency, radiation efficiency, and coverage.
Development of nanobatteries is also very chal-
lenging at this scale. What is required at this
scale is a battery that measures no more than
100 nm. However, by reducing the size of the
battery, the stored energy is also considerably
decreased. Therefore, it is necessary to not only
design very-low-energy-consuming NMs by
reducing energy in every part of the system
(i.e., sensing, computing, actuating,
sending/receiving), but also find innovative
approaches to self-recharge the battery in vivo
using the energy available in the environment
(e.g., conversion of movements, vibrations,
hydraulic, thermal energy into electricity to
recharge the battery). When an NM wants to
communicate with another NM, the informa-
tion is encoded into an electromagnetic wave
modulated at very high frequency. It is envi-
sioned to use an adapted modulation scheme
that works properly at this frequency. Among
44
the possibilities, continuous waves or tiny bursts
of a few nanoseconds similar to ultra wideband
(UWB) modulation are possible to implement.
Transmitting nanomachine can modulate the
sequence of bits 0 or 1 using appropriate modu-
lation schema such as quadrature amplitude
modulation (QAM), phase shift keying (PSK),
pulse position modulation (PPM), and pulse
rate modulation (PRM). Here again, there are
a number of challenges that have not been
solved so far at this high frequency band such
as channel access control, synchronization, path
loss, interference, and noise. The challenge is
exacerbated at a very low scale and in vivo
since the interactions between the waves and
the molecules are much more important. In
wireless communication, interference is an
important aspect to address. The interference
could come from either the environment itself
(e.g., interaction between electromagnetic
waves and molecules) or between competing
transmissions. To mitigate interference, it is
necessary to reduce the transmission power (to
reduce inter-NM interference) and use relaying
techniques to increase the range of communica-
tion. Indeed, it may not be possible to cover the
whole target area with only one NM; therefore,
numerous NMs will be deployed in the target
area and communicate with each other using
multihop communication using relaying NM
nodes.
Another way of communicating at this scale is
by molecular communication (Fig. 1). In this
approach, NMs are equipped with special reser-
voirs that contain specific molecules called sig-
naling molecules. When a transmitting NM aims
to communicate with a receiving NM, it releases
molecules that encode information toward the
receiving NM. Following this, the concentration
of molecules around the nanodevice increases
abruptly [10], and the molecules move toward
the receivers and disperse randomly. Molecules
propagate and eventually collide with other
molecules following a Brownian movement. It
actually follows the transport properties that give
rise to a flow of material from one region to
another when a gradient of concentration exists
between the two regions. In this non-equilibrium
state, the molecular dynamic will create a wave
of molecules that will propagate toward a low
concentration region, hopefully where the recep-
tor is [13]. When the molecular concentration
wave reaches the receiver, the concentration of
the molecule will increase, which will facilitate
the binding of the molecule with the receiver
sensors. When the number of binding events
increases enough, the receiver can decode the
signal and interpret the received information.
The results presented in [7] show that the maxi-
mum capacity of the diffusion-based channel can
be derived as a function of the physical parame-
ters, the bandwidth of the system as well as the
transmitter power (initial concentration of
molecules). The receiving nanomachine is
equipped with specific sensors that are capable
of binding to the signaling molecules, decoding
the message, and possibly launching another
action; for example, releasing drug molecules
(contained in a different reservoir), sensing
other molecules, and/or retransmitting the same
IEEE Wireless Communications • October 2012
AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 45
Nanocomputing Signaling molecules
reservoir
Nanosensors
Nanobatterie
Emitter NM
Concentration
gradient
Drug
Inner molecules
concentration
reservoir
Cin>>C
out
Codes CMi C energy available in
1 C’1’
0 0 C’1’
C: Molecules concentration
t: Time duration
C=0
NM: Nanomachine
Bit duration
Figure 1. Molecular communication between two nanomachines.
or a different message to other nanomachines
(e.g., relaying the information to another zone).
In this type of communication, the concentra-
tion of the molecule represents the valence of
the signal; therefore, it is necessary to use two
levels of concentration to allow the receiver to
differentiate between two binary values. This
approach is not really efficient since it is neces-
sary to send molecules for both digits while the
NM reservoir of molecules is physically limited
in size. To increase the lifetime of the NMs, it is
possible to define a certain level of concentra-
tion above which the transported information is
1, otherwise 0. Since the concentration of the
molecules will decrease due to the diffusion of
the molecules in the environment, it is necessary
to wait a certain time to be able to send a 0 so
that the concentration decreases below the
determined level, which basically reduces the bit
rate. It is possible to enhance the rate of the
transmission by increasing the valence of the sig-
nal. For that, the system could use different
molecules, each of them modulated in concen-
tration (Fig. 2).
This communication scheme based on
molecules is very challenging compared to the
use of electromagnetic waves. Indeed, the propa-
gation of molecules in the body environment is
subject to various phenomena closer to fluid
than signal propagation. Several parameters can
impact them negatively (temperature, viscosity,
flow, pressure, dispersion, etc.). Fortunately,
from a systemic point of view, some well-known
characteristics of signal transmission (noise, fad-
IEEE Wireless Communications • October 2012
It is not only
Molecules
reservoir necessary to design
Nanoreceptors
very low energy con-
suming nanoma-
Molecules
chines by reducing
energy in every part
of the system but
Controllable
Receptor NM
gate also find innovative
approaches to self-
recharge the battery
Propagation environmnet
(diffusion model, Brownian movement) in vivo using the
Bit=’1’ the environment.
Detection threshold
-
-
-t
ing, drifting, etc.) remain applicable and help to
determine the channel capacity based on Shan-
non information theory [7].
Similar to the modulation scheme in electro-
magnetic wireless communication, we can use
increase in the valence of the signal using N
types of molecules (instead of N levels of fre-
quency in the electromagnetic wave) and two
levels of concentration (instead of two levels of
amplitude in the electromagnetic wave). Given
the maximum modulation rate Rmax that can be
derived from the bandwidth W of the channel
and following the formula of Shannon (Rmax =
2W), the maximum bit rate that can be achieved
with this modulation scheme is D max =
R max Log 2 (2*N) [11]. In the presence of noise
(i.e., molecular noise in this case) that will
impact positively or negatively the concentration
of the molecules (alternatively the amplitude of
the electromagnetic wave) at the receiver [7], the
maximum molecular signal-to-noise ratio
(MSNR) can be determined. Based on this
MSNR and the sensitivity of the receptor, the
initial concentration (amplitude) may be calcu-
lated. If the distance between the emitter and
the receptor is defined as d, Fick’s second law
can be used to predict how diffusion causes the
concentration to change in time and space [13]
(in the case of the electromagnetic waves, this
will follow the Maxwell equations). The concen-
tration Ci of the molecule i for the diffusion in
three dimensions (i.e., over the axis between the
emitting NM and the receiving NM) can be for-
mulated as follows:
45
AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 46

Nanocomputing Nano antenna

Relay
Receiver A
Drug molecules
Drug molecules release
Electromagnetic release
Nanosensors wave Codes Amplitude Phase
Emitter propagation 00 A1 π/2
Drug reservoir
01 A1 -π/2
Nanobattery
11 A2 π
Electromagnetic wireless communications 10 A1 -π/2
Receiver B

Nanocomputing Controllable Signaling molecules

gates

Relay Receiver A Drug molecules

Drug molecules release
Nanosensors Molecules release Codes CMi CMj
propagation
00 0 0

Nanobattery Emitter 01 0 Cj
Drug reservoir
11 Ci Cj
10 Ci 0
Molecular communications
Receiver B

Figure 2. Electromagnetic wireless vs. molecular communication between nanoscale devices.

2
For example, the diffusivity D is a difficult
⎛ d ⎞ parameter to estimate, but it has a huge impact
−⎜ ⎟
C i (d , t ) = C i (d = 0, t = 0 )
1
e
(
⎜⎝ 2 Dt ) ⎟⎠ on the performance of the molecular communi-

( ) 3 cation system and at the same time is very sensi-

2 π Dt tive to the composition and the temperature of
the environment. Nevertheless, what is really
important here is that the principle of molecular
where t is time, d is the distance from the emit- communications [5] could work along with the
ter NM, D is the diffusivity (m 2 /s) and C i (0,0) electromagnetic wireless communication; howev-
the concentration at the egress of the NM er, more theoretical as well as experimental
molecule
——
i reservoir at time = 0. The parameter work is needed for both approaches to further
÷ Dt. is called the diffusion length and gives investigate the possibility for implementing the
information about the distance the concentration corresponding mechanisms in devices at the
has reached by diffusion from the emitter NM nanoscale.
toward the receptor NM. Diffusion coefficient of
typical proteins that range in size from 20 to 100
kDa is 10–75 mm2 s–1. We can find several exam- SENSOR/ACTUATOR NANOMACHINES
ples of such diffusion in cell biology such as elec- IMPLEMENTATION
trical signal propagation in axons and Ca 2+
waves in oocytes. This section provides some results from our
With Fick’s equation and the general theory preliminary efforts in developing the sensing
of communication, some researchers have part of the NM. Actually, the sensing part of
attempted to derive a general formulation of the the NM is not only dedicated to the detection
in-body molecular communication channel and of the molecules that serve as a vector to trans-
derived very important results [7, 10]. The results fer information but also to the detection of
show the complexity of molecular transmission other molecules that are important to achieve
and, more particularly, its implementation [5]. the objectives of the B2N. This means that the

46 IEEE Wireless Communications • October 2012

AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 47
<TEM image of nanowire>
1 μm
<SEM image of 20 parallel nanowires>
Figure 3. a) Schematic of the silicon nanowire Bio-FET; b) electron microscopy image of the fabricated
device.
NM is envisioned to embark on as a function of
an effective laboratory-on-a-chip system, which
may include monitoring of pH, cholesterol,
complete blood count, white blood cell count,
troponin-I for heart attack, bilirubin, and
metabolic panel including Na, K, and Ca. A
laboratory-on-a-chip is a system aimed at
replacing manual work by several technicians
analyzing blood, urine, and other human sam-
ples. This automated approach will be cost
effective and rapid, and could reduce health
care costs associated with diagnostics. Until
now, such systems have not been developed for
injection into the body; rather, lab-on-a-chip
systems have been investigated for automating
laboratory analytical work involving blood,
urine, or other samples. Regardless, a well
designed sensor system is expected to be small,
low-power-consuming, reliable, robust, capable
of performing multiple laboratory functions
from the list above, reasonably fast, and usable
in the home wherever possible.
Systems meeting the above requirements are
under development in many laboratories across
the world. They vary in numerous ways: materi-
als used, types of probes, transduction tech-
niques, and so on. For example, a sensor may be
affinity-based: a probe is chosen that selectively
binds to the target (i.e., the type of bio-molecule
to detect). The result of the probe-target binding
may manifest in the form of an electrical, elec-
trochemical, or optical signal. Here we have cho-
sen to measure electrical response arising from
the selective probe-target binding. Our platform
is a bio field effect transistor (Bio-FET). This is
similar to conventional FET except for the
replacement of the gate with an electrolyte (i.e.,
the sample and reference electrode). Another
departure from the conventional FET is the use
of silicon nanowires as the channel material
instead of epitaxial silicon layer. The nanoscale
IEEE Wireless Communications • October 2012
The sensing part of
(b) Nanosensors for
the NM is not only
nanomachines
dedicated to the
detection of the
Ag
Si nanowire
(Undoped) Ag
molecules that serve
Source
Tsi=40nm
Drain
as a vector to
Ag/AgCI
electrode transfer information
Bottom oxide
Si substrate but also to the
(p-sub, NA=1015cm-3)
(a) Silicone nanowire Bio- detection of other
FET schema
molecules that are
important to achieve
(b) 20-50 parallel nanowires the objectives of the
Active region
B2N.
offers advantages such as large surface-to-vol-
ume ratio and interesting electronic properties.
This approach allows us to keep the standard
integrated circuit manufacturing practice while
adding the advantages of nanotechnology. As a
result, sensitivity of detecting the disease can be
improved while attempting to keep the cost of
the devices down.
Figure 3 shows the schematic of the silicon
nanowire Bio-FET and a scanning electron
microscopy image of the fabricated device. The
fabrication details can be found elsewhere [9]
but are briefly given below. A 150 mm silicon-
on-insulator substrate with boron doping of 1015
cm –3 and 100 nm thick top silicon layer was
used. The top layer was thinned first to 40 nm to
form rectangular-shaped nanowires. Then
nanowires of 50 nm width and 10 micron length
were formed using electron beam lithography
and inductive plasma etching. These were fol-
lowed by source and drain ohmic contact forma-
tion, source/drain doping, gate contact
formation, and creation of the reference elec-
trode. Typically 20–50 parallel nanowires were
used to form the active channel region.
The Bio-FET is capable of detecting charges
from the biomolecules. The charge distribution
is expected to be different at every stage of the
operation: bare device vs. after attaching the
probe vs. after probe-target binding. The mea-
sured current-voltage (I-V) characteristics at
each stage would be different, and a characteris-
tic shift in the threshold voltage (VT) is expect-
ed. As a preliminary demonstration, we used the
Bio-FET to measure pH since it is one of the
functions of a lab-on-a-chip. Figure 4 shows the
drain current vs. reference electrode behavior
for various pH values. As the pH decreases from
12 to 2, the curves shift toward the negative
direction. The device shows a pH sensitivity of
40 mV/pH.
47
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10-7
10-8
Drain current [A]
From pH 12 to pH 2
with pH 2 step
10-9
10-10
10-11
@ VD=0.1V
10-12
0.0 0.3 0.6 0.9 1.2 1.5
Figure 4. Drain current vs. gate voltage for various pH values.
The results above demonstrate the prelimi-
nary capability of the fabricated Bio-FET to
function as a lab-on-a-chip. Further work would
involve testing for the various analytes men-
tioned earlier, integration with microfludics for
automated sample delivery, and system integra-
tion with communication and networking aspects
of the complete NM. Deployment of sensors in
vivo would require addressing issues related to
biocompatibily, power supply, and many others.
NANOMACHINES SYNERGY TO ANOMALIES
DETECTION AND RESPONSE
The results above demonstrate the preliminary
capability of the fabricated Bio-FET to function
as a lab-on-a-chip. This is of course a first step
towards developing new solutions to implement-
ing a full B2N for future e-health. The devices as
presented here have not been attempted in any
type of in vivo applications yet; this requires
major development in terms of material/device
selection from a biocompatible point of view.
Communication among NMs will also require
the design of a full communication protocol
between the NMs (i.e., how to communicate
between NMs to achieve a global response). We
envision a B2N composed of various NMs
achieving multiple goals such as some measuring
cholesterol, and others pH and blood glucose.
Doctors can identify the equilibrium among
these different physiological parameters and the
corresponding thresholds. We envision that NMs
will be manufactured and programmed with this
information. These NMs will be embedded with-
in the human body at different locations of inter-
est to monitor tissues, organs, and molecules in
the blood. Once the NMs are introduced in the
body, they can start to sense the environment
and possibly communicate with each other using
the embedded communication technology (i.e.,
electromagnetic wireless communication or
molecular communication). Whenever an abnor-
mal situation happens (e.g., initial signs of a
heart attack), the bio-nanosensors will detect the
48
increase in charges inducted by the increase in
concentration of the corresponding biomarker,
and if this concentration goes beyond the identi-
fied and preprogrammed threshold, the equilib-
rium is violated and the NM will react as
programmed. The NM that detects the problem
will propagate the information to other NMs to
trigger a global response. In the case when NMs
use molecular communication, this could of
course take several hours, which may still be
acceptable depending on the type of disease.
When a more immediate response is needed,
NMs using electromagnetic wireless communica-
tion will be used instead. When molecular com-
munication is used, the sending NM releases
signaling molecules, which are received and
interpreted by the receiving NMs and eventually
perform other actions such as activating the
sensing of other biomaterials with predefined
thresholds (e.g., to confirm other aspects of the
anomaly) or release other signaling molecules to
amplify and relay the signal to other NMs. Ulti-
mately, some NMs will eventually release drug
molecules to mitigate the problem (i.e., to miti-
gate the heart attack). These actions require
NMs to be capable of performing some basic
application functions, for example, basic logic
actions such as “and,” “or” may be incrementing
simple counters, testing, activating/deactivating
reservoir gates, and so on. Similar to the report
in [8], a simple protocol stack can be designed
for a molecular-based protocol as presented in
Fig. 5.
COMMUNICATION PROTOCOL BETWEEN
NANOMACHINES
The interaction protocol between NMs needs to
be as simple as possible to avoid increasing the
required computing capabilities of NMs, which
are limited. It is not possible or even desirable
at this level to identify an NM individually.
Network addressing should be based on a
group. Each NM, based on its capabilities, will
belong to a particular class of bio-nanosensor;
for example, an NM with glucose sensing capa-
bilities will belong to one group and another
NM capable of sensing blood pH will belong to
a different group. Communication between
NMs will be based on a multicast scheme where
one NM transmits electromagnetic waves or
releases molecules to communicate with a par-
ticular class of NMs and not a particular one.
In addition, there is no need to have a com-
plete communication stack here; at the applica-
tion layers, some level of computing will be
achieved to identify the proper actions to trig-
ger based on the results of sensing. To send
information to a remote NM, the information
will be transmitted to the network layer, which
will identify the type of wave or molecules to
send and the signal power level or molecule
concentration level at which to encode the mes-
sage. In both communication techniques, the
NM will first need to sense the channel to avoid
collision (i.e., there is no other transmission
already in progress); if it is free, it sends the
data using the appropriate modulation scheme
(electromagnetic or molecular). At this level,
IEEE Wireless Communications • October 2012
AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 49

Class 1 nanomachine Interaction

Application layer (message)

Class 2
Network layer Cell nanomachine
(packet structure)
Cell
Link layer
(frame structure) Class 3
nanomachine
Physical layer
Sensing (wireless frame)
Si nanowire
Ag (Undoped) Ag
Tsi=40nm
Cell
Source
Ag/AgCI
Drain
Antenna
electrode Electromagnetic
Bottom oxide
Si substrate
waves
(p-sub, NA=1015cm-3)

Diffusion
Class 1 nanomachine

Application layer (message)

Network layer Class 2

(packet structure) nanomachine
Link layer
(frame structure)
Physical layer Collision
Sensing Class 3
(molecular frame)
nanomachine

Ag
Si nanowire Reservoir A
(Undoped) Ag
Tsi=40nm
Source Drain
Ag/AgCI
electrode
Bottom oxide
Reservoir B Noise Diffusion
Si substrate
(p-sub, NA=1015cm-3)

Encoding Modulation Transmitting Channel Receiving Demodulating Decoding

Figure 5. Nanomachine communication stack and binding with lower level bio-nanosensors and reservoirs of molecules.

there is no need for a transport layer, which is
useless in this type of system since it will be
very difficult to recover from transmission
errors (except carefully designing the system
initially). It is very important to design very
simple protocols that do not need to handle any
unnecessary flow control since the capacity of
the channel is expected to be low, particularly
for molecular communications. Hence, we envi-
sion the system to be highly specialized, which
means there may be only one application run-
ning in the NMs. In this case, there is no need
to identify any application process in the receiv-
ing NM, and ideally communications should be
group communication where individual entities
are not important (similar to biological sys-
tems). However, as for natural biological sys-
tems, even with simple interactions between
NMs and very low embedded computing capa-
bilities, the entire system could globally self-
organize, adapting efficiently to exhibit
emerging group intelligence that will allow to
solve health problem [14]. In Fig. 6, we show an
example of how these NMs can collectively
coordinate their action to destroy threat
molecules that have been detected by some
dedicated NMs. In this figure, when some
molecules (yellow triangles) are detected by the
red NM, a message is delivered to the blue NM
via yellow circle signaling molecules. When
some condition is verified (e.g., high number of
red MS that have detected a concentration of
triangle molecules above a certain threshold),
the blue MS NMs communicate the informa-
tion to the orange NM (which contains the
drug molecules to destroy the yellow molecules)
using the red circle signaling molecules. Once
the yellow NM receives the information from
the blue NM, it starts to release the drug
molecules to destroy the yellow triangle
molecules. The same process could happen if
we use electromagnetic wireless communica-
tions. The main difference will be the time to
deliver the messages, the reliability of the com-
munication, and the energy usage (i.e., lifetime
of the system), as previously discussed.
CONCLUSION
Electromagnetic wireless communication and
molecular communication are two promising
approaches to enable communication at the
nanoscale between nanomachines. Developing
nanomachines with biological sensing capabili-

IEEE Wireless Communications • October 2012 49

AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 50
Electromagnetic wire- Electromagnetic wireless bio sensor network
less communication MS
MS
and molecular com-
MS
munication are two MS
MS MS
MS
promising approach-
es to enable commu- MS Recognises high concentration biomolecules
MS Sends signal to MS using an electromagnetic wave MS Receives the signal and delivers drug molecules
nication at the MS Is activated and senses additional parameters
nanoscale between Molecular bionanosensor network
nanomachines.
MS
Developing nanoma- MS
MS
chines with biological MS MS
sensing capabilities MS MS
and coordination MS Recognises high concentration biomolecules
capabilities will cer- MS Sends signal to MS using molecules
tainly revolutionize MS Is activated and senses additional parameters
future ubiquitous Figure 6. Cooperative cooperating nanomachines triggering collective response to a possible threat: from
biomolecules detection (e.g. protein) to drug delivery.
healthcare.
ties and coordination capabilities will certainly
revolutionize future ubiquitous healthcare. With
the advances in nanotechnology and the increas-
ing level of understanding of biological mecha-
nisms, opportunities for innovative nanoscale
networked bio-nanosensors are being created.
In this article, we have listed some challenges in
developing a new generation of nanoscale sen-
sor networks. We have presented and discussed
two possible approaches to enable communica-
tion at the nanoscale: electromagnetic and
molecular communications. Molecular commu-
nication is part of this evolution driven by sever-
al research teams worldwide to design artificial
nanomachines capable of communicating
together using molecules that do not harm the
body. Based on the current state of the art, we
have presented a possible architecture for nan-
odevices that includes biosensing capabilities,
with some level of computing and actuating. We
have discussed the energy problem to empower
these nanodevices to be programmed for pro-
viding appropriate response action to health
anomalies. The benefit of using electromagnetic
communication is that the community has vast
knowledge in this area. Nevertheless, at the
nanoscale and in vivo some problems appear
since the interactions between the electromag-
netic wave and molecules are not negligible.
Molecular communication is a more recent
approach which is promising and natural for
biological systems since a similar communica-
tion scheme is used in natural systems. Howev-
er, there is still much work needed to achieve
the implementation of this solution in vivo,
which will require addressing several issues such
as biocompatibility, power supply, and nanoma-
chine embedding, among others.
50
MS MS
MS MS
MS MS MS
MS
MS MS
MS
MS MS
MS Sends signal to MS using another electromagnetic wave
MS MS
MS MS
MS MS MS MS
MS
MS MS MS MS
MS Sends signal to MS using molecules
MS Receives the signal and delivers drug molecules
ACKNOWLEDGMENT
This research was supported by the World Class
University program funded by the Ministry of
Education, Science and Technology through the
National Research Foundation of Korea (R31-
10100).
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BIOGRAPHIES
NAZIM AGOULMINE (nazim.agoulmine@iup.univ-evry.fr) is a full
professor at the University of Evry, France, since 2000 and
head of the National Research Programme on Software and
Hardware Infrastructures for Future ICT at ANR (National
French Research Funding Agency). He is leading a the research
group LRSM (Software for Networked Multimedia Systems) as
part of the IBISC Research Laboratory. He received his Engi-
neer degree in 1988 from USTHB, Algeria, and his Master’s
and Ph.D. degrees in computer science in 1989 and 1992
from the University of Paris XI, France. His research interests
are mainly wired and integrated network and service manage-
ment, autonomic systems, wire and wireless networks,
ehealth, and bio-inspired networking and computing. He is an
area editor of Elsevier’s International Journal on Computer
Networks and Secretary of the e-health IEEE Technical Com-
mittee. He served several times as a general TPC co-chair for
IEEE/IFIP conferences and workshops (IM, GIIS, MMNS,
DANSM, LANOMS, etc.). He is author and co-author of five
books in the areas of autonomic networking, self-managed
networks, network and system management, and multimedia
management. He has participated in numerous European pro-
jects from the first EU programs (RACE ESPRIT, ACTS, IST, FP,
ITEA, CELTIC) He is acting as an expert for several national and
international research agencies ANR (France), NSERC/FCAR
(Canada), HETAC (Ireland), and NRK (South Korea).
KIHYUN KIM received his B.S. degree from the Department
of Electrical Engineering at Hanyang University, Korea, in
2009. Since 2009, he is currently working toward his M.S.
and Ph.D. degrees through an integrative program course
with the Department of Electrical Engineering, Pohang Uni-
versity of Science and Technology (POSTECH). His research
interests include nanoscale biosensor devices and nanode-
vice fabrication.
S UNGHO K IM received B.S. and M.S. degrees in electrical
engineering from POSTECH, Korea, in 2008 and 2010,
IEEE Wireless Communications • October 2012
respectively. Currently, he is a Ph.D. student in the Nanode-
vices and Circuits Lab at POSTECH. His research interests There is still much
are nanoscale Si MOSFETs and technology, and bio and
chemical sensors based on nanoscale Si devices. work needed to
T AIUK R IM received his B.S. degree in the Department of achieve the imple-
Electrical Engineering from POSTECH, Korea, in 2008. Since
2008, he is currently working toward M.S. and Ph.D.
degrees through an integrative program course with the
mentation of this
Department of Electrical Engineering, POSTECH. His
research interests include nanoscale biosensor devices and solution in vivo
the surface immobilization of biological molecules on inor-
ganic surface. which will require
M. MEYYAPPAN [F] is chief scientist for Exploration Technolo- addressing several
gy at NASA Ames Research Center in Moffett Field, Califor-
nia. He has authored or co-authored over 240 articles in
peer-reviewed journals and made over 200 invited/
issues such as bio-
keynote/plenary talks in nanotechnology subjects across the
world. His research interests include carbon nanotubes,
compatibility, power
graphene, and various inorganic nanowires, their growth
and characterization, and application development in supply, nanomachine
chemical and biosensors, instrumentation, electronics, and
optoelectronics. He is a Fellow of the Electrochemical Soci- embedding and
ety, American Vacuum Society, Materials Research Society
(MRS), Institute of Physics (IOP), and the American Institute
of Chemical Engineers (AIChE). He served as President of
many others.
the IEEE’s Nanotechnology Council in 2006–2007. He cur-
rently serves as the Vice President of the IEEE-Electron
Devices Society for Educational Activities.
JEONG-SOO LEE (ljs6951@postech.ac.kr) received B.S., M.S.,
and Ph. D. degree in electrical engineering from POSTECH,
Korea, in 1991, 1993, and 1996, respectively. From 1996
to 2001, he joined Samsung Electronics as a senior engi-
neer working on the development of gate dielectrics in
CMOS device. In 2001, he was with the EECS department
of the University of California at Berkeley as a visiting sci-
entist, where he worked on the fabrication and characteri-
zation of FinFETs and UTBFETs. From 2002 to 2005, he
joined the University of Texas, Dallas as a research assistant
professor in the Electrical Engineering Department where
he worked on the synthesis of nanowires and their applica-
tion in biosensors. Since August 2008, he has been an
assistant professor with the Department of Electrical Engi-
neering, POSTECH. He is currently vice director of National
Centre for Nanomaterials Technology (NCNT), POSTECH. His
research interests include nanoscale silicon devices and
technology, and nanostructures for biosensors and chemi-
cal sensors. He is a member of the IEEE Electron Device
Society and currently serves as a committee member of
IEEE-EDS for Educational Activities.
51