Você está na página 1de 10

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 wireless, and fixed communication networks


have pushed the deployment of new e-health
Bio-nanosensors and communication at the services, being a very useful and real testbed for
nanoscale are a promising paradigm and tech- the R&D activities applied to communication-
nology for the development of a new class of e- based services. Additionally, the use of nano and
health solutions. While recent communication micro devices (within personal and body area
Relay technologies such as mobile and wireless com- networks) and the new wireless standards
bined with medical sensors have allowed new demand innovative, efficient, interoperable, and
Drug molecule
c release successful eHealth applications, another level of scalable solutions for the deployment of e-health
innovation is required to deliver scalable and systems in a massive and affordable manner,
cost-effective solutions via developing devices with clear societal benefits. This study reveals
that operate and communicate directly inside the that the current services are too expensive, inad-
body. This work presents the application of equate, and cannot respond to the growing
nanotechnology for the development of minia- demands in spite of currently available advanced
turized bio-nanosensors that are able to commu- technologies.
Receiver B nicate and exchange information about sensed Non-intrusive, non-invasive, and continuous
molecules or chemical compound concentration health monitoring solutions are key elements of
The authors present and therefore draw a global response in the case the envisioned ubiquitous health or U-Health in
of health anomalies. Two communication tech- the future. In order to reduce the cost of health
the application of niques are reviewed: electromagnetic wireless care in an era characterized by an aging society
communication in the terahertz band and molec- and the emergence of new diseases, diagnostic
nanotechnology for ular communication. The characteristics of these tools have to evolve from the stethoscope and
two modes of communication are highlighted, blood sampling to networked bio-nanosensors
the development of and a general architecture for bio-nanosensors is capable of communicating at the level of cells;
miniaturized bio- proposed along with examples of cooperation
schemes. An implementation of the bio-nanosen-
we call such networks bio-nanosensor networks
(B2Ns). These bio-nanosensors, equipped with
nanosensors which sor part of the nanomachine is presented along communication capabilities, will certainly revolu-
with some experimental results of sensing tionize medical practice, allowing the extraction
are able to communi- biomolecules. Finally, a general example of coor- of important information from a very specific
dination among bio-nanomachines using both part of the human body and communicating it to
cate and exchange communication technologies is presented, and doctors. With their communication capabilities,
challenges in terms of communication protocols, these bio-nanosensors could also provide imme-
information about data transmission, and coordination among diate response to anomalies detected in the
sensed molecules or nanomachines are discussed. human body. While traditional diagnostic tools
still offer information that is nothing more than
chemical compound INTRODUCTION a “snapshot in time,” the golden opportunity
afforded by B2Ns lies in their ability to monitor
concentration. Recently, telemedicine and e-health activities a patient’s physical and biochemical parameters
have produced a large number of successful continuously, directly, in vivo, and under natural
applications in health care delivery through dif- physiological status. B2Ns can even provide con-
ferent communication technologies. Mobile, tinuous and sustainable responses such as deliv-

42 1536-1284/12/$25.00 © 2012 IEEE 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
nication is very difficult at the nanoscale level
due to the lack of biocompatibility of many
Applications of nan-
of information and communications technologies nanodevices and the signal propagation proper- otechnology are
(ICTs) with emerging areas such as nanotechnol- ties of body tissues. The solutions that are inves-
ogy (NT) and biotechnology (BT) offers a new tigated today are either nanomechanical via today impacting
opportunity for pushing this progress forward mechanical contacts, electromagnetic, chemical,
while dramatically reducing the cost of future U- or molecular. In the nanomechanical approach, numerous aspects of
Health solutions. The cost of the whole health communication between the transmitter and the
care system could decrease significantly, which is receiver is pursued through mechanical contacts; our society such as
very important for many countries where the
aging population and the population with chron-
more specifically, it is through hard junctions
between a transmitting NM and a receiving NM;
computing, commu-
ic diseases are increasing drastically. This work is but this limits the range of communication to a nications, manufac-
undertaken in the framework of a global picture few nanometers. In the case of nano electromag-
called “Future eHealth,” and these technologies netic wireless communication, the aim is to use turing, energy,
should be integrated with other solutions such as electromagnetic signals, and send and receive
computation services (localization, fall detection, them using nanoscale antennas, nanotransmit- healthcare, trans-
etc.) in U-Health smart homes. These character- ters, and nanoreceivers. Indeed, using existing
istics are especially important for medical appli- wireless technology to communicate in vivo will portation, security,
cations, since a heavy burden on the hospital will
be eased radically by introducing innovative,
not be acceptable for many reasons such as bulk-
iness of the devices and potential radiation dam-
etc. With this tech-
highly efficient, and cost-effective solutions [15]. age. However, materials such as graphene and nology, it is possible
In this article, we describe how nanotechnolo- carbon nanotubes (CNTs) have opened opportu-
gies combined with existing or novel communica- nities for developing nanoscale batteries, anten- to build devices in
tion techniques, wireless or molecular, can help nas, electronics, and nano electron mechanical
to design B2Ns that can be used to develop systems (NEMSs) that are necessary to consti- the nanometer
innovative healthcare solutions. Nanoscale tute the communication chain [1]. Molecular
devices open up amazing opportunities in health communication is another innovative approach scale range.
care. Indeed, these systems can be introduced aiming to use specific molecules to encode and
into the human body and could intervene very transmit information [5]. The transmitting
closely with organs and cells. Inspired directly by nanomachine uses natural or artificial molecules,
natural biological interactions [4], nanodevices or even bacteria or a virus to carry the message
intervening at the molecular level will allow to the receiving nanomachines [6]. In the
novel healthcare solutions to be developed that Molecules Concentration Approach (MCA), the
could be not only more efficient but also cost emitter changes the concentration of the emitted
effective because of the possibility of large-scale molecules to encode information, while in DNA
production. Based Communications (DBC), the emitter
This article is divided into three parts. The introduces a fragment of DNA representing the
first part introduces the concept of bio-nanosen- information to transmit directly in the bacteria
sor networks, the second part describes some or virus. In the MCA, molecules move from the
implementation work with bio-nanosensors, and emitter to the receptor via a random diffusion
the last part is a discussion about the use of process [12] while in DBC, bacteria and viruses
wireless or molecular communication protocols are attracted by specific attractors in the
to achieve cooperation among nanomachines to receivers [7].
address medical problems. While all these solutions are possible, there is
increasing complexity in implementing them.
BIO-NANOSENSOR NETWORKS The community today has much expertise in
wireless communications that could be used in
Nanotechnology is a multidisciplinary field that designing nano wireless protocols and systems.
requires competencies from several fields such However, despite the availability of strong theo-
as chemistry, physics, molecular biology, material retical models and practical knowledge, imple-
science, computer science, and engineering. mentation on the nanoscale is very challenging
Applications of nanotechnology are today due to the lack of understanding of energy and
impacting numerous aspects of our society such propagation issues at this scale. Nevertheless,
as computing, communications, manufacturing, coverage range with this technology could be the
energy, healthcare, transportation, and security. greatest challenge. Molecular communication is
With this technology, it is possible to build another option that is specifically adequate
devices on the nanometer scale. The basic unit because this mechanism is already successfully
function may be called a nanomachine (NM), used in natural systems. Hence, the logic to
which can perform simple tasks of computation, implement may be simpler than DBC; however,
sensing, and actuation (e.g., detection of the communication range is only in the range of
molecules, generation of motion, or performing a few centimeters. There is actually no consen-
chemical reactions) in a close environment. With sus about the best approach to follow, and dif-
communication capabilities, these can form a ferent research teams pursue research in
network of NMs with enhanced capabilities. At numerous directions. To summarize these differ-
the simplest level, it can be a sensor network ent techniques, we present in Table 1 a compari-
with sensing being the only function. son of various approaches.
With communication capabilities, NMs can In this work, we aim to address the two main
exchange information and collaborate together approaches, nano wireless communication and
to provide enhanced functionalities and/or cover molecular communication, and discuss in the fol-
a larger area of applications. However, commu- lowing sections how nanomachines implement-

IEEE Wireless Communications • October 2012 43


AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 44

the possibilities, continuous waves or tiny bursts


Approach Range in body Rate Biocompatibility Energy
of a few nanoseconds similar to ultra wideband
(UWB) modulation are possible to implement.
Nano wireless 1 cm to 1 m ~kb/s Medium to low High Transmitting nanomachine can modulate the
sequence of bits 0 or 1 using appropriate modu-
Nano acoustic 1 cm to 10 cm ~kb/s Low High lation schema such as quadrature amplitude
modulation (QAM), phase shift keying (PSK),
Molecular 1 nm to 1 cm ~b/h High to medium Very low pulse position modulation (PPM), and pulse
rate modulation (PRM). Here again, there are
Nanomechanic 1 mm to 1 nm ~b/s Medium to low Very low a number of challenges that have not been
solved so far at this high frequency band such
Bacteria-based 1 mm to 1 cm ~b/s High to medium Very low as channel access control, synchronization, path
loss, interference, and noise. The challenge is
Table 1. Comparison between different communication modes at the exacerbated at a very low scale and in vivo
nanoscale. since the interactions between the waves and
the molecules are much more important. In
wireless communication, interference is an
ing one of these techniques could communicate important aspect to address. The interference
with each other to coordinate their actions in the could come from either the environment itself
face of a health anomaly. (e.g., interaction between electromagnetic
waves and molecules) or between competing
transmissions. To mitigate interference, it is
DIFFUSION OF INFORMATION AND necessary to reduce the transmission power (to
COORDINATION OF ACTIONS reduce inter-NM interference) and use relaying
techniques to increase the range of communica-
As previously stated, the aim is to deploy several tion. Indeed, it may not be possible to cover the
NMs that communicate in order to achieve col- whole target area with only one NM; therefore,
lectively and in a distributed manner a coordi- numerous NMs will be deployed in the target
nated task such as global sensing or globally area and communicate with each other using
actuating the environment in space and time. multihop communication using relaying NM
The interconnection and communication of nodes.
functional components at the nanoscale is Another way of communicating at this scale is
defined here by the term nano networks. We by molecular communication (Fig. 1). In this
consider in this work two types of communica- approach, NMs are equipped with special reser-
tions, nano wireless communication and molecu- voirs that contain specific molecules called sig-
lar communication. naling molecules. When a transmitting NM aims
Nano wireless communication aims at allow- to communicate with a receiving NM, it releases
ing NMs to communicate using electromagnetic molecules that encode information toward the
waves similar to existing wireless technologies. receiving NM. Following this, the concentration
However, existing technology cannot be used at of molecules around the nanodevice increases
the nano scale due to the requirements in terms abruptly [10], and the molecules move toward
of size of the devices, required energy, and also the receivers and disperse randomly. Molecules
the frequency band. Recent works have shown propagate and eventually collide with other
that it was possible to design nano-antennas of molecules following a Brownian movement. It
a few hundred nanometers operating in the ter- actually follows the transport properties that give
ahertz band. Some experimental antennas have rise to a flow of material from one region to
already been implemented using graphene or another when a gradient of concentration exists
carbon nanotubes (CNTs) [1], but further work between the two regions. In this non-equilibrium
is needed to identify the exact operating fre- state, the molecular dynamic will create a wave
quency, radiation efficiency, and coverage. of molecules that will propagate toward a low
Development of nanobatteries is also very chal- concentration region, hopefully where the recep-
lenging at this scale. What is required at this tor is [13]. When the molecular concentration
scale is a battery that measures no more than wave reaches the receiver, the concentration of
100 nm. However, by reducing the size of the the molecule will increase, which will facilitate
battery, the stored energy is also considerably the binding of the molecule with the receiver
decreased. Therefore, it is necessary to not only sensors. When the number of binding events
design very-low-energy-consuming NMs by increases enough, the receiver can decode the
reducing energy in every part of the system signal and interpret the received information.
(i.e., sensing, computing, actuating, The results presented in [7] show that the maxi-
sending/receiving), but also find innovative mum capacity of the diffusion-based channel can
approaches to self-recharge the battery in vivo be derived as a function of the physical parame-
using the energy available in the environment ters, the bandwidth of the system as well as the
(e.g., conversion of movements, vibrations, transmitter power (initial concentration of
hydraulic, thermal energy into electricity to molecules). The receiving nanomachine is
recharge the battery). When an NM wants to equipped with specific sensors that are capable
communicate with another NM, the informa- of binding to the signaling molecules, decoding
tion is encoded into an electromagnetic wave the message, and possibly launching another
modulated at very high frequency. It is envi- action; for example, releasing drug molecules
sioned to use an adapted modulation scheme (contained in a different reservoir), sensing
that works properly at this frequency. Among other molecules, and/or retransmitting the same

44 IEEE Wireless Communications • October 2012


AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 45

Nanocomputing Signaling molecules


It is not only
reservoir Molecules
reservoir necessary to design
Nanoreceptors
very low energy con-
Nanosensors
suming nanoma-
Molecules
chines by reducing
energy in every part
Nanobatterie of the system but
Emitter NM
Controllable
Receptor NM
gate also find innovative
Concentration
gradient approaches to self-
Drug
Inner molecules
concentration
reservoir recharge the battery
Cin>>C Propagation environmnet
out
(diffusion model, Brownian movement) in vivo using the
Codes CMi C energy available in
1 C’1’
Bit=’1’ the environment.
0 0 C’1’

Detection threshold

C: Molecules concentration -
t: Time duration -
C=0 -t
NM: Nanomachine
Bit duration

Figure 1. Molecular communication between two nanomachines.

or a different message to other nanomachines ing, drifting, etc.) remain applicable and help to
(e.g., relaying the information to another zone). determine the channel capacity based on Shan-
In this type of communication, the concentra- non information theory [7].
tion of the molecule represents the valence of Similar to the modulation scheme in electro-
the signal; therefore, it is necessary to use two magnetic wireless communication, we can use
levels of concentration to allow the receiver to increase in the valence of the signal using N
differentiate between two binary values. This types of molecules (instead of N levels of fre-
approach is not really efficient since it is neces- quency in the electromagnetic wave) and two
sary to send molecules for both digits while the levels of concentration (instead of two levels of
NM reservoir of molecules is physically limited amplitude in the electromagnetic wave). Given
in size. To increase the lifetime of the NMs, it is the maximum modulation rate Rmax that can be
possible to define a certain level of concentra- derived from the bandwidth W of the channel
tion above which the transported information is and following the formula of Shannon (Rmax =
1, otherwise 0. Since the concentration of the 2W), the maximum bit rate that can be achieved
molecules will decrease due to the diffusion of with this modulation scheme is D max =
the molecules in the environment, it is necessary R max Log 2 (2*N) [11]. In the presence of noise
to wait a certain time to be able to send a 0 so (i.e., molecular noise in this case) that will
that the concentration decreases below the impact positively or negatively the concentration
determined level, which basically reduces the bit of the molecules (alternatively the amplitude of
rate. It is possible to enhance the rate of the the electromagnetic wave) at the receiver [7], the
transmission by increasing the valence of the sig- maximum molecular signal-to-noise ratio
nal. For that, the system could use different (MSNR) can be determined. Based on this
molecules, each of them modulated in concen- MSNR and the sensitivity of the receptor, the
tration (Fig. 2). initial concentration (amplitude) may be calcu-
This communication scheme based on lated. If the distance between the emitter and
molecules is very challenging compared to the the receptor is defined as d, Fick’s second law
use of electromagnetic waves. Indeed, the propa- can be used to predict how diffusion causes the
gation of molecules in the body environment is concentration to change in time and space [13]
subject to various phenomena closer to fluid (in the case of the electromagnetic waves, this
than signal propagation. Several parameters can will follow the Maxwell equations). The concen-
impact them negatively (temperature, viscosity, tration Ci of the molecule i for the diffusion in
flow, pressure, dispersion, etc.). Fortunately, three dimensions (i.e., over the axis between the
from a systemic point of view, some well-known emitting NM and the receiving NM) can be for-
characteristics of signal transmission (noise, fad- mulated as follows:

IEEE Wireless Communications • October 2012 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

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
<TEM image of nanowire> 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
1 μm Active region
B2N.
<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 offers advantages such as large surface-to-vol-


an effective laboratory-on-a-chip system, which ume ratio and interesting electronic properties.
may include monitoring of pH, cholesterol, This approach allows us to keep the standard
complete blood count, white blood cell count, integrated circuit manufacturing practice while
troponin-I for heart attack, bilirubin, and adding the advantages of nanotechnology. As a
metabolic panel including Na, K, and Ca. A result, sensitivity of detecting the disease can be
laboratory-on-a-chip is a system aimed at improved while attempting to keep the cost of
replacing manual work by several technicians the devices down.
analyzing blood, urine, and other human sam- Figure 3 shows the schematic of the silicon
ples. This automated approach will be cost nanowire Bio-FET and a scanning electron
effective and rapid, and could reduce health microscopy image of the fabricated device. The
care costs associated with diagnostics. Until fabrication details can be found elsewhere [9]
now, such systems have not been developed for but are briefly given below. A 150 mm silicon-
injection into the body; rather, lab-on-a-chip on-insulator substrate with boron doping of 1015
systems have been investigated for automating cm –3 and 100 nm thick top silicon layer was
laboratory analytical work involving blood, used. The top layer was thinned first to 40 nm to
urine, or other samples. Regardless, a well form rectangular-shaped nanowires. Then
designed sensor system is expected to be small, nanowires of 50 nm width and 10 micron length
low-power-consuming, reliable, robust, capable were formed using electron beam lithography
of performing multiple laboratory functions and inductive plasma etching. These were fol-
from the list above, reasonably fast, and usable lowed by source and drain ohmic contact forma-
in the home wherever possible. tion, source/drain doping, gate contact
Systems meeting the above requirements are formation, and creation of the reference elec-
under development in many laboratories across trode. Typically 20–50 parallel nanowires were
the world. They vary in numerous ways: materi- used to form the active channel region.
als used, types of probes, transduction tech- The Bio-FET is capable of detecting charges
niques, and so on. For example, a sensor may be from the biomolecules. The charge distribution
affinity-based: a probe is chosen that selectively is expected to be different at every stage of the
binds to the target (i.e., the type of bio-molecule operation: bare device vs. after attaching the
to detect). The result of the probe-target binding probe vs. after probe-target binding. The mea-
may manifest in the form of an electrical, elec- sured current-voltage (I-V) characteristics at
trochemical, or optical signal. Here we have cho- each stage would be different, and a characteris-
sen to measure electrical response arising from tic shift in the threshold voltage (VT) is expect-
the selective probe-target binding. Our platform ed. As a preliminary demonstration, we used the
is a bio field effect transistor (Bio-FET). This is Bio-FET to measure pH since it is one of the
similar to conventional FET except for the functions of a lab-on-a-chip. Figure 4 shows the
replacement of the gate with an electrolyte (i.e., drain current vs. reference electrode behavior
the sample and reference electrode). Another for various pH values. As the pH decreases from
departure from the conventional FET is the use 12 to 2, the curves shift toward the negative
of silicon nanowires as the channel material direction. The device shows a pH sensitivity of
instead of epitaxial silicon layer. The nanoscale 40 mV/pH.

IEEE Wireless Communications • October 2012 47


AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 48

increase in charges inducted by the increase in


concentration of the corresponding biomarker,
and if this concentration goes beyond the identi-
10-7 fied and preprogrammed threshold, the equilib-
rium is violated and the NM will react as
programmed. The NM that detects the problem
10-8 will propagate the information to other NMs to
trigger a global response. In the case when NMs
Drain current [A]

From pH 12 to pH 2
with pH 2 step use molecular communication, this could of
10-9 course take several hours, which may still be
acceptable depending on the type of disease.
When a more immediate response is needed,
10-10
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
10-11
interpreted by the receiving NMs and eventually
@ VD=0.1V perform other actions such as activating the
sensing of other biomaterials with predefined
10-12
0.0 0.3 0.6 0.9 1.2 1.5 thresholds (e.g., to confirm other aspects of the
anomaly) or release other signaling molecules to
Figure 4. Drain current vs. gate voltage for various pH values. 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-
The results above demonstrate the prelimi- gate the heart attack). These actions require
nary capability of the fabricated Bio-FET to NMs to be capable of performing some basic
function as a lab-on-a-chip. Further work would application functions, for example, basic logic
involve testing for the various analytes men- actions such as “and,” “or” may be incrementing
tioned earlier, integration with microfludics for simple counters, testing, activating/deactivating
automated sample delivery, and system integra- reservoir gates, and so on. Similar to the report
tion with communication and networking aspects in [8], a simple protocol stack can be designed
of the complete NM. Deployment of sensors in for a molecular-based protocol as presented in
vivo would require addressing issues related to Fig. 5.
biocompatibily, power supply, and many others.
COMMUNICATION PROTOCOL BETWEEN
NANOMACHINES SYNERGY TO ANOMALIES NANOMACHINES
DETECTION AND RESPONSE
The interaction protocol between NMs needs to
The results above demonstrate the preliminary be as simple as possible to avoid increasing the
capability of the fabricated Bio-FET to function required computing capabilities of NMs, which
as a lab-on-a-chip. This is of course a first step are limited. It is not possible or even desirable
towards developing new solutions to implement- at this level to identify an NM individually.
ing a full B2N for future e-health. The devices as Network addressing should be based on a
presented here have not been attempted in any group. Each NM, based on its capabilities, will
type of in vivo applications yet; this requires belong to a particular class of bio-nanosensor;
major development in terms of material/device for example, an NM with glucose sensing capa-
selection from a biocompatible point of view. bilities will belong to one group and another
Communication among NMs will also require NM capable of sensing blood pH will belong to
the design of a full communication protocol a different group. Communication between
between the NMs (i.e., how to communicate NMs will be based on a multicast scheme where
between NMs to achieve a global response). We one NM transmits electromagnetic waves or
envision a B2N composed of various NMs releases molecules to communicate with a par-
achieving multiple goals such as some measuring ticular class of NMs and not a particular one.
cholesterol, and others pH and blood glucose. In addition, there is no need to have a com-
Doctors can identify the equilibrium among plete communication stack here; at the applica-
these different physiological parameters and the tion layers, some level of computing will be
corresponding thresholds. We envision that NMs achieved to identify the proper actions to trig-
will be manufactured and programmed with this ger based on the results of sensing. To send
information. These NMs will be embedded with- information to a remote NM, the information
in the human body at different locations of inter- will be transmitted to the network layer, which
est to monitor tissues, organs, and molecules in will identify the type of wave or molecules to
the blood. Once the NMs are introduced in the send and the signal power level or molecule
body, they can start to sense the environment concentration level at which to encode the mes-
and possibly communicate with each other using sage. In both communication techniques, the
the embedded communication technology (i.e., NM will first need to sense the channel to avoid
electromagnetic wireless communication or collision (i.e., there is no other transmission
molecular communication). Whenever an abnor- already in progress); if it is free, it sends the
mal situation happens (e.g., initial signs of a data using the appropriate modulation scheme
heart attack), the bio-nanosensors will detect the (electromagnetic or molecular). At this level,

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

and coordination MS Recognises high concentration biomolecules MS Sends signal to MS using molecules
capabilities will cer- MS Sends signal to MS using molecules MS Receives the signal and delivers drug 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 ACKNOWLEDGMENT
revolutionize future ubiquitous healthcare. With
the advances in nanotechnology and the increas- This research was supported by the World Class
ing level of understanding of biological mecha- University program funded by the Ministry of
nisms, opportunities for innovative nanoscale Education, Science and Technology through the
networked bio-nanosensors are being created. National Research Foundation of Korea (R31-
In this article, we have listed some challenges in 10100).
developing a new generation of nanoscale sen-
sor networks. We have presented and discussed REFERENCES
two possible approaches to enable communica- [1] I. Akyldiz and J. M. Jornet, “Electromagnetic Nanosen-
tion at the nanoscale: electromagnetic and sor Networks,” Nano Commun. Networks J., Elsevier 1,
DOI: 10.1016/J.nancom.2010.04.001, 2010, pp. 3–19.
molecular communications. Molecular commu- [2] S. Parveen, R. Misra, and S. Sahoo, “Nanoparticles: A
nication is part of this evolution driven by sever- Boon to Drug Delivery, Therapeutics, Diagnostics and
al research teams worldwide to design artificial Imaging,” J. Nanomedecine, Nanotechnology, Biology
nanomachines capable of communicating and Medicine, vol. 8, issue 2, 2012, pp. 147–66.
[3] J. Philibert, “One and Half Century of Diffusion: Fick,
together using molecules that do not harm the Einstein, Before and Beyond,” Open-Access J. Basic
body. Based on the current state of the art, we Principles of Diffusion Theory, Experiment and Applica-
have presented a possible architecture for nan- tion, Diffusion Fundamentals 4, 2006, pp. 6.1–6.19.
odevices that includes biosensing capabilities, [4] L. Dehmelt and P. I. H. Bastiaens, “Spatial Organization
of Intracellular Communication: Insights from Imag-
with some level of computing and actuating. We ing,” Nature Reviews Molecular Cell Biology 11, 2010,
have discussed the energy problem to empower pp. 440–52.
these nanodevices to be programmed for pro- [5] T. Nakato et al., “Molecular Communication Through
viding appropriate response action to health Gap Junctions Channels: System Design, Experiments
and Modelling,” Proc. 2nd Int’l. Conf. Bio-inspired
anomalies. The benefit of using electromagnetic Models of Network, Info. and Computing Sys., DOI:
communication is that the community has vast 10.1109/BIMNICS.2007.4610100, 2007, pp. 139–46.
knowledge in this area. Nevertheless, at the [6] M. Gregori and I. F. Akyildiz, “A New NanoNetwork
nanoscale and in vivo some problems appear Architecture Using Flagellated Bacteria and Catalytic
Nanomotors,” IEEE JSAC, vol. 28, no. 4, DOI:
since the interactions between the electromag- 10.1109/JSAC.2010.100510, 2010, pp. 612–19.
netic wave and molecules are not negligible. [7] M. Perobon and I. F. Akyildiz, “Information Capacity of
Molecular communication is a more recent Diffusion-based Molecular Communication in Nanonet-
approach which is promising and natural for works,” Proc. INFOCOM ’11, 2011, pp. 506–10.
[8] F. Walsh et al., “Synthetic Protocols for Nanosensor Trans-
biological systems since a similar communica- mitting Platforms Using Enzyme and DNA Based Comput-
tion scheme is used in natural systems. Howev- ing,” Elsevier Nano Commun. Networks, pp. 50–62.
er, there is still much work needed to achieve [9] K. T. Rim et al., “Silicon Nanowire Ion Sensitive Field
the implementation of this solution in vivo, Effect Transistor with Integrated Ag/AgCl Electrode: pH
Sensing and Noise Characteristics,” Analyst, vol. 136,
which will require addressing several issues such 2011, pp. 5012–16.
as biocompatibility, power supply, and nanoma- [10] B. Atakan and O. Akan, “An Information Theoretical
chine embedding, among others. Approach for Molecular Communications,” Proc. 2nd

50 IEEE Wireless Communications • October 2012


AGOULMINE LAYOUT_Layout 1 10/11/12 3:21 PM Page 51

Conf. Bio-inspired Models of Network, Info. and Com-


puting Sys., Dec. 2007, pp. 33–40.
respectively. Currently, he is a Ph.D. student in the Nanode-
vices and Circuits Lab at POSTECH. His research interests There is still much
[11] C. E. Shannon, “A Mathematical Theory of Communica- are nanoscale Si MOSFETs and technology, and bio and
tion,” Bell Sys. Tech. J., vol. 27, 1948, pp. 379–43, 623–56. chemical sensors based on nanoscale Si devices. work needed to
[12] E. L. Cussler, Diffusion Mass Transfer in Fluid Systems,
Cambridge University Press, 1986.
[13] A. R. Leach, Molecular Modeling: Principles and Appli-
T AIUK R IM received his B.S. degree in the Department of achieve the imple-
Electrical Engineering from POSTECH, Korea, in 2008. Since
cation, 2nd ed., Prentice Hall, 2001.
[14] A.S. Griffin, S.A. West and A. Buckling, “Cooperation
2008, he is currently working toward M.S. and Ph.D.
degrees through an integrative program course with the
mentation of this
and Competition in Pathogenic Bacteria,” Nature 430,
2004, pp. 1024–27.
Department of Electrical Engineering, POSTECH. His
research interests include nanoscale biosensor devices and solution in vivo
[15] N. Agoulmine et al., “U-Health Smart Home,” IEEE the surface immobilization of biological molecules on inor-
Nanotechnology Mag., 2011, pp. 7–11. ganic surface. which will require
BIOGRAPHIES M. MEYYAPPAN [F] is chief scientist for Exploration Technolo- addressing several
NAZIM AGOULMINE (nazim.agoulmine@iup.univ-evry.fr) is a full gy at NASA Ames Research Center in Moffett Field, Califor-
professor at the University of Evry, France, since 2000 and nia. He has authored or co-authored over 240 articles in
peer-reviewed journals and made over 200 invited/
issues such as bio-
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
keynote/plenary talks in nanotechnology subjects across the
world. His research interests include carbon nanotubes,
compatibility, power
group LRSM (Software for Networked Multimedia Systems) as
part of the IBISC Research Laboratory. He received his Engi-
graphene, and various inorganic nanowires, their growth
and characterization, and application development in supply, nanomachine
chemical and biosensors, instrumentation, electronics, and
neer degree in 1988 from USTHB, Algeria, and his Master’s
and Ph.D. degrees in computer science in 1989 and 1992 optoelectronics. He is a Fellow of the Electrochemical Soci- embedding and
from the University of Paris XI, France. His research interests ety, American Vacuum Society, Materials Research Society
are mainly wired and integrated network and service manage- (MRS), Institute of Physics (IOP), and the American Institute
of Chemical Engineers (AIChE). He served as President of
many others.
ment, autonomic systems, wire and wireless networks,
ehealth, and bio-inspired networking and computing. He is an the IEEE’s Nanotechnology Council in 2006–2007. He cur-
area editor of Elsevier’s International Journal on Computer rently serves as the Vice President of the IEEE-Electron
Networks and Secretary of the e-health IEEE Technical Com- Devices Society for Educational Activities.
mittee. He served several times as a general TPC co-chair for
IEEE/IFIP conferences and workshops (IM, GIIS, MMNS, JEONG-SOO LEE (ljs6951@postech.ac.kr) received B.S., M.S.,
DANSM, LANOMS, etc.). He is author and co-author of five and Ph. D. degree in electrical engineering from POSTECH,
books in the areas of autonomic networking, self-managed Korea, in 1991, 1993, and 1996, respectively. From 1996
networks, network and system management, and multimedia to 2001, he joined Samsung Electronics as a senior engi-
management. He has participated in numerous European pro- neer working on the development of gate dielectrics in
jects from the first EU programs (RACE ESPRIT, ACTS, IST, FP, CMOS device. In 2001, he was with the EECS department
ITEA, CELTIC) He is acting as an expert for several national and of the University of California at Berkeley as a visiting sci-
international research agencies ANR (France), NSERC/FCAR entist, where he worked on the fabrication and characteri-
(Canada), HETAC (Ireland), and NRK (South Korea). zation of FinFETs and UTBFETs. From 2002 to 2005, he
joined the University of Texas, Dallas as a research assistant
KIHYUN KIM received his B.S. degree from the Department professor in the Electrical Engineering Department where
of Electrical Engineering at Hanyang University, Korea, in he worked on the synthesis of nanowires and their applica-
2009. Since 2009, he is currently working toward his M.S. tion in biosensors. Since August 2008, he has been an
and Ph.D. degrees through an integrative program course assistant professor with the Department of Electrical Engi-
with the Department of Electrical Engineering, Pohang Uni- neering, POSTECH. He is currently vice director of National
versity of Science and Technology (POSTECH). His research Centre for Nanomaterials Technology (NCNT), POSTECH. His
interests include nanoscale biosensor devices and nanode- research interests include nanoscale silicon devices and
vice fabrication. technology, and nanostructures for biosensors and chemi-
cal sensors. He is a member of the IEEE Electron Device
S UNGHO K IM received B.S. and M.S. degrees in electrical Society and currently serves as a committee member of
engineering from POSTECH, Korea, in 2008 and 2010, IEEE-EDS for Educational Activities.

IEEE Wireless Communications • October 2012 51