18-06-2012, 11:24 AM
Medical Nanorobot Architecture Based on Nanobioelectronics
Abstract:
This work describes an innovative medical nanorobot architecture based on important discoveries in
nanotechnology, integrated circuit patents, and some publications, directly or indirectly related to one of the most
challenging new fields of science: molecular machines. Thus, the architecture described in this paper reflects, and is
supported by, some remarkable recent achievements and patents in nanoelectronics, wireless communication and power
transmission techniques, nanotubes, lithography, biomedical instrumentation, genetics, and photonics. We also describe
how medicine can benefit from the joint development of nanodevices which are derived, and which integrate techniques,
from artificial intelligence, nanotechnology, and embedded smart sensors. Teleoperated surgical procedures, early disease
diagnosis, and pervasive patient monitoring are some possible applications of nanorobots, reflecting progress along a
roadmap for the gradual and practical development of nanorobots. To illustrate the described nanorobot architecture, a
computational 3D approach with the application of nanorobots for diabetes is simulated using clinical data. Theoretical
and practical analysis of system integration modeling is one important aspect for supporting the rapid development in the
emerging field of nanotechnology. This provides useful directions for further research and development of medical
nanorobotics and suggests a time frame in which nanorobots may be expected to be available for common utilization in
therapeutic and medical procedures.
Keywords: Biomedical instrumentation, CMOS, diabetes, DNA molecular machine, equipment design, lithography, medical
nanorobotics, nanoelectronics, nanomanufacturing design, nanomechatronics, nanomedicine, nanorobot architecture,
nanotubes, photonics, remote inductive powering.
INTRODUCTION
This paper presents a nanorobot architecture for biomedical
applications in nanomedicine [1]. The advent of
biomolecular science and new manufacturing techniques is
helping to advance the miniaturization of devices from micro
to nanoelectronics. A first series of nanotechnology prototypes
for molecular machines are being investigated in
different ways [2-5], and some interesting device propulsion
and sensing approaches have been presented [6-8]. More
complex molecular machines, or nanorobots, having embedded
nanoscopic features may provide new tools for medical
procedures [1,2,9]. Sensors for biomedical applications are
advancing through tele-operated surgery and pervasive
medicine [10,11].
SYSTEM SIMULATION
The use of microdevices in surgery and medical treatments
is a reality which has brought many improvements in
clinical procedures in recent years. For example, catheterization
has been used as an important methodology for
many cardiology procedures [12] and aneurysm surgery [13].
In the same way as the development of microtechnology in
the 1980s has led to new tools for surgery, emerging
nanotechnologies will similarly permit further advances
providing better diagnosis and new devices for medicine
through the manufacturing of nanoelectronics based on new
*Address correspondence to this author at the CAN Center for Automation
in Nanobiotech, Herminio Lemos 449, Sao Paulo, SP 01540 Brazil; E-mail:
adrianocavalcanti[at]canbiotechnems.com
CMOS technologies [14]. Nanorobots may be considered a
new possibility for medical instrumentation to solve many
problems in health care [15-17], including cardiology
interventions, medical analysis, cancer early diagnosis,
diabetes monitoring, and minimally invasive brain surgery.
For effective manufacturing progress we consider a
nanorobot architecture design using embedded devices with
nanoelectronic circuits [18] based on RF CMOS transducers
[19,20], to integrate the sensing, communication, energy
transfer, and actuation for the nanorobots as the most
effective way to accomplish the work to advance molecular
machines. Devices based on CMOS are achieving 45nm
sizes, with functional sensors and actuators being produced
with sizes equal and smaller than 500nm [21-23]. The
correct architecture for medical nanorobots may include the
minimal number of embedded devices for its effective
application [1], having embedded sensors and actuators for
specified tasks. It is important to define actual capabilities to
enable Nano-Build Hardware Integrated Systems [24],
establishing how to enable pathways to help on research and
development of nanorobots based on the present stages of
nanotechnology development. Nanoelectronics integrated
circuits using nanowires, nanotubes and photonics are
leading to smaller sizes on complex devices [14,25]. Allied
with this fact, the mobile phone as a widely used device in
everyday life could be applied as a source of coupling energy
and data transmission for communication, control, and
energy supply for the operation of a nanorobot inside a
human body.
2 Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 Cavalcanti et al.
The feasibility of advancing techniques for control [26]
and manufacturing molecular machines should be understood
as emergent results from actual and upcoming stages
of nanotechnology, based on nanoelectronics [27] and new
materials [24,28]. New possibilities are coming from these
developments which will enable new medical procedures
[1,9,15-17,28].
PATENT REVIEW
Current developments and patents in nanoelectronics and
nanobiotechnology may provide feasible technology development
pathways to enable molecular machine manufacturing,
including embedded and integrated devices which
may comprise the main sensing, actuation, data transmission,
remote control uploading, and coupling power supply subsystems
providing the basics for operation of medical
nanorobots.
For example, surgical robots and other telepresence
systems employ enhanced grip actuation for manipulating
tissues and objects having extremely small sizes [10]. An
actuator with biologically-based components has also been
proposed [29]. This actuator has a mobile member that
moves substantially linearly as a result of a biomolecular
interaction between biologically-based components within
the actuator. Such actuators can be utilized in nanoscale
mechanical devices to pump fluids, open and close valves, or
to provide translational movement [29].
A power supply implanted behind a tissue barrier in a
human body and operating a medical device and incorporating
a high frequency power receiver antenna coil [30]
demonstrates the use of remote energy powering for
implanted medical devices. A similar approach could supply
exogenous energy to a molecular machine system possessing
embedded nanoelectronics. To help control nanorobot
position, a system for tracking an object in space may
comprise a transponder device connectable to the object [31].
The transponder device has one or several transponder
antennas through which a transponder circuit can receive an
RF signal. The transponder device adds a known delay to the
RF signal thereby producing an RF response for transmitting
through the transponder antenna [31]. A series of several
transmitters and antennas allow a position calculator
associated with the transmitters and receivers to calculate the
position of the object as a function of the known delay and
the time period between the emission of the RF signal and
the reception of the RF response from the first, second and
third antennas [31].
Monitoring devices coupled to a transceiver and a memory
component for remote patient monitoring are currently
in use, and provide a central monitoring system platform for
monitoring a large number of physiological parameters [11].
For example, methods of monitoring patients and evaluating
the status of a tumor in a patient undergoing treatment
includes monitoring in vivo at least one physiological
parameter associated with a tumor, transmitting data from an
in situ sensor to a receiver external to the subject, analyzing
the transmitted data, repeating the monitoring and
transmitting steps at sequential points in time, and then reevaluating
the treatment strategy [32]. This method can also
include identifying in a substantially real time manner when
conditions are favorable for treatment, and it can be used to
verify or quantify how much of a known drug dose or
radiation dose was actually received at the tumor. This
method can include remote transmission from a non-clinical
site to allow oversight of the tumor’s condition even during
non-active treatment periods (in between active treatments)
[32]. The disclosure also includes monitoring systems with
in situ in vivo biocompatible sensors and telemetry based
operations and related computer program products. The RF
telemetry antenna comprises an LC tank circuit including an
RF head telemetry coil and a tuning capacitor and has a
predetermined antenna Q. A transmit telemetry pulse is
generated for establishing a pulse width of the telemetry RF
pulse [33]. Upon termination of the telemetry transmit pulse,
antenna Q is reduced from the predetermined antenna Q and
the declining amplitude oscillations are thereby attenuated
[33]. The sensor can receive data transmitted from an
external device and can also transmit data to an external
device [19]. A tuning circuit comprising capacitors and/or
varactors is used, thus creating a sufficiently large effective
signal aperture.
For diabetes application, the most important use of
nanorobots is monitoring daily the patient’s glucose levels, if
possible without interfering in their way of life. Thus, one
mobile phone is enough for data transferring and monitoring
purposes. Whether the doctor wants to track the nanorobots
current positions due some medical reason, it can be done
clinically or at home with at least two additional transmitters,
which may comprise other ancillary preprogrammed cellular
phones or transponder devices.
Nanotechnology is moving fast towards nanoelectronics
fabrication. Chemically assembled electronic nanotechnology
provides an alternative to using Complementary Metal
Oxide Semiconductor (CMOS) for constructing circuits with
feature sizes in the tens of nanometers [23]. Such structures
can be operated both as a transistor and as a memory. The
thin active silicon channel and the thin front oxide provide
dual function of the device, using two voltage ranges. At
small voltages the structure operates as a normal transistor,
and at higher voltages the structure operates as a memory
device [34]. A CMOS component can be configured in a
semiconductor substrate as part of the circuit assembly [14].
An insulating layer is configured on the semiconductor
substrate, which covers the CMOS component. A nanoelectronic
component is configured above the insulating
layer. If several nanoelectronic components are provided,
they are preferably grouped in nanocircuit blocks [14].
Three-dimensional (3D) integration schemes of fabricating a
3D integrated circuit in which the nFETs are located on an
optimal crystallographic surface for that type of device can
also be applied [35]. Semiconductor devices are pre-built on
a semiconductor surface of a first silicon-on-insulator (SOI)
substrate and second semiconductor devices are pre-built on
a semiconductor surface of a second SOI substrate [35].
A method of fabricating a nano SOI wafer having an
excellent thickness evenness without performing a chemical
mechanical polishing and a wafer fabricated by the same
have been announced [36]. The provided method includes
preparing a bond wafer and a base wafer, and forming a
dielectric on at least one surface of the bond wafer.
Medical Nanorobot Architecture Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 3
Thereafter, an impurity ion implantation unit is formed by
implanting impurity ions into the bond wafer to a predetermined
depth from the surface of the bond wafer at a low
voltage. The dielectric of the bond wafer and the base wafer
contact each other in order to be bonded. Next, a thermal
process of low temperature is performed to cleave the
impurity ion implantation unit of the bond wafer. Finally, the
cleaved surface of the bond wafer bonded to the base wafer
is etched to form a nanoscale device region. Here, the
cleaved surface may be etched by performing a hydrogen
surface process and a wet etching [36].
Nanotube/nanofiber electrodes are integrated with
electronic devices to form a single-chip nano-bio-sensor
[37]. The single-chip nano-bio-sensor which uses nano-meter
scale electronic devices, includes sensing transistors in close
proximity to nano-tube/nano-fiber electrodes, and provides
an arrangement of the nano-tube/nano-fiber electrodes into
high density clusters and groups so that sensitive, low noise
detection of the activities of small cells, large cells and a
network of cells is possible. The integrated, single-chip
approach provides that differential signal extraction is
possible. The single-chip nano-bio-sensor includes small
feature size transistors [37]. New methods allow the
fabrication of novel gated field emission structures that
include aligned nanowire electron emitters localized in
central regions within gate apertures [38], and novel devices
using nanoscale emitters for microwave amplifiers, electronbeam
lithography, field emission displays and X-ray sources.
For lithographic processes, an optical device can include
an array of heterogeneous optical waveguides. The elements
to be excited are selected for each line by intensities of light
rays in the first optical waveguides functioning as horizontal
waveguides; light rays in the second waveguides functioning
as vertical waveguides are modulated in intensity on the
basis of data signals, and the data signal light rays whose
intensities have been modulated are extracted to the outside
via the selected elements to be excited [25]. The alignment
material orients the subsequently deposited photoactive
material such that the photoactive material interacts with or
emits light preferentially along a selected polarization axis
[39]. Additional layers and sublayers optimize and tune the
optical and electronic responses of the device. An integrated
circuit package includes a chip having a number of chip pads
adapted to receive a variety of signals from, or to output the
same to, an external circuit, with nanoceramic materials in
thermal communication with the chip employed for efficient
heat removal from the chip [18].
Nanosensors are a related area of rapidly progressing
research and development. For example, coating nanomagnets
with biological molecules produces ultra-small, highly
sensitive and robust biomagnetic devices which combine
molecular electronics and spin electronics. When these
nanosensors are integrated into microfluidic channels, highly
efficient single-molecule detection chips for rapid diagnosis
and analysis of biological agents are constructed [27]. A
magnetic sensor device formed using SOI CMOS techniques
includes a substrate, a silicon oxide layer and in some cases a
variety of gated regions [40]. Electromagnetic field sensors
can employ the motion of a mechanical oscillator caused by
electromagnetic interaction, such as a magnetic polarization
with a magnetic field or an electric polarization with an
electric field [41]. For monitoring patients with diabetes,
methods are described for a novel chemosensor that involves
the modulation of hSGLT3 protein glucosensor activity [42].
This natural glucose sensor molecule is expressed in
cholinergic neurons that regulate muscle activity, and in
tissues including the brain and pancreas [42].
Biosensors may incorporate living components including
tissues or cells which are electrically excitable or are capable
of differentiating into electrically excitable cells, and which
can be used to monitor the presence or level of a molecule in
a physiological fluid [43]. Nanotubes and DNA are recent
candidates for new forms of nanoelectronics [44]. These may
be combined to create new genetically programmed selfassembling
materials for facilitating the selective placement
of nanotubes on a substrate by functionalizing nanotubes
with DNA. Through recombinant DNA technology, targets
labeled with distinct detectable biomarkers can be defined,
such as fluorescent labels, enzyme labels, and radioactive
patterns, and employed in suitable biomolecular transducers
[45]. Such biosensors can be used to detect labels selected
from among those known in the art, including, but not
limited to, radioactive labels, enzymes, specific binding pair
components, colloidal dye substances, fluorochromes, reducing
substances, latexes, digoxigenin, metals, particulates,
dansyl lysine, antibodies, protein A, protein G, electron
dense materials, and chromophores [45].
Finally, current developments in implant biocompatibility
have demonstrated suitable composites that could
permit a nanorobot to operate continously inside the human
body. For example, surfactant polymers which are useful for
changing the surface properties of biomaterials have been
presented [46]. Such surfactant polymers comprise a polymeric
backbone of repeating monomeric units having
functional groups for coupling to side chains, with separate
hydrophobic and hydrophilic side chains linked to said
backbone via the functional groups. The hydrophobic side
chains comprise an alkyl group (CH3 (CH2 -)n) possessing
from about 2 to 18 methylene groups [46]. This “artificial
Fig. (1). Medical complications can arise due to diabetes problems.
Nanorobots use sensors to detect glucose levels in bloodstream.
4 Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 Cavalcanti et al.
glycocalyx,” currently intended for use on biomedical
implants, could also provide biocompatibility for nanorobots
to operate inside the human body while remaining largely
invisible to the immune system.
NANOROBOT MEDICAL APPLICATIONS
The use of nanorobots may advance biomedical intervention
with minimally invasive surgeries [1,16,47], help
patients who need constant body function monitoring, and
improve treatment efficiency through early diagnosis of
possibly serious diseases [48,49]. Implantable devices in
medicine have been used for continuous patient data
acquisition. Patient monitoring can help in preparing for
neurosurgery [50], early stage diagnostic reports to fight
cancer [51], and blood pressure control for cardiology
problems [52]. The same approach is quite useful in
monitoring patients with diabetes [53,54].
To visualize how stages of the actual technologies can be
used to medicine, based on current discoveries, publications,
and patents, we implemented a system simulation of
nanorobots monitoring blood glucose levels (Fig. 1). Actual
advances in wireless technologies, nanoelectronics devices,
and their use in the implementation of nanorobots applied to
diabetes can illustrate what upcoming technologies can
enable in terms of medicine applications. The software
implemented from our group is used as a practical tool for
control and manufacturing design analyses.
As an example, patients with diabetes must take small
blood samples many times a day to control glucose levels.
Such procedures are uncomfortable and extremely inconvenient.
Serious problems may affect the blood vessels if the
correct target levels of glucose in the blood are not
controlled appropriately. Improper glucose control may
result in a large range of consequences for the nervous
system, kidney, eyes, exacerbate heart problems, and can
even lead to stroke [55].
The level of sugar in the body can be observed via
constant glucose monitoring using medical nanorobotics.
This important data may help doctors and specialists to
supervise and improve the patient medication and diary diet.
The glycemic levels and parameters for an adult with
diabetes stay inside the desired ranges, the patients must try
to keep their glucose between 90-130 mg/dl (5.0-7.2 mmol/l)
before refection, and <180 mg/dl (<10.0 mmol/l) after
refection, here including 2 hours concluded it. Upon waking
the expected blood pressures should be <130/80 mmHg. The
glycated hemoglobin (A1C) time series results must stay
<7.0% [55], as a result of good blood sugar levels [54, 56]. A
red blood cell lifespan is 120 days. Thus the A1C reflects the
blood sugar levels correlation for this time length.
Notoriously, each person may have some particularities that
may require a different prescription given by his doctor.
NANOROBOT ARCHITECTURE
The main parameters used for the medical nanorobot
architecture and its control activation, as well as the required
technology background that may lead to manufacturing
hardware for molecular machines, are described next.
Manufacturing Technology
The ability to manufacture nanorobots may result from
current trends and new methodologies in fabrication,
computation, transducers and manipulation. The hardware
architecture for a medical nanorobot must include the
necessary devices for monitoring the most important aspects
of its operational workspace: the human body. Depending on
the case, different gradients on temperature, concentration of
chemicals in the bloodstream, and electromagnetic signature
are some of relevant parameters when monitoring patients.
Teams of nanorobots may cooperate to perform predefined
complex tasks in medical procedures. To reach this aim, data
processing, energy supply, and data transmission capabilities
can be addressed through embedded integrated circuits,
using advances in technologies derived from nanotechnology
and VLSI design [57]. CMOS VLSI design using deep
ultraviolet lithography provides high precision and a
commercial way for manufacturing early nanodevices and
nanoelectronics systems [41]. The CMOS industry may
successfully drive the pathway for the assembly processes
needed to manufacture nanorobots, where the joint use of
nanophotonic and nanotubes may even accelerate further the
actual levels of resolution ranging from 248nm to 157nm
devices [22]. To validate designs and to achieve a successful
implementation, the use of VHDL has become the most
common methodology utilized in the integrated circuit
manufacturing industry [58].
Chemical Sensor
Manufacturing silicon-based chemical- and motionsensor
arrays using a two-level system architecture hierarchy
has been successfully conducted in the last 15 years [59].
Applications range from automotive and chemical industry
with detection of air to water element pattern recognition
through embedded software programming, and biomedical
uses. Through the use of nanowires, existing significant costs
of energy demand for data transfer and circuit operation can
be decreased by up to 60% [60]. CMOS-based sensors using
nanowires as material for circuit assembly can achieve
maximal efficiency for applications regarding chemical
changes, enabling new medical applications [17,61].
Sensors with suspended arrays of nanowires assembled
into silicon circuits can drastically decrease self-heating and
thermal coupling for CMOS functionality [62]. Factors like
low energy consumption and high-sensitivity are among
some of the advantages of nanosensors. Nanosensor manufacturing
array processes can use electrofluidic alignment to
achieve integrated CMOS circuit assembly as multi-element
systems [60]. Passive and buried electrodes can be used to
enable cross-section drive transistors for signal processing
circuitry readout. The passive and buried aligned electrodes
must be electrically isolated to avoid loss of processed
signals.
Some limitations to improving BiCMOS, CMOS and
MOSFET methodologies include quantum-mechanical
tunneling for operation of thin oxide gates, and subthreshold
slope [63]. Surpassing expectations, the semiconductor
branch nevertheless has moved forward to keep circuit
capabilities advancing. Smaller channel length and lower
voltage circuitry for higher performance are being achieved
Medical Nanorobot Architecture Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 5
with new materials aimed to attend the growing demand for
high complex VLSIs. New materials such as strained channel
with relaxed SiGe layer can reduce self-heating and improve
performance [21]. Recent developments in 3D circuits and
FinFETs double-gates have achieved astonishing results and
according to the semiconductor roadmap should improve
even more. To further advance manufacturing techniques,
Silicon-On-Insulator (SOI) technology has been used to
assemble high-performance logic sub 90nm circuits [40,64].
Circuit design approaches to solve problems with bipolar
effect and hysteretic variations based on SOI structures has
been demonstrated successfully [21]. Thus, already-feasible
90nm and 45nm CMOS devices represent breakthrough
technology devices that are already being utilized in
products.
Energy Supply
The most effective way to keep the nanorobot operating
continuously is to establish the use of a continuous available
source of power. The energy may be available and delivered
to the nanorobot while it is performing predefined tasks in
the operational environment. For a medical nanorobot, this
means that the device must keep working inside the human
body, sometimes for long periods, and must have easy access
to clean and controllable energy to maintain efficient
operation.
Fig. (2). Accepted levels of glucose. The nanorobot sends a signal
to the mobile phone at every observed critical level.
Some possibilities to power the nanorobot can be provided
from ambient energy [1]. Temperature displacements
could likewise generate useful voltage differentials. Cold and
hot fields from conductors connected in series may also
produce energy using the well-established Seebeck effect.
Electromagnetic radiation from light is an option for energy
generation in determined open workspaces [65] but not for in
vivo medical nanorobotics, especially since lighting conditions
in different kinds of workspaces could sharply change
depending on the application. Kinetic energy can be
generated from the bloodstream due to motion interaction
with designed devices embedded with the nanorobot [66],
but this kinetic process would demand costly room within
the nanorobot architecture.
Most recently, remote inductive powering has been used
both for RFID and biomedical implanted devices to supply
power on the order of milliwatts [67-69]. To operate
nanorobots, a low frequency energy source may be enough.
This functional approach presents the possibility of
supplying energy in a wireless manner [70] in order to
operate sensors and actuators necessary for the controlled
operation of nanorobots inside the human body.
The use of CMOS for active telemetry and power supply
is the most effective and secure way to ensure energy as long
as necessary to keep the nanorobot in operation. The same
technique is also appropriate for other purposes like digital
bit encoded data transfer from inside a human body [71].
Thus nanocircuits with resonant electric properties can
operate as a chip providing electromagnetic energy supplying
1.7 mAat 3.3V for power, allowing the operation of
many tasks with few or no significant losses during transmission
[50]. RF-based telemetry procedures have demonstrated
good results in patient monitoring and power transmission
with the use of inductive coupling [32,67,72,73], using well
established techniques already widely used in commercial
applications of RFID [74]. The energy received can be also
saved in ranges of ~1μW while the nanorobot stays in
inactive modes, just becoming active when signal patterns
require it to do so. Some typical nanorobotic tasks may
require the device only to spend low power amounts, once it
has been strategically activated. For communication, sending
RF signals ~1mW is required. Allied with the power source
devices, the nanorobots need to perform precisely defined
actions in the workspace using available energy resources as
efficiently as possible.
A practical way to achieve easy implementation of this
architecture will obtain both energy and data transfer
capabilities for nanorobots by employing mobile phone in
such process [75]. The mobile phone should be uploaded
with the control software that includes the communication
and energy transfer protocols.
Data Transmission
The application of devices and sensors implanted inside
the human body to transmit data about the health of patients
can provide great advantages in continuous medical
monitoring [54,76]. Most recently, the use of RFID for in
vivo data collecting and transmission was successfully tested
for electroencephalograms [50]. For communication in liquid
workspaces, depending on the application, acoustic, light,
RF, and chemical signals may be considered as possible
choices for communication and data transmission [2].
Chemical signaling is quite useful for nearby communication
among nanorobots for some teamwork coordination [51].
Acoustic communication is more appropriate for longer
distance communication and detection with low energy
consumption as compared to light communication approaches
[77]. Although, optical communication permits faster
rates of data transmission, its energy demand makes it not
ideal for nanorobots [1].
Work with RFID (Radio Frequency Identification
Device) has been developed as an integrated circuit device
for medicine [69,74,78]. Using integrated sensors for data
transfer is the better answer to read and write data in
implanted devices. Teams of nanorobots may be equipped
with single-chip RFID CMOS based sensors [79]. CMOS
6 Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 Cavalcanti et al.
with submicron SoC design could be used for extremely low
power consumption with nanorobots communicating collectively
for longer distances through acoustic sensors [80]. For
the nanorobot active sonar communication frequencies may
reach up to 20μW@8Hz at resonance rates with 3V supply
[77].
Fig. (3). In the proposed model, the nanorobots monitor the BGL. A
patient with diabetes can benefit from monitoring the metabolism
uninterruptedly. The same architecture can also serve to early
stages of diagnosis of different health problems.
More widely accepted and usual than an RF CMOS
transponder, mobile phones can be extremely practical and
useful as sensors for acquiring wireless data transmission
from medical nanorobots implanted inside the patient’s
body. Such phones can be a good choice for monitoring
predefined patterns in various biomedical applications, such
as helping in the treatment of diabetes, and likewise for
many other health problems. To accomplish that, chemical
nanosensors may be embedded in the nanorobot to monitor
glucose levels. The nanorobot will emit signals to send an
alarm in case the patient urgently needs medications
prescribed by his doctor. In our nanorobotic system
architecture, the mobile phone is applied [50,75,81]. It uses
electromagnetic radio waves to command and detect the
current status of nanorobots inside the patient. This occurs as
a transponder device emits magnetic signature to the passive
CMOS sensors embedded in the nanorobot, which enables
sending and receiving data through electromagnetic fields
[72]. The nanorobots monitoring data convert the wave
propagation generated by the emitting signal through a well
defined protocol. From the last set of events recorded in
pattern arrays, information can be reflected back by wave
resonance [81]. For nanorobot passive data transferring ~4.5
kHz frequency with approximate 22 ms delays are possible
ranges for data communication.
Frequencies ranging from 1 to 20MHz can be successfully
used for biomedical applications without any damage
[78]. To avoid possibly loss of information in monitoring the
patient’s glucose levels it is used a team of nanorobots. It
serves to solve some signal noise interference. A small loop
planer antenna working as an electromagnetic pick-up with a
good matching to the Low Noise Amplifier is used with the
nanorobot.
SYSTEM IMPLEMENTATION
Real time 3D prototyping tools and simulation are
important aids in nanotechnology development. Such tools
have significantly helped the semiconductor industry to
achieve faster VLSI development [57]. It may have similarly
direct impact on the implementation of nanomanufacturing
techniques and also on nanoelectronics progress [82].
Simulation can anticipate performance and help in new
device design and manufacturing [83,84], nanomechatronics
control design and hardware implementation [36,85].
The nanorobot design includes integrated nanoelectronics
[60,64]. The nanorobot architecture involves the use of
mobile phones for, e.g., the controlled measurement of
glucose levels in diabetes monitoring [74,75]. The nanorobot
uses a RFID CMOS transponder system for in vivo
positioning [1,74], using well established communication
protocols which allow track information about the nanorobot
position [75]. The simulation consists of adopting a multiscale
view of the scenario. It incorporates the physical
morphology of the biological environment along with
physiological fluid flow patterns, and this is allied with the
nanorobot systems for orientation, drive mechanisms, sensing
and control. Thus, these simulations are used to achieve
high-fidelity control modeling. The simulation includes the
NCD (Nanorobot Control Design) software for nanorobot
sensing and actuation.
The nanorobot exterior shape consists of a diamondoid
material [86-88], to which may be attached an artificial
glycocalyx surface [46], that minimizes fibrinogen (and
other blood proteins) adsorption and bioactivity, ensuring
sufficient biocompatibility to avoid immune system attack
[45,89]. Different molecule types are distinguished by a
series of chemotactic sensors whose binding sites have a
different affinity for each kind of molecule [1,37]. These
sensors can also detect obstacles which might require new
trajectory planning [26]. We simulate the nanorobot with
sensory capabilities allowing it to detect and identify the
nearby possible obstacles in its environment, as well as the
biomedical target for its task, such as glucose molecules in
the case of diabetic monitoring. A variety of sensors are
possible [43,59,62]. For instance, chemical detection can be
very selective, e.g., for identifying various types of cells by
markers [1]. Acoustic sensing is another possibility, using
different frequencies to have wavelengths comparable to the
object sizes of interest [77,79].
SYSTEM SIMULATION
The use of microdevices in surgery and medical
treatments is a reality which brought many improvements for
clinical procedures in the last years [19]. In the same way as
the development of microtechnology has lead on the 1980s
to new tools for surgery [90], now nanotechnology will
equally permit further advances providing better diagnosis,
and new devices for medicine through the manufacturing of
nanoelectronics [14,44,31,82]. As a result from the advances
on nanoelectronics, nanorobots may be considered a
promising new technology to help with new treatments for
medicine [16,17], here including improvement to assist
patients who suffer from diabetes.
Medical Nanorobot Architecture Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 7
The bloodstream keeps the human body alive. The
plasma represents 55% of the blood volume which is 8% of
the body weight; the size of red blood cells is about 7.5 mm
in diameter; for the vessels geometry, the lumen diameters
ranges from the Vena Cava with ~3cm in the heart, to
~10mm of capillary vessels. Glucose carried through the
blood stream is important to maintain the human metabolism
working healthfully, and its correct level is a key issue in the
diagnosis and treatment of diabetes. Intrinsically related to
the glucose molecules, the protein hSGLT3 has an important
influence in maintaining proper gastrointestinal cholinergic
nerve and skeletal muscle function activities, regulating
extracellular glucose concentration [42]. The hSGLT3 also
regulates the gradient of membrane potential. But for our
study interest, the hSGLT3 molecule can serve to define the
glucose levels for diabetes patients. The hSGLT3 protein
was classified through genome analyses being identified in
chromosome 22, encoding the structural RNAs [56]. The
most interesting aspect of this protein is the fact that it serves
as a sensor to identify glucose [42]. Through its onboard
chemical sensor, the nanorobot can thus effectively
determine if the patient needs to inject insulin or take any
further action, such as any medication clinically prescribed.
The simulated nanorobot prototype model has embedded
CMOS nanobioelectronics. It features a size of ~2 micronmeter,
which permits it to operate freely inside the body. The
nanorobot computation is performed through embedded
nanosensor; for pervasive computing, performance requires
low energy consumption as described on page 5. Whether
the nanorobot is invisible or visible for the immune
reactions, it has no interference for detecting glucose levels
in blood-stream. For the glucose monitoring the nanorobot
uses embedded chemosensor that involves the modulation of
hSGLT3 protein glucosensor activity [56]. Even with the
immune system reaction inside the body, the nanorobot is
not attacked by the white blood cells due biocompatibility
[46].
The image of the NCD simulator workspace shows the
inside view of a venule blood vessel with grid texture, red
blood cells (RBCs) and nanorobots (Fig. 1). They flow with
the RBCs through the bloodstream detecting the glucose
levels. At a typical glucose concentration, the nanorobots try
to keep the glucose levels ranging around 130 mg/dl as a
target for the Blood Glucose Levels (BGLs). A variation of
30mg/dl was adopted as a displacement range (Fig. 2),
though this can be changed based on medical prescriptions -
glucose levels were detailed on page 4. At any time, if the
glucose achieves critical levels, the nanorobot emits an alarm
through the mobile phone. In the simulation, the nanorobot is
programmed also to emit a signal based on specified lunch
times, and to measure the glucose levels in desired intervals
of time. In the medical nanorobot architecture, the significant
measured data can be then transferred automatically to the
mobile phone.
The nanorobot can be programmed to activate sensors
and measure regularly the BGLs early in the morning, before
the expected breakfast time. Levels are measured again each
2 hours after the planned lunch time. The same procedures
can be programmed for other meals through the day times.
Figs. (4-9). Set of different camera views in the simulator. The nanorobots are inside the vessel (with grid texture); they can be either
observed in 3D real time with or without the visualization of red blood cells.
8 Recent Patents on Nanotechnology 2007, Vol. 1, No. 1 Cavalcanti et al.
Occasionally, if the doctor asked for shorter intervals of time
for measurement, such information can be sent to reprogram
the nanorobot to perform the tasks on different schedules. As
a matter of standard for measurements, the nanorobot is
programmed in our work to measure BGLs at intervals of 2
hours throughout the day. Thus, every two hours the
nanorobot keeps the sensor activated 2 minutes and transmits
the BGL measurements directly to the mobile phone (Fig. 3).
Different programs and commands can easily be sent to the
nanorobot, and it may also serve for the nanorobot to
communicate with the patient or with the medical specialists.
This approach to in vivo chemical concentrations control can
also be useful for monitoring other diseases [71,78]. In order
to simulate various levels of glucose, we used a time series
of events based on clinical data where a patient with diabetes
is monitored 24 hours a day for 30 days. Significant
concentrations of hSGLT3 will determine the glucose
gradients. Each time the glucose achieves critical levels (Fig.
2), the nanorobot sends a signal of alert. Beyond that, all the
historical BGLs can be transferred every two hours to the
mobile phone which records the information for later clinical
analyses.
Deployment of large numbers of independent nanorobots
can offer many other advantages over the use of a single
blood-contacting implant having similar function (Figs. 4-9).
A multiplicity of blood borne nanorobots will allow glucose
monitoring not just at a single site but in many different
locations simultaneously throughout the body, thus permitting
the physician to assemble a whole-body map of serum
glucose concentrations. Examination of time series data from
many locations allows precise measurement of the rate of
change of glucose concentration in the blood that is passing
through specific organs, tissues, capillary beds, and specific
vessels. This will have diagnostic utility in detecting anomalous
glucose uptake rates which may assist in determining
which tissues may have suffered diabetes-related damage,
and to what extent. Other onboard sensors can measure and
report diagnostically relevant observations such as patient
blood pressure, early signs of tissue gangrene, or changes in
local metabolism that might be associated with early-stage
cancer. Whole-body time series data collected during various
patient activities levels (e.g., resting, exercising, postprandial,
etc.) could have additional diagnostic value in assessing
the course and extent of disease. Data reporting rates could
be increased from 2-hour intervals up to continuous sampling
if necessary to obtain sufficiently high resolution
temporal discrimination.
CURRENT & FUTURE DEVELOPMENTS
A nanorobot architecture for data transmission, manufacturing
approach, and telemetric control was presented,
building from advances represented in several recent patents.
This paper also described how mobile phones can play an
important role to bring the application of medical nanorobot
therapies into people’s lives. Meanwhile, manufacturing
methodologies may advance progressively, and the use of
computational nanomechatronics and virtual reality may also
help in the process of creating transducers and actuators
relevant to nanorobotic equipment design, along with RFID
and advances in nanobiotechnology applied to medical
nanorobotics. This paper has outlined a pathway toward
effective ways to advance nanotechnology as a diagnostic
and treatment tool for patients with diabetes, and showed at
the same time how actual developments in new manufacturing
technologies are enabling innovative works and
patents which may help in constructing and employing
nanorobots most effectively for biomedical problems.
The implemented 3D simulator is a practical tool for
exploring new techniques, nanomanufacturing strategies, and
nanorobot mobility considerations including actuation and
data transmission, helping designers to define the appropriate
molecular machine architecture. The joint use of nanophotonic
and nanotube-based technologies may further
accelerate the actual levels of CMOS resolution ranging
down to 45nm devices.
ACKNOWLEDGMENT
The authors thank Lior Rosen, Tad Hogg, and Warren W.
Wood, for their helpful comments. This project was partially
supported by the Australian Research Council (ARC).