by Professor Esteve Juanola-Feliu
E. Juanola-Feliua*, J.
Colomer-Farraronsa, P. Miribel-Catalàa,
J. Samitiera,b,c, J. Valls-Pasolad
aCEMIC-Department of Electronics, Bioelectronics and Nanobioengineering
Research Group (SIC-BIO), University of Barcelona
b IBEC-Institute for Bioengineering of Catalonia, µnanosystems
Engineering for Biomedical Applications Research Group
cCIBER-BBN-Biomedical Research Networking Center in Bioengineering,
Biomaterials and Nanomedicine
dDepartment of Economics and Business Organization, University
Corresponding author: firstname.lastname@example.org
Nanotechnology and Economy
Convergence of Technologies in Nanomedicine
The Biomedical Device for in-Vivo Analysis
Architecture of the Implantable Device
The Choice of the Nanobiosensor
Nanobiotechnology and Nanomedicine
Nano-Related Papers and Patents
Scientific Policies and Global Investment
Research Challenges for Nanobiotechnologies
Conclusions and Final Recommendations
Nanotechnology and Economy
It is widely recognized that the welfare of the most advanced economies is
at risk, and that the only way to tackle this situation is by controlling the
knowledge economies. To achieve this ambitious goal, we need to improve the
performance of each dimension in the "knowledge triangle": education,
research and innovation. Indeed, recent findings point to the importance of
strategies of adding-value and marketing during R+D processes so as to bridge
the gap between the laboratory and the market and so ensure the successful commercialization
of new technology-based products. Moreover, in a global economy in which conventional
manufacturing is dominated by developing economies, the future of industry in
the most advanced economies must rely on its ability to innovate in those high-tech
activities that can offer a differential added-value, rather than on improving
existing technologies and products. It seems quite clear, therefore, that the
combination of health (medicine) and nanotechnology in a new biomedical device
is very capable of meeting these requisites.
Nanotechnology provides breakthroughs that support endless sources of innovation
and creativity at the intersection between medicine, biotechnology, engineering,
the physical sciences and information technology, and the discipline is opening
up new directions in R+D, knowledge management and technology transfer. A number
of nanotech products are already in use and analysts expect markets to grow
by hundreds of billions of euros during the present decade. After a long R+D
incubation period, several industrial segments are already emerging as early
adopters of nanotech-enabled products1 (Fuji-Keizai,
2007); in this context, surprisingly rapid market growth is expected and high
mass market opportunities are envisaged for targeted research sub-segments.
Findings suggest that the Bio&Health market will provide some of the greatest
advances over the next few years and that, as a result, the applications of
nanoscience and technology to medicine will benefit patients by providing new
prevention assays, early diagnosis, nanoscale monitoring, and effective treatment
via mimetic structures. Doubtless, there are considerable challenges in the
design of nanostructures which can operate reliably over extended timescales
in the body.
The scale-length reduction that has been achieved through nanosynthesis (bottom-up
technology) and nanomachining (top-down technology) has the potential to interact
with the biological world as never before. The bio-nanotechnologies operate
at the interface between organized nanostructures and biomolecules, which are
key control routes for achieving new breakthroughs in medicine; dentistry and
therapeutics; in food of animal and vegetable origin; and in daily care products
such as cosmetics. According to the GENNESYS White Paper (2009), this new field
of research will provide significant breakthroughs in the near future in the
realms of bioreactors, biocompatible materials and lab-on-chip technologies.
Convergence of Technologies in Nanomedicine
nanomedicine is defined as the application of nanotechnology to health. It
exploits the improved and often novel physical, chemical, and biological properties
of materials at the nanometric scale. Nanomedicine has a potential impact on
the prevention, early and reliable diagnosis, and treatment of diseases. In
the nanomedicine case, there is a wide range of technologies that can be applied
to medical devices, materials, procedures, and treatment modalities. A closer
look at nanomedicine introduces emerging nanomedical techniques such as nanosurgery,
tissue engineering, nanoparticle-enabled diagnostics, and targeted drug delivery.
Still in its infancy, much of the work in the discipline involves R+D and it
is, therefore, crucial that health institutions, research institutes and manufacturers
work together efficiently.
In particular, multidisciplinary research groups and technology transfer offices
are playing a key role in the development of new nano-enabled implantable biomedical
devices through an advanced understanding of the microstructure/property relationship
for biocompatible materials and of their effect on the structure/performance
of these devices. To proceed further, a general framework is required that can
facilitate an understanding of the technical and medical requirements so that
new tools and methods might be developed. Moreover, in medicine there is a pressing
need to ensure close cooperation between University-Hospital-Industry-Administration
while specific tools and procedures are developed for use by clinicians. Drawing
on the experience of the authors, in this case study we seek to demonstrate
the importance of cooperation and collaboration between these four stakeholders
and the citizens involved in the innovation process leading to the development
of new biomedical products ready for the market.
The interaction between medicine and technology allows the development of
diagnostic devices to detect or monitor pathogens, ions, diseases, etc. Today,
the integration of rapid advances in areas such as microelectronics, microfluidics,
microsensors and biocompatible materials allows the development of implantable
biodevices such as the Lab-on-Chip and the Point-of-Care devices2,3.
As a result, continuous monitoring systems are available to develop faster and
cheaper clinical tasks - especially when compared with standard methods.
It is in this context that we present an integrated front-end architecture for
The Biomedical Device for in-Vivo Analysis
The system introduced in this paper is designed to be implanted under the
human skin. The powering and communication between this device and an external
primary transmitter are based on an inductive link. The architecture presented
is designed for two different approaches: defining a true/false alarm system
based on either amperometric or impedance nano-biosensors. Among the diseases
that might be monitored by in-vivo analysis, it is the aim of this paper to
focus on diabetes given that its incidence and prevalence is increasing worldwide,
reflecting lifestyle changes and aging populations. Specifically, this growing
prevalence is closely linked to that of obesity, creating significant market
opportunities as reported in the World Diabetes Market Analysis 2010-20254,
and, especially, because the World Health Organization estimates that the number
of diabetics will exceed 350 million by 2030.
For this in-vivo implantable biomedical device, we also examine an ambitious
approach that covers the entire value chain (from basic research, through engineering
and technology, to industry), the infrastructure required and the implications
for society of these and similar current market challenges. In this instance,
the entire value chain is hosted by the university system, which highlights
the social turnover of public research investment. We also consider the extent
to which recent technological innovations in the biomedical industry have been
based on academic research, and the time lags between investment in such academic
research projects and the industrial application of their findings - i.e., so
as to estimate the social rate of return from academic research. Because the
results of academic research are so widely disseminated and their effects so
fundamental, subtle and widespread, it is often difficult to identify and measure
the links between academic research and industrial innovation. Nevertheless,
there is convincing evidence, particularly from industries such as drugs, instruments,
and information processing, that the contribution of academic research to industrial
innovation has been considerable5.
State-of-the-Art Innovative Biomedical Device
Many different problems need to be overcome in obtaining the ideal implantable
device6. First and foremost, the device must be
biocompatible to avoid unfavorable reactions within the body. Secondly, the
medical device must provide long-term stability, selectivity, calibration, miniaturization
and repetition, as well as power in a downscaled and portable device. In terms
of the sensors, label-free electrical biosensors are ideal candidates because
of their low cost, low power and ease of miniaturization. Recent developments
in nanobiosensors provide suitable technological solutions in the field of glucose
monitoring7, pregnancy and DNA testing8. Electrical measurement, when the target analyte is captured by the probe,
can exploit either voltmetric, amperometric or impedance techniques. Ideally
then the device should be able to detect not just one target agent or pathology,
but rather different agents and it should be capable of working in a closed-loop
feedback, as described by Wang9 in the case of glucose monitoring.
Several biomedical devices for in-vivo monitoring are currently being developed.
Thus, highly stable, accurate intramuscular implantable biosensors for the simultaneous
continuous monitoring of tissue lactate and glucose have recently been produced,
including a complete electrochemical cell-on-a-chip. Moreover, with the parallel
development of the on-chip potentiostat and signal processing, substantial progress
has been made towards a wireless implantable glucose/lactate sensing biochip10.
Elsewhere, implantable bio-micro-electromechanical systems (bio-MEMS) for the
in situ monitoring of blood flow have been designed. Here, the aim
was to develop a smart wireless sensing unit for non-invasive early stenosis
detection in heart bypass grafts11. Interestingly,
this study examines the use of surface coatings in relation to biocompatibility
and the non-adhesion of blood platelets and constituents. In this case, nanotechnology
presents itself as being a useful tool for improving the biocompatibility of
silicon bio-MEMS structures when nanoscale metallic titanium layers are used,
since it enhances biocompatibility.
The next step involves developing a configurable application-specific integrated
circuit (ASIC) working with a multiplexed array of nanosensors designed to be
reactive for a set of target agents (enzymes, viruses, molecules, chemical elements,
molecules, etc.). Multiple sensors of the array can then be used for one specific
target, while other arrays can be prepared for the other targets, while also
seeking a redundant response. Thus, a panel of biomarkers needs to be developed.
In this way, the reproducibility and accuracy can be improved for each target,
and different targets can be assayed simultaneously. The configuration capacity
of the ASIC should also be defined in terms of the type of measurement that
is to be conducted, as in the studies undertaken by Hassibi and Lee12 and
Beach et al.13: it could be amperometric, measuring current variations
and detecting threshold values14, or it could be electrochemical
impedance spectroscopic, for a fixed frequency, detecting both impedance variations
crossing threshold values and anomalies. The combination of both techniques
of measurement could be used to obtain a more reliable method of detection.
Power and communications are also key features in the design of implantable
devices. The former is concerned with methods of transferring sufficient energy
to the devices, whereas the latter involves the integration of instrumentation
and communication electronics to control the sensors and to send the information
provided by the sensors through human skin. However, if the detection of vital
signs or the threshold detections are sufficient for monitoring purpose, it
is not necessary to measure and send raw data with a high degree of accuracy
from the user to an external data processing unit. Indeed, local processing
within the same sensor would reduce power and communication requirements.
RF power harvesting through inductive coupling is an increasingly used alternative
for transmitting energy to the implanted device, as opposed to using batteries
or wires15,16. Furthermore, this
alternative permits a bidirectional communication to be established between
the implanted device and an external base or reader. A number of implantable
telemetry circuits based on inductive coupling can be found in the literature17,18,19.
By contrast, several studies have developed integratable electronics for in-vivo
monitoring. Examples of this are provided in the studies by Gore et al.20,
where femtoampere-sensitivity applications for conductometric biosensor are
used, and by Haider et al.21, where a signal processing
unit based on a current-to-frequency converter and a communication protocol
Architecture of the Implantable Device
At this juncture, the architecture presented represents an initial approach
for the development of applications based on biosensors aimed at detecting the
presence or absence of certain levels of proteins, antibodies, ions, oxygen,
glucose, etc. These in-vivo detection circuits, or true/false applications20,
work as an alarm. When the concentration level under analysis falls outside
a range of accepted values, a threshold value activates the alarm. For instance,
in the case of glucose monitoring, the detection of a threshold decrease in
glucose levels would be mandatory for avoiding critical situations such as hypoglycaemia21,22.
Such detection would be achieved when the amplitude of the measured signal falls
below a specified threshold value.
Various approaches have been developed for the continuous monitoring of glucose23.
These range from commercial solutions such as the blood glucose tester marketed
by Cygnus Inc. to subcutaneous Minimed Medtronic and Abbott Inc. solutions that
control the glucose level every 3-5 minutes. These devices, placed just under
the skin, have a closed-loop control to deliver insulin and enjoy an autonomy
of 3-5 days. Solutions that seek minimum biological impact so as to resist biofouling
include an inhibitor (nitric oxide)24 in addition
to coated needle-type electrochemical sensors25,26,27.
The generic implantable, front-end architecture is based on inductive coupling
for the in-vivo monitoring of the presence or absence of pathogens, ions, oxygen
concentration levels, etc.
Conception of the implantable device
The system in Fig.1 shows a platform with a true/false alarm for the monitoring
of different targets. The data are transferred to a central database where all
the inputs can be personalized for each patient. The data collected can be measured
in different scenarios: when the patient is at rest, undertaking a certain type
of physical activity, etc., depending on the particular medical interest, and
hence an accurate prognosis and diagnosis can be obtained28.
The system has a research application in the constant monitoring of patients
as they carry out their daily activities in normal conditions (outdoors) and
in this way secondary effects such as the psychological alterations caused by
the stress of being in a hospital, with unknown people, etc. can be avoided.
The proposed architecture (see Fig.2) is at this stage analyzed as a threshold
detector for one sensor, working amperometrically, and includes on-chip biasing,
the potentiostast to drive the biosensor, a conditioning module, and the modulation
and data-processing block. The conditioning module is designed to adapt to the
level of the signals measured. The detection of targets using the threshold
methodology needs to guarantee sufficient signal level so as to ensure a sufficiently
high signal-to-noise ratio (SNR).
This modulation and data processing block is designed to analyse and send to
the external reader the levels it detects. Two different approaches are defined:
a generic amperometric biosensor application and an impedance biosensor, for
label-free systems, based on an integrated analogue lock-in amplifier, which
will proceed with analogue processing on the sensor for detection and transmission.
For future implementation, this module will be designed so that it can be re-configured.
To validate the first proposal (amperometric), a full custom IC has been designed
including several modules of the architecture and a PCB-transponder antenna
(30mm x 15mm), tuned to 13.56MHz, to provide the power and communication link.
The design also incorporates an integrated analogue lock-in amplifier in case
of impedance detection.
The proposal for the generic implantable architecture is presented in Fig.
2. It comprises a nanobiosensor, an antenna and the electronic modules.
Proposed generic implantable front-end architecture.
nanobiosensor or nanosensor is generally defined as a nanometre size scale
measurement system comprising a probe with a sensitive biological recognition
element, or bioreceptor, a physicochemical detector component, and a transducer
in between. Two types of nanosensors with potential medical applications are
cantilever array sensors and nanotube/nanowire sensors and nanobiosensors, which
can be used to test nanolitres or less of blood for a wide range of biomarkers.
In our work, a nanobiosensor with three electrodes has been selected to explain
and develop the system. Its topology can be readily adapted for any kind of
sensor. The three electrodes making up the sensor are: a) the working electrode
(W), which serves as a surface on with the electrochemical reaction takes place;
b) the reference electrode (R), which measures the potential at the W electrode,
and c) the auxiliary or counter electrode (A/C), which supplies the current
required for the electrochemical reaction at the W electrode.
The system is designed as a wireless powered active RFID Tag29,30
where the inductively coupled link, generated by the implantable and the external
antenna, is able to supply enough energy to power the entire system and to provide
wireless bidirectional communication through the human skin. Thus it can transmit
the information obtained by the nanobiosensor and receive data from the external
reader who in turn can configure the implanted electronics and read the data
The Choice of the Nanobiosensor
The most promising solution for an effective nanobiosensor involves using
the electrochemical impedance spectroscopy (EIS) technique. EIS represents a
more effective method for probing the interfacial properties of the modified
electrode by measuring the change in electron transfer resistance at the electrode
surface due to the adsorption and desorption of chemical or biological molecules.
Several studies have been published on this subject. The classical approach
is the ELISA test31, based on the use of semiconducting
polymers and the use of the EIS technique, while polystyrene (PS) is the typical
insulating polymer used in biomedical research.
A widely reported application is the glucose biosensor32,33,34,
which is based on the electron transfer that occurs during the enzymatic reduction
of glucose. In recent years, several studies have been published in this field,
including Patel et al.35 who present an electro-enzymatic
glucose sensor. Other interesting studies are provided by Huang et al. (2009),
who introduce a capacitively based MEMS affinity sensor for continuous glucose
monitoring applications; Teymoori, Mir Majid et al., who describe
a MEMS for glucose and other generic sensors with medical applications; and
Rodrigues et al.36, who developed a new cell-based biochip dedicated to
the real-time monitoring of transient effluxes of glucose and oxygen, using
arrays of amperometric microsensors integrated in the inlet and the outlet of
a PDMS cell chamber. A complete design is provided by Rahman et al.37,
who present the design, microfabrication, packaging, surface functionalization
and in vitro testing of a complete electrochemical cell-on-a-chip (ECC) for
the continuous amperometric monitoring of glucose, performing cyclic voltammetry,
electrical impedance spectroscopy (EIS) and microscopic examination.
Various examples of the development of nanosensors for application in this
field are reported by Usman Ali et al.38. Here
ZnO Nanowires are used for a GCM application directly connected to the gate
of a standard low-threshold MOSFET. Lee et al.39
design a flexible enzyme-free glucose micro-sensor with a nanoporous platinum
working electrode on a bio-compatible PET film. Goud et al.40
introduce a nanobioelectronic system-on-package (SOP) with an integrated glucose
sensor based on carbon-nanotube working electrodes. Jining Xie et al.41
suggest platinum nanoparticle-coated carbon nanotubes for amperometric glucose
biosensing; and Ekanayake et al.42 describe the
manufacture and characterization of a novel nano-porous polypyrrole (PPy) electrode
and its application in amperometric biosensors, with enhanced characteristics
for glucose sensing.
Nanobiotechnology and Nanomedicine
Scientific Policies and Global Investment
The availability of in-vivo biomedical devices, such as the one described above,
is closely linked to advances in nanobiotechnology. Nanotechnology is expected
to have a rapid impact on society43: creating future
economic scenarios, stimulating productivity and competitiveness, converging
technologies, and promoting new education and human development. Evidence of
this rapid impact of nanotechnology can be seen in government investment figures
for nanotechnology R+D activities, facilities and workforce training. The 2008
US National Nanotechnology Initiative budget request for nanotechnology R+D
across the Federal Government was over US$1.44 billion (NNI, 2007). In Europe,
the VIIth Framework Programme (FP) will contribute about €600 million per
year to nanotechnology research until 2013, with an additional, similar amount
being provided by individual countries. This gives Europe a larger yearly expenditure
on nanotechnology than the United States or Japan44.
In the context of European policy, N&N is a key area for the European Commission:
the VIIth FP (2007-2013) provides a specific programme for the nanosciences,
nanotechnologies, materials and new production technologies with a budget of
€3,475 million (10.72% of the VIIth FP total budget). Moreover, several
specific programmes are involved in nanoscale research, and thus the total budget
invested in nanoactivities will be increased by several thousands of €millions
(Meur) coming from the following programmes: Health (6 100 Meur); Food, agriculture
and biotechnology (1 935 Meur); ICT (9 050 Meur) and Energy (2 350 Meur)
Nano-Related Papers and Patents
Several overviews and comparative studies of the worldwide expansion of nanopublications
and nanopatents are available45,46,47.
Scientific papers and patents in the nanotechnology sector have grown exponentially
over the last two decades. The relative growth in number of "nano-title-papers"
in various bibliographic databases, i.e. the increase in the number of "nano-title-papers"
as a proportion of all papers has been dramatic: if we take the Science Citation
Index as being representative of all the sciences (albeit that chemistry is
somewhat underrepresented), the proportion of "nano-title-papers"
grew from 1985 to mid-2003 by about 1.2% at an average annual growth rate of
about 34%, which means it has doubled every 2.35 years. Since the mid-1990s
the speed has slowed somewhat to an annual growth rate of about 25% (doubling
every 3.1 years)48.
In 2007 over 15,000 nanoscience and nanotechnology-related papers were published,
and there is now intense activity as regards intellectual property (IP) - the
ownership of innovations, inventions, ideas and creativity - in the nanoscale
field. Nanotechnology is increasing the shift towards a knowledge-oriented economy
and so intellectual property is in a position to increase wealth creation, growth
and development across the world49. Several reports
have sought to map nano-related patents50, and
figures for nanotechnology-related IP are startling. In the European Patent
Office a nanotechnology working group (NTWG) was created in 2003 and 90,000
patents were tagged to class Y01N. The proportion of nanotechnology patents
more than doubled between the mid-1990s and the mid-2000s (USA 40%, Japan 19%,
and Germany 10%). The Compendium of Patent Statistics 200751
p rovides internationally comparable data on patents.
Before 1980, 250 nanotechnology-related patents were granted annually to universities
worldwide, but by 2003 this number had increased 16-fold to 3,993 patents, which
have been filed for the fundamental building blocks, materials and tools required
to develop this technology. The US patent office has received applications regarding
the composition of matter, devices, apparatus, systems and control of nanomaterial
and devices, and methods. Cross-industry patent claims are being made for single
nanoscale innovations that may have diverse applications. Thus, applications
have been identified in major patent classes such as electricity, human necessities,
chemistry and metallurgy, performing operations and transporting, mechanical
engineering, physics, fixed construction, fabrics and paper. In order to analyse
the impact on the industrial sector, the OECD has categorised nanotechnology
patents into six fields of application: Electronics, Optoelectronics, Medicine
and biotechnology, Measurements and manufacturing, Environment and energy, and
As the research of Miyazakia52 revealed, universities
account for a particularly large share of the research in nanotechnologies (representing
70.45% of nanotech-related research worldwide). In this they are complemented
by public research institutes (who account for 22.22% of articles). Thus, it
is estimated that universities now hold 70% of key nanotechnology patents. The
private sector plays a more limited role (7.33% of articles globally), but it
is a more prominent player in the US (12.41%). In Asia, Japan holds a strong
share (12.30%) in the private sector, while South Korea (8.25%) and to a lesser
extent India (3.52%) compete with Japan. In the future, nanotechnology development
is likely to shift from large publicly funded organisations and universities
to small start-up companies that seek to exploit the earlier publicly funded
research efforts to generate the first commercial applications, in a similar
way to what we have witnessed in the biotechnology industries.
Research Challenges for Nanobiotechnologies
Nanobiotechnology is a rapidly developing area of scientific and technological
opportunity that provides advances in the food industry, energy, environment
and medicine. In nanomedicine, there is a wide range of technologies that can
be applied to medical devices, materials, procedures, and treatment modalities.
A closer look at nanomedicine identifies such emerging nanomedical techniques
as nanosurgery, tissue engineering, nanoparticle-enabled diagnostics, and targeted
drug delivery. According to an expert group of the European Medicines Evaluation
Agency (EMEA), the majority of current commercial applications of nanotechnology
to medicine are devoted to drug delivery. More novel applications of nanotechnology
include tissue replacement, transport across biological barriers, remote control
of nanoprobes, integrated implantable sensory nanoelectronic systems and multifunctional
chemical structures for targeting of disease. Thus, nanobiotechnology can provide
not just the miniaturisation of implantable biomedical devices (microfluidics,
microelectronics, etc) but also reliable multifunctional arrays for disease
detection. There is probably no better example of the technological convergence
of the top-down (miniaturisation) and bottom-up (design and creation of new
functional structures) strategies, which seek the point of equilibrium where
technological advances and market demands might meet.
Finally, it has been argued that current nanoscale research reveals no particular
patterns and degrees of interdisciplinarity and that its apparent multidisciplinarity
consists of different, largely mono-disciplinary fields which are quite unrelated
to each other and which have little more in common than the prefix "nano"
48. At this point, the discussion regarding the
discontinuous or incremental nature of nanotechnology might arise in the innovation
and technology transfer process. Based on the empirical findings of the survey
conducted by Nikulainen and Palmberg53, it seems
that, at the moment, there is no need for nano-specific technology transfer
related initiatives. This conclusion may nonetheless have to be revisited if
nanotechnology becomes more radical and discontinuous. Today, chemists developing
drugs, reactors and catalysts are working at the nanoscale, as they have for
many years, even though they simply refer to their work as chemistry. Certainly,
policymakers need to take into account relevant environmental, health and safety
issues by setting standards and implementing regulations to facilitate the diffusion
Conclusions and Final Recommendations
In this paper, the design of a generic in-vivo implantable biomedical device
capable of detecting threshold values for targeted concentrations (i.e. detection
of glucose levels) has been presented. Given the speed with which diabetes can
spread and the improvements that are possible in its diagnosis and control if
needle-free systems are available, the medical device introduced in this paper
is designed to reach a huge market over the next few years. Moreover, when the
entire value chain is publicly funded, this means that the goals of technology
transfer from university to industry and the social returns on the public investment
have been fully realized. Thus, a successful model for research, innovation
and technology transfer can be introduced to a particular scenario typified
by the convergence of technologies and disciplines, as well as by the convergence
of various stake-holders combining representatives from research centers, hospitals,
market, policy centers and citizens as well.
The complete overview provided here of the value chain of research and technology
transfer processes highlights the importance of a common framework in which
multidisciplinary teams and organizations can work together directed by determined
scientific leadership. In this specific case, the Department of Electronics
at the University of Barcelona has had overall charge of the research and commercialization
activities. The resulting biomedical device is nano-enabled in a dual sense:
when miniaturizing the system (fluidics, electronic, energy autonomy) and when
new functional structures are included (nanobiosensors developed by the IBEC).
The CIBER-DEM joins the value chain when clinical research and commercialization
are considered. Still an emerging technology, the future ASIC will work with
an array of nanobiosensors with different targets, and it will define the configuration
of the measurement method. Each array will be used to detect a specific type
of target, and the multiplexed system will be used to analyze each array focusing
on a particular target. Then, top down approaches using nanoengineering and
nanofabrication and bottom up approaches using supramolecular chemistry can
produce novel diagnostics which will increasingly focus on delivering a personalized
solution based on the analysis of array data in real time, and where appropriate,
applying this decision to deliver an automated therapy (theranostics).
In conclusion, despite the somewhat limited availability of information discussing
the safety of medical nanomaterials, the case history presented in this paper
is a clear demonstration of how to strengthen the bonds between the science
community, hospitals and industry. The process described offers an efficient
method for performing experiments at large test and clinical facilities, within
an innovative framework that takes advantage of new scientific tools and discoveries.
Biomedical devices represent a strategic gamble for the future of Spain's
scientific and technological policy areas as they seek accelerated economic
growth within the knowledge-based society. In this way, the country's
regions can strengthen the network links between their R&D agents - science
and technology parks, institutes and research centres, hospitals, technology
platforms and incubators - as they explore and confront the new scientific
and market challenges presented by the nanotech life sciences.
- Fuji-Keizai USA, 2007. Worldwide Market Research: Nanotechnology-based Product
Market and Business Opportunities-Current & Future Outlook.
- E.Ghafar-Zadeh, E., M.Sawan, M., 2008. Toward Fully Integrated CMOS Based
Capacitive Sensor for Lab-on-Chip Applications. International Workshop on
Medical Measurements and Applications. 9 (10), 77-80.
- Barretino, D., 2006. Design considerations and recent advances in CMOS-based
microsystems for point-of-care clinical diagnostics. Proceedings of the IEEE
International Symposium on Circuits and Systems, 4362-4365.
- Visiongain Ltd., 2010. http://www.visiongain.com/Report/453/World-Diabetes-Market-Analysis-2010-2025
- Mansfield, E., 1991. Academic research and industrial innovation. Research
Policy 20, 1-12.
- Sadik, O. A., Aluoch, A. O., Zhou, A., 2009. Status of biomolecular recognition
using electrochemical techniques. Biosensors and Bioelectronics 24, 2749-2765.
- Nim Choi, H., Hoon Han, J., Park, A., Mi Lee, J., Won-Yong, L., 2007. Amperometric
Glucose Biosensor Based on Glucose Oxidase Encapsulated in Carbon Nanotube-Titania-Nafion
Composite Film on Platinized Glassy Carbon Electrode. Electroanalysis 19 (17),
- Erdem, A., Karadeniz, H., Caliskan, A., 2009. Single-Walled Carbon Nanotubes
Modified Graphite Electrodes for Electrochemical Monitoring of Nucleis Acids
and Biomolecular Interactions. Electroanalysis 21 (3-5), 461-471.
- Wang, J., 2008. In vivo glucose monitoring: Towards 'Sense and Act'
feedback-loop individualized medical systems", Talanta 75, 636-641.
- Rub, A., Rahman, A., Justin, G., Guiseppi-Elie, A., 2009. Towards an implantable
biochip for glucose and lactate monitoring using microdisc electrode arrays
(MDEAs). Biomed Microdevices 11, 75-85. DOI 10.1007/s10544-008-9211-6
- Steeves, C. A., Young, Y. L., Liu, Z., Bapat, A., Bhalerao, K., Soboyejo,
A. B. O., Soboyejo, W. O., 2007. Membrane thickness design of implantable
bio-MEMS sensors for the in-situ monitoring of blood flor. The Journal of
Materials Science: Materials in Medicine 18, 25-37. DOI 10.1007/s10856-006-0659-8
- Hassibi, A., Lee, T.H., 2006. A Programmable 0.18-µm CMOS Electrochemical
Sensor Microarray for Biomolecular Detection. IEEE Sensors Journal 6 (6),
- Beach, R.D., Conlan, R.W., Godwin, M.C., Moussy, F., 2005. Towards a Miniature
Implantable In Vivo Telemetry Monitoring System Dynamically Configurable as
a Potentiostat or Galvanostat for Two- and Three-Electrode Biosensors. IEEE
Tran. On Instrumentation and Measurement 54 (1), 61-72.
- Gosselin, B., Sawan, M., 2008. An ultra low-power CMOS action potential
detector. Proceedings of the IEEE International Symposium on Circuits and
- Zierhofer, C.M., Hachmair, E.S., 1996. Geometric approach for coupling enhancement
of magnetically coupled coils. IEEE Tran. On Biomedical Engineering 43, 708-714.
- Sawan, M., Yamu, H., Coulombe, J., 2005. Wireless smart implants dedicated
to multichannel monitoring and microstimulation. IEEE Circuits and Systems
Magazine 5, 21-39.
- Sauer, C., Stanacevic, M., Cauwenberhs, G., Thakor, N., 2005. Power harvesting
and telemetry in CMOS for implanted devices. IEEE Transl. on Circuits and
Systems 52 (12), 2605-2613.
- Li, Y., Liu, J., 2005. A 13.56MHz RFID transponder front-end with merged
load modulation and voltage doubler-clamping rectifier circuits. IEEE International
Symposium on Circuits and Systems, 5095-5098.
- Myny, K., Van Winckel, S., Steudel, S., Vicca, P., De Jonge, S., Beenhakkers,
M. J., Sele, C. W., van Aerle, N. A. J. M., Gelink, G. H., Genoe, J., Heremans,
P., 2008. An inductively-coupled 64b organic RFID tag Operating at 13,56MHz
with a data rate of 787b/s. IEEE International Solid-State Circuits Conference,
- Gore, A., Chakrabartty, S., Pal, S., Alocilja, E., 2006. A multi-channel
femtoampere-sensitivity conductometric array for biosensing applications.
28th IEEE Engineering in Medicine and Biology Science Conference, 6489-6492.
- Haider, M. R., Islam, S. K., Zhang, M., 2007. A low-power processing unit
for in vivo monitoring and transmission of sensor signals. Sensors & Transducers
Journal 84 (10), 1625-1632.
- Wolpert, H.A., 2007. Use of continuous glucose monitoring in the detection
and prevention of hypoglycemia. Journal of Diabetes Science and Technology
11 (1), 146-150.
- Newman, J.D., Turner, A.P.F., 2005. Home blood glucose biosensors: a commercial
perspective. Biosensors and Bioelectronic 20, 2435-2453.
- Frost, M., Meyerhoff, M.E., 2006. In Vivo Chemical Sensors: Tackling Biocompatibility.
Analytical Chemistry 78 (21), 7370-7377.
- Jung, M.W., Kim, D.W., Jeong, R.A., Kim, H.C., 2004. Needle-type Multi-electrode
Array Fabricated by MEMS Technology for the Hypodermic Continuous Glucose
Monitoring System. Proceedings of the International Conference of EMBS, 1987-1989.
- Zimmermann, S., Fienbork, D., Stoeber, B., Flounders, A.W., Liepmann, D.,
2003. A microneedle-based glucose monitor:fabrication on a wafer-level using
in-device enzyme immobilization. Proc.Internatioal Conference on Solid-state
Sensors, Actuators and Microsystems, 99-102.
- Kim, Y.T., Kim, Y.-Y., Jun, C.-H., 1999. Needle-shaped glucose sensor with
multi-cell electrode fabricated by surface micromachining. Proc. SPICE, Design,
test, and Microfabrication of MEMS and MOEMS 3680, 924-930.
- Lin Tan, E., Pereles, B.D., Horton, B., Shao, R., Zourob, M., Ghee Ong,
K., 2008. Implantable Biosensors for Real-time Strain and Pressure Monitoring.
- Lin, Y., Su, M., Chen, S., Wang, S., Lin, C., Chen, H., 2007. A study of
ubiquitous monitor with RFID in an elderly nursing home. IEEE International
Conference on Multimedia and Ubiquitous Engineering.
- Tesoriero,R., Gallus, J. A., Lozano, M., Penichet, V. M. R., 2008. Using
active and passive RFID technology to support indoor location-aware system.
IEEE Transl. on Consumer Electronics 54 (2), 578-583.
- Cantarero, L.A., Butler, J.E., Osborne, J.W., 1980. The adsorptive characteristics
of proteins for polystyrene and their significance in solid-phase immunoassays.
Anal. Biochem. 105, 375-382.
- Hiller, M., Kranz, C., Huber, J., Bauerle, P., Schuhmann, W., 1996. Amperometric
biosensors produced by immobilization of redox enzymes at polythiophene-modified
electrode surfaces. Adv. Mater. 8, 219-222.
- Kros, A., Van Hovell, W.F.M., Sommerdijk, N.A.J.M., Nolte, R.J.M., 2001.
Poly (3, 4-thylenedioxythiophene)-based glucose biosensors. Adv. Mater. 13,
- Fiorito, P.A., De Torresi, S.I.C., 2001. Glucose amperometric biosensor
based on the co-immobilization of glucose oxidase (Gox) and ferrocene in poly(pyrrole)
generated from ethanol/water mixtures. J. Braz. Chem. Soc. 12, 729-733.
- Patel, J.N., Kaminska, B., Gray, B., Gates, B.D., 2007. Electro-Enzymatic
Glucose Sensor Using Hybrid Polymer Fabrication Process. Electronics, Circuits
and Systems, ICECS 2007-14th IEEE International Conference, 403-406.
- Rodrigues, N.P., Kimura, H., Sakai, Y., Fujii, T., 2007. Cell-Based Microfluidic
Biochip for Electrochemical Real-Time Monitoring of Glucose and Oxygen, Solid-State
Sensors, Actuators and Microsystems Conference, 843-846.
- Rahman, A.R.A., Justin, G., Guiseppi-Wilson, A., Guiseppi-Elie, A., 2009.
Fabrication and Packaging of a Dual Sensing Electrochemical Biotransducer
for Glucose and Lactate Useful in Intramuscular Physiologic Status Monitoring.
Sensors Journal, IEEE Volume 9 (12), 1856-1863.
- Usman Ali, S.M., Nur, O., Willander, M., Danielsson, B., 2009. Glucose Detection
with a Commercial MOSFET using a ZnO Nanowires Extended Gate. IEEE Transactions
on Nanotechnology 8 (6), 678-683.
- Lee, Y.J., Kim, J.D., Park, J.Y., 2009. Flexible enzyme free glucose micro-sensor
for continuous monitoring applications. Solid-State Sensors, Actuators and
Microsystems Conference-TRANSDUCERS 2009, 1806-1809.
- Goud, J.D., Raj, P.M., Jin Liu, Narayan, R., Iyer, M., Tummala, R., 2007.
Electrochemical Biosensors and Microfluidics in Organic System-on-Package
Technology. Proceedings of the Electronic Components and Technology Conference-ECTC2007,
- Jining Xie, Shouyan Wang, Aryasomayajula, L., Varadan, V.K., 2007. Material
and electrochemical studies of platinum nanoparticle-coated carbon nanotubes
for biosensing. Nanotechnology, 2007. IEEE-NANO2007, 1077-1080.
- Ekanayake, E.M.I., Preethichandra, D.M.G., Kaneto, K., 2007. Fabrication
and characterization of nano-structured conducting polymer electrodes for
glucose biosensor applications. Industrial and Information Systems-ICIIS2007,
63 - 66.
- Roco M.C., Bainbridge W.S., 2005. Social implications of nanoscience and
nanotechnology: Maximising human benefit . Journal of Nanoparticle Research
- Swarup A., 2007. How Will Nanotech Fare in Europe?. http://sciencecareers.
- Heinze, T., 2004. Nanoscience and Nanotechnology in Europe: Analysis of
Publications and Patent Applications including Comparisons with the United
States. Nanotechnology Law & Business 1 (4), article 10.
- Braun, T. Schubert, A., Zsindely, S., 1997. Nanoscience and nanotechnology
on the balance. Scientometrics 38 (2), 321.
- Hullmann, A., Meyer, M., 2003. Publications and Patents in Nanotechnology:
An Overview of Previous Studies and the State of the Art. Scientometrics 58,
- Schummer, J., 2004. Multidisciplinarity, interdisciplinarity, and patterns
of research collaboration in nanoscience and nanotechnology. Scientometrics
59 (3 ), 425-465.
- Aditeya, Singh K., 2007. Intellectual Property in the Nanotechnology Economy:
trends, patent landscape and the challenges. Institute of Nanotechnology,
- Scheu, M. Veefkind, V., Verbandt, Y., Molina Galan, E., Absaloma, R., Förster,
W., 2006. Mapping nanotechnology patents: The EPO approach. World Patent Information
28 (3), 204-211, doi:10.1016/j.wpi.2006.03.005
- Dernis, H., 2007. Compendium of Patent Statistics 2007. STI OECD Paris,
- Miyazaki, K., Islam, N., 2007. Nanotechnology systems of innovation-An analysis
of industry and academia research activities. Technovation 27 (11), 661-675.
- Nikulainen T., Palmberg C., 2010. Transferring science-based technologies
to industry-Does nanotechnology make a difference?. Technovation 30,
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