R&D Road Map for Optronic Biosensing

TWINFUSYON
Twinning for Improving Capacity of Research in
Multifunctional Nanosystems for Optronic Biosensing
H2020-TWINN-2015-692034
Work Package: WP2
Task: T2.3
Deliverable due date: 31/10/2018
Responsible partner: CEITEC
Editors: Josef Humlicek
Maria Losurdo
Deliverable number: D2.3
Deliverable type: R
Dissemination level: PU
First Created: 15/09/2018
Last Updated: 30/10/2018
Version: v.1
D2.3 Road Map on R&D in optronic biosening
Ref. Ares(2018)5916928 - 19/11/2018

TWINFUSYON D2.3 Road Map on R&D in optronic biosening
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Executive summary – key findings from the report
The biosensor sector represents a significant market to optical-electronic-microsystems developers while at
the same time there is a strong pull for new technology solutions.
Applications of biosensors in environment, food and health monitoring enable the improvement of the
quality and safety of life, enhance the sustainability of the processes because of better process control, and
enable product innovations that benefit consumers and society. The TWINFUSYON project has identified
many opportunities for further applications of opto-electronic biosensors. However, the project also
identified problems in the articulation of demands by the various sectors that can be solved by optronics
biosensors, and expression of opportunities by technology companies that could benefit the environment,
food and health.
The challenges to be addressed are more in innovation than research: e. g., a pure technology push approach,
and technology providers need to know the targeted sector very well in order to provide a solution that can
be an integrated part of the process management system of the companies. To address these constraints,
innovation projects driven by users are needed and not only projects that primarily target research and
development.
With “price/cost” as the most important decision factor for the deployment of new technologies, the current
situation can be considered a chicken and egg situation (price depends on quantity, quantity depends on
price).
To fully benefit from all the opportunities further coordination of the cross-sector exchange of knowledge,
ideas and research is required. The project therefore recommends follow-up to identify targeted information
exchanges and R&D derived from existing and future roadmaps on the different application fields that are
supported by both biosensors and nanoelectronics companies. Coordination activities across the different
funding areas/programmes involved (sensing, environment, health and ICT) at European Commission level
will also be beneficial. In addition to delineating the more promising applications it should take care of other
collateral aspects such as increasing the awareness of the end-user industry, taking the appropriate role of
this industry (mostly SMEs with limited R&D capacity) into consideration. Additionally fostering a better
interconnection of technologist players into reserach innovations can help ascertain business models that will
be more appropriate for successful exploitation.
Advances in science and technology required to meet challenges faced in several areas are addressed,
together with suggestions on how the field could evolve in the near future.

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Table of Contents
1 INTRODUCTION..............................................................................................................................................5
2 TRIGGER TECHNOLOGY.............................................................................................................................7
3 INDUSTRY TRENDS........................................................................................................................................8
4 OPTICAL LASER-BASED SENSORS..........................................................................................................10
5 PLASMONIC NANOSYSTEMS FOR SENSING AND IMAGING...........................................................13
6 GRAPHENE AND RELATED 2D-MATERIALS FET SENSORS ............................................................15
7 BIOMICRO AND NANO-ENGINEERED & NON-INVASIVE SENSORS..............................................18
8 SUMMARY OF KEY RECOMMENDATIONS...........................................................................................19
9 WHAT DOES THE FUTURE LOOK LIKE: THE NEXT GENERATION OF SENSORS ....................20

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1 Introduction
The main ambition of the TWINFUSYON project was to stimulate the implementation of innovative
solutions in biosensing based on integrated opto-electronic concept exploiting novel 2D materials and
plasmonic nanosystems.
Situational awareness encompasses three fundamentals: perception of elements, comprehension of what
those elements mean and, use of that understanding to project future states. To attain situational awareness
operators must be aware of the range of threats and have the technology available to assess his immediate
environment. The ability to maintain this level of understanding in real-time on a global scale for biological
defense will require a leap forward within the current arena of bio-threat agent detection.
Figure 1. Traditional biothreat technologies use laboratory tests and diagnostic devices to identify threats
Current technology is capable of detecting biological agents with enough time to treat those exposed prior to
the onset of symptoms. Efforts are currently underway to develop detect-to-warn capabilities that include 1-
minute or less detection response time, capacity for continuous operation, high sensitivity, low false alarm
rates, and low costs for both procurement and operation and maintenance. Difficulties in expanding the
capabilities of the current technologies to fit these requirements include obtaining desired specificity,
sensitivity, and false alarm rates while maintaining cost requirements, speed of detection, the ability to sense
at environmental extremes, and the effective management of the trade-offs required to meet these goals.
The biosensors sector needs technological innovation to meet its future challenges - this demand for
solutions to guarantee safety is expected to increase in the coming years. The biosensors technological area
has the capacity to meet these demands by offering a wide range of new solutions for processing, measuring,
sensing, tracking or tracing.
Biosensors differ with respect to the biorecognition layer, which is crucial for the biosensors. In fact, most of
the recent and probably future advances in biosensing systems are more related to the performances of the
biolayer than to the transducer itself. Biosensor development is a multidisciplinary activity combining
biotechnology know-how with microsystems and microelectronics technologies and chemometrics.
Thanks to the biological part and its associated specificity, biosensors are able to measure the concentration
of a single component, even in a complex mixture. Thus, biosensors can be good alternative methods to
some of the complex laboratory analyses. Biosensors have been very popular at the research level in many
applied fields, due to their performance in terms of measurement time, sensitivity, and potential low cost. In
fact, biosensors for healthcare and environmental monitoring, e.g. the detection of toxic substances in water,
have shown their potentialities also at industrial level.

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The aim of this TWINFUSYON deliverable was to develop recommendations, based on team expertise and
community feedback to encourage the development of science and technology for detection, identification,
and tracking of biological warfare agents both before and after a release.
Building on the findings from the reports on the market demand and the technologies available, the following
roadmap has been elaborated. A great variety of devices and technologies have been developed that can be of
use. Each section contains information on the types of devices that are needed as well as a roadmap for
guiding the technological developments within the next 3 to 10 years.
The main identified trends associated to the optronic biosensors development can be summarised as follows:
• to introduce new material that ease the chemical and biological recognition
• to develop and use new methods of immobilisation of the biomaterials on the surface of the transducer: new
membranes, gels, magnetic particles etc, for improving the sensitivity, stability and life-time
• to develop simple label-free systems
• to achieve sufficient degree of miniaturisation that gives at the same time good performances and low cost
•to develop systems that combine single use cartridges and highly performing reading systems
• to develop portable systems, with low power electronics and wireless communication for in-situ monitoring
of systems/health.
Figure 2: Technological trends for optronic bio sensor
One of the major advances that TWINFUSYON sees in the horizon of optronic biosensing is the availability
of photonics and specifically photonic integrated circuits (PICs) to the mainstream academic, industry and
government communities. Pictured above in Figure 3 is a notional PIC for biosensing with fiber optic input,
microfluidic interface and electronic readout. Numerous other design architectures are available with varying
degrees of on-chip integration including light sources and photodetectors. Clearly, integrated photonics can
provide a platform to previous work on planar waveguide sensors and open up new avenues for continued
examination of micro-ring resonators and other optical structures such as Bragg gratings and interferometric
configurations.

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Figure 3: Graphical representation of a photonic integrated circuit.
[Source: Paul M Pellegrino, J. Opt. 19 (2017) 083001]
2 Trigger Technology
Biotrigger devices monitor the air, water, or surfaces for the presence of any biological agent and sound an
alarm when background levels rise above normal. The performance of the available devices varies with
respect to limit of detection (LOD), specificity, and response time
A biodetection trigger must be able to operate continuously with low maintenance and few consumables and
detect low-level agent concentrations against a complex environmental background requiring high-sensitivity
and few false positives. Most environmental aerosol biotrigger technologies in use are based on UV-based
fluorescence. These devices use a combination of particle sizing and fluorescence to detect the presence of
suspect aerosols.
Some biotrigger technologies, such as ultra-violet laser induced fluorescence (UV-LIF), can also be used to
detect the presence of biologicals in water and on surfaces. In addition, near real-time biosensor technologies
employing antibody-antigen interactions, hormone-receptor interactions, and nucleic acid based assays are
often used in multi-use detection platforms. These sensors are useful in a narrow band of applications
requiring high specificity for agent identification and are often used for confirmatory analysis. Emerging
detection systems incorporate novel stand-off and point-source trigger technologies such as Light Detection
and Ranging (LIDAR) and IR Spectroscopy, and Spark Induced Breakdown Spectroscopy (SIBS). These
triggers offer the promise of improved response time and low-cost continuous monitoring.
The paradigm shift from detection of a specific agent following an event to anomaly detection perhaps
relating to activities prior to a release may provide enough notification to approach the detect-to-warn ideal.

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3 Industry Trends
Figure 4: Sensors market evolution
Biosensors Market
size was valued over USD 17 billion in 2017 and is expected to witness growth of around 8% CAGR from
2018 to 2024. Extended use of biosensors in various industries such as medical diagnostics, agricultural and
food diagnostic industry (see Figure 5) has stimulated the demand for biosensors. Growing awareness for
maintaining healthy lifestyle has stimulated demand for wearable biosensors that monitor various health
parameters such as blood pressure, pulse rate, heartbeats and others. Increasing adoption rate of wearable
biosensors amongst the population in developed countries will propel the industry growth. However, high
cost associated with development of biosensor may hinder the industry growth.
Figure 5: Biosensors Market, By Application, 2013 – 2024 (USD Billion)

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Application Insights
Based on the applications, the space is segmented as medical, food toxicity, bioreactor, agriculture,
environment, and others. In 2013, medical segment dominated the market with around 66% of the revenue
share. The medical segment comprises use of biosensors in the field of cholesterol testing, blood glucose
monitoring, blood gas analyzer, pregnancy testing, drug discovery and infectious diseases. They are
considered as an essential tool in the detection and monitoring of a wide range of medical conditions from
diabetes to cancer.
Agriculture is anticipated to be the fastest growing segment during the forecast period. Biosensors provide
rapid and specific detection of various funguses as compared to the older techniques that are adopted to
reduce the loss of livestock and crops by natural threats and bioterrorism. Biosensors are used to measure the
concentrations of pesticides, heavy metals and herbicides, and pesticides in the ground and soil water. These
are also used to forecast the possible occurrence of soil disease, which was not feasible with the conventional
technology and hence providing reliable, advanced ways for the decontamination and prevention of soil
disease at an early stage. Such factors are contributing to the growth of the market.
Biosensors Market, By Technology
Based on technology, the market is categorized into thermal, electrochemical, piezoeletric, and optical.
Electrochemical technology segment generated revenue of more than USD 11 billion in 2017, as shown in
Figure 6. Electrochemical biosensors have advantages such as wide linear response range, low detection
limits, reproducibility, and optimum stability, which lead to their greater usage as compared to other
biosensing technologies. Electrochemical transduction presents considerable advantages over thermal,
piezoelectric or optical detection, thereby leading to high consumption and greater market penetration. These
advantages include robustness, compatibility with new microfabrication technologies, disposability, low
cost, ease-of-operation, independence from sample turbidity, and minimal power requirements. The segment
dominates biosensors industry due to high efficiency and accuracy provided by the electrochemical
biosensors. Increased use of electrochemical biosensors in food analysis and diagnosis of diseases has driven
the segment growth significantly during the forecast period. Moreover, rising number of chronic diseases
have elevated the demand for electrochemical biosensors to aid accurate diagnosis. Optical biosensors
segment is anticipated to grow at CAGR of 8.9% throughout the forecast period due to increasing demand
for optical biosensor. Optical biosensors are applicable for structural studies, fermentation monitoring,
receptor-cell interactions, concentration, kinetic, and equilibrium analysis, thereby resulting in high market
usage and penetration of the segment in 2014. Optical fibre biosensors are used in optical biosensing devices
in critical care and surgical monitoring. Benefits offered by optical biosensor are specificity, real-time
measurement, remote sensing, fast, compact design that helps in minimally invasive detection; which in turn,
drive the market growth
Figure 6: Biosensors Market, By Technology, 2013 – 2024 (USD Billion)
Optical sensors features various advantages for biomedical applications. Unlike micro- (MEMS) or
nanomechanical (NEMS) sensors, optical sensors are not compromised due to viscous damping in fluids.

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They are also immune to ionic screening— one of the biggest challenges for nanoelectronic sensors— and,
therefore, are more compatible with physiological conditions. It is also possible to obtain molecular
information of the test subject via Raman or absorption spectroscopy, in addition to the conventional
biological recognition specificity offered by antibodies, aptamers, oligonucleotides, etc. Furthermore, optical
measurements have a natural way to scale up by expanding a single biosensor into arrays and implementing
imaging modalities.
Concerning the optical technology used, the largest market share (33%) is expected for Raman scattering
(DTS) sensors. They will be followed by quasi-distributed sensors based on optical fibers (26%). DAS
(Rayleigh scattering), which is rapidly gaining market share, is projected to be around 10% by 2019 (see
Figure 7).
Figure 7: Distributed optical sensor market forecast by application sector and (inset) by technology type
[Source: Gatekeepers Inc. Information 2015 Photonic Sensor Consortium Market Survey Report Light Wave Venture LLC]
Nevertheless, as constrained by the light diffraction limit, traditional optical biosensors generally exhibit
inferior sensitivity as compared to their electronic, mechanical or MEMS (micro-electro-mechanical
systems) counterparts. The integration and packaging are also challenging due to more strict requirements for
light coupling than electronic wiring. The rapid advances in nanotechnologies have significantly boosted the
performance of traditional optical biosensors, offering a new level of sensitivity, enhanced specificity, as
well as improved integration capability as shown in the following paragraphs.
4 Optical laser-based sensors
Laser-based sensors are distinguished from other optical sensors from the perspective that the measurement
is entirely based upon the direct detection of laser light itself without relying on any external signal-
transducing elements to the target object besides its ambient medium. The types of laser-based sensors can
be classified into several groups as illustrated in Figure 8, depending on which parameter of laser light and
which standpoint of the nature of light is most exploited for sensing. No matter what sensing mechanisms are
utilized, they all inherently allow for non-invasive measurements with high precision and accuracy as well as
a fast response.
Consequently, demands and challenges for laser-based sensors have never stopped growing in science and
technology.

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Figure 8: Classification of laser-based sensors
Laser ellipsometry is based upon detection of the changes in the strength and polarization state of laser
light. Typically its sensitivity can go down to 0.01 nm or a sub-monolayer thickness. Non-specular reflection
or scattering can be a potential issue, depending on the surface roughness condition. Further improvements in
both theoretical models and measurement techniques are strongly in demand.
Laser spectroscopy is based upon detection of the changes in the spectral properties of laser light, utilizing a
variety of different spectroscopic mechanisms, such as Raman scattering, Brillouin scattering, laser-
induced breakdown, laser-induced fluorescence, etc. The availability of lasers that can operate at the desired
wavelength matched for the material to be traced is a critical issue. In addition, the improvement of
sensitivity remains a challenge in that the technology should be able to deal with a low concentration atomic
or molecular sample with high fidelity.
Laser Doppler vibrometry is based upon detection of the Doppler-shift frequency in the reflected laser light
that is incurred by the vibration or movement of the target object. A state-of-the-art vibrometer offers a sub-
Hz resolution.
Technical advances for multidimensional and multi-channel measurements in combination with increased
spatial and temporal resolutionare strongly in demand. The multi-channel capability for transient
measurements will play a crucial role in various micro-scale applications, including micro-electromechanical
systems (MEMS) and biomedical applications.
Laser interferometry is based upon detection of the change in the phase of laser light, utilizing an optical
interferometer that includes the Mach-Zehnder interferometer, Michelson interferometer, etc. Since the phase
change is caused by various physical origins, it has a wide range of applications, from gravitational wave
detection to biomedicine. While the ultimate sensitivity of the phase detection is limited by shot noise, it is
also severely affected by mechanical and thermal fluctuations of the components of the interferometer. In
particular, the axial resolution of laser-based optical coherence tomography (OCT) is determined by the
bandwidth or tuning range of the laser as well as the group velocity dispersion of the material, which is
currently limited to a few μm.
Laser light detection and ranging (LIDAR) is based upon measurement of ‘time of flight’ of laser light, in
general, which determines the distance of the target object, while the technology can also be combined with
the other aforementioned sensing technologies. Typically, its resolution can be as small as tens of cm,
depending on the distance range which can reach a hundred km. Since the technology is often implemented
into airborne and spaceborne systems as well as ground-based systems, improvements in miniaturization and
efficiency are invariably desired for both transmitters (i.e., lasers) and receivers (i.e., photodetectors or
photon counters). Other issues and challenges include power scaling of lasers, reliable wavelength
conversion, eye safety, improvement in the data compression and extraction, etc. In particular, diode or fiber-
laser-based sources will continue to receive great attention from the standpoint of miniaturization and
efficiency.

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Laser-based quantum-enhanced sensing can be regarded as quantum optical forms of all the
aforementioned laser-based optical sensing technologies, exploiting non-classical states of light and their
quantum optical nature. This can beat the classical diffraction or shot-noise limit, thereby eventually leading
to super-resolution or super-sensitivity. However, the main issues and challenges of such techniques include
photon loss, dephasing noise, detector inefficiency, etc in that they substantially degrade the ideal precision
that the quantum enhanced sensing offers. There also remain inherent challenges, such as difficulty,
complexity and inefficiency (low probability), in producing non-classical states of light.
Advances in science and technology to meet challenges. An in-depth understanding of light–matter
interaction, particularly, at the mesoscopic level is also crucial for further success. In contrast, the selective
elimination of coherence from laser light is another area to watch because of its rich dynamics in light–
matter interaction and great potential for novel sensing applications.
Optical micro-nanostructured sensors
Concerning the way for light manipulation, micro- and nano-engineered optical sensors can be classified into
two categories: using propagation light (usually guided by non-resonant structures) or localized optical fields
(usually confined by resonant structures), as shown in Figure 9. Mature platforms for the non-resonant
approach are fiber- and chip-based structures.
Figure 9. Typical structures for micro and nano-engineered optical Sensors
[Source: L. Tong, J. Opt. 19 (2017) 083001]
The photonic crystal fiber (PCF), or more generally the microstructure optical fiber (MOF) is an example for
measuring liquids or gases with high robustness, compact structure and less requirement on samples. More
recently, optical sensing with optical micro- or nanofibers (MNFs) or nanowires, showed that, by reducing
the diameter of a fiber-like waveguide to the subwavelength scale, it is possible to generate tightly confined
high-fractional evanescent fields for optical sensing with miniaturized footprint and high sensitivity.
Chip-based optofluidic systems are another excellent platform for micro and nano-engineered optical
sensors. Using microfluidic channels to confine and deliver the liquid sample and/or the probing light, it is
possible to operate the sensor with much less amount of samples, and perfect isolation from environmental
disturbance. Also, fiberbased structures, such as a MNF can be integrated into the lab-on-chip system for
better light manipulation.

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For the resonant type, in terms of feature size and material used for light localization, there are typically two
kinds of platforms: photonic microcavities and plasmonic nanocavities. The microcavities, usually made of
micro- or nano-engineered dielectric structures, can offer high quality (high-Q) resonance and consequently
high sensitivity for both particle and bulk samples . To date, a variety of microcavities such as microspheres,
microdisks, microtoroids, optofluidic resonators and photonic crystal cavities have been demonstrated for
optical sensing. Relying on localized surface plasmonic resonance (LSPR) in metal nanostructures, the
nanocavity can provide a mode size much smaller than the vacuum wavelength of the light and comparable
with the crosssection of biomolecules, and is therefore highly sensitive in detecting nanoscale particle
samples. Moreover, as a result of tight confinement, the significant field enhancement in the LSPR structure
is also highly desired for applications such as surface-enhanced Raman scattering.
Overall, micro or nanoscale structurization is a highly efficient approach to better light manipulation for
better optical sensors with higher sensitivity, smaller footprints, smaller amount of sample, higher resolution
and greater versatility, which have been one of the main driving forces in the advances of optical sensors in
recent years. However, the physics and techniques of reducing the structure and mode sizes below the
wavelength of light have their own limitations, which present challenges for pushing the limits of optical
sensors.
One of the biggest challenges in opttronic sensing is the maturation of the optical sensor platforms that
would make optical sensors for chemicals more commonplace and affordable, and the other resides more in
the information provided through the optical sensing. There are areas where these sensor platforms have
excelled in the detection of volatile organic compound (VOC) detection for certain industries, but full
ubiquitous use has not occurred.
Clearly new sources, detectors and material developments such as quantum cascade lasers (QCLs) and
plasmonics have become more routine, but the full translation of these more compact embodiments has yet to
produce optical chemical sensors with deep market or widespread commercial use. One possible explanation
of the popularity could be linked to the ease with which these platforms can control and manipulate light.
The other and possibly more fundamental challenge stems from the lack of information afforded by certain
optically based sensor architectures. Despite all their shortcomings and difficulties, certain types of direct
methods (e.g. Raman) have succeeded due solely to their ability to provide clear information for chemical
identification that is fundamental and thereby adaptable to multitudes of targets.
5 Plasmonic nanosystems for sensing and imaging
Plasmonic nanosystems are currently based on the response of noble metals nanoparticles. A recent
comprehensive review (J. Opt. 18 (2016) 063003) relates the basic ingredients according the following Fig. 10.

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Figure 10. Interrelations bdetween different systems/detection techniques of enhancing the optical response
[Source: Di Fabrizio, J. Opt. 18 (2016) 063003]
Each of the techniques presents unique oportunities; however, some of them are less suited for routine
applications, as the measurement systems are slow and demanding. For example, the near-field plasmonic
probes are very attractive and promising to offer very high spatial resolution, and even the on-chip
integration (Fig. 11). However, their complex 3D shapes are difficult to fabricate.

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Figure 11. An on-chip spectrometer
[Source: Calafiore et al., J. Opt. 18 (2016) 063003]
Thus, efficient use of this type of sensing depends critically on the availability of cheap alternatives to nanostructuring,
such as nanoimprinting. Further, the optical functionality has to be complemented by microfluidics.
Potentially efficient systems beyond the Au (Ag) nanoparticles rely on exceptional properties of graphene
and other 2D materials. A short survey of current status in sensing is given in the following paragraph.
6 Graphene and related 2D-Materials FET Sensors
Effective detection of radiation in the THz spectral range, which basically interconnects the world of
electronics-based and optics-based devices, still remains to be a considerable challenge for current
technologies. Interests in such detection go far beyond the scientific use. THz-based systems, by a rule fast
and non-invasive, can find their applications in medical imaging, security measures or communication. The
quest for fast electronics devices implies necessity to use higher operational frequencies (band widths),
reaching nowadays up to the THz spectral range.
Two-dimensional (2D) systems, which confine the motion of electrons to a plane, have been proposed, and
subsequently tested, as efficient detectors of THz radiation. In the very first approach, these were standard
commercial (electric-)field-effect transistors (FETs), based on various semiconducting systems such as
GaAs/AlGaAs or InGaP/ InGaAs/GaAs, but also, most common silicon-based MOSFET devices, which
were explored as THz detectors. Such devices are sensitive to THz radiation due to specific response of free
electron gas via confined 2D plasmon modes. The current possibilities to achieve a relatively high-
integration of many FET devices directly allows us to use such detectors as imaging systems with a high
spatial resolution. The technology based-on conventional FETs nowadays is nowadays competing with new
ways of detecting THz radiation, notably with those based on novel strictly 2D systems.
More recently, with the fabrication of novel strictly 2D materials, new possibilities for sensing techniques
appeared. A wide range of 2D materials, which comprises insulators, semiconductors, semimetals, metals but
also, superconductors, offers a broad variety of detecting schemes, from THz to UV spectral ranges, due to

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the response of 2D electron gas or due to interband excitations. Notably, the concept of THz detection in
graphene-based FET devices, using the confined 2D plasmon excitations, but also more conventional, but
equally efficient, bolometric detection, have been successfully demonstrated, including possibility to
achieved room temperature operation.
At the moment, however, we are at too early a stage to provide some solid estimates of the final impact of
these emergent technologies, let alone to judge the possible size and dynamics of future markets. In most
cases, not more than the proof-of-concept stage has been achieved. Nevertheless, fast developing THz
technologies based on graphene and other 2D materials are nowadays discussed as a possible platform for
future 5G communication scheme.
Graphene‐based electrical and mechanical biochemical sensors have already been demonstrated for efficient
sensing of DNA, proteins, and antibodies. However, in terms of device level, compared to electrical and
mechanical sensing devices, optical sensing devices have many desirable advantages, such as
ultra‐sensitivity, long‐term stability, immunity to electromagnetic interference, compact form, light weight,
cost‐effectiveness, remote measuring capability, multiplexing or distributed sensing capability,
multi‐functionality, and lab‐on‐fiber capability.
Figure 12: Various graphene‐coated optical sensors for biochemical sensing.
[Source: B. N. Shivananjiu et al. Adv. Funct. Mater 27, 160391 (2017)]

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Graphene has been shown to be extremely sensitive to the surface charge density of the cells interfacing with
it compared to other materials. It has been demonstrated a graphene‐based highly sensitive optical refractive
index sensor (4.3 × 107
mV/RIU) with a high resolution of 1.7 × 10–8
, used for ultrasensitive flow sensing of
single cancer cells. This ultrasensitive graphene optical refractive index sensor can be used for the
ultra‐accurate detection of living, label‐free single cancer cells with a very low volume concentration, where
the refractive index and size of the cancer cells are significantly larger than for the normal cells.
The roadmap for graphene‐based optical biochemical sensing and health care sector applications for the next
few decades is shown in Figure 13, and looks very promising in terms of competitive sensing technology
with newly identified applications. This technology is now moving from the early stage of proof‐of‐concept
demonstration to practical implementation in diagnostic and health care applications.
Graphene‐based optical biochemical sensors are currently in the production line and reaching end users in a
few years. Various international patents are being filed based on graphene optical sensors. We expect that the
market for graphene‐based optical biochemical sensors will become larger than the market for electrical
sensors in approximately 5–10 years. The availability of graphene‐based optical biochemical sensor products
for the end user depends on collaboration between industry and research institutes. Extensive efforts are in
progress at both research institutes and industries to replace most of the currently adopted biochemical
optical sensors with graphene, other 2D materials (black phosphorous (BP), molybdenum disulfide (MoS2),
tungsten diselenide (WS2), and boron nitride (BN)) and heterostructure‐based optical sensors due to
outstanding performance in terms of sensitivity, selectivity, and ultrafast detection. Strategies for the
enhancement or modification of optical biochemical sensors to achieve ultrasensitivity and selectivity must
be pushed further. In future work, graphene sensors based on plasmonic, MID‐infrared, terahertz (THz), and
spintronic approaches may lead to novel sensing platforms for single molecule detection. The final goal is to
develop compact and cost‐effective single graphene‐based photonic on‐chip devices with an integrated
source, sensor arrays, and optical readout elements for ultrasensitive, highly selective, and ultrafast
biochemical sensing applications.
Figure 13: The roadmap of graphene‐based optical biochemical sensors.
[Source: B. N. Shivananjiu et al. Adv. Funct. Mater 27, 160391 (2017)]

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7 Biomicro and nano-engineered & non-invasive sensors
More than ever, companies are showing a growing interest in the healthcare domain. In the last 2 -3 years,
major players like Google, Apple, and Amazon have highlighted challenging projects, i.e. measuring blood
glucose via smart watches or smart lenses. Also, sensor makers are developing new technologies and
platforms to answer the specific requirements of medical grade products.
Demand for MEMS devices is increasing exponentially thanks to a democratization of medical devices that’s
bringing them closer to consumers and creating a high demand for portable and wearable devices enabling
patient monitoring at the point of need. In order to satisfy demand, almost all MEMS foundries are proposing
manufacturing services dedicated to healthcare applications.
With the addition of microfluidic chips (Si-based, polymer-based, glass-based) the BioMEMS market,
represented by silicon MEMS devices used for life sciences and healthcare applications, is expected to more
than double - from $3B in 2017 to $6.9Bin 2023, with a CAGR of 14.9% from 2017 - 2023. This makes
bioMEMS a must-have for today’s global sensor makers.
Figure 14: BioMEMS market dynamic 2017-2023 forecast
[Source: BioMEMS & Non-Invasive Sensors:Microsystems for Life Science & healthcare 2018, Yole Development,
August 2018]
Microfluidics demand still drives the BioMEMS market thanks to point of care applications and an
increasing demand for next generation sequencing. Also, the “acquisitions race” by large diagnostics
companies is still ongoing. Pressure sensors are more mature sensor devices used in respiratory and blood
monitoring, still reaching volumes of several hundred million units per year. Nevertheless, these mature
devices are expected to enjoy a new wave of interest thanks to fresh demand for smart connected objects like
inhalers and sleep apnea monitoring systems.
It is also worth noting that the transformation of global healthcare is spurring strong efforts to acquire new
functionalities and access to new diagnostic capabilities with micromachined ultrasound transducers and gas
sensors. Moreover, MEMS sensor innovation has triggered developments in neurotechnologies, with neural
implants for therapeutic applications(still at research level today) paving the way for better quality-of-life for
patients with neurodegenerative diseases.
MEMS technology is now mature enough to offer medical-grade measurement with miniaturized and low
power-consumption sensors, at a lower price than conventional technologies.

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BioMEMS devices are key solutions for a high level of electronic integration, contributing to development of
a new generation of easy-to-use medical devices for consumer and patients, with a lower rate of
hospitalization and the ability to help avoid unnecessary visits. For example, asthma detection devices
integrating MEMS microphones and accelerometers can prevent an asthma attack by alerting the patient
through his smartphone at exactly the right moment, prompting him to take his medicine and thus avoid a
medical emergency.
8 Summary of key recommendations
Recommendation Issues Benefit/Impact
1 Promote the combination of
a better fabrication
technique and new physical
effects
Convince especially SMEs
in investing in new
fabrication methods
New market opportunities
for micro- and nano-
engineered optical sensors
2 Favour, low-cost high-
throughput nanofabrication
techniques such as self-
assembly or nanoimprint
Prepared skilled personnel Materials with lower
dimension usually show
higher mechanical strength
and flexibility
3 Promote eco-design to save
costs and become more
environment friendly
Convince the key
stakeholders that they will
save money
Stakeholders will
acknowledge that the use of
optronic biosensors can be
cost effective
4 Favour real-time monitoring Increase time resolution Improved confidence of the
consumer
5 Favour materials and
systems that promote both
green practices & end-user
markets
For example the
development of low cost
routs to 2D materials
Good impact since a large
market can be shared by
consumers and producers
6 Promote interdisciplinarity
not only at R&D but also in
SMEs/industry
there are few cross-over
disciplines that capture the
necessary skills needed to
detect and identify
chemicals/biagents in a
meaningful way
Developmnt of ultrasensitive
and multiplex transduction
mechanisms bringing the
bio/chemical information
needed and mediation
technology
7 Favour financial support to
push-up the development of
R&D based solution
Updating of standards and
regulation. Companies are
seeking for technology
candidates in which they can
safely invest.
Economic benefit thanks to
a huge market
8 Support optronic systems
that bring new markets for
manufacturers & consumers
Handheld spectro & opto
analyzers
Save energy. Improve safety

-20/20-
9 What does the future look like: The next generation of sensors
Integrated optical-electrical devices, circuits and subsystems are expected to improve their technical
characteristics and drive drastic reductions in the sensor costs. In addition, in the coming years, new quantum
based concepts and metamaterials with exotic optical properties, among others, will be explored and
potentially developed for sensing purposes. All mentioned R&D directions in this roadmap will contribute to
significantly increasing the real use of optronics technologies in real applications and hence to expand their
market.
Along with sensor miniaturization, new optronic devices are creating opportunities for next-generation
medical and environmental sensors. After years of development, ultrasound transducers based on capacitive
detection or piezoelectric detection are finally emerging, with the first handheld imaging diagnostic systems
Much effort is being invested in non-invasive devices for better environment as well as patient comfort. For
instance, Apple has invested lots of money and manpower to develop an optical non-invasive sensor in its
smartwatch, which constantly checks the wearer’s blood glucose level.
Exceeding “wearable”, the next generation of sensor integrating medical devices should be “forgettable”:
that is, sensors must adapt to all wearables, textiles, and other accessories. Flexibility and stretchability are
pending parameters for the next sensor generation, likely in the form of body “stickers” that detect the
presence of certain molecules in sweat. Meanwhile, electrochemical sensors are leveraging printed
electronics development and new biocompatible substrate research, and should offer supplementary
This TWINFUSYON roadmap contain a lot of information that will provide ideas to researchers for new
research directions, to decision-makers for designing future research programmes and to companies for
programming future developments. The partners of the project encourage all stakeholders to use the
roadmaps as a tool for planning their future activities.

R&D Road Map for Optronic Biosensing

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