Biosensors and Bioelectronics - IFM - Linköping University

Biosensors and
Bioelectronics
STAFF
Professors: Anthony Turner and Fredrik Winquist
Emeritus Professor: Ingemar Lundström
Assistant Professors: Edwin Jager, Ashutosh Tiwari
and Valerio Beni
Visiting Researcher: Dr Raeann Gifford
Visiting Scientists: Dr Masoud Mehgardi, Dr
Mohammad Kamyabi, Dr Christine Reinemann
Visiting PhD Students: Aysu Yarman, Sudheesh
Shukla, Silvia Taccola, Daniel Melling
Diploma Student: Henrik Höckerdal
Stipendiat: Christopher Aronsson
Consultant: Dr Claes Nylander
Managing Editor: Dr Alice Tang
Administrative Staff: Anette Andersson
GENERAL INFORMATION
Our mission is to harness the fundamental
research activities and innovation at LiU to
facilitate the creation of the next generation of
bioelectronic devices and to support the
national and worldwide development of the
field of Biosensors and Bioelectronics. The
broader activities of the Linköping Biosensors
and Bioelectronics Centre (LBB) are
described elsewhere in this report and this
section focuses on our research. We have
expanded rapidly since our foundation at the
end of 2010, with the development of several
key collaborations, successes in winning
external support, the launch of a new course
and the appointment of three new Assistant
Professors and a senior Visiting Researcher.
We have hosted a number of international
visitors and our international profile is
developing apace. The biosensor laboratory
has been refurbished and is now fully
operational. We have purchased a full
spectrum of electroanalytical equipment and
are acquiring all the facilities necessary to
support our wide ranging research interests.
HIGHLIGHTS
Stimuli-responsive Zipper-like
Nanobioreactors. EU Marie Curie
Fellowship IIF254955: (2011-2013)
This International Incoming Fellowship funds Dr
Ashutosh Tiwari to work on bioreactors and stimuliresponsive,
intelligent nano-carriers for
bioelectronics, drug delivery, imaging and tissue
engineering. Integrated nanobiosytems are one of the
emerging frontiers in materials science and
biomedical studies. This area deals with induced
conformational changes in biological structures at
nano dimensions. Temperature, pH, magneto and
photo switchable nanobioreactors are used to
construct and evaluate a new generation of
nanobioreactors. These find application in the
fabrication of high-order diagnostic devices with
switchable nano-bioelectronics and modulated
biochemical processing within nano-systems.
Intelligent Nanobioreactors for Auto-switchable
Bio-catalysis. Swedish Research (VR) Council
(2012-16), 4m SEK
This project won in 2011, involves the design of
novel auto-switchable nanobioreactors for the
production of positively responding nano-surfaces
by creating unique “zipper” nanoarchitectures.
Model reactions, with applications in both analysis
(e.g. biosensors) and energy production, (e.g.
biological fuel cells) are used as proof-of-principle
platforms in the areas of bioanalysis and
biocatalysis.The fundamental design behind the
present strategy could make significant contributions
to the advancement of both bio-catalysis and
material science, leading to self-switching biocatalysis
utilising reusable, cost-effective and simply
made materials.
(A) (B)
Auto-switchable
bioreactors
i/A
20 o C
0.0 0.4
E/V
(A) SEM image of self assembled sunflower-shaped
bioreactors and (B) cyclovotammograms of
bioreactors at various temperature ranging from 37
to 20 ° C.
Smart Drug Delivery
We are exploring targeted drug delivery using smart
nanocarriers with magnetic resonance imaging
(MRI) and hyperthermic properties for tumor
treatment. In general, nanoscopic therapeutic
systems that incorporate therapeutic agents,
molecular targeting and diagnostic imaging
capabilities are emerging as the next generation of
multifunctional nanomedicines to improve the
therapeutic outcome of drug therapy. Among the
many nanoparticulate systems, stimuli-responsive
polymeric unimolecular micelles from pH- and
temperature-responsive block copolymers provide a
unique core-shell architecture wherein the
hydrophobic core serves as a natural carrier
environment for hydrophobic drugs and the
hydrophilic shell allows particle stabilisation in
aqueous solution. In addition, it is also possible to
37 o C

introduce a metallic core, giving the particle optical,
magnetic, or hyperthermic properties. The goal of
this programme is to develop unimolecular micelles
with magnetic resonance imaging (MRI) contrast
and hyperthermic characteristics for targeted drug
delivery. These novel micelles will be composed of
three key components: (i) a chemotherapeutic agent
doxorubicin that will be released from polymeric
micelles through a pH-dependent mechanism; (ii) a
biological ligand, i.e., specific aptamer that can
target tumor cells and subsequently induce receptormediated
endocytosis for cell uptake; and (iii) a
metallic core for ultrasensitive MRI or hyperthermic
properties.
Molecularly Imprinted Nanoparticles
The high selectivity and affinity of molecularlyimprinted
polymer (MIP) nanoparticles offers a
promising approach to develop a new generation of
biosensors, therapeutics and imaging agents,
incorporating plastic receptors with desirable
catalytic, affinity and DNA sequence-specific
properties. Compared to other types of biosensors,
which use biologically active molecules such as
enzyme, antibody and DNA strands immobilised
onto the electrode surface as sensing elements,
biosensors based on MIPs offer three key
advantages: 1) high affinity and selectivity to the
imprinted template (i.e., the target molecules); 2)
superior stability compared with those using natural
biomolecules in the biosensor structure; and 3) ease
of fabrication and adaptation for various types of
biosensors. Our MIP research relates to the
development of biomimetic biosensors, for
biomarkers of disease and for the direct detection of
genetic and infectious diseases.
(A) Electrochemical preparation of ss-ODN
imprinted MIP electrode and (B) Re-usable
biosensor to recognise sequence-specific ss-ODN.
Cardiac troponin immunosensor. LIST (2011-12)
200k SEK.
This project aims to design a tunable cardiac
troponin immunosensor with a sensitivity in the
picograms/mL range or less, and a doubleswitchable
cardiac troponin immunosensor using
core-shell nanocomposite. The model strategy will
aid in the effective diagnosis of acute coronary
syndrome. Ideally, it will make significant
contributions to advanced bioelectronics and
material sciences, leading to construction of ultra
sensitive immunosensors.
Computational Design of Aptamers
Under an ongoing programme of collaboration with
the University of Florence, we have elucidated an
entirely new approach to the selection of aptamers
by using computational approach. Starting from
information on the 15-mer thrombin binding
aptamer (TBA), a library of mutated DNA
sequences was generated and screened using
Shapegauss a shape-based scoring function from
Openeye Software to generate computationally
derived binding scores. The TBA and three other
mutated oligonucleotides, selected on the basis of
their binding score, were incorporated into surface
plasmon resonance (SPR) biosensors. By reducing
the ionic strength in order to match the simulated
condition, the analytical performances of the four
oligonucleotide sequences were compared using
signal amplitude, sensitivity, linearity and
reproducibility. The experimental results were in
agreement with the simulation findings. This work
could have a significant impact on the efficiency and
effectiveness of aptamer selection for sensors and
diagnostics, by facilitating the partial pre-selection
of aptamer sequences to be further tested in an
experimental screening process.
Reagentless Genosensor
Dr. Valerio Beni is collaborating with Prof. Ciara
O'Sullivan, in the development of novel approaches
for performing electrochemical melting curves
analysis. This work, carried out at the Universitat
Rovira i Virgili, Tarragona, Spain aims at the
development of novel electrochemical labels suitable
for conjugation with oligonucleotides and
subsequent incorporation in PCR products.
The presence of the electrochemical labels will
allow the hybridisation between a PCR product and
surface immobilised oligonucleotides probes to be
followed as a function of the solution/surface
temperature, using simple and inexpensive
hardware.

Loss in hybridisation, melting of the duplex results
in a reduction in the electrochemical response.
Studies of the melting temperature of probe/PCR
product are foreseen as an improved method to
allow rapid and effective identification of specific
genetic sequences.
Salivary Amylase (sAA) as a Stress Marker.
NovaMedTech, New Tools for Health and
Innovation Bridge (2011-2012), 1m SEK.
A pilot study on the associations between sAA,
psychosocial factors, self-rated health and
inflammation markers has been conducted in
cooperation with researchers at the Health
University having a saliva bank within a study called
Life conditions, Stress and Health. Levels of sAA
just after awakening were positively associated with
depression scores and level of ongoing
inflammation, and negatively associated with selfrated
health. Levels of sAA 30 minutes after
awakening and just before going to bed point in the
same direction, but may be influenced by recent
daily activity to a higher extent. The findings
support the hypothesis that sAA might be a reliable
marker of ANS activity in saliva.
Reaction kinetics due to amylase activity can be
measured with simple instrumentation using a light
source (LED) and a detector (phototransistor) or
with a disposable plastic electrochemical strip.
Preliminary comparison with an established method
for determination of saliva amylase activity is shown
below. Pink triangles = measurements on diluted
saliva, blue = standard method.
4,00
3,50
3,00
2,50
2,00
1,50
1,00
0,50
Calibration curve
0,00
0 20000 40000 60000 80000 100000 120000
A spin-off has been initiated to develop a
commercially viable biosensor system to monitor
wellness and therapy effectiveness and about one
million SEK in seed funding from several Swedish
innovation funding agencies has been secured. A
preliminary market study has been completed and
initial contacts for clinical studies have been
established. With support from LiU Innovations and
Uppsala University patent office, the patent strategy
is underway. Activities continue to develop a
prototype and conduct a clinical benefit study, which
are fundamental to demonstrate commercial
viability. The success of this endeavor demonstrates
how our research can generate applications that
improve quality of life and increase the
sustainability of healthcare.
Reagent paper Instrumentation
Skin Emissions studies for Bed Sore Prevention.
NovaMedTech
Pressure ulcers are a major problem for bed-ridden
patients, causing pain and intense suffering for the
individual. Furthermore, treatment is very costly and
labour intensive. A lot can be gained therefore if
early precursors of pressure ulcers can be spotted
and measures taken before an ulcer occurs. In
collaboration with researchers at the Health
University in Linköping and at the University of
Rome “Tor Vergata”, we have performed an initial
study to find out if there is a difference in the
emissions from the skin of compressed tissue
compared with uncompressed tissue. The
experiments were performed on hospitalised patients
in an intensive care unit and on healthy volunteers.
This GC-MS study indicates that difference in
general emission patterns are seen between
hospitalised and healthy people, respectively.
Furthermore within each group it was possible to
differentiate between compressed and uncompressed
tissue. This lays the foundation for the development
of smart technology to prevent this costly and
damaging trauma.
Artificial Olfaction
A further collaboration with the University of Rome
“Tor Vergata” in the area of artificial olfaction and
colour indicators for volatile organic compounds has
resulted in improved modeling of the olfactory
system based on optical chemical sensing, where
each pixel in a response image is regarded as an
olfactory receptor neuron. Our results indicate that
the average firing rate of the output spike sequences
shows the best separation among the experienced
vapours, however the latency code is able in a
shorter time to correctly discriminate all the tested
volatile compounds. This behavior is qualitatively
similar to those recently found in natural olfaction,
and in particular it provides a practical route to tailor
the measurement conditions of artificial olfactory
systems, defining for each specific case a proper
measurement time
Bioelectronics
We are currently focusing on electroactive surfaces
and scaffolds for regenerative medicine as a part of
the LiU Integrative Regenerative Medicine (IGEN)

Center network and mechanobiology in
collaboration with Dr. Ana Teixeira’s group at
Karolinska institutet. We have developed new
scaffolds for the electrical stimulation of stems cells
and as well as microfabricated devices for
mechanical stimulation of Notch cells.
Actuators
In the field of polymer actuators, we are exploring
the development of new materials, micromechanics
and microrobotics, and novel actuator designs. We
have developed novel polypyrrole-based actuator
materials and currently are investigating the role of
crosslinking in the actuation mechanism. We are
collaborating with Cranfield University (UK) on
synthesising and quantifying these new materials
and with the Italian Institute of Technology, Center
for Micro-BioRobotics, Pontedera, Italy, developing
all polymer soft actuators and new bioinspired
propulsion schemes. In addition, Dr. Edwin Jager
spent 2.5 months at the Intelligent Polymer Research
Institute, at University of Wollongong, Australia,
working on microfabricating new soft actuators that
work in air. Dr. Edwin Jager is a part of one of the
six remaining FET Flagships, “Robot Companion
for citizens”, which is in its closing phase of drafting
the final application to be submitted in 2012. In
addition, he is an active member of the COST
Action MP1003: European Scientific Network for
Artificial Muscles. He is the national representative
of Sweden in the management committee, chairman
and vice-chairman of the medical devices working
group and short term training missions working
group, respectively.
COST Action TD1003 Bioinspired
Nanotechnologies: Short Term Scientific Missions
Dr Christine Reinemann (Helmholtz-Centre for
Environmental Research,Leipzig, Germany) visited
to work on novel aptamers for electrochemical
biosensors. A new electrochemical aptasensor was
developed for ethylamines such as diethanolamine,
triethanolamine, ethylamine, diethylamine,
triethylamine, methylamine, lysine and arginine.
Aysu Yarman (Fraunhofer-Institut für
BiomedizinischeTechnik, Potsdam, Germany) was
also sponsored by this COST action to visit LiU to
work on peroxygenase or microperoxidase catalysed
substrate conversion of aromatic drugs with
molecular recognition using MIPs. The model
analytes were catechol, diclofenac and propanolol.
MIP layers were generated by electropolymerisation
of o-phenylenediamine and aminophenyl boronic
acid.
Nanomaterial-based aptasensors for early
diagnosis of prostate cancer
Dr Masoud Mehrgardi (Dept. Chemistry, University
of Isfahan, Iran) came to the Centre to work on an
RNA aptamer that specifically binds prostate
specific membrane antigen. The aptamer bound to
functionalised gold nanorods, was immobilised on a
gold electrode using 1, 6-hexanedithiol and the
impedance followed after incubation with LnCap
and PC-3 cell cultures medium. The biosensor was
able to differentiate LnCap cells from PC-3 cells.
3D- Aptamers
nano-probe
Gold nanorods conjugated with PSMA
586.01
Fabrication of a switchable glucose biosensor
based on nanoparticles
Dr Mohammad Kamayabi (Dept. of Chemistry,
Zanjan University, Iran) came to work on the design
and development of switchable glucose sensors
based on magneto and photo responsive polymers
and direct electron transfer. In the magnetoswitchable
glucose biosensor, functionalised Fe3O4
or NiO nanoparticles were successfully used to
activate the electrical contact between the redox
units of the enzyme and the electrode.
TEACHING
The division of Biosensors and Bioelectronics has
launched a new course on biosensor technology
(Introduction to biosensor technology, TFYA62), for
2 nd year students of the Biomedical Engineering
bachelor degree. The course and its associated
practical exercises were designed to stimulate the
interest of the students in the area of biosensors and
associated technologies in support of this key sector
of the biomedical industry in Sweden. The division
also runs the course Biosensor Technology
(TFTB34) by Fredrik Winquist and participated with
several lectures in the course Microsystem
Technology and Nanobiology (TFTB33) and the
PhD course Organic Electronics (both Edwin Jager).
We also participated in “NanoTechnas” the 5th-
Nanoschool that took place on Vilnius, Lithuania
(15 th -17 th of November).

Biosensors and
Bioelectronics
Centre
The Linköping Biosensors and Bioelectronics Centre
(LBB) was set up in 2010, with the aim of bringing
together the many competences, activities and
resources at LiU that are already working on, or can
bring valuable contributions to the development of
biosensors and bioelectronic devices. The Centre is
also a gateway for international contacts and
collaborations within this broad and rapidly
expanding field. It has expanded apace during 2011,
with the development of several key collaborations,
successes in winning external support and the
appointment of three new Assistant Professors and a
senior Visiting Researcher. It has hosted a number of
international visitors and its international profile is
developing rapidly.
Director: Prof Anthony Turner
Professors: Anthony Turner and Fredrik Winquist
Emeritus Professor: Ingemar Lundström
Assistant Professors: Edwin Jager, Ashutosh Tiwari
and Valerio Beni
Visiting Researcher: Dr Raeann Gifford
Visiting Scientists: Dr Masoud Mehgardi, Dr
Mohammad Kamyabi, Dr Christine Reinemann
Visiting PhD Students: Aysu Yarman, Sudheesh
Shukla, Silvia Taccola, Daniel Melling
Diploma Student: Henrik Höckerdal
Stipendiat: Christopher Aronsson
Consultant: Dr Claes Nylander
Managing Editor: Dr Alice Tang
Administrative Staff: Anette Andersson
GENERAL INFORMATION
The LBB was set up to capitalise on the experience
and potential of Linköping University (LiU) in the
fields of Biosensors, Biosensing and Bioelectronics.
LiU houses a world-leading group of biosensor
scientists, who have arguably had the most
significant impact on this rapidly expanding field to
date. Our work on Surface Plasmon Resonance
(SPR) for real-time bioaffinity monitoring and on
mediated amperometric biosensors helped establish
the true commercial potential for the field and kick
started the current multi-billion dollar industry.
Work continues today across the full range of core
technologies including:
• Bioimaging and drug delivery
• Bio-inspired and bio-specific ligands
• Biointerfaces
• Biomolecular electronics
• Biosensors
• Chemical transducers
• Clinical trials
• Printing and microfabrication
• Nanomaterials and nanostructures
• User interfaces and electronic design
LBB’s mission is to harness the fundamental
research activities and innovation at LiU to facilitate
the creation of the next generation of bioelectronic
devices and to support the national and worldwide
development of the field. It is building on the legacy
of S-SENCE, the Swedish Centre of Excellence for
sensor research established at LiU in the mid-90s.
LBB is also working closely with the Joint Research
Centre for Biosensors in Singapore, headed by
Professor Bo Liedberg, which was recently set up by
LiU, together with Austrian Institute of Technology
(AIT) and Nanyang Technological University
(NTU). In addition, LBB has formed close links
with the Integrative Centre for Regenerative
Medicine (IGEN) in the Health University and
several joint events have been held resulting in a
number of collaborative grant proposals. LBB also
supports the New Tools for Health initiative and has
played a leading role in Linköping Center for Life
Science Technologies (LIST), which is chaired by
Prof Lundström. A further key external collaborator
has been the Swedish Defense Research Agency
(FOI). LBB has won a VINNOVA grant together
with FOI to work with Uppsala University, Ericsson
and two other companies to develop wearable
sensors to assist the elderly.
BIOSENSORS AND BIOELECTRONICS
(ELSEVIER)
LBB is home to the principal journal in the field,
Biosensors and Bioelectronics, published by
Elsevier. Prof Turner is the Editor-In-Chief, Dr Tang
is the Managing Editor and Prof Lundström is an
Editor. The journal has the highest Impact Factor
(5.4) for a research publication in the broad field of
Electrochemistry, as defined by ISI, and is also the
highest ranking journal in Sensors. The team
handled nearly 2,000 submissions in 2011.
www.elsevier.com/locate/bios
ADVANCED MATERIAL LETTERS (VBRI)
Dr Ashutosh Tiwari is Editor-In-Chief of Advanced
Materials Letters, published by VBRI Press, and Dr
Raeann Gifford is an Associate Editor. This new
journal seeks to promote studies of the structure,
synthesis, characterisation and application of novel
nanomaterials. Dr Tiwari also edited two books in
this area during 2011.

JOURNAL
VBRI Press
A rapid publication platf orm
ADVANCED
MATERIALS
Letters
Structure, synthesis &
processing, characterization,
advanced-state properties
and applications of materials
Copyright © 2012 VBRI Press
Editor-In-Chief
Ashutosh Tiwari
THE INTERNATIONAL CONFERENCE ON
NANOTECHNOLOGY (ICNANO 2011)
LBB, together with the International Association of
Advanced Materials (IAAB), the University of Delhi
and the journal Advanced Materials Letters,
organised ICNANO in Delhi in December 2011. Dr
Ashutosh Tiwari was General Secretary of the
Conference and over 1,500 delegates attended
sessions on optoelectronics, biomaterials and
biomedicine, advanced materials, fabrication, green
energy and the environment, computational
simulation and theory, materials characterisation and
applications of nananotechnology. Prof Turner was
the Honorary Chair and he, Prof May Griffith
(IGEN) and Dr Raeann Gifford presented Plenary
Lectures.
THE WORLD CONGRESS ON BIOSENSORS
LBB is the co-organiser, together with Elsevier, of
the 22 nd Anniversary World Congress on Biosensors,
which will be held in Cancun, Mexico 15-18 May
2012. The World Congress is the largest and most
prestigious event in the field and is expected to host
a thousand delegates. LiU will present a number of
scientific papers at the conference and will also
mount an exhibition stand to promote the activities
of LiU.
www.biosensors-congress.elsevier.com
EU NETWORK FOR INITIAL
TRAINING IN CHEMICAL
BIOANALYSIS ITN264772: CHEBANNA
This Marie Curie Initial Training Network (ITN)
commenced in December 2010 for four years and is
being carried out in collaboration with Cranfield
University in the UK, Roche Diagnostics and ten
other European partners.
CHEBANA provides a European hub for research
and training in the fast developing field of Chemical
Bioanalysis with co-supervised PhD theses,
postdoctoral training, workshops and summer
schools to help furnish the highly specialised experts
that are urgently required by European industry.
Chemical Bioanalysis aims to retrieve selective
information out of complex biological systems.
Sensors, probes and devices are the future tools of
medicinal diagnostics, environmental monitoring,
food analysis and molecular biology. CHEBANA
provides interdisciplinary research training for both
early stage and experienced researchers and focuses
on the most important techniques in the field:
electrochemistry, fluorescence and mass
spectrometry. The research activities are divided into
four overlapping areas:
• Sensor development for the detection of
small analytes
• Monitoring of biomolecular interactions
• Analysis of cellular function
• Development of diagnostic tools
EU COST ACTION TD1003: BIO-INSPIRED
NANOTECHNOLOGIES: FROM CONCEPTS
TO APPLICATIONS
This four-year COST action commenced in 2010,
with Professors Turner and Lundström as the
Swedish representatives. This cross-disciplinary
research consortium is constructing multi-scale
structures in order to organise functional materials in
nanodevices. The marriage of top-down and bottomup
fabrication methods paves the way to arrange
complex molecular nano units, to electronically
address them and integrate them into functional
devices.
Several national and international networks and
foundations are participating in the COST action
including C’Nano GSO, NanoSpain, Portugal Nano,
Phantoms Foundation, SUDOE Interbio, nanoICT
(bioICT Working Group). These networks have the
technical facilities and power to provide technical
support to the summer schools, give international
workshops and hold meetings with businesses and
governmental organisations. LBB and LIST will
host a joint workshop on Bioinspired
Nanotechnologies for Distributed Diagnostics,
together with the COST Action, in Linköping, 26-27
April 2012.
INTERNATIONAL AGREEMENTS
The Biosensors and Bioelectronics Centre signed an
Erasmus agreement with the Universitat Rovira I
Virgili, Tarragona, Spain and with the Institute for
bioengineering of Catalonia (Ibec), Barcelona, Spain
for the exchange of postgraduate students.