Overview and Introduction to Biosensors Anthony P F Turner

Biosensors & Bioelectronics Centre IFM-Linköping University

Biosensor Technology TFTB34, Linköping, , Linköping, Thursday 24 January 2013

Contents

• What is a biosensor?

• Why are biosensors important?

• Electrochemical biosensors

• Affinity biosensors

• Whole-cell biosensors

• Emerging technologies

• Conclusions & further reading

The Atlas moth can follow a trail of pheromones from severl km downwind

Fully Integrated Sensors

Non-invasive Sensing

Wearable and

Distributed Sensors

Biosensors & Bioelectronics Centre

Applications

Biosensors harness the immensely powerful molecular recognition properties of living systems and engineer these into electronic devices to provide easy-to-use sensing devices with applications in: – Medicine – Biomedical research – Drug discovery – Environmental monitoring – Food content, quality and safety – Process control – Security and defence

The two most successful biosensors to date: • Mediated amperometric glucose biosensor • Real-time bioaffinity interaction analysis

Newman, J.D. and Turner, A.P.F. (2005) Home blood glucose biosensors: a commercial perspective. Biosensors and Bioelectronics 20, 2435-2453.

Defence and Security Challenges

• Detection of threat agents • Military heath care • Policing • Environmental contamination

The Biosensor

Bioreceptor

Transducer

GAS!!!

Inhibition enzyme electrodes

Flow Cell

Printed Acetylcholinesterase Electrodes

Davis, F., Law, K.A., Chaniotakis, N.A., Fournier, D., Gibson, T., Millner, P., Marty, J-L., Sheehan, M.A., Ogurtsov, V.I., Johnson, G., Griffiths, J., Turner, A.P.F. and Higson, S.P.J. (2007). Ultra-Sensitive determination of pesticides via cholinesterase-based sensors for environmental analysis. In: Comprehenive Analytical Chemistry: Electrochemical Sensor Analysis. (Eds. S. Alegret and A. Mercoki). Elsevier, Netherlands.

Economic Impact of Healthcare • Healthcare spending is growing fast: 18% of GDP for USA, 9.5% of GDP for Europe

• Global Healthcare spending is more than 5 Trillion Dollars per year

• This spending trend is unsustainable for the future economy

• To counter this trends, the Healthcare industry must change

• What does this mean for Healthcare Industry ?

• A boom in Home Diagnostics

• A boom in Personalised Medical Devices

The Healthcare Challenge 2013 • Diabetes - the fastest growing chronic disease in the World

• Asia is home to 4 of the 5 largest diabetic populations and 2% of the World‘s population is afflicted

• Heart Disease and stroke - kill 17m people / year, one-third of all deaths globally

• By 2020, they will be the leading cause of both death and disability worldwide

• Fatalities projected to increase from 17m p.a. (2008) to 25m (2030)

• Cancer - 10.9m people p.a. worldwide diagnosed with cancer, 45% are in Asia • Around 12% of deaths worldwide are from cancer: Africa 4%, N America

23%; UK 24%. Annual cancer deaths rising from 7.6m to 13 m (2030)

• Aging Populations – The Demographic Time Bomb • The proportion of people in the world aged ≥60 years old has doubled

since 1980 and will reach 2 billion by 2050

• Infectious diseases - 16.2% of worldwide deaths. • Poverty: malaria (0.8m deaths p.a., HIV/AIDS (1.8m deaths p.a.), TB (1/3rd world pop. infected; 1.4 m deaths p.a. but falling by 2.2% p.a.) • Epidemic & emerging: meningitis, cholera, yellow fever, flu, resistance

0500

100015002000250030003500400045005000

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

2012

Scopus “biosensor*”

This simple search shows 1 paper on Biosensors identified in 1980, 75 papers in 1985 and 4,470 in 2012

Biosensor Publications

~10% of all papers ever published on biosensors

appeared in 2012

A Changing World

Biosensors 2000-05

USAAsiaEuropé

Biosensors 2005-12

USAAsiaEuropé

Nanotech 2000-05

USAAsiaEuropé

Nanotech 2005-12

USAAsiaEuropé

Biosensors: World

Market

85% of Biosensor market is still for glucose measurement

World Market for Biosensors (US$m)

Newman, J.D. and Turner, A.P.F. (2010) Biosensors: a mixed market. The 20th World Congress on Biosensors: Biosensors 2010, Glasgow, Scotland, 26-28 May 2010. Elsevier.

02000400060008000

1000012000140001600018000

1996 2000 2002 2004 2006 2009 2010 2018

Roche Diagnostics

Lifescan

Bayer Diagnostics

Abbott

Molecular Devices Corporation

Affymetrix

Nova biomedical

Biacore

Others

China

Biosensors: $13b Market

Share

Beijing Yicheng JPS-5

Roche Accu-Check Aviva Nano

Lifescan OneTouch Ultra

Bayer Contour

Abbott FreeStyle Lite

The Market leaders in 2009 Biosensor Sales

14

“A biosensor is an analytical device incorporating a biological or biologically derived sensing element either intimately associated with or integrated within a physicochemical transducer. The usual aim is to produce a digital electronic signal which is proportional to the concentration of a chemical or set of chemicals.” “Biosensors usually yield a digital electronic signal which is proportional to the concentration of a specific analyte or group of analytes. While the signal may in principle be continuous, devices can be configured to yield single measurements to meet specific market requirements.” (One-shot biosensors) Turner, A.P.F., Karube, I. and Wilson, G.S. (1987). Biosensors: Fundamentals and Applications. Oxford University Press, Oxford. 770p. ISBN: 0198547242 & The international journal Biosensors & Bioelectronics

Biosensors

Receptors for Biosensors

• Biological materials: e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, natural products etc

• Biologically derived materials: (e.g. recombinant antibodies, engineered proteins, aptamers etc

• Biomimics: e.g. synthetic receptors, bimimetic catalysts, combinatorial ligands, imprinted polymers etc

Transducers for Biosensors

• Electrochemical: e.g. amperometric, potentiometric, conductimetric, impedimetric etc

• Optical: e.g. surface plasmon resonance (SPR), fluorescence, interferometric, holographic

• Thermometric: e.g. enzyme thermistor, thremal enzyme-linked immunosorbent assay etc

• Piezoelectric: e.g. quartz crystal microbalance (QCM), surface acoustic wave devices (SAW)

• Magnetic: e.g. magneto resistive devices, paramagnetic labels etc • Micromechanical: e.g. resonating beam structures

The Biosensor

(Bio)receptor(affinity or catalytic)

TransducerElectronics

Electrochemical

Optical

Thermometric

Piezoelectric

Magnetic

Micromechanical

Electrochemical

Optical

Thermometric

Piezoelectric

Magnetic

Micromechanical signal

Analytes

TissuesMicroorganismsOrganellesCell receptors

EnzymesAntibodiesNucleic acidsSynthetic receptors

The Biosensor

Types of Biosensor

Catayltic Biosensor e.g.enzyme electrode

Labeled Affinity Sensor e.g. Fluorescence or Enzyme labeled Immunosensor

Label-free or direct Immunosensors e.g. SPR or piezoelectric

The Starting Point: Clark Oxygen Electrodes

1955

Yellow Springs Instrument Company Inc (YSI)

Glucose Biosensor 1975

YSI, Ohio 1987

The original YSI serum-glucose biosensor for diabetes clinics 1975

Clark, LC & Lyons, C (1962). Annals New York Academy of Sciences 102, 29.

1987

21

The YSI Analyser

1500 Sport Analysers

22

Enzyme Electrochemistry

Cass, A.E.G., Davis, G., Francis, G.D., Hill, H.A.O., Aston, W.J., Higgins, I.J., Plotkin, E.V., Scott, L.D.L. and Turner, A.P.F. (1984) Ferrocene-mediated enzyme electrode for amperometric determination of glucose. Analytical Chemistry 56, 667-671.

Glucose oxidase or PQQ Glucose Dehydrogenase

Mass Production: Screen Printing

• Bayer’s DIDGET™ blood glucose meter plugs into a Nintendo DS™ or Nintendo DS™ Lite system

• This helps encourage consistent testing with reward points that children can use to buy items and unlock new game levels

The Importance of the User Interface

Blood Glucose: “We’ve got an App For That”

Lifescan popularised the iPhone route 2009

AgaMatrix Nugget iPhone

plug-in glucose meter gained FDA 510(k) on 7 December 2011, to be marketted by Sanofi Aventis with iBGStar app, early 2012.

The Evolution of Home Blood Glucose Monitoring

Evolution of Blood Glucose Monitor products Past Present Future

CGM Medtronic Guardian

The original Miles

Glucometer Supramolecular

Devices?

Newman, J.D. and Turner, A.P.F. (2008) Historical perspective of biosensor and biochip development. In: Handbook of Biosensors and Biochips (Eds R. Marks, D. Cullen, I. Karube, C. Lowe and H. Weetall) John Wiley & Sons. ISBN 978-0-470-01905-4

MediSense Mediated sensor

Non-invasive monitoring? (research)

Clinically Important Enzyme Electrodes

Electrode Enzymes Amperometric

Oxygen electrode, hydrogen peroxide detection at platinum or carbon electrodes or mediated amperometry

Oxidases e.g. Glucose oxidase (GOx), Lactate oxidase, Galactose oxidase, Pyruvate oxidase, L-Amino Acid oxidase, Alcohol oxidase. Oxalate oxidase, Cholesterol oxidase, Xanthine oxidase, Uricase.

Platinum, carbon, chemically-modified, mediated amperometric electrodes

Dehydrogenases e.g. Alcohol dehydrogenase, Glucose dehydrogenase (NAD and PQQ), Lactate dehydrogenase

Potentiometric

Ammonia Gas-Sensing Potentiometric Electrode, Iridium Metal Oxide semiconductor probe

Creatinase, Adenosine deaminase

pH Electrode, Filed-effect Transistor (FET) Penicillinase, Urease, Acetylcholinesterase, GOx

Carbon Dioxide Gas Sensor Uricase, inhibition of dihydrofolate reductase, salicylate hydroxylase

Key bioelectrochemical reactions

D-glucose + H2O + O2 gluconic acid + H2O2

H2O2 2H+ + O2 + 2e-

D-glucose + 2 Medox+ gluconic acid + 2 Medred

(NH2)2CO + 2H2O + H+ HCO3- + 2NH4

+ 2NH3 + 2H+

C2H5OH + NAD+ C2H5O + NADH

NADH NAD+ + 2e- + H+

GOx

Anode

GOx

Urease

ADH

Anode

28

Nova Biomedical CRT 16 Na+, K+, Cl-, TCO2, Glu, BUN (urea), Creatinine & Hct

29

Glucose Creatinine Lactate Urea Sodium Calcium Potassium Chloride pH pCO2 Haematocrit

i-Stat Clinical Analyser

1992

30

On-line Urea Biosensors for Monitoring Haemodialysis

Sintong, Taiwan 1999 Nova Biostat made for Baxter 1999

Electrochemical Immunoassay

Analytes: Simulated threat agents Toxins (eg Algal toxins) Pesticides (eg Atrazines, isoproturon) Carcinogens (eg PCB) Hormones (eg Estradiol) Environmenta Biomarkers (eg Vitellogenin)

A simple four electrode array of screen-printed immunosensors

Kröger, S., Setford, S.J. and Turner, A.P.F. (1998) Immunosensor for 2,4-dichlorophenoxyacetic acid in aqueous/organic solvent soil extracts. Analytical Chemistry 70, 5047-5053.

Schematic representation of five different nanoparticle-based labelling routes: A) Conductimetric detection; B) Au dissolving and Au(III) stripping accumulation and detection; C) Silver precipitation, dissolution (with HNO3) and Ag+ stripping; D) Multilabelling with different quantum dots and detection of the corresponding ions; E) Molecular beacons for hybridisation and apatamer sensors.

Electrochemical Transduction Strategies

Berti, F. and Turner, A.P.F. (2011). New micro- and nano-technologies for electrochemical biosensor development. In: Biosensor Nanomaterials (Eds. S. Li, J. Singh, H. Li and I .A. Banerjee). Wiley. pp 1-35. ISBN 978-3-527-32841-3

E A B

C D

Label-free Electrochemical Immunosensors

Li, H., He, J., Wei, Q., Li. S., and Turner, A.P.F. (2012) Electrochemical Immunosensor with N-Doped Graphene-Modified Electrode for Label-Free Detection of the Breast Cancer Biomarker CA 15-3. (Submitted)

Highly conductive N-doped graphene sheet-modified electrode, exhibited significantly increased electron transfer and sensitivity towards breast cancer marker CA 15-3. This novel immunosensor, with a low detection limit of 0.012 U/mL, worked well over a broad linear range of 0.1-20 U/mL.

An Electrochemical Immunobiosensor for Direct Detection of Veterinary Drug Residues in Undiluted Complex Matrices Khor, S., M., Liu, G., Peterson, J. R., Iyengar, S. G. and Gooding, J. J. (2011). Electroanalysis 23, 1797-1804.

Displacement assay for drug residues in undiluted milk using a mixed layer of oligo(phenylethynylene) molecular wire, to allow electrochemical communication and oligo(ethylene glycol) to control the interaction of proteins and electroactive interferences with the electrode surface.

A

Short Break

Surface Plasmon Resonance (SPR) - BIAcore

Ingemar, Claes & Bo, LiU

Bo Liedberg, Claes Nylander and Ingemar Lunström (1983) Surface plasmon resonance for gas detection and biosensing Sensors and Actuators 4, 299-304

Texas Instruments Speeta

SPR Imaging Aptasensors

Scarano, S, Mascini, M., Turner, A.P.F. and Minunni, M (2010) Surface Plasmon Resonance Imaging for Affinity-Based Biosensors. Biosensors & Bioelectronics 25, 957-966

Kretschmann configuration for SPRi; p-polarised light is directed to the prism, on which the biomolecular probe is tethered, and a CCD camera collects the output signal as variations in reflectivity

Horiba – up to 900 spots Light activated peptide synthesis 2,500 spots; target 7,500 for epitope mapping etc

Localised Surface Plasmon Resonance

Tiwari, A., Mishra, A.K., Kobayashi, H. and Turner, A.P.F. (2012) Intelligent Nanomaterials, Wiley-Scrivener Publishing, USA. 838 pp. ISBN 978-0-470-93879-9.

LSPR requires only a light source and a spectrophotometer to measure the wavelength change in the reflected light from a nanostructured material or surface. While the penetration depth of the plasmon field for SPR is between 200-1000nm, it is 15-30nm for LSPR. Hence bulk effects have less influence.

Biosensors Applications AB: technology for drug and explosives detection

Biosens 600

www.biosensor.se

Border control Security Correctional & Police authorities Rehabilitation & Workplace control

Geier, P., Mascini, M. and Turner, A.P.F. (2011) . Aptasensors for C-reactive protein. In: Encyclopedia of Nanoscience and Nanotechnology (Ed. H. S. Nalwa) American Scientific Publishers. www.aspbs.com/enn (in press).

• C-reactive protein is used to indicate infections and inflammations, but marginally increased levels have recently been associated with a number of chronic diseases such as an increased risk for the development of Diabetes mellitus. • Prospective studies have shown that CRP might represent a strong and independent biomarker of future coronary events especially in patients with a previous coronary heart disease.

Aptasensors for C-reactive Protein

Microbial Growth Detection with Resonating Beams Resonating Beam Structures for Antibiotic Testing

Fluoresence-based affinity sensors

Up to 6.5 m assays on a

1.3 cm2 chip Fluorescence immunoassay-based biosensor for real time or near real time detection of microbial pathogens, typical

assay times of 10-15 minutes; 4 disposable optical

waveguide sensors; may be reused if test results continue

to be negative.

DNA Chip

Confocal scanners and other microscopy techniques are now routinely used for imaging genomic and proteomic arrays

Leading methods for multianalyte detection based on total internal reflection on planar waveguides

Zeptosens (Bayer)

Raptor www.resrchintl.com

Lateral Flow Immunoassay

Original visually read pregnancy test format patented by Unipath and launched in 1988, based on blue latex label resulting in one or two blue lines indicating hCG

Pregnancy Tests with Conception Indicator Launched July 2008, measures urinary hCG using both a low sensitivity and a high sensitivity strip. Control lines and results read using red light to measure density of lines by reflectometry yielding 4 possible semi-quantitative results: 1) Not pregnant 2) Pregnant with conception 1-2 weeks ago 3) Pregnant with conception 2-3 weeks ago 4) Pregnant with conception >3 weeks ago

Swiss Precision Diagnostics GmbH is a joint venture between Procter and Gamble and Inverness Medical

>99% accurate in detecting pregnancy & 92% accurate in time predictions. Same price as visual strips.

Diversification of Lateral Flow Immunoassay

Growing range of tests for clinical, veterinary, agricultural, food industry, bio-defence and environmental applications

Oxoid Xpect™ (UK): Legionella, Influenza, RSV, C. difficile, Cryposporidium, Giardia, Rotavirus

POCT-Dx Uniscan™ (British Virgin Islands / Canada platform technology for “all kinds of membrane-based lateral flow immunoassays”

Alfa Scientific Designs Inc. (USA): INSTANT-VIEW® H. pylori test. Designs for drugs of abuse, fertility hormones, cancer markers and infectious disease

Molecular Devices Threshold System

The Threshold Immunoligand Assay (ILA) measures a broad range of analytes such as proteins, peptides, and microorganisms. The Threshold Total DNA Assay quantitatively measures picograms of single-stranded DNA.

www.moleculardevices.com/Products/Instruments/Threshold-System.html

Complex sandwich immunoassay with light-activated potentiometric (LAPS) detection

A

B

Whole-cell biosensors: BOD

Whole-cell Biosensors • Microorganisms engineered to react to the presence of

chemical signals with the production of an easily quantifiable marker protein

• The regulatory system in the bacterial cell is exploited to drive expression of a specific reporter gene, such as bacterial luciferase, green fluorescent protein, beta-galactosidase

• This is achieved by fusing the DNA for a promoterless reporter gene to an extra copy of the selected regulatable promoter and introducing this construction into the bacterial or yeast cell

• Examples include heavy metal resistance (heavy metal sensors), organic compound degradation (organic compound sensors), cellular stress responses (to obtain general toxicity sensors) and DNA damage repair (mutagenicity).

Computational Design of Aptasensors

A

B

Thrombin-aptamer interaction

Retrospective docking study of thrombin aptamer (TBA) 5’-GGTTGGTGTGGTTGG-3’. TBA interacts specifically with the Fibrinogen recognition exosite through the two TT loops The computational approach confirmed results observed in SELEX.

Bini, A., Mascini, M., Mascini, M. and Turner, A.P.F. (2011). Selection of Thrombin-binding aptamers by using computational approach for aptasensor application. Biosensors and Bioelectronics 26, 4411-4416.

Active box in the fibrinogen- binding Exosite

• SELEX only searches 1014 of possible 1018 20-60mers • Non-specific recognition of support • pcr tends not to amplify 2ndary structures

Nanotechnology Materials The market for pure nanomaterials (carbon nanotubes, nanoparticles, quantum

dots, dendrimers etc.) was about $3.6 billion by 2010 (Lux Research). Many of these materials will find application in diagnostics

Poma, A., Turner, A.P.F. and Piletsky, S. (2010) Advances in the manufacture of MIP nanoparticles. Trends in Biotechnology 28, 629-637.

Synthetic Receptors e.g. Molecular Imprinting

Reversible interactions between the template and the polymerisable functional monomer may involve: (a) reversible covalent bonds, (b) covalently attached polymerisable binding groups that are activated for non-covalent interaction by template cleavage, (c) electrostatic interactions, (d) hydrophobic or van der Waals interactions. Following polymerisation, the template is then removed through the disruption of the interactions with the polymer, and subsequently extracted from the matrix. The target analyte or his analogues can then be selectively rebound by the polymer.

Nano-MIPs (Plastic Antibodies) a)

c)

b)

d)

e)

0

0.005

0.01

0.015

0.02

0.025

0.03

0.035

0.04

0.045

0 5 10 15 20 25 30 35 40

Time, min

Po

lym

eri

zati

on

rate

a)

b)

AB A + B. .λν

.A + B. A B

+ M .A . A

BA λν .+ BA .

Piletsky, S.A., Guerreiro, A., Piletska, E.V., Chianella, I., Karim, K. and Turner, A.P.F. (2005). UK Patent Application 0511116.6. Published Dec 2006

MIP Nanoparticle Synthesiser

• Yield – 100 mg particles/cycle • Manufacturing time 6 hours • Measured affinities (KD) range between

• 1.9x10-10 M for vancomycin

• 7x10-10 M for melamine, 5.5x10-12 M for a model peptide

• 10-11-10-9 M for proteins (trypsin, pepsin, amylase, peroxidase)

Poma, A., Guerreiro, A., Whitcombe, M., Piletska, E., Turner, A. P. F. and Piletsky, S. (2012). Automatic Synthesis of Molecularly Imprinted Polymer Nanoparticles – “Plastic Antibodies”. Advanced Materials (submitted).

(A) Electrochemical preparation of ss-ODN imprinted MIP electrode and (B) Re-usable biosensor to recognise sequence-specific ss-ODN.

Ashutosh Tiwari, Hisatoshi Kobayashi, Anthony P.F. Turner (2012). Detection of p53 gene point mutation using sequence-specific molecularly-imprinted PoPD electrode. Biosensors and Bioelectronics 35, 224-229.

ss-DNA biosensor fabricated by electropolymerisation on indium-tin oxide coated glass substrate using single-stranded oligodeoxyribonucleotides (ss-ODNs) as the template and o-phenylenediamine as the functional monomer. Linear response to 0.01 to 300 fM in 14 secs.

Sequence-specific DNA MIP Sensor

Switchable Immunosensors

Deshpande, S., Tiwari, A. and Turner, A.P.F. (2012). Label-free nano immunosensor for diagnosis of cardiac injury based on localised surface plasmon resonance. Label-free Technologies, 1-3 November 2012, Amsterdam, Elsevier.

Poly(N-isopropylacrylamide) {PNIPAAm} temperature-responsive polymer at >32°C undergoes a reversible lower critical solution temperature phase transition (LCST) from swollen hydrated state to shrunken dehydrated state, losing ~90% of mass

Gold nanorod-based plasmonic biosensing displayed much higher selectivity and sensitivity in the picograms/ml range for trace analytes

Conducting Polymer-MIP Artificial Enzyme Electrode

A

B

NPEDMA nanostructures mediate conduction of electrons between the catalytic sites in the MIP and the electrode. The MIP exhibits Michaelis-Menton kinetics and competitive inhibition properties similar to those of the enzyme tyrosinase (polyphenol oxidase)

Berti, F., Todros, S., Lakshmi, D., Chianella, I., Ferroni, M., Piletsky, S.A. Turner, A.P.F. and Marrazza, G (2010) Quasi-monodimensional polyaniline nanostructures for enhanced molecularly imprinted polymer-based sensing. Biosensors and Bioelectronics 26, 497–503

Putting the “Bio” into Printed Electronics

Dry Phase Patterning - Metallic (Al) foil laminates - Patterning through dry

process - Up to 150 m/min - Web width: 300 mm - Environmentally friendly

Dimatix Inkjet - Bioprinting: DNA, lipids, proteins - Ag ink, PEDOT:PSS ink - 1-10 pL drops - Min ink amount to be printed: 0.5 ml - Substrate thickness 40 µm-25 mm - Substrate heating up to 60 °C

NILPETER Roll-to-roll label printer for screen & flexo - 5 printing stations (flexo/screen) - Dryers (hot air/UV curing)

- Web width: 180-330 mm - Web velocity: speed 3-180 m/min - Die cutting - Lamination - Min feature size: 100 µm - Flexible substrates

Flat bed screen printer & Conveyor feed dryer - Rigid/flexible substrates - Vacuum substrate table - Substrate size <DIN A6-DIN A3 - Pneumatic driven filler and squeegee - Registration accuracy ~50 µm - Minimum feature size: 100 µm - Min ink 150 ml/printing unit (screen) - Hot air/UV/IR drying units

1 Roll-to-roll label printer (flexo, screen) 2 Flat-bed screen printers 1 Conveyor feed dryer 2 UV dryers 2 Ink Jet printers 1 Dry Phase Roll-to-roll patterning machine

• Kliche making • Inspection and quality control • Environmental testing • Ink development and manufacturing • Design

Printable components developed by Acreo, Linköping University (and partners)

Monochrome Emissive or reflective Paper or plastic 1-3 V (reflective) 110 V (emissive)

Displays

All-printed , Mn -ZnO Capacity: 1-10 mA h (www.enfucell.com)

Enzyme electrodes Electrolyte sensors Piezo and Pyroelectrical Humidity, temperature, heat

,pressure, vibrations Electrochemically &

electrolyte gated OFET 0.5 – 1.5 V Switch time: 10-6 to 10-2 s

Non-volatile and flexible Based on ferroelectric

polymers Retention time: > 10

years 109 cycles Read/write: ms Fully qualified (www.thinfilm.se)

Metal Al, Cu 1 kHz – 1 GHz Resolution: 100 mm Material thickness: 1-10

mm Fully qualified (www.webshape.se)

All-printed on antennas/electrodes

High frequency Performing

qualification

Transistors

Sensors

Batteries

Memories Antennas

Diodes

Integrated Printed Disposable Biosensor

21/01/2013

Printed Transistors For Display control

Silicon chip

Printed Display

Biosensor Sample Deposition

Printed Battery

Conclusions • Biosensors have achieved considerable success in both the commercial and academic arenas and the need for new, easy-to-use, home and decentralised diagnostics is greater than ever

• Amperometric biosensors continue to dominate the market

• Electrochemical biosensors are available for a range of decentralised analyses, including medical, food and environmental applications

• Array-based fluorescence sensors are now well established for genomic and proteomic assays

• Label-free assays based on SPR dominate the laboratory affinity sensor market especially in drug development

• The search continues for a new disruptive technology!

www.ifm.liu.se/biosensors

5.602

2011

Turner, A.P.F. (2013). Biosensors: sense and sensibility. Chemical Society Reviews (in press) Newman, J.D. and Turner, A.P.F. (2008). Historical perspective of biosensor and biochip development. In: Handbook of Biosensors and Biochips (Eds R. Marks, D. Cullen, I. Karube, C. Lowe and H. Weetall) John Wiley & Sons. ISBN 978-0-470-01905-4 www.wiley.com/go/biosensors Newman, J.D. and Turner, A.P.F. (2005). Home blood glucose biosensors: a commercial perspective. Biosensors and Bioelectronics 20, 2435-2453.

62

Some Web Sites www.ysilifesciences.com www.minimed.com/products/guardian www.glucodr.com (video) www.accu-chek.com.au/au/products/metersystems/advantage.html www.bayerdiabetes.com/sections/ourproducts/meters/breeze2 www.lifescan.com/ www.abbottdiabetescare.com/index.htm www.biacore.com/lifesciences/index.html www.novabiomedical.com/company/ !!! www.abbottpointofcare.com/ www.moleculardevices.com/Products/Instruments/Threshold-System.html www.ifm.liu.se/biosensors