Biosensors-thetechnologythatcanrevolu3onisediagnos3cs

AnthonyP.F.TurnerBiosensorsandBioelectronicsCentre,LinköpingUniversity,Sweden

anthony.turner@liu.se h@ps://liu.se/en/employee/an@u13

ITinCareDay2017,5December2017,Münchenbryggeriet,Stockholm.

Biosensors and Bioelectronics Centre, Linköping University

Established at the end of 2010, the Centre’s ambition is to

harness the many synergies, fundamental research activities

and innovation in Sweden to facilitate the creation of the next

generation of bioelectronic devices and to support the national

and worldwide development of the field.

•  Biosensors and Bioelectrochemistry

•  Bioelectronics and Actuators (Soft Robotics)

•  Functional Materials and Biointerfaces

•  Smart Materials and Biodevices

•  Synthetic Receptors and Imprinted Polymers

Founder members of the Nordic Sensor Realisation Centre in collaboration with Skåne Innovation and Malmö University

Biosensors - the technology that can revolu<onise diagnos<cs

•  Frictionless generation and movement of health information: the Internet of Living Things (IoLT)

•  The role of biosensors

•  Printed bioelectronics

•  Next generation Diabetes management

•  Preventing acute kidney injury

•  Conclusions

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SJ is the first travel company in the world to allow travellers to use chip implants as <ckets

www.mynewsdesk.com/se/sj/pressreleases/sj-world-premieres-the-microchip-ticket-1978523 (22 May 2017)

In-body sensors US$1 trillion healthcare opportunity

“There is an obvious omission from the above list: there is presently no way to measure aspects of blood chemistry, or other parameters that can only be measured by sensor technology that resides inside the body.”

Gate & speed Head impact (sports)

Heart, skin, breathing Exposure to sun

Body temperature Biomechanical data

Calories & distance Altitude & rate ascent

Sleep patterns Location (3D)

Brainwaves & control Speed & acceleration

Posture Repetitive activity

Wearable Technology: 2014. Company Profiles, Market Analysis & Forecasts. www.generatorresearch.com

Applica<ons 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.

World market for biosensors (US$m)

>76 000 papers published on biosensors; 75% of $15b market is still for glucose, but we are on the cusp of a new era

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Turner, A.P.F. (2013) Biosensors: sense and sensibility. Chemical Society Reviews 42 (8), 3184-3196.

Internet of Living Things (IoLT) - Some key drivers

Healthcare spending as a percentage of GDP is growing unsustainably: USA 17.1%, Sweden 11.9%, EU 10% (WHO: 2014) •  Individual choice and ownership of data

•  Consumer-driven delivery with evidence-based reimbursement

•  Decentralisation and radical restructuring of services

•  Personalised Medicine

•  Mobility

As much data as all of humanity as a whole created from the dawn of civilisation until 2013, is now being created every other day.

Amperometric Glucose Sensors

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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.

MediSense ExacTech™ 1987

ClarkandLyons(1962)

Machine manufacture

Sheet printer for display and circuitry manufacturing

R2R label printer for display and circuitry manufacturing

Automatic sheet based screen printer (< 240 sheets/h) Solvent, water and UV inks Automated sheet handling with liner 50 – 500 um sheet thickness

–  Inkjet ( variety of print heads) –  Aerosoljet (Optomec) –  Novacentrix Xenon flash curing

Flip chip bonder. Pick and place of IC, battery, etc. for hybrid systems

Printed Electronics Arena at our Norrköping campus

Integrated biosensor plaQorm

●Display

●Sensors

●PushBu@on

●Ba@ery

●ChipformeasurementsLMP91000

●Chipforcommunica3onPIC24F16KA101

●PrintedInter-connects&resistors

Components

Beni, V., Nilsson, D., Arven, P., Norberg, P., Gustafsson, G. and Turner, A.P.F. (2015). Printed Electrochemical Instruments for Biosensors. ECS Journal of Solid State Science & Technology 4, 3001-3005.

Printed layers

1.Pedotlayerforthedisplay

2.Electrolytelayerforthedisplay

3.Carbonlayer

4.Silverlayer

5.Chipmoun3ng

6.Sensormoun3ng

7.Ba@erymoun3ng

8.Graphicaloverprint

Beni, V., Nilsson, D., Arven, P., Norberg, P., Gustafsson, G. and Turner, A.P.F. (2015). Printed Electrochemical Instruments for Biosensors. ECS Journal of Solid State Science & Technology 4, 3001-3005.

The first demonstra<on

14Enzyme electrodes for glucose, lactate, creatinine, β-hydroxybutyrate etc. demonstrated ; Applicable to heavy metals, gas sensors and in combination with lateral-flow immunosensors.

Envisaged formats (concepts)

Applica<ons

Next genera<on diabetes management •  Diabetes is a major worldwide health problem which currently has a no reliable cure, the ONLY

current option is better management

•  Existing home-based monitors focus on Glucose. Glucose measurement alone cannot improve diabetes management

•  Glucose fluctuation is the manifestation of metabolic perturbations, but there is no device to understand the holistic health status of diabetic patients and consequent diabetic complications

•  Next generation devices for collective data analysis will combine glucose and other insulin related multi metabolites to generate meaningful real time data reflecting the pathophysiology of patients.

Preven<ng Acute Kidney Injury - A Priority

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•  AcuteKidneyInjury-Asuddenlossofkidneyfunc3onwithinhoursordays•  AKIacommon,seriousandharmfulillness-a“silentkiller”•  UKenquiryintopa3entoutcomesshowed43%delayinrecogni3on•  Upto100,000UKdeathsayear,athirdcouldbeprevented•  CostsintheUKalone£500m/yr•  AGlobalissue;AKIis1003mesmoredeadlythanMRSA

Lackofknowledgeaboutourkidneysbythe

publiccouldleadtoriseinunnecessarydeaths

duetoacutekidneyinjury(AKI)

ThinkKidneysistheNHScampaigntoimprovethecare

ofpeopleatriskof,orwith,acutekidneyinjury.

TheClinicalChallenge:

ThecurrentclinicalpathwayformonitoringrenalfuncConishospitalbased,disorganisedandinefficientresulCngindelayeddiagnosis,needlessexpense

andwasteofresourcesforpaCentandhealthcaresystem

Crea<nine Alert Device

•  Simpletooperate•  Painandblood-free•  Readoutinminutes•  Providesreassurancetopa3entsorearlywarning(without

clinicvisit)•  ISFisadvantageoustomeasureanalytes(e.gBloodless,

cheapersensors)•  Affordable •  ReducingoverallhealthcarecostofmonitoringkidneyfuncKon

*DesignConcept

Crea<nine Alert Pathway

Action is triggered by creatinine rise over several readings

Key Features No Travel; Can be performed anywhere ;

Simplified algorithm ; Early Recognition ; Immediate intervention

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Health Economic Modelling

Without Monitoring Using Creatinine Alert

Modelling shows that the device will prevent hospital admissions and significantly reduce hospital costs for renal care

HCDEconomics

Conclusions

•  A frictionless approach empowers users to efficiently manage the health of the elderly anywhere and anytime, while providing them with confidence in the integrity of data and the security of any automated actions.

•  Implicit in this vision is the ability to supplement advanced information management with real-time measurements of both individuals and their immediate environment.

•  The recent boom in wearable sensors has highlighted the potential of continuous measurement and the appetite amongst users for personalised information.

•  The major bottleneck at the current time is the availability of reliable sensors that directly measure key biochemical parameters, which are essential to higher level algorithms for personalised management of health.

•  The future importance of biosensors in health management is clear and we need to bring engineers, clinicians, management and companies with new business models together to implement effective ways forward.

https://liu.se/en/employee/anttu13

Impact Factor 7.476

12-15June2018Hya@RegencyMiamiinMiami,Florida,USA