biosensors part one

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., Karub

“First part”

• Introduction to biosensors

• QCM – principle

• QCM – application (drugs and explosives)

• Fluorescence – molecular beacons

• DNA detection/DNA chips

“Second part” : Two successful technologies

• Electrochemically based glucose monitors

• Biospecific interaction analysis with SPR

Economic Impact of Healthcare

• Healthcare spending is growing fast: 15% of GDP for USA, 8% 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 Biosensor

Bioreceptor

Transducer

GAS!!!

5

“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

The Biosensor

(Bio)receptor(affinity or catalytic)

Thermometric Piezoelectric Magnetic Micromechanical signal

Analytes

Tissues Microorganisms Organelles

Cell receptors

Enzymes Antibodies Nucleic acids Synthetic receptors

The Biosensor

Type of biosensors

Affinity based (molecular recognition)

• Antigen – antibody

• Receptor – ligand (drugs, neurotransmitters,…)

• DND, RNA – complementary strands

Reaction based

• Enzymes

• Whole cells

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) (mass changes)

• Magnetic: e.g magneto resistive devices, paramagnetic labels etc

• Micromechanical: e.g resonating beam structures (mass changes)

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

– Security and defence

The two most successful biosensors to date:

• Mediated amperometric glucose biosensor

• Real-time bioaffinity interaction analysis

“First part”

• Introduction to biosensors

• QCM – principle

• QCM – application (drugs and explosives)

• Fluorescence – molecular beacons

• DNA detection/DNA chips

• Aptamers

• Lab-on-a-chip

• Whole cell biosensing

Quartz crystal microbalance

In liquid (QCM – D: delta eta)

Biosensor Applications AB: technology

for drug and explosives detection

Biosens 600

www.biosensor.se

Border control Security

Correctional & Police authorities Rehabilitation & Workplace control

Border control

Security

Correctional & Police authorities

Rehabilitation & Workplace control

Small molecules: Drugs and explosives

Use of displacement reaction to detect small molecules

Slides from Biosensor Applications: Courtesy of Dr.Per Månsson

DNA - chips

Affymetrix: Photochemistry and combinatorial masks

to produce oligonucleotides

Molecular beacon- principle

Aptamers –protein binding oligonucleotides

SELEX PROCESS

FRET: Fluorescence resonance energy transfer Blue light causes emission (green) which excites

neighbouring fluorophore (red)

Biosensing with aptamers

Optical (FRET) Electrochemical

Protein molecule

Lab-on-a-chip: Microfluidics plus optical

(fluorescence,microscopy, SPR,…), electrochemical detection…

Daniel Filippini (May 3 lectures)

IFM - Applied Physics

S 581 83 Linköping, Sweden

Xenopus laevis (an African frog)

Melanophore

IFM - Applied Physics

S 581 83 Linköping, Sweden

G – protein coupled receptors (prevalent also in humans for signaling and regulation: for

hormones and neurotransmitters, olfaction, taste and vision,… )

Important targets for (new) drugs

Sensitivity also to adrenergic

hormones, β2 –adrenergic drugs:

Adrenaline, formoterol, salbutamol,

(cell line from Arena Pharmaceuticals,

San Diego, CA., USA) Large sensitivity is obtained for

molecules acting early in the biochemical cascade [(sub)femtomolar]

e.g pertussis (whooping cough) toxin

IFM - Applied Physics

VERSATILITY OF NATURAL NANOSYSTEMS:

Reacts on agonists (“the analytes”), antagonists, toxins, inhibitors,…

at several positions in the “transduction” chain

This kind of versatility has not (yet) been achieved with man made biosensors

IFM - Applied Physics

S 581 83 Linköping, Sweden

Genetic modification: Melanophores expressing OP3

control

stimulated

-12 -11 -10 -9 -8 -7 -6 -5 -0.2

-0.1 0.0 0.1

IFM - Applied Physics

Biophysics on (single) cell level

Advantages: Self replication; functional nano machinery; versatility Disadvantages: Supply and distribution

Acknowledgements:

Prof Anthony Turner (slides regarding background)

Dr Per Månsson (Biosensor Applications slides)

Microcantilevers

(resonating thin

silicon structures)

Biosensors & Bioelectronics Centre

The Centre’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

Prof Anthony P F Turner (director),

Prof Ingemar Lundström, Prof Fredrik Winquist,

Dr Claes Nylander,

Dr Edwin Jager (Assistant Prof),

Dr Ashutosh Tiwari (Assistant Prof)

Dr Valerio Beni (Assistant Prof

Key targets:

• Nanobioreactors and smart supramolecular structures

• Semi synthetic and synthetic ligands – Plastic antibodies & catalytic electrodes

• Bioinspired nanotechnolgies for sensing and therapy

• Targeted imaging and release technologies

• Controlled surfaces for cellular interaction

• In vivo devices for regenerative medicine

• Arrays, biomimetics and tele-interfaces