biosensors part one

“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 Biosensors Ingemar Lundström Department of Physics, Chemistry and Biology, Linköping University May 22, 2012 “Second part” : Two successful technologies • Electrochemically based glucose monitors • Biospecific interaction analysis with SPR • Microcantilevers • Molecular imprints • Nanoparticles (Au, silica, ) • Nanotubes • Graphene • Ion sensitive field effect devices • “Forgotten items” 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) Transducer Electronics Electrochemical Optical Thermometric Piezoelectric Magnetic Micromechanical Electrochemical Optical 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 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 [...]...“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... – protein coupled receptors (prevalent also in humans for signaling and regulation: for hormones and neurotransmitters, olfaction, taste and vision,… ) Important targets for (new) drugs Native receptors Melatonin Aggregation MSH Non-native receptor β2 –adrenergic Dispersion Sensitivity also to adrenergic hormones, β2 –adrenergic drugs: Adrenaline, formoterol, salbutamol, (cell line from Arena Pharmaceuticals,... 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 Selectivity of living systems: Simple to modify Genetic modification: Melanophores expressing OP3 control Af/Ai-1 0.1 0.0 -0.1 -0.2 -12 -11 -10... (”brute force method”) Surviving transfected cells simple to spot: React on morfin IFM - Applied Physics S 581 83 Linköping, Sweden SUMMARY: Use of melanophores for Drug screening/evaluation Biosensing: hormones; toxins; inhibitors Environmental monitoring Arrays of different genetically modified cell cultures for biochemical imaging Combinations of natural nanosystems and micro/nanotechnology (Arrays of... Physics S 581 83 Linköping, Sweden 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 . Lab-on-a-chip • Whole cell biosensing Biosensors Ingemar Lundström Department of Physics, Chemistry and Biology, Linköping University May 22, 2012 “Second part : Two successful technologies. 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. The two most successful biosensors to date: • Mediated amperometric glucose biosensor • Real-time bioaffinity interaction analysis “First part • Introduction to biosensors • QCM – principle