NANOBIOSENSORSbiosensors on the nano-scale size
BIOSENSORS• A device incorporating a biological sensing  element either intimately connected to or  integrated within a tr...
Biosensor Development• 1916 First report on the immobilization of proteins: adsorption of  invertase on activated charcoal...
Theory
Biosensors                 Bio-receptor   Transducer          Molecular                     OpticalDNA                    ...
Bio-receptor/ analyte complexes• Antibody/antigen interactions,• Nucleic acid interactions• Enzymatic interactions• Cellul...
Signal transduction methods1. Optical measurements - luminescence,   absorption, surface plasmon resonance2. Electrochemic...
Electrical sensing  Nano-bio interfacing  how to translate the  biological information onto electrical signal ?• Electroc...
Electrical sensorsFET based methods – FET – Field Effect Transistors     ISFET – Ion Sensitive FET     CHEMFET – Chemic...
Nanowires Biosensors             Field Effect        Nanobiosensors (FET)• Functionalize the nano-wires• Binding to bio-mo...
Nanowire Field Effect Nanobiosensors (FET)                    Sensing Element   Semiconductor channel                     ...
NANOWIRE
NANOTUBE
NW grow across gap between electrodesGrowing NW connect to the second electrode
Form trench in Si and   NW grows        NW connects to oppositeDeposit catalyst        perpendicular   sidewall
Schematic shows twonanowire devices, 1 and 2,where the nanowires aremodified with differentantibody receptors.Specific bin...
Other optical methods• Surface Plasmon Resonance (SPR)
Surface Plasmon Resonance (SPR)
Mechanical sensingCantilever-based sensing
Bio-molecule sensing                        Detection of biomolecules by                        simple mechanical transduc...
resonance frequency mass-sensitive detector                                                                             A ...
Magnetic sensing• magnetic fields to sense magnetic nano-  particles that have been attached to biological  molecules.
Stabilization of Magnetic Particles with various Streptavidin Conc.  Ligand-functionalized                                ...
Magnetic sensing                                            Sensing plateMagnetic head                                    ...
Magnetic-optic sensing                      Polarization   Sensing plate             Optics                      DetectorL...
Applications of NanobiosensorsBiological Applications• DNA Sensors; Genetic monitoring, disease• Immunosensors; HIV, Hepat...
Optical detection of analyte binding
Fluorescence sensors• Biological materials – using photo-biochemical  reaction –   – Photo induced luminescence – photolum...
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
7 nanosensors
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7 nanosensors

  1. 1. NANOBIOSENSORSbiosensors on the nano-scale size
  2. 2. BIOSENSORS• A device incorporating a biological sensing element either intimately connected to or integrated within a transducer.• Recognition based on affinity between complementary structures like: enzyme-substrate, antibody-antigen , receptor- hormone complex.• Selectivity and specificity depend on biological recognition systems connected to a suitable transducer.
  3. 3. Biosensor Development• 1916 First report on the immobilization of proteins: adsorption of invertase on activated charcoal.• 1956 Invention of the first oxygen electrode [Leland Clark]• 1962 First description of a biosensor: an amperometric enzyme electrode for glucose. [Leland Clark, New York Academy of Sciences Symposium]• 1969 First potentiometric biosensor: urease immobilized on an ammonia electrode to detect urea. [Guilbault and Montalvo]• 1970 Invention of the Ion-Selective Field-Effect Transistor (ISFET).• 1972/5 First commercial biosensor: Yellow Springs Instruments glucose biosensor.• 1976 First bedside artificial pancreas [Clemens et al.]• 1980 First fiber optic pH sensor for in vivo blood gases.• 1982 First fiber optic-based biosensor for glucose• 1983 First surface plasmon resonance (SPR) immunosensor.• 1987 Launch of the blood glucose biosensor[ MediSense]
  4. 4. Theory
  5. 5. Biosensors Bio-receptor Transducer Molecular OpticalDNA Bio-luminescenceProtein PhotoluminescenceGlucose ElectricalEtc….. Electronic Cell Electrochemical Bio-mimetic Mechanical Resonance Bending
  6. 6. Bio-receptor/ analyte complexes• Antibody/antigen interactions,• Nucleic acid interactions• Enzymatic interactions• Cellular interactions• Interactions using bio-mimetic materials(e.g. synthetic bio-receptors).
  7. 7. Signal transduction methods1. Optical measurements - luminescence, absorption, surface plasmon resonance2. Electrochemical - potentiometric, amperometric, etc.3. Electrical – transistors, nano-wires, conductive gels etc.4. Mass-sensitive measurements- surface acoustic wave, microcantilever, microbalance, etc.).
  8. 8. Electrical sensing Nano-bio interfacing  how to translate the biological information onto electrical signal ?• Electrochemical – Redox reactions• Electrical – FET (Nano wires; Conducting Electro-active Polymers)
  9. 9. Electrical sensorsFET based methods – FET – Field Effect Transistors  ISFET – Ion Sensitive FET  CHEMFET – Chemically Sensitive FET  SAM-FET – Self Assembly Monolayer Based FET K Corrente elettrica
  10. 10. Nanowires Biosensors Field Effect Nanobiosensors (FET)• Functionalize the nano-wires• Binding to bio-molecules will affect the nano-wires conductivity.
  11. 11. Nanowire Field Effect Nanobiosensors (FET) Sensing Element Semiconductor channel (nanowire) of the transistor.• The semiconductor channel is fabricated using nanomaterials such carbon nanotubes, metal oxide nanowires or Si nanowires.• Very high surface to volume radio and very large portion of the atoms are located on the surface. Extremely sensitive to environment
  12. 12. NANOWIRE
  13. 13. NANOTUBE
  14. 14. NW grow across gap between electrodesGrowing NW connect to the second electrode
  15. 15. Form trench in Si and NW grows NW connects to oppositeDeposit catalyst perpendicular sidewall
  16. 16. Schematic shows twonanowire devices, 1 and 2,where the nanowires aremodified with differentantibody receptors.Specific binding of a singlevirus to the receptors onnanowire 2 produces aconductance change(Right) characteristic of thesurface charge of the virusonly in nanowire 2. Whenthe virus unbinds from thesurface the conductancereturns to the baselinevalue.
  17. 17. Other optical methods• Surface Plasmon Resonance (SPR)
  18. 18. Surface Plasmon Resonance (SPR)
  19. 19. Mechanical sensingCantilever-based sensing
  20. 20. Bio-molecule sensing Detection of biomolecules by simple mechanical transduction: target molecule - cantilever surface is covered receptor molecule by receptor layer gold (functionalization) SiNx cantilever - biomolecular interaction between receptor and target molecules (molecular recognition) target binding deflection d - interaction between adsorbed molecules induces surface stress change bending of cantilever
  21. 21. resonance frequency mass-sensitive detector A 1 kf1 2 m eff f1 f1 f A 1 k mf2 2 m eff m f2 f2 f A mass sensitive resonator transforms an additional mass loading into a resonance frequency shift mass sensor B. Kim et al, Institut für Angewandte Physik - Universität Tübingen
  22. 22. Magnetic sensing• magnetic fields to sense magnetic nano- particles that have been attached to biological molecules.
  23. 23. Stabilization of Magnetic Particles with various Streptavidin Conc. Ligand-functionalized Magnetic nano - particle Analyte 10 min reaction None 1 ng/ml 100 ng/ml 100 g/ml Cleaning 5 min depositionAnti-analyte Antibody T. Osaka, 2006
  24. 24. Magnetic sensing Sensing plateMagnetic head Activated pixel Idle pixel Magnetic field sensor Magnetic sensing
  25. 25. Magnetic-optic sensing Polarization Sensing plate Optics DetectorLightsource Activated pixel Idle pixel Polarizer
  26. 26. Applications of NanobiosensorsBiological Applications• DNA Sensors; Genetic monitoring, disease• Immunosensors; HIV, Hepatitis,other viral diseas, drug testing, environmental monitoring…• Cell-based Sensors; functional sensors, drug testing…• Point-of-care sensors; blood, urine, electrolytes, gases, steroids, drugs, hormones, proteins, other…• Bacteria Sensors; (E-coli, streptococcus, other): food industry, medicine, environmental, other.• Enzyme sensors; diabetics, drug testing, other.Environmental Applications• Detection of environmental pollution and toxicity• Agricultural monitoring• Ground water screening• Ocean monitoring
  27. 27. Optical detection of analyte binding
  28. 28. Fluorescence sensors• Biological materials – using photo-biochemical reaction – – Photo induced luminescence – photoluminescence – example: Green Fluorescent Proteins (GFP) – Chemically induced florescence – Bioluminescence - Example: Lux• Physical effects – Luminescence from nano- structured materials – Semiconductor nano-particles,
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