1. Biosensor
서울대학교 화학생물공학부
박 태 현

2. Biosensor
Device that uses a biological element as an intimate part of a sensor
Organism-based biosensor
Cell-based biosensor
Biomolecule-based biosensor

3. Organism-Based Biosensor
Human – 5 senses
(2 chemical senses)
Canary – sensing for methane and carbon
monooxide in coal mine
(more than 100 years ago)
Fish, Daphnia – water quality
Dog – drug, explosive

4. Cell-Based Biosensor Magnetic bacteria – water quality
Olfactory biosensor – smell sensing
Organism- or cell-based biosensors are not specific for certain compounds but are capable of responding to a wide range of biologically active compound and offers the potential to gather information content.

5. Biomolecule-Based Biosensor
Protein : enzyme, antibody, receptor
DNA, RNA
Aptamer

6. Olfactory and Taste Biosensor
Using Human Receptors 6

7. in Physiology or Medicine Discovery of Smell Sensing Mechanism
2004 Nobel Prize
in Physiology or Medicine
Discovery of Smell Sensing Mechanism

8. Olfactory System
General Smell
Nasal Cavity
Sexual
Information

9. Olfactory System
Olfactory Bulb
Olfactory Epithelium
Vomeronasal Organ

10. Olfactory Receptor
Brain
Bone
Olfactory Epithelium
Olfactory
Receptor

11. Olfactory Signal Transduction
Receptor

12. Receptor and Cell for Biosensor
Receptor-Based Biosensor
E. coli
HEK-293 (Human Cell)
Cell-Based Biosensor
HEK-293 (Human Cell)

13. Expression of Receptor in E. coli
Western Blot
Sung, Ko, and Park, Biosensors and Bioelectronics, 21, (2006)
Kim et al., Advanced Materials, 21, (2009)

14. Purification of Receptor
Song, Lee, Oh, and Park, Current Microbiol., 21, (2009)

15. Expression of Receptor
on Surface of HEK-293 Cell
Western Blot
84 KDa
79 KDa
118 KDa
(I7)
Ko, and Park, Biological Chemistry, 387, (2006)

16. Development of Biosensor
Cell-Based
Receptor-Based
Biological Recognition Element
(Primary Transducer)
Whole Cell
Biochip Hardware
Platform
(Secondary Transducer)
Sensor Platform

17. Primary Transducer Receptor-Based Receptor expressed in E. coli
Receptor expressed on HEK-293 cell surface
Cell-Based
HEK-293 cell with receptor expressed on the cell surface

18. Secondary Transducer Nanotube QCM (Quartz Crystal Microbalance)
SPR (Surface Plasmon Resonance)
Microelectrode
Nanotube

19. QCM (quartz crystal microbalance)
: Odorant
: Olfactory receptor protein
: Dried cell
: Coated gold
: Quartz crystal
ΔF = -F Δm / (A r t)

20. SPR G
Golf
PLC G
Odorant Solution
Ca2+
Ca2+
IP3
Ca2+
PIP2
Ca2+ ER

21. Planar Microelectrode
Glass substrate
Buffer
Recording electrode
Odorant injection
Cell
Oscilloscope OR
Reference
electrode

22. Carbon Nanotube

23. Receptor & Carbon Nanotube
Olfactory Receptor
Carbon
Nanotube
Electrodes

24. Current Change
Kim et al., Advanced Materials, 21, (2009)

25. Conducting Polymer Nanotube

26. Receptor & Conducting Polymer Nanotube
Olfactory Receptor
Nanotube

27. Sensitivity
Yoon et al., Angewantde Chemie, 48, (2009)

28. Selectivity Yoon et al., Angewantde Chemie, 48, 2755-2758 (2009)
Amyl Butyrate (AB)
Butyl Butyrate (BB)
Hexyl Butyrate (HB)
Propyl Butyrate (PB)
Yoon et al., Angewantde Chemie, 48, (2009)

29. Dose-Dependent Relationship
Yoon et al., Angewantde Chemie, 48, (2009)

30. Signals of Artificial Olfactory Cells
Human genomic DNA
Cloning
Expression
Indole
10 μM
100 μM
1000 μM
Amyl butyrate

31. Sense of Taste

32. Human Taste System Salty and Sour Tastes
Ions interact with ion channels.
Bitter, Sweet and Umami Tastes
Detected by receptor-mediated signaling
like the smell sensing mechanism

33. Bitter Taste Receptor About 25 genes
Similar structure with olfactory receptors
Bitter Tastant
hTAS2R

34. Sweet Taste Receptor Heterodimer Sugars, Aspartame Neotame, Sucralose
TAS1R2
TAS1R3
Sugars, Aspartame
Neotame, Sucralose
Monellin etc.
Heterodimer

35. Umami Taste Receptor
MSG
Heterodimer
TAS1R1
TAS1R3

36. Taste Sensor Using Bitter Taste Receptor
(Bitter) (Sweet) (Umami)

37. Dose-Dependent Relationship
PTC (Bitter), PROP (Bitter), MTU (Mild bitter)

38. Bitter Taste Receptor (hTAS2R38)
Non-Taster
MLTLTRIRTVSYEVRST [FLFISVLEFAVGFLTNAFVFL] VNFWDVVKRQPLSNSDC [VLLCLSISRLFLHGLLFLSAI] QLTHFQKLSEPLNHSYQA [IIMLWMIANQANLWLAACLSL] LYCSKLIRFSHTFLICLASWVSRKISQ [MLLGIILCSCICTVLCVWCFF] SRPHFTVTTVLFMNNNTRLNWQIKDLN [LFYSFLFCYLWSVPPFLLFLV] SSGMLTVSLGRHMRTMKVYTRNSRDPSLEAHIKALKSLVS [FFCFFVISSCAAFISVPLLIL] WRDK [IGVMVCVGIMAACPSGHAAVL] ISGNAKLRRAVMTILLWA QSSLKVRADHKADSRTLC
MLTLTRIRTVSYEVRST [FLFISVLEFAVGFLTNAFVFL] VNFWDVVKRQALSNSDC [VLLCLSISRLFLHGLLFLSAI] QLTHFQKLSEPLNHSYQA [IIMLWMIANQANLWLAACLSL] LYCSKLIRFSHTFLICLASWVSRKISQ [MLLGIILCSCICTVLCVWCFF] SRPHFTVTTVLFMNNNTRLNWQIKDLN [LFYSFLFCYLWSVPPFLLFLV] SSGMLTVSLGRHMRTMKVYTRNSRDPSLEAHIKALKSLVS [FFCFFVISSCVAFISVPLLIL] WRDK [IGVMVCVGIMAACPSGHAAIL] ISGNAKLRRAVMTILLWA QSSLKVRADHKADSRTLC

39. PTC (Bitter Tastant)

40. Development of Artificial Sense
Human Olfactory Receptor Genes
Whole set of genes
potential candidates
Human Taste Receptor Genes
Bitter taste receptor (about 25 genes)
Sweet taste receptor
Umami taste receptor

41. Natural Sense & Artificial Sense

42. Applications Standardization of smell
(classification, code for each smell …)
Smell Industry
(perfume, cosmetics, wine…)
Disease diagnosis
Monitoring of food freshness
Environment monitoring by smell sensing
Process monitoring by smell sensing
Public safety (explosive, toxicant)
Smuggling (drugs…)
Security (smell sensing security system)
New sweeteners and umami materials