4. Luminescent molecular switchable systems can gather and process information Optical response Chemical stimulus level Analog region Digital 1 Digital 0
6. Org. Biomol. Chem. 2008, 6 , 2468 OFF state Spacer h PET Fluorophore Receptor ON state h PET h M + Spacer Fluorophore Receptor The PET design generalized in Colombo/Belfast Chem. Rev . 1997, 97 , 1515
9. Anslyn, Demas Kotschy, Kele Bojinov, Grabchev Lu Sung Suzuki, Holdt, Plenio, Sauer Nielsen, Kilsa Yunus, Hofkens Hall, Watkinson Meallet, Mallet, Vicens Ghosh Zhu, Wang, Kim, Hong, Zuo, Guo, Huang, Liu, Yao, Fu De Costa Wainwright Yoshida, Ooyama, Sasamoto Todd Nakamura Saleh Seeberger Mashraqui Hancock Ramamurthy He, Ji You Houston Heagy Cho Burdette Lin Magri Rudkevich Sango Toyooka
10. J. Mater. Chem . 2005, 15 , 2640 ‘ Off-On’ sensors selective for Na + and K + Jim Tusa, Marc Leiner Hua-Rui He, Mark Mortellaro (Roche)
11. hydrophilic polymer O O O N H N O O N O N O N O O O O hydrophilic polymer N O O O O O N H N O O O Sodium Potassium receptor hydrophilic polymer hydrophilic polymer spacer fluorophore linker
12. Disposable Cassette and OPTI Critical Care Analyzer (CCA) Na + K + Ca ++ or Cl - CO 2 O 2 pH tHb 60M USD Cassette sales ambulances, hospitals, GP and vet surgeries
13. J. Chem. Soc., Chem. Commun . 1985, 1669 N Et 2 N Et 2 O N N N H N Et 2 Fluorescent PET pH Sensors LysoSensor TM Blue and Green (Molecular Probes) DAYA RUPASINGHE NIMAL GUNARATNE
14. Cancer cells respond to radiation by developing acidic vesicular organelles. Sensor: Lysosensor Blue Paglin et al (Sloan-Kettering Center, NY) Cancer Res . 2001, 61 , 439 18 m
15. Robots for Mapping Small Nanospaces Seiichi Uchiyama (University of Tokyo) Kaoru Iwai (Nara Women’s University) Angew. Chem. Int. Ed . 2008, 47 , 4667
17. A Useful Robot Mars Rover ‘ Opportunity’ January 2005 ‘ Phoenix’ May 2008
18. fluorophore spacer receptor ICT fluorophore spacer receptor H H + fine positioner gross positioner N S O O N O N N H N O O H 10
19. . S 1 thexi S 1 thexi S 0 FC S 0 FC non polar solvent polar solvent + + E . Solvent Polarity Effect on ICT Fluorescence hexane CH 2 Cl 2 CH 3 OH I f
20. 450 500 550 600 650 700 750 800 0 pH Wavelength (nm) I F
21. 20 30 40 70 50 60 0 – 0.4 – 0.8 – 1.6 – 1.2 20 30 40 80 0 – 0.4 – 0.8 – 1.2 p p 10 0 – 0.4 – – – 10 20 40 50 60 70 – – – 1.2 p Δ p K a Δ K a 80 O O H 10 O O H O H O H O O H Polarity ( ε ) Polarity ( ε )
23. Kim, Yoon, Jang, Choi, Zhang Rurack, Desouter-Lecomte, Lehn Bouas-Laurent, Desvergne, Bassani, McClenaghan Balzani, Credi, Venturi, Gentili Bharadwaj, Khan Samanta Adleman, Ghadiri, de Silva, Pina, Pischel Garcia- Espana, Brown Raymo, Zhu Akkaya Ji Gunnlaugsson, MacDonaill Birge, Stojanovic, Seeman, Avouris, Katz, Sokolov, Privman Langford Stefanovic, Wasielewski, Levine, Speiser, Shanzer, Willner, Shabat, Ashkenasy, Lotan, Van der Boom, Rabani, Shapiro, Eichen Konermann Remacle Reif Diederich, Constable, Schluter de Silva Wettig Perez- Jin Schneider, Uchiyama, Aida, Leigh, Callan James, Stoddart, Parker, Beer, Chin, Jones, Williams, Tucker, Zauner, Fallis, Aldridge, Steed Szacilowski Chiu Gust, Moore Steer, Iwai, Okamoto, Sugimoto, Hirai, Redmond, Miranda Kimura Miyashita, Suzuki Tian, Wang, Jin, Lu Lerner, Barbas, Wang Wu Toma Conrad, Liu Bazan Andreasson, Sun Liu Tanaka, Fujita, Breaker, Das Kumar Lu Zhang, Zhu, Yan, Li, Fu, Huang, Zhang, Mihara, Nojima, Tomizaki, Matsui, Pischel Fujimoto, Akashi Qian, He, Yu Yang Benenson Stoddart, Vasquez- Lopez Yuan, Fang, Voegtle Shi, Tong, Wang Kinbara, Ariga, Magri Yurke Yeow, Hamilton Doorn Hill, Miyashita, Stoddart, Smith, Zink, Heath, Smolke Walt, Pandey Matsui Inestrosa,
24. Combining Several Diagnostic Tests and Data Processing in a “ Lab-on-a-Molecule” David Magri, Gareth McClean, Gareth Brown J. Am. Chem. Soc . 2006, 128 , 4950
25. Full Blood Count Date : 20.08.2005 Description Result Units Reference Ranges Remarks Haemoglobin 8.70* g/dl 12.00 17.50 Low RBC 2.34* x 10x6/mm3 3.50 6.00 Low PCV 26.70* % 40.00 54.00 Low MCV 114.10* fl 70.00 96.00 High MCH 37.20 pg 27.00 32.00 High MCHC 32.60 g/dl 30.00 ….35.00 …Normal PLATELETS 140,000.00 mm3 150,000.00 450,000.00 Low WBC 8,200.00 mm3 4,000.00 11,000.00 Normal NEUTROPHILS 48.00 % 40.00 75.00 …normal LYMPHOCYTES48.00 % 10.00 45.00 High EOSINOPHILS 2.0 % 1.00 6.00 Normal MONOCYTES 2.00 % < 10.00 Normal Performed by Sysmex/Hycell Automated Haematology Analyzers Logical combination of ‘high’ and ‘low’ parameters identifies disease
26. Spacer Receptor Receptor Spacer Spacer Fluorophore Receptor O O O O O N N C O 2 C O 2 - - H H + Na + Zn 2+
27. Wavelength / nm 400 440 480 520 + Na + , H + , Zn 2+ Na + , H + Na + , Zn 2+ Na + H + , Zn 2+ Zn 2+ H No inputs 0 I F
30. Molecular Computational Identification (MCID) of Small Objects in Populations Sheenagh Weir , Bernie McKinney Dave Pears, Mark James (Avecia) Nature Mater . 2006, 5 , 787
31. Radiofrequency Identification (RFID): The semiconductor technology approach to identifying each object (Goods, People) in an entire population 1 mm x 1 mm RFID chip (Hitachi)
33. Prefabricated logic gates fixed to polymer beads YES O N H PASS 1 N O N H NOT 0 3 5 7 9 11 pH 100 I F 1 YES PASS 1 NOT
34. Multi-valued logic is available for molecular computational identification c.f. binary logic needed in semiconductor computing Combinations of: Many (>5) excitation colours Many (>5) emission colours Many (>5) types (YES, NOT, PASS 1 , AND,…) Many (>5) chemical inputs (H + , Na + ,…) Many (>2) thresholds (pH 7, pH 4,…) Many (>5) combinations ( YES + PASS 1 , YES + 2 PASS 1 ,…) Conservatively, millions of m objects can be encoded!
35. acid alkali A A B B C C D D E E F F G G I I J J A ; PASS 1 B ; NOT C ; PASS 1 D ; PASS 1 + YES (1:1) E ; YES F ; NOT G ; PASS 1 I ; YES J ; PASS 0
36. J. Am. Chem. Soc . 2007, 129 , 3050 Parallel Processing of Analog Sensory Information Sisira de Silva, Nalin Goonesekera, Suram Patuwathavithana, Sydney Ramyalal (Colombo) Nimal Gunaratne, Mark Lynch, Kemuel Nesbitt
37. I F pH Parallel processing to produce greatly increased dynamic range RECEPTOR 1 SPACER FLUOROPHORE RECEPTOR 4 SPACER FLUOROPHORE RECEPTOR 3 SPACER FLUOROPHORE RECEPTOR 2 SPACER FLUOROPHORE
38. N R 1 R 2 N R 1 R 2 a ; R 1 = R 2 = CH 2 CH 3 b ; R 1 = R 2 = CH 2 CH 2 OH c ; R 1 = H, R 2 = CH 2 CH 2 N(CH 2 CH 3 ) 2 d ; R 1 , R 2 = CH 2 CH 2 N(CH 3 )CH 2 CH 2 1.4 404, 426, 443 (0.56, 0.008) 393(4.01), 372(4.01), 353(3.76) d 4.1 404, 426, 443 (0.55, 0.014) 395(4.03), 374(4.03), 355(3.81) c 6.1 405, 427, 445 (0.56, 0.005) 395(4.10), 374(4.09), 355(3.87) b 8.1 405, 427, 445 (0.59, 0.004) 393(4.03), 372(4.02), 353(3.81) a pK a Emission ( max , min ) Absorption (log )
39. 0 4 2 8 6 10 0 20 60 40 100 80 I F pH 390 500 0 Wavelength (nm) I F 100
41. R L S R L Self-Assembled YES Logic: Covalently bound YES Logic: Assembler: Non-ionic Detergent Micelle N N 2 N N n - C 9 H 1 9 n - C 9 H 1 9 Ru II O O H 10 O - Long-lived (100 ns) lumophore
43. R 1 L R 2 S S R 1 L R 2 Self-Assembled AND Logic: Covalently bound AND Logic: O - N C O 2 C O 2 O n - C 8 H 1 7 - - pK a = 9.9 pK a = 5.8 Log Ca2+ = 1.5
44. 11; 10 -8 M H + and 0.2 M Ca 2+ 01; 10 -12 M H + and 0.2 M Ca 2+ 10; 10 -8 M H + only 00; 10 -12 M H + only O - N C O 2 C O 2 O n - C 8 H 1 7 - -
45. R L S R L Self-Assembled OR Logic: Covalently bound OR Logic: Non-selective Receptor N C O 2 C O 2 O n - C 8 H 1 7 - - binds H + or Ca 2+ pK a = 5.8 Log Ca = 1.5
46. 11; 10 -4 M H + and 0.2 M Ca 2+ 10; 10 -4 M H + only 01; 10 -8 M H + and 0.2 M Ca 2+ 00; 10 -8 M H + only N C O 2 C O 2 O n - C 8 H 1 7 - -