The document discusses various applications of luminescent molecular systems for sensing, computing, and identification. It describes sensors that can detect ions and pH and molecular logic gates that can perform Boolean operations. It also discusses using combinations of these systems fixed to beads to allow identification and parallel processing of large numbers of objects.

1. Useful Nanotechnologies Based on Molecular Information Handling

2. Robot: A machine or device that operates automatically or by remote control Computer: A device that ... processes information

3. Ion-Switchable Fluorescence Spacer M + Fluorophore Receptor Constant Fluorescence Fluorophore Spacer Fluorophore Receptor < 1 nm > 1 nm

4. Luminescent molecular switchable systems can gather and process information Optical response Chemical stimulus level Analog region Digital 1 Digital 0

5. The Miniature James Bond Luminescent Sensing

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

8. Imperiali, Marcus, Cary Stoddart, Selinger Shinkai, Kubo, Hamachi Fabbrizzi, Quici, Rettig, Resch, Wolfbeis, Daub, Verhoeven Bouas-Laurent, Desvergne, Lapouyade, Fages, McClenaghan Balzani, Prodi, Barigelletti, Campagna, Soumillion Bharadwaj, Khan Zinic Samanta Grigg, Moore, Brown, James, Davidson, Beer, Stoddart, Parker, Williams, Ward, Sutherland Kuhn, Yang Czarnik, Pearson Morawetz, Pardo Masilamani Turro, Garcia- Espana, Costero, Miranda, Escriche, Luis, Perez- Inestrosa D’Souza Inoue Brown Gawley, Leblanc Lakowicz, Pu Roche, Fahrni Wang, Lindsey Roche Wang, Ma, Moller, Rurack, Schuster, Greiner Reymond Ji Kumar Rajasekharan, Ajayaghosh, Ramaiah, Varma Lawrence, Adams, Qian Das Lincoln Walt, Miller, Lippard Smith Jin Qian, Tian, Chen Bianchi, Pallavicini Lippolis Akkaya, Valkan Koide Chattopadyay Hsu, Chiu Whitten Leigh, Callan Plater, Gunnlaugsson, O’Shea, Kruger Bruckner Shizuka, Teramae, Chatterjee, Kimura, Osa, Sakamoto, Iwai, Nakatsuji, Fukuzumi, Tanaka, Nagano, Imai, Nagamura, Akasaka Gee Chang Tsien, Barbas, Rebek Kulatilleke de Silva, McCoy Pina, Pischel, Lodeiro Shanzer, Eichen, Willner Wu, Li, Chen, Chang, Kim Yoon, Bhattacharya, Maitra Guo, Lin Tang de Silva Diaz-Fernandez Valeur, Lehn, Weiss, Leray Jiang de Silva, Kruger Pfeffer Yagi Levine,

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

16. A Popular Robot

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 )

22. generalization integration numeracy games reconfiguring object identification improved sensing Molecular Logic Gates Nature 1993, 364 , 42 Nature Nanotechnol . 2007, 2 , 399 George Boole 1849-64, Cork

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

29. 1 (high, 0.020) 1 (high) 1 (high) 1 (high) 0 (low, 0.006) 1 (high) 0 (low) 1 (high) 0 (low, 0.007) 0 (low) 1 (high) 1 (high) 0 (low, 0.006) 0 (low) 0 (low) 1 (high) 0 (low, 0.003) 1 (high) 1 (high) 0 (low) 0 (low, 0.002) 1 (high) 0 (low) 0 (low) 0 (low, 0.001) 0 (low) 1 (high) 0 (low) 0 (low, 0.001) 0 (low) 0 (low) 0 (low) 3-Input AND Logic Truth Table Output Fluor n  F Input 3 Zn 2+ Input 2 H + Input 1 Na +

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)

32. EXCITATION WAVELENGTH: 368 nm 500 Wavelength (nm) Fluorescence Intensity 385 100 Increasing pH 422 401 446 Prefabricated YES logic gate fixed to polymer bead (0.1 mm) 0

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

40. “ Plug-and-Play” Logic via Self-Assembly Vinny Vance, Catherine Dobbin, Boontana Wannalerse Chem. Commun . 2009, 1386

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

42. O - pK a = 9.9

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 - -

47. Providence Luck Serendipity EPSRC DENI EUROPEAN COMMISSION JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE