Udine, February 2007 An Introduction to Science at the Nanoscale and its Impact on Modern Medicine. Fourth Lecture. G. Scoles

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1 Udine, February 2007 An Introduction to cience at the Nanoscale and its Impact on Modern Medicine. Fourth Lecture. G. coles (B. anavio, F.M. Toma M. Melli) CBM Chemistry Dept. Intern. chool for incrotrone Princeton Univ. Advanced tudies Trieste & CENTER FOR BIOMOLECULAR MEDICINE

2 A Quick Introduction of elf-assembled Monolayers (AMs) : 1) Classes Nuzzo, R. G.; Allara, D. L. J. Am. Chem. oc. 1983, 106, 4481.

3 A Quick Introduction of elf-assembled Monolayers (AMs) : 2) Alkythiols on Gold top view 4.99 Å ( 3x 3)R Å Au(111) H

4 A Quick Introduction of elf-assembled Monolayers (AMs) : 3) Binding Bond energy C-C: 145 kcal/mol C-: 171 kcal/mol C-H: 81 kcal/mol -Au: 60 kcal/mol van der Waals energy per CH2 group is ~ 1.5 kcal/mol

5 THE ADORPTION of ALKYLTHIOL on GOLD H--R thiol R--R dialkyl sulfide (R---R disulfide) R H + R H H-O-R alcohol R-O-R dialkyl oxide? H2 Au(111) + R? R R ( ) chemisorbed CH3CH3 sticks to gold with unit probability CH3H very low sticking probability CH3CH3 does not stick

6 elf-assembled monolayers of alkanethiols on gold are much studied systems because: 3) Very stable and easily formed 4) Frequently used for electrode surface modification (Chemical ENOR) 5) Model systems for interfacial electron transfer 6) oft lithography & surface patterning (micro printing) 7) Model systems for surface passivation against corrosion (also bio passivation). 8) Model systems for study of friction 9) Colloid coating and linking for cluster-based materials 10)uitable films for nanografting (i.e. locally induced chemistry) 11)Last but not least, AMs have, recently, become the building blocks of a new wave of promising molecular electronic devices (FETs, switches etc).

7 Membrane-like monolayers: 2) Langmuir 2) Langmuir-Blodgett 3) Preparation of Thiol AMs (elf-assembled Monolayers) on Au(111) olution Deposition We prepare a thiol monolayer by placing a clean gold(111) substrate in less than 0.1 micromolar ethanolic thiol solution for 18 hours. Au Immersion of gold substrate Alkyl thiol: CH3(CH2)nH:

8 Formation of Alkanethiol AM on Au(111) We soak a gold (111) sample in a solution of Alkanethiols (i.e. C10) in alcohol (i.e. in ~ 20 μm for 2 days For example the so called C10: H(CH2)9CH3 The molecules start to self assemble on the Gold (111) surface The density of the molecules Incrase and they start to stand on the surface The self assembly as saturated the surface and the system stabilize Matteo Castronovo 2004

9 AFM Filtered image Typical ( 3 3)R 30 (hexagonal) structure of a well assembled monolayer. E. Barrena C.Ocal (J.C.P.) M.almeron In some of the well aged monolayers also the (3 2 3) superlattice (well known from our work using He atom and X-ray diffraction and the TM work of the late Greg Poirier) is detectable. What happens when the imaging force is increased? Topography image Topography image Lateral force image

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11 Topographic vs. Lateral Force Data Topographic Data Lateral Force Data C18 pattern written into C10 matrix Jordan Amadio(2002)

12 80nm Friction in trace direction 80nm Friction in retrace direction 80nm ubtraction

13 Different materials Different heights When the heights are almost the same a friction image may still show contrast 40nm Height image ( left ) and friction image ( right ) of a (2000Å 2000Å) H-(CH2)14-CF3 square nanografted into a H-(CH2)17-CH3 layer 40nm

14 urface Manipulation Three powerful methods to manipulate the chemical composition of surfaces on the nanoscale. Nanoshaving Nanografting These techniques have been introduced in 1997 by Gang-Yu Liu At Wayne tate University. he is now at the U. of C. Davis. Dip Pen Nanografting This method is similar to Mirkin s but it is less affected by molecule diffusion and hence has 10 times higher resolution. G.Y.Liu Acc. Chem. Res. 2000

15 AFM-based Nanolithography of Monolayers: Nanografting tudents: Ying Hu and Jian Liang (A) A thiol AM on an Au surface is imaged at low force in a solution of a different ( longer ) thiol; (B) At a greater force, the tip displaces the adsorbates in desired areas, allowing the longer molecules in the solution to self-assemble onto the exposed gold sites; (C) The newly formed nanopattern is then imaged at low force levels. Liu, G.-Y. et al. Langmuir 1999, 15,

16 In solution: BAIC NANOGRAFTING Expected height difference: 8.7Å C10 nanografted into a C18 AM (400 Å 400 Å) Adriana Gil (2000) A 70 Å line of C10 nanografted into a C18 AM (800 Å 800 Å)

17 How do we know how much force to use? High Force 20nN AFM tips Atomic resolution image of gold(111) (100 Å 100 Å) AFM tips Low Force 1nN Molecular resolution image of C18 (100 Å 100 Å)

18 An Example of Nanografting H C18 ection of C10 grafted into C C10 height(nm) nm nm C10 grafted into C18 (100nm 100nm) and the corresponding height measurement X axis(nm) Calculated height measurement between C10 and C18 is 0.86 nm. (Ying Hu 2002) Princeton

19 Example nanostructures of organic molecules 22xx44nm nm 22 dot dotof ofcc (32 (32thiol thiolmolecules) molecules) Left: Left:30 30xx60 60nm nm Right: Right:20 20xx60 60nm nm H H 10 10xx nm nm 22 line lineof ofcc H H xx nm nm positive positivepattern patternofofcc (8 (8 ÅÅ above abovethe the CC 1010 H H matrix) matrix) 22 of ofcc 2222 H H 22 of ofcc 1818 H H H H high highspatial spatial resolution resolution xx nm nm 60 60xx60 60nm nm xx60 60nm nm of ofcc 1818 H H of ofhc HC 1010 CHO CHO 22 of ofhc HC 1010 CHO CHO control controlofoflocal local environment environment multiple multiple components components ability abilitytotochange change nanostructures nanostructures can canin incc 18 H H can canin incc 10 H H xx nm nm negative negativepattern patternofof HC HC 22 CHO CHO(4 (4 ÅÅ below belowthe the CC66 H H matrix) matrix) in in situ can canin incc H H

20 Advantages of Nanografting Nanografting allows investigation of multiple AMs composed of different molecules with well-defined boundaries in addressable locations; Multiple patterns can be made simply by changing the solution in the liquid cell, with all other experimental conditions being held constant. Two C18H nanoislands in a C10H monolayer Liu, G.-Y. Acc. Chem. Res. 2000, 33, 457 coles, G. et al. Nano Lett. 2003, 3, 425

21 Dip-Pen Nanolithography C.Mirkin and Coll. cience, μm

22 Dip Pen Nanografting 40nm 40nm H-(CH2)14-CF3 nanografted into H-(CH2)17-CH3 layers (2000Å 2000Å) in air Topographic Data Lateral Force Data C18 pattern written into C10 matrix Jordan Amadio (2002)

23 Construction of 3D Nanostructures Pattern transfer via surface reactions

24 Construction of 3D Nanostructures CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 i OH OHOH OH OH OH OHOHOHOH i i i i O OH O O O O OHO O O O C18H37iCl3 C10H18 Gold film Gold film Reaction of surface -OH groups with octadecyltrichlorosilane (C18H37iCl3 )in decahydronaphthalene(c10h18)

25 Construction of 3D Nanostructures a b (a) B A He ight / A ngstro m 40 c 30 B after reaction 20 A before reaction Dist ance/ A ngstro m AFM images (a, b) and height-distance plots (c) before (a) and after (b) reaction of the surface hydroxyl groups with 11 mm octadecyltrichlorosilane in decahydronaphthalene

26 Production of Protein Nanopatterns

27 pace filling models for the three proteins used in this study Lysozyme Human erum Albumin LYZ HA M.W. (KD) Dimensions IEP 66.6 ~ Immunoglobulin IgG X 3.0 X X 8.5 X

28 Procedure of nanofabrication of Protein Patterns X = CH3, EG3 (inert matrix) Z = COOH, CHO, NH3+, Biotin, etc. Y= Protein scan xxxxxxxxxxxxxxxxxxxxxxx scan z z xxxx zz zzz z zzzzzzzzzzzzz xxxx xxxxx scan xxxxx zzzzzzzzzzzzz xxxx xxxxx Wadu-Mesthrige, K.; Xu,.; Amro, N. A.; Liu, G-Y.; Langmuir, 1999, 15,

29 Commonly used strategies for bioreceptor immobilization + O C + - OH O C treptavidin + NH2 - OH O OH C CH3 CH3 CH3 CH3 CH3 O C OH O C O NH2 O C OH O CH O CH O H CH Biotinilated AM H gold pka < ph < IEP + + ph ~ IEP ph = 8 ph = 5 7 self-assembly O OH O O O OH C C C CH3CH3 CH3 CH3 CH3 O C OH O C NH O C OH O CH N CH O CH Electrostatic Hydrophobic Peptide Linkage Amide Linkage Chemisorption Biospecific Linkage

30 Nanopatterning of Lysozyme via Covalent Binding C2CHO pattern in C10 matrix LYZ adsorption B C10CHO pattern in C6 matrix distance / nm LYZ adsorption E 300 F 6 height / nm D nm 250 nm C 3 height / nm A nm 250 nm distance / nm Wadu-Mesthrige, K.; Amro, N. A.; Garno, J. C.; Liu, G. Y.; Biophysical J., 80, 2001,

31 Nanopatterning of IgG via Covalent Binding IgG adsorption C2CHO pattern in C10 matrix A B height / nm nm 100 nm E height / nm nm 50 distance / nm 100 F nm 75 distance / nm IgG adsorption C2CHO pattern in C10 matrix D 0 0 Wadu-Mesthrige, K.; Amro, N. A.; Garno, J. C.; Liu, G. Y.; Biophysical J., 80, 2001,

32 Nanopatterning of BA via Covalent Binding Nanografted -CHO pattern B 6 height / nm A Cursor profiles Adsorption of BA nm 250 nm distance / nm Wadu-Mesthrige, K.; Amro, N. A.; Garno, J. C.; Liu, G. Y.; Biophysical J., 80, 2001, Wadu-Mesthrige, K.; Amro, N. A.; Liu, G-Y. canning, 2000, 22,

33 Activity of Proteins in within Nanopatterns: an Antibody Antigen Reaction A matrix 14 B -CHO rabbit IgG height / nm nm 0 0 C distance / nm secondary IgG 14 height / nm nm 0 0 Liu, G. Y.; Amro, N. A. PNA, 2002, 99, distance / nm D

34 ummary 2. Nanopatterns of organic and biomolecules can be produced with high precision using scanning probe lithography 3. Complicated patterns can be produced using automated scanning probe lithography 4. The arrangement of these molecules and the local environment of each site are engineered characterized with nanometer to molecular precision 5. Protein molecules within the nanostructures maintain their activities, e.g. antibody can bind to the antigen proteins within the nanostructures.