Development of Local and Scanning Probe Techniques Heinrich Hoerber NanoBioPhysics University Bristol

200 nm Haberle, W., J. K. H. Horber, and G. Binnig, 1991, Journal of Vacuum Science & Technology B 9, 1210 Combining AFM and optical microscopy

AFM image sequence of a pox virus release at the end of a microvillus EM image by Stokes 1976 Scanning fast - making movies Horber, J.K.H., et al., 1992, Scanning Microscopy 6, 919

Horber, J. K. H., W. Haberle and B. Sakmann, 1995 Biophysical Journal 68, 1687 Combination with electro-physiological techniques Combination with electro-physiological techniques

Koitschev, A., S. Fink, U. Rexhausen, K. Loffler, J. K. H. Horber, H. P. Zenner, J. R. Ruppersberg, and M. G. Langer, 2002, Hno 50, AFM in hearing research

Cantilever development IBM Research Laboratory Rueschlikon M. Despont, G. Binnig, P. Vettiger and C. Gerber

Heat flow between cantilever and substrate Heat transfer through cantilever arms (~4 mW) Cantilever with heater through tip in contact nW Through air to substrate (10-20 μW) C Δ R / R: –10 -5 /nm

2 μm Lipid vesicles with reconstituted membrane proteins (SNAP25, B.Jena) 2 μm 1 μm SiC GaN Metal connection on a storage chip structure underneath a SiO 2 layer (Zarlink) Cut through a transistor structure (M. Kubal) Heat conductivity Haeberle, W, Pantea, M & Hoerber, JKH. 2006, Ultramicroscopy, 106 (8-9), 678

100  m1  m length 260  m, width 1  m, thickness 200 nm, spring constant 0.03 pN/nm Smaller cantilevers James Vicary

AFM with the cantilever vertical Massimo Antognozzi, Arturas Ulcinas

Maximal cantilever bending Molecular Motor movement Massimo Antognozzi, Tim Scholz

0.5 nm 200 nm 200 μm 0.02 N/m Florin, E. L., A. Pralle, E. H. K. Stelzer, and J. K. H. Horber, 1998, Applied Physics A-Materials Science & Processing 66, S75 Spatial resolution ~ 1nm Time resolution ~ 1 μsec Photonic Force Microscopy

Agarose polymer network Tischer, C. et al., 2001, Appl. Phys. Lett. 79, 3878 Thermal fluctuation imaging

Membrane diffusion 2D / 3D

Confining potential map Viscosity map Interaction map of an LDL receptor

Parallelisation of PFM

Producing many independent focused laser beams Producing many independent focused laser beams

Nano-particles crossing the cell membrane

Types of nano-particles

Gold nano-particles interacting with light

Nearfield fluorescence excitation

Raman Spectroscopy Chemical sensing Surface Enhanced Raman Spectroscopy

 Nano-Sensors (Scanning Probe Microscopies)  Nano-toxicology  Nano-medicine (markers, drug delivery) Nano-particles - areas of interest