Scanning Probe Microscopy

Our group focusses considerable effort in the development of novel scanning probe microscopy techniques and their application to biological systems and nanoscience in general. Improvements are focussed on two main areas:

Ultra-soft cantilever

Development of novel cantilevers

This research is based on the design and microfabrication of novel cantilever sensors. In collaboration with other members of the Nanophysics and Soft Matter Group in the School of Physics, these sensors have found application in lateral molecular-force microscopy, transverse dynamic force microscopy and mass sensing for medical diagnostics.

Atomic Force Microscopy (AFM) - High speed AFM

Scanning probe microscopy, and AFM in particular is a well-understood and mature technology that is present in tens of thousands of research institutions all over the world. Invented in 1986 by Binnig, Quate, and Gerber (IBM) the AFM quickly became one of the most popular tools for imaging biological samples at the nanoscale under physiological conditions. It can be understood by thinking of an old record player shrunk down by 1 million times and the ultra sharp tip used to ‘feel’ the surface rather than using light to ‘see’ a surface. AFM is a serial technique in which the imaging tip is raster scanned across the sample in order to build up a 3D image of some surface property, typically height. As such, the pixel rate is inherently limited by the mechanical resonances within the scanning system, i.e. the scan stage and the cantilever force sensor. Conventional AFMs will typically have scan stages with low mechanical resonances, 100 Hz or less, preventing them from reaching sub-second frame rates. Given that most biological processes occur on the millisecond timescale, improving the temporal resolution of AFM is the subject of intense research. Here at Bristol we have developed the fastest AFM in the world (>1,200 fps), 10,000 times faster than commercial AFMs [9]. Until now our HSAFM development has focussed on providing millisecond temporal resolution of biological processes in air and liquid.

The high speed AFM is capable of imaging very delicate samples such chromosomes in liquid at frame rates many orders of magnitude faster than any other nano-resolution imaging device in the world. At Bristol we are in the unique position to be able to image biological processes as they happen in real time at the nano and micro scale. We currently upgrading our system to enable real-time surface property measurements along with a huge increase in the area that the microscope can image. We are now ahead of what current technology is capable of processing. We will soon be able to image an area 2x2cm large with a resolution of 2nm providing a theoretical Terra pixel image in a matter of hours. After years of development the high speed AFM is almost ready to answer and explain many long standing industrial, biological, environmental and medical questions.

Clockwise from left: 1) A conventional 10x10 µm image collected in five minutes of nanoparticles on glass. 2) A composite image of the central region made from 400 tiled HSAFM images using a simple spiral scanning pattern and 80% overlap between frames. 3) HSAFM image, collected in <17 ms. Note: the periodic lines overlaying the nanoparticle in the HSAFM image is an example of the ringing produced as a result of using a conventional deflection detection system.

Molecular mechanics and its future development

Dr Massimo Antognozzi

My laboratory has focussed on molecular mechanics using micro-sensors technology. We have developed the lateral molecular-force microscope (LMFM) with a patented de- tection system and this technique is already demonstrating to be a unique tool for mea- suring and manipulating bio-molecular systems with nanometer resolution and femto- Newton sensitivity. Reducing the sensor size to the nanoscale, as pioneered in Bristol, will disclose an unprecedented level of detail of bio-molecular structures and their dy- namic behaviour in vivo.

The next strategic objective is to combine mechanical measurements of bio-molecules with other physical properties, in particular: electron transfer, polarisability and optical spectroscopy. The technology to access these combined measurements is not currently available, and we are in a unique position to integrate these new functionalities in our current nano-sensors. My Laboratory will develop, in an initial proof-of-concept stage, the methods and the procedures necessary to produce and use force sensors with the ability to measure extremely small currents or capacitance in a liquid environment. The following stage will require high-level interdisciplinary collaborations to address crucial questions in bio-molecular science and explore commercialisation avenues of these nano- devices.

Latest publications

  • Harniman,R.L., Vicary J.A., Hoerber, J.K.H., Picco L.M., Miles M.J.M. and Antognozzi M. Methods for imaging DNA in liquid with lateral molecular-force microscopy Nanotechnology (2012) in Press.
  • Scholz, T. et al. Processive behaviour of kinesin observed using micro-fabricated cantilevers. Nanotechnology 22, 5707 (2011).
  • Ulcinas, A. et al. Shear Response of Nanoconned Water on Muscovite Mica: Role of Cations. Langmuir 27, 10351(2011).
  • Agnew, C. et al. Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis adhesin UspA1 with bronectin and receptor CEACAM1 binding. P Natl Acad Sci Usa 108, 15174 (2011).
  • Amrute-Nayak, M., Antognozzi, M., Scholz, T., Kojima, H. and Brenner, B. Inorganic phosphate binds to the empty nucleotide binding pocket of conventional myosin II. J. Biol. Chem. 283, 3773 (2008).
  • Antognozzi, M. et al. A new detection system for extremely small vertically mounted cantilevers. Nanotechnology 19, 384002 (2008).

Imaging Chromosomes in Liquid

Imaging DNA at High Speed

Multitouch High-Speed Atomic Force Microscope

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