Robustness and adaptivity: advanced control and estimation algorithms for the transverse dynamic atomic force microscope

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Observing the dynamic behaviour and interactions of single biomolecules is a long-standing goal to facilitate bio-medical research. Standard practice is to use one of several scanning probe microscopes (SPMs), principally atomic force microscopy (AFM). The principle of an AFM is simple: a horizontally oriented cantilever with a very sharp tip is moved across the object of interest, allowing the capture of a three dimensional topographical image. However, the low forces and fast timescales of the fundamental inter-molecular events of interest in bio-medical sciences, generally lie far outside the operational range of commercial AFMs, which typically require several minutes per image. Thus, while AFMs can provide sub-molecular resolution of biomolecules under physiological conditions (cf. electron microscopy which uses a vacuum) there are two significant disadvantages of AFMs still to be overcome.- slow imaging rates: A typical 256x256 pixel image takes 60 seconds to produce.- excessive interaction forces during imaging: A significant challenge to imaging biomolecular interactions is that the forces typically present between the probe and the sample disturb or even damage the biomolecules.To counter these issues, we will combine the latest advances in control theory with the novel SPM instrumentation, currently in development in Bristol, to produce a new scanning probe microscope capable of imaging these fragile samples without damaging them: Thus, Bristol's transverse dynamic force microscope (TDFM) will represent a breakthrough in both SPM instrumentation and the study of biomolecules.In Bristol's TDFM, the probe is aligned perpendicularly to the sample surface (rather than parallel to it, as in AFMs) and oscillates in the plane of the sample. The amplitude of oscillation decreases as the tip-sample separation distance decreases. The amplitude of the probe oscillation can be used as a measurement signal to control the probe-sample separation with sub-nanometer precision. When using this control method, at no point during scanning should the probe come into contact with the sample surface.Novel control methods will create a high-speed TDFM (HS-TDFM) by-controlling the fast movement of the cantilever height (z-motion)-controlling the fast placement of any (biological) specimen to be observed (x-y-motion)-estimating sample-cantilever forces, e.g. Van-der Waals forces, to better understand the wealth of measured information for faster and simpler fusion & processing of data obtained from the HS-TDFM.Before any of this is possible, the TDFM will be redesigned to incorporate highly precise sensor technology and to obtain the best possible dynamic behaviour. The modern control approaches will include linear robust control approaches, nonlinear sliding mode control, nonlinear adaptive (neural network) control, modern estimation/observer techniques using sliding modes, and adaptive principles.The challenges will be to-achieve practical control at bandwidths above 1MHz;-understand & exploit the nonlinear HS-TDFM dynamics for better data interpretation;-develop novel estimators/observers combining the paradigms of adaptive and sliding mode methods, for signal and parameter identification;-incorporate novel estimation and control approaches for improving the control system of the HS-TDFM.The resulting HS-TDFM will be a true non-contact imaging technique capable of comparable spatial resolution and lower interaction forces than AFMs. The HS-TDFM will display pico-Newton force-sensitivity and provide a wealth of information from direct observation of the interacting biomolecules. It will collect multiple images per second as required for observing biological processes. This will not only benefit life-sciences but also support SPM users in material science, producers of nano-sized systems, and in nano-electronics, e.g. microprocessors.