The laboratory is typically populated by an eclectic mixture of molecular biologists, physiologists, and physicists. We develop all the protein engineering, software and instrumentation necessary for our measurements. One aspect of our work that is under continued improvement effort is the construction of an ever faster and more accurate AFM spectrometer (figure). We have developed a simple automatic force-clamp spectrometer that can accurately set the pulling force with a sub-millisecond time constant and very low drift and can be left running automatically for long periods of time. Direct readout of single protein lengths has an effortless resolution of 1 nm. With digital filtering it reaches 0.1 nm. We are starting to use HaloTag technology to covalently attach single proteins to both the pulling cantilever and the substrate. Our aim is to extend the observation time of a single protein to hours/days.
The new machine is ideal to probe the conformational dynamics of single proteins. This instrument was shipped to Spain and demonstrated at the experimental workshop that we taught in Bilbao(September of 2010). This spectrometer is now being manufactured by the company Luigs and Neumann of Rattingen/Germany and will be available soon by September of 2012. We have already tested a prototype which generated the most amazing force-clamp recordings ever. This instrument will become a standard tool in protein biochemistry laboratories around the world.