Research is focussed on scanning probe methods (Atomic Force Microscopy, nanomotion detection, scanning probe lithography) to measure and manipulate individual biomolecules, i.e. investigate biomolecule interactions such as protein-DNA, protein lipid bilayers, protein-protein, protein-carbohydrate, and protein-biomaterial interactions.
The metabolic state of living organisms that are immobilized on an AFM cantilever surface can be detected by cantilever nanomotion analysis in physiological conditions. In nanomotion analysis mode, the sample is directly deposited onto the cantilever, and the analysis is performed with the functionalised cantilever in liquid. If the sample is alive, its nanometric-scale motions are transmitted to the cantilever, causing it to oscillate. These oscillations are detected by monitoring the cantilever displacements with the traditional laser–photodiode system. The cantilever and the sample of interest are immersed in an analysis chamber equipped with an inlet and an outlet that permits measurement in liquids, and, importantly, the exchange of liquids during measurements. It has been observed that any type of organism induces oscillations of the cantilever that only last while the organism is alive. Once an efficient killing agent is applied, the cantilever oscillations stop. In the case of motile organisms, such as mammalian cells or flagella-equipped bacteria such as E. coli, the answer is straightforward. However, in the case of immotile microorganisms such as yeast or Staphylococcus aureus, the explanation is more challenging. Probably, a direct momentum transfer between the sample’s surface proteins that undergo conformational changes and the cantilever plays an important role.
This very sensitive nanovibration sensor has been used to detect the activity of living cells (bacteria, fungal cells, plant and mammalian cells); it was even shown that conformational changes of proteins can be detected. This nanosensor can be used as a life detector, and is being evaluated for simple assessment of the presence of living organisms in extreme environments.