Next generation atomic force microscopy for solving problems in biomedicine

AFM has unique capabilities for understanding life, and is able to image living systems in their native state under physiological conditions with molecular resolution.

However, technologically, it is where EM was in the 1990s – far from delivering its theoretical potential when imaging biology.

By understanding the physical principles of the technique and systematically optimising the instrumentation, the potential of EM has been unleashed in recent years.

We aim to drive a similar “resolution revolution” in AFM, developing an instrument that can: - Image functioning biological molecules in intact systems, including living cells, without perturbing their function or structure. - Obtain these images with sufficient resolution to identify biomolecules by their topography. - Accurately measure the organisation of biological molecules in complex, native samples.

We will do this by targeting fundamental weaknesses in AFM technology: - Reducing the thermal noise of the cantilever by producing smaller and softer cantilevers, and a microscope that can use them, reducing the imaging force 10-100x compared to the current state-of-the-art. - Reducing positioning noise and drift by developing a hierarchical, interferometric closed-loop scanner that reduces noise by >10x and drift by 100-1000x compared to the current state-of-the-art, providing traceably accurate measurements of size and position.