NanoBioPhysics and Medical Physics

We address questions of biological and medical relevance using physical methods. Our main tools are various species of scanning probe microscopes. Seeking to descend deeper and deeper into the nanoworld, we place the development of new instruments and methods with high-speed and low-noise characteristics at the foundation of our research. Our applications include visualizing the dynamic interactions of single biomolecules, revealing morphological and mechanical properties of living cells and tissues, exposing biomaterials on the molecular scale, and illuminating transport processes in artificial and natural membranes. We also develop elastography methods for tissue differentiation in minimally invasive surgery.

Contact
Prof. Dr. Tilman Schäffer

Institute of Applied Physics
University of Tübingen
https://www.bioforce.uni-tuebingen.de/en

Topics

NanoAnalytics, nanomedicine, mechanics of cells and tissues, elastography, sensor technology, surfaces, scanning probe microscopy, single molecule force spectroscopy.

Atomic Force Microscopy (AFM)

One of our goals is to map dynamical and mechanical properties of structures at the molecular, cellular, and tissue level. For this purpose, we are continuously improving scanning probe microscopy instrumentation and methods. For example, we are improving resolution and measurement speed by designing and building atomic force microscopes for small cantilevers. These small cantilevers have mechanical resonance frequencies in the megahertz range and can be used to image dynamic interactions between single biomolecules in real-time (e.g., protein-DNA interactions), or the complex mechanics of living cells.

Scanning Ion Conductance Microscopy (SICM)

Scanning ion conductance microscopy (SICM) is based on an electrolyte-filled nanopipette. The nanopipette serves as a probe for spatially resolved measurements of the ion current over a sample surface immersed in an electrolyte. Topography and elastic modulus images of the surface can be recorded with SICM non-invasively over many minutes or even hours. This is especially useful for the long-term study of soft and sensitive samples such as living cells.

Time-lapse SICM imaging of the topography and elastic modulus of a spreading human platelet. Reproduced from Rheinlaender et al. 2015, Thromb Haemost 113, 305.

Water Flow Elastography (WaFE)

In the context of tissue differentiation and cancer, mechanical properties are important indicators of pathological processes. We therefore develop novel elastography techniques that can be used for diagnostic purposes, e.g., to differentiate cancerous from healthy tissue. One intended area of application is minimally invasive surgery (MIS), where the limitations are the probe size and a restricted handling space. Recently, we developed water flow elastography (WaFE), where a small, cost-effective probe directs pressurized water against the tissue surface to create a localized indentation. From the measurement of the indentation volume with a flow meter and utilizing finite element simulations, the Young’s modulus of the tissue can be quantified. We have used WaFE for ex vivo measurements on human bladders and found a significantly larger Young’s modulus for cancerous vs. healthy tissue.