A label-free optical sensor system on silicon: Determining the thermodynamic and kinetic quantities of protein-ligand interactions

• Applicants: Professor Dr. Klaus Petermann, Ph.D.; Professorin Dr. Karola Rück-Braun; Dr. Rudolf Volkmer
• Subject Area: Electronic Semiconductors, Components and Circuits, Integrated Systems, Sensor Technology, Theoretical Electrical Engineering ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257184830

Optical label-free biosensors using free-space optics like surface plasmon resonance devices have successfully entered the market. Meanwhile it becomes clear that chip-integrated solutions for optical label-free biosensing feature many advantages like significant size reduction enabling a large number of sensor elements on a small chip, highly parallel operation and a minimal demand of biomaterial. In this proposal a multidisciplinary approach brings together the expertise in silicon photonics, chemistry and biochemistry. The overall goal is to develop a silicon based optical biosensor system for highly parallel assays and the necessary chemistry to get a real world biosensor system for parallel real time measurements of several kinds of biological protein-ligand interactions.The group of Petermann/Bruns brings in their knowledge on silicon photonics, the group of Rück-Braun the expertise on silicon surface chemistry including analysis, and the group of Volkmer brings in the biological models on which the biosensor can be optimized and tested extensively.The sensor itself will be realized in SOI (silicon-on-insulator). We combine well known ring resonators as sensing elements with a new approach for massive parallel sensing based on thermo-optical modulation. To maximize the applicability of the sensor, a new structure for large dynamic sensing will be developed. Furthermore, to achieve the best solution for our applications, several variations of the sensor structure like waveguide type and ring shape will be performed.On the biochemical side, established silicon surface chemistry and well described protein-ligand interactions will be used to functionalize and verify the sensor system.Using microfluidics, parallel quantitative affinity measurements of the biological interactions under investigation will be performed. Temperature dependent measurements will be established to determine the thermodynamic parameters such as Gibbs free energy, enthalpy, entropy and reaction activation energy. Finally, the very challenging determination of the protein-protein interaction stoichiometry will be investigated. We will try to determine the oligomeric state of a protein complex using our label-free biosensor system. This biosensor system will give us the possibility to determine the thermodynamic, kinetic and stoichiometric parameters of protein-ligand interactions with a single experimental run.

• DFG Programme: Research Grants