Project Details
Projekt
Integrated microstructures for label-free interrogation of protein conformational dynamics by plasmon-enhanced THz spectroscopy
Applicants
Professor Giovanni Capellini, Ph.D.; Professor Dr. Jacob Piehler; Professor Dr. Bernd Witzigmann
Subject Area
Electronic Semiconductors, Components and Circuits, Integrated Systems, Sensor Technology, Theoretical Electrical Engineering
Biophysics
Biophysics
Term
from 2015 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 272553338
The conformational organization and dynamics of proteins critical determine their biological function and their malfunction in diseases. Current structural biology techniques largely fail when it comes to highly dynamic or largely unstructured cases. As a complementary approach, THz spectroscopy holds tremendous promises as a new approach to study structurally flexible proteins as it is highly sensitive to collective vibrational modes, charge distribution and hydration of proteins. While the unique potential of THz spectroscopy for label-free interrogation of protein conformations and conformational dynamics is broadly accepted, the application to biologically and medically relevant target proteins is still severely limited by the very high quantities and concentrations required for traditional THz measurements. Our project aims to overcome this limitation by a comprehensive THz sensor design dedicated for spectroscopic analysis of proteins available in low amounts and concentrations. By an interdisciplinary approach between membrane biology (UOS), computational physics (UKS) and Si engineering (IHP), the project targets to set up a high performance, cost-effective THz protein sensor platform based on Si CMOS compatible, resonant THz near field optics. During the first 24 month of the project, we have by close collaboration between UKS and IHP successfully designed and fabricated Ge/Si microstructures with THz microresonators that were characterized with respect to material properties and THz resonance. IHP together with UOS developed material- and geometry-specific surface modification of Ge/Si microstructures that allowed site-specific protein capturing and sample concentration in resonance hotspots directly from cells. These efforts will lead to the proof-of-concept to demonstrate THz sensing of proteins using Ge microresonators. In the second phase of the project, we will focus on optimizing material properties and sensor design. By including metallic nanoparticles and spoof plasmonic structures, further field enhancement and sensitivity will be achieved. To further increase signal to noise, we will use functionalized hydrogels by photopolymerization to cover the entire sensor hots with protein samples and hybrid surface architectures incorporating metallic nanoparticles. Advanced surface functionalization will be combined with sensor designs that facilitate sample handling via microfluidics. Using a set of representative model proteins cover structurally well defined, flexible and intrinsically disordered proteins, we will explore capabilities and limitations of our THz microdevices.
DFG Programme
Priority Programmes
