Novel complex nanopores for the detection of natural and mutated DNA

• Applicant: Professorin Maria Fyta, Ph.D.
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508324943

Nanopores opened-up in materials have the ability to electrophoretically thread nucleic acids and perform single-molecule analysis in real-time, ultra-fast, and at a very low cost. A number of materials have been proposed for nanopore sensors, often exhibiting low read-out sensitivity or failing to achieve long read-lengths. The goal of this project is to promote the development of nanopores for biosensing technologies and epigenetics analysis by revealing the influence of important factors and nanopore structures on the signal-to-noise ratio (SNR). The SNR is in turn strongly related to the efficiency and accuracy of the read-out that is the sensing ability of the nanopore. To this end, a number of solid-state nanopores will be explored: functionalized, two dimensional, and combinations of 2D and 3D pores. For the functionalization, small molecules, 'sensing’ defects or charged patterns will be utilized to modify the pore surface. The nanopore complexity will be explored to tune their properties and optimize the SNR. For the realization of this research, a bottom-up multi-level computational approach will be applied to address issues from various spatial and temporal scales. Quantum-mechanical and electronic transport computations will be performed followed by classical all-atom, coarse-grained, as well as mesoscopic calculations approaching the experimental conditions. This in-depth investigation will result in selective pore designs for de novo genome sequencing and mutation detection, adding in this way a milestone towards personalized medicine. The outcome will also drive model-based discovery of novel materials with tunable properties.

• DFG Programme: Research Grants