Proactive Manipulation Techniques for Protein Transport at Confined Nanoscale

Proteins are important components of human cells and tissues and are closely related to numerous metabolic activities, and some small changes in them may trigger major diseases in the human body. Therefore, protein detection is an important topic in the field of biochemistry. Nanopore technology is capable of real-time protein detection at the single molecule level or even at the single amino acid level, and is expected to be one of the lowest costs and most efficient protein detection methods. However, when using nanopores to detect proteins, the experimental conditions and detection strategy make the protein residence time in the nanopore too short to clearly reflect more detailed biological information from the electrical signal captured by the protein. The critical solution to this problem lies in controlling the transport rate of proteins through the nanopore to meet the bandwidth of the sensor device. In this paper, the active manipulation techniques of protein transport in nanopores are reviewed from the perspectives of external force field competition, internal force field interaction, hydrophilic interaction, and spatial resistance effect, with the aim of improving the capture frequency of proteins by nanopores and prolonging the residence time of proteins in nanopores to achieve high-resolution protein detection, fully reveal the conformational change mechanism of protein molecules, reaction kinetics, and even realize protein sequencing, etc. Finally, the great challenges and development trends of nanopore sensing technology for protein detection are described in detail.