DNA-Functionalized Solid-State Nanochannels with Enhanced Sensing

After billions of years of evolution, organisms in nature have almost completed the intelligent manipulation of all life processes. Biological nanopores embedded in the cell membrane of organisms are representatives with intelligent manipulation capabilities. Biological nanopores can achieve controllable transmembrane transport of various ions and molecules, playing an important role in molecular biology processes such as substance exchange, signal transmission, energy conversion, and system function regulation in cells. Scientists have utilized biological nanopores for sensing analysis, such as gene sequencing and single-molecule detection. However, due to the characteristic that proteins (components of biological nanopores) cannot exist stably for a long time, scientists have developed solid-state nanopores/nanochannels with high mechanical strength, strong plasticity, and easy surface modification.

The sensing technology based on solid-state nanopores/nanochannels has attracted widespread attention in research fields such as biology, chemistry, and physics due to its advantages of fast speed, high throughput, and label free. Specific target capture can be achieved by probe modification at the inner walls of solid-state nanopores/nanochannels. When the target binds to the probe, the spatial hindrance, charge distribution, and hydrophilicity/hydrophobicity inside the channel change, thereby affecting the ion current output signal. At present, the sensing technology based on solid-state nanopores/nanochannels has achieved in situ detection of targets with sizes ranging from 100 pm-100 nm. It is worth noting that due to the inability of targets larger than 1 μm, such as cells, to pass through the channel, inner wall functionalized nanopores/nanochannels cannot achieve direct in situ detection of cells.

In fact, the surfaces of nanopores/nanochannels that can be used for functionalization include an inner wall and outer surface. Our group has first conducted a series of experiments to distinguish the probes at the inner wall and outer surface of nanochannels and proved that the probes on the outer surface can also be helpful for detection. In recent years, our research has focused on the outer surface of solid-state nanochannels, which presents a highly controllable model to study the ability to independently regulate ion transport. In addition, our work is followed by many groups in a short period. Here, we mainly summarize the DNA functionalization that distinguishes the inner wall and outer surface of nanochannels to enhance the sensitivity, specificity, and accuracy of nanochannel sensing. The challenges and future development opportunities faced by nanochannels in the field of sensing are explored. We believe that the content of this Account has certain guiding significance for the DNA functionalization of nanochannels and their applications in sensing.