Manipulation and analysis of large DNA molecules by controlling their dynamics using micro- and nano-gaps

Manipulation and analysis methods for large DNAs are critical for epidemiological, clinical, diagnostic, and fundamental research on bacteria, membrane vesicles, plants, yeast, and human cells. However, the physical properties of large DNAs often challenge their manipulation and analysis with high accuracy and speed using the conventional methods such as gel electrophoresis and column-based methods. This review presents the approaches that leverage micrometer- and nanometer-sized gaps within microchannels to control the dynamics and conformations of large DNAs, thereby overcoming these challenges. By designing gap structures and migration conditions based on the relationship between gap parameters and the physical characteristics of large DNAs-such as diameter and persistence length-these methods enable swifter and more precise manipulation and analysis of large DNAs, including size separation, concentration, purification, and single-molecule analysis.