Identification of Single Biomolecules Could Soon Be Even Faster

Gathering and identifying molecules for analysis can be done by passing molecules in solution through a nanopore and detecting the change in electric current the molecules create. The problem with this technique, “nanopore sensing,” is that it is usually diffusion-limited, and so relies on molecules drifting close to the nanopore before being captured.

Now, a team led by researchers at Imperial College London (London, UK) in collaboration with colleagues at University of Minnesota (Minneapolis – St. Paul; MN; USA) have demonstrated a technique to attract molecules towards the nanopore, making the process up to 1,000 times more efficient.

“By pulling molecules towards the detector instead of relying purely on diffusion, we can access a much larger volume, and by doing so can detect the same number of molecules from a much smaller concentration,” said senior author Dr. Joshua Edel from Imperial, “What might currently take 5 hours to analyze could be done in a couple of minutes with our new method.”

The technique, “single molecule dielectrophoretic trapping,” will also allow for analysis of very dilute samples. Capability to analyze molecules in low-concentration samples could be particularly important when looking for evidence of epigenetic modifications such as DNA methylation. The team tested their method with DNA molecules, but said it could be modified to detect a wide range of medically important molecules, from proteins to whole cells.

The technique uses an electrically-charged nano-pipette that exerts an electrical attraction force on the molecule that draws it close to the pipette tip, the nanopore. The shape and minute size of the tip, less than 50 nanometres, enables detection of single molecules.

Detecting and analyzing each molecule individually also avoids the problem of averaged results that obscure rare, but possibly important, events. “We can now capture needle-in-a-haystack events,” said coauthors Dr. Aleksandar Ivanov and Dr. Kevin Freedman of Imperial. “The huge increase in efficiency brought about by this technique paves the way for high-speed and high-throughput detection of rare events in ultra-dilute samples.” The team has filed a patent for their invention and expect that it will have application implications in the near future.

The study, by Freedman KJ et al., was published 2016, in the journal Nature Communications.

Related Links:
Imperial College London
University of Minnesota