Scientists should soon be able to capture biological molecules a thousand times faster, allowing better detection of important health issues.
DNA mutations, which can lead to cancers and other problems, can be difficult to detect in biological samples as they are relatively rare. In order to analyse all DNA molecules for signs of mutation, it is important to gather as many as possible, but this is often time-consuming.
Gathering and identifying molecules for analysis can be done by passing molecules in solution through an extremely small hole, known as a nanopore, and detecting the change in current that the molecules create. The problem with this technique, dubbed ‘nanopore sensing,’ is that it is usually diffusion limited – it relies on waiting for the molecules to drift close to the nanopore, before being captured.
Now, a team led by a LCN researcher based at Imperial College London, in collaboration with colleagues at the University of Minnesota, have demonstrated a way to attract molecules towards the nanopore, making the process up to 1,000 times more efficient.
Law of Attraction
“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 LCN study co-author Dr Joshua Edel from Imperial’s Department of Chemistry. “What might currently take five hours to analyse could be done in a couple of minutes with our new method.”
This will also allow researchers to analyse more dilute samples, as it will be much easier to find and detect molecules even when there are not so many around. This could be important when looking for evidence of DNA methylation, a process that plays a role in cancerous tumour development.
The team tested their method with DNA molecules, but say it could be modified to detect a wide range of medically important molecules, from proteins to whole cells.
Capturing rare events
The technique, published today in the journal Nature Communications, uses an electrically-charged ‘nanopipette’, which exerts a force on the molecule to draw it closer to the tip. The shape and minute size of the tip, less than 50 nanometres, ensures the set up can detect single molecules.
Detecting and analysing each molecule individually also avoids the problem of average results obscuring rare, but important, events. “We can now capture needle-in-a-haystack events,” said co-authors Dr Aleksandar Ivanov and Dr Kevin Freedman from Imperial’s Department of Chemistry.
“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 have filed a patent for their invention and expect that it will have commercial implications in the near future.
'Nanopore Sensing at Ultra-low Concentrations using Single Molecule Dielectrophoretic Trapping' by Kevin J. Freedman, Lauren M. Otto, Aleksandar P. Ivanov, Avijit Barik, Sang-Hyun Oh, and Joshua B. Edel is published in Nature Communications.