Scientists are interested in being able to study individual molecules in order to determine characteristics that might not be evident when studying en masse. Being able to isolate a single molecule is tricky, but researchers during the past 20 years have been developing ways to use nanopore sensors for the task. The difficulty of this method lies with the extremely small size of the nanopores compared with the volume of solution containing the molecules of interest. It is especially difficult when the solution is diffuse – finding and isolating the molecules becomes extremely inefficient when dependent on diffusion alone.
MSI researchers have developed a new way to efficiently isolate and detect individual molecules. Principal Investigator Sang-Hyun Oh (associate professor, Electrical and Computer Engineering), graduate students Lauren Otto and Avijit Barik, and their colleagues Dr. Joshua Edel, Dr. Kevin Freedman, and Dr. Aleksandar Ivanov (all at Imperial College London), recently published a paper in the journal Nature Communications that describes their method. They used a dielectrophoretic (DEP) trapping mechanism that induces an electrothermal flow (ETF) to efficiently guide and trap molecules near the nanopore detection site (called a nanopipette). Molecules were then detected individually as they were drawn into the nanopipette with a DC voltage. This method was demonstrated with concentrations as low as 5 fM.
The authors used MSI resources to perform finite element modeling with the software package COMSOL Multiphysics. They used models to vary the strength of the electric field intensity gradient, which showed what strength of the field at the tip would isolate molecules near the nanopipette opening. Additional models were constructed to show the effects of solution flow generated by the applied electric field, which was responsible for overcoming diffusion limits in low concentration solutions. The article can be found on the Nature Communications website: KJ Freeman, LM Otto, AP Ivanov, A Barik, S-H Oh, and JB Edel. 2016. Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping. Nature Communications 7:10217. DOI:10.1038/ncomms10217.
Image description: Two-dimensional-axisymmetric electrostatic modeling of a 50 μm electrode gap between the nanopipette tip and a conductive flat electrode was simulated with a 10 V DC signal applied. Plots of the magnitude of the field intensity gradient, which is proportional to the force on a particle, are shown for regions (a) near the end of the pipette (scale bar, 25 nm) and (b) the DEP trapping volume and surrounding area (scale bar, 10 μm). The logarithmically scaled arrows show the direction of the force. The black contour line in b is along |∇|E|2|=1016.4 V2 m−3, which corresponds approximately to the threshold field intensity gradient for trapping 10 kbp DNA against Brownian motion. Image and description adapted from KJ Freeman et al, NatComms 7:10217 (2016).
posted on May 11, 2016