Minimally Invasive Nanotweezers For Single-cell Biopsies

A new technique enables researchers to extract single molecules from live cells, without destroying them. The research, developed by a team led by Professor Joshua Edel and Dr. Alex Ivanov at Imperial College London, could help scientists in building up a human cell atlas, providing new insights into how healthy cells function and what goes wrong in diseased cells.

“With our tweezers, we can extract the minimum number of molecules that we need from a cell in real time, without damaging it. We have demonstrated that we can manipulate and extract several different parts from different regions of the cell—including mitochondria from the cell body, RNA from different locations in the cytoplasm and even DNA from the nucleus,”

Professor Joshua Edel, from the Department of Chemistry at Imperial, said.

Dielectrophoresis

The tweezers are formed from a sharp glass rod terminating with a pair of electrodes made from a carbon-based material much like graphite. The tip is less than 50 nanometers (a nanometre is one-millionth of a millimetre) in diameter and is split into two electrodes, with a 10 to 20-nanometre gap between them.

By applying an alternating current voltage, this small gap creates a powerful highly localised electrical field that can trap and extract the small contents of cells such as DNA and transcription factors — molecules that can change the activity of genes.

The method is based on a phenomenon called dielectrophoresis.

The tweezers generate a sufficiently high electric field enabling the trapping of certain objects such as single molecules and particles. The ability to pick out individual molecules form a cell sets it apart from alternative technologies.

Studying Living Cells

The technique could potentially be used to carry out experiments not currently possible.

For example, nerve cells require much energy to fire messages around the body, so they contain many mitochondria to help them function. However, by adding or removing mitochondria from individual nerve cells, researchers could better understand their role, particularly in neurodegenerative diseases.

“These nanoscale tweezers could be a vital addition to the toolbox for manipulating single cells and their parts. By studying living cells at the molecular level, we can extract individual molecules from the same location with unprecedented spatial resolution and over multiple points in time. This may provide a deeper understanding of cellular processes, and in establishing why cells from the same type can be very different to each other,”

Dr. Alex Ivanov, from the Department of Chemistry at Imperial, said.

“The whole project was only made possible by the unique know-how and abilities and enthusiasm of the young team members, including Dr. Binoy Paulose Nadappuram and Dr. Paolo Cadinu, amongst others, who all have diverse expertise and backgrounds,”

Professor Edel added.

Binoy Paulose Nadappuram, Paolo Cadinu, Avijit Barik, Alexander J. Ainscough, Michael J. Devine, Minkyung Kang, Jorge Gonzalez-Garcia, Josef T. Kittler, Keith R. Willison, Ramon Vilar, Paolo Actis, Beata Wojciak-Stothard, Sang-Hyun Oh, Aleksandar P. Ivanov & Joshua B. Edel
Nanoscale tweezers for single-cell biopsies
Nature Nanotechnology (2018)

Image: Imperial College London