BioEd Online

A tiny needle that can perform keyhole surgery on a single living cell could aid biologists researching gene therapy and developing new drugs.

Using microscopic lances to remove material from fertilized eggs is now a routine technique. But these microcapillaries are still quite clumsy and difficult to control precisely without damaging the cell. As they press through the cell wall, it is often deformed so badly that the cell dies.

Now, Japanese researchers have turned an atomic force microscope (AFM) into a surgical tool for cells that could add or remove molecules from precise locations inside a cell without harming it.

An AFM looks like the arm of a record player, with a tiny tip attached to the end of a cantilever that can sense minute changes in force as it drags across a surface. These devices are routinely used to make molecular-scale maps of new materials.

Unlike a microcapillary, the AFM can sense the force it exerts on the cell, making it extremely responsive, says Chikashi Nakamura, a cell scientist from the National Institute of Advanced Industrial Science and Technology, Hyogo, Japan, who describes the tool along with colleagues from Tokyo University of Agriculture and Technology, Japan, in the journal NanoLetters¹.

Needle sharp

The team used a beam of energetic ions to sharpen a standard silicon AFM tip into a needle just eight micrometres long and 200 nanometres wide.

When the researchers inserted the needle into a human embryonic kidney cell, the cell wall was indented by only 1 micrometre. That's much more delicate than comparable microcapilliary procedures, they say.

The cell membrane quickly returned to its original shape, and the needle was pushed into the cell's nucleus. The researchers claim this is the first time that solid material has been inserted into a nucleus of a living cell so accurately.

Responsive probe

The needle will allow researchers to inject molecules into specific regions of a cell, says Saul Tendler, a biophysicist at Nottingham University, UK, who uses AFM to investigate biological systems. For example, strands of DNA could be inserted directly into the nucleus to test new gene therapy techniques.

It would also be possible to monitor the chemistry of a cell in real time, Tendler adds, by coating the needle's tip with molecules that grab onto chemicals produced inside the cell. If the tip were designed to fluoresce when the molecules bind, or to change its electrical charge in a detectable way, scientists could watch the cell's response to a new drug, for example.

Ian Hall, who researches molecular medicine also at Nottingham University, says the tool could be particularly useful for studying human cells in diseases such as asthma or cystic fibrosis. Because such cells are often in short supply, a reliable way to monitor the chemistry of just one diseased cell could be invaluable, he says: "The key problem for me is a shortage of cells."