You’ve seen this: A guy goes up to a wall and slaps a probe onto it. Then he connects earphones to the probe and starts listening. Picture something like this happening to the wall of a living cell. It’s become almost routine for nanotechnology to come up with astonishing things. This qualifies: A probe 600 nanometers in size (that’s 6/1000 the diameter of a human hair) can now be attached to the outer membrane of a living cell, where it can reside for days monitoring the electrical activity inside the cell.
Nick Melosh, assistant professor, and Benjamin Almquist, grad student, and engineers at Stanford University (California, USA) crafted the probe out of a nanoscale silicon post. The hard part was trying to make the post integrate with the cell membrane in a way similar to that of the natural protein ‘gates’ of the membrane.
A living cell encloses a special environment. The cell wall, a highly specialized protein membrane, maintains the interior environment of the cell while permitting some things (especially energy supply) to move through it. The motion of material into and out of a cell goes through gates (protein channels). The channel imitates the water orientation sections of the membrane, hydrophilic (water attracting) at the outside and inside, hydrophobic (water avoiding) on the inside. This arrangement keeps unwanted molecules from crossing the membrane.
Creating a probe to mimic the hydrophilic/hydrophobic arrangement was difficult. It began with using semiconductor industry nanofabrication methods to create the nanoscale silicon post. The tips of the post were then coated with a gold layer between two chromium layers at the ends (the chromium is hydrophilic, the gold is conductive). Finally the middle section of gold was coated with carbon molecules to make it hydrophobic. Coating the tips was especially difficult; at 200 nanometers in diameter applying the thin layers required invention of a new technique for metal deposition.
The effort was successful. The nanoprobes not only penetrated living cells without breakup of the membrane, but they became so well integrated they could not be removed without ripping. This particular probe construction is designed to allow monitoring of electrical activity within the cell (the world’s tiniest patch clamp). It is also probable that instead of a post, a tube could be constructed with the same properties and used as a means for introducing materials into the cell – an artificial protein channel.
The applications for this technology are many:
Everything from signals generated as cells communicate with each other to “digestive rumblings” as cells react to medication could be monitored for up to a week, say Stanford engineers.
Current methods of probing a cell are so destructive they usually only allow a few hours of observation before the cell dies. The researchers are the first to implant an inorganic device into a cell wall without damaging it.
The key design feature of the probe is that it mimics natural gateways in the cell membrane, said Nick Melosh, an assistant professor of materials science and engineering in whose lab the research was done. With modification, the probe might serve as a conduit for inserting medication into a cell’s heavily defended interior, he said. It might also provide an improved method of attaching neural prosthetics, such as artificial arms that are controlled by pectoral muscles, or deep brain implants used for treating depression.
The 600-nanometer-long, metal-coated silicon probe has integrated so smoothly into membranes in the laboratory, the researchers have christened it the “stealth” probe.
The next step is testing the probe with a variety of living cells.