If engineers at Stanford have their way, biological research may soon be transformed by a new class of light-emitting probes small enough to be injected into individual cells without harm to the host.
Welcome to biophotonics, a discipline at the confluence of engineering, biology and medicine in which light-based devices – lasers and light-emitting diodes (LEDs) – are opening up new avenues in the study and influence of living cells.
The team described their probe in a paper published online Feb. 13, 2013 by the journal Nano Letters. It is the first study to demonstrate that tiny, sophisticated devices known as light resonators can be inserted inside cells without damaging the cell. Even with a resonator embedded inside, a cell is able to function, migrate and reproduce as normal.
The researchers call their device a "nanobeam," because it resembles a steel I-beam with a series of round holes etched through the center. This beam, however, is not massive, but measure only a few microns in length and just a few hundred nanometers in width and thickness. It looks a bit like a piece from an erector set of old. The holes through the beam act like a nanoscale hall of mirrors, focusing and amplifying light at the center of the beam in what are known as photonic cavities.
Structurally, the new device is a sandwich of extremely thin layers of the semiconductor gallium arsenide alternated with similarly thin layers of light-emitting crystal, a sort of photonic fuel known as quantum dots. The structure is carved out of chips or wafers, much like sculptures are chiseled out of rock. Once sculpted, the devices remain tethered to the thick substrate.
For biological applications, the thick, heavy substrate presents a serious hurdle for interfacing with single cells. The underlying and all-important nanocavities are locked in position on the rigid material and unable to penetrate cell walls.
Shambat's breakthrough came when he was able to peel away the photonic nanobeams. He then glued the ultrathin photonic device to a fiberoptic cable with which he steers the needle-like probe toward and into the cell.
Once inserted in the cell, the probe emits light, which can be observed from outside. For engineers, it means that almost any application of these powerful photonic devices can be translated into the previously off-limits environment of the cell interior. In one finding that the authors describe as stunning, they loaded their nanobeams into cells and watched as the cells grew, migrated around the research environment and reproduced. Each time a cell divided, one of the daughter cells inherited the nanobeam from the parent and the beam continued to function as expected.
This inheritability frees researchers to study living cells over long periods of time, a research advantage not possible with existing detection techniques, which require cells be either dead or fixed in place.
"Our nanoscale probes can reside in cells for long periods of time, potentially providing sensor feedback or giving control signals to the cells down the road," said Shambat. "We tracked one cell for eight days. That's a long time for a single-cell study."