NANOBIOSENSING/BIOLOGICAL RESEARCH/ PERSONALIZED MEDICINE: Non-damaging, light-emitting nanoprobes enable long-term study of living cells

A new study is the first, according to its authors, to demonstrate that sophisticated, engineered light resonators can be inserted inside cells without causing damage.1 With such a resonator (or, "nanobeam") embedded, a cell can function, migrate, and reproduce as usual.

The device gets its name from the fact that it is shaped like a steel I-beam. A set of holes etched through the center serve as photonic cavities to focus and amplify light. "Devices like the photonic cavities we have built are quite possibly the most diverse and customizable ingredients in photonics," said Professor Jelena Vukovic, the paper's senior author and director of the Nanoscale and Quantum Photonics Lab at Stanford University, where the work was done. Applications in the life sciences realm include biosensors that could have profound impact on biological research.

Scanning electron microscopy (SEM) depicts a nanobeam, including a large part of the handle tip, inserted in a typical cell
Scanning electron microscopy (SEM) depicts a nanobeam, including a large part of the handle tip, inserted in a typical cell. (Image courtesy of Gary Shambat, Stanford School of Engineering)

Like a sharp needle, the nanobeam penetrates cell walls without injury, and once inside, emits light. The researchers note that while other groups have inserted simple nanotubes and electrical nanowires into cells, none had placed such complicated optical components intracellularly. "We think this is quite a dramatic shift from existing applications and will enable expanded opportunities for understanding and influencing cellular biology," said the paper's first author, Gary Shambat, a doctoral candidate in electrical engineering.

The primary and most immediate use would be in the real-time sensing of specific proteins within the cells, but the probe could be adapted to sense any important biomolecules such as DNA or RNA. To detect such key molecules, researchers coat the probe with organic molecules or antibodies known to attract the target proteins. If the desired proteins are present within the cell, they accumulate on the probe and cause a detectable shift in the wavelength of the light being emitted. This shift is a positive indication that the protein is present and in what quantity.

In a study designed to test whether a certain drug produces or inhibits a specific protein, the biosensor would be able to tell definitively if and how well the drug was working based on the color of emitted light. As such, it would represent a key development in personalized medicine, wherein drugs are targeted to patients based on their particular efficacy.

Structurally, the device is a sandwich of extremely thin layers of gallium arsenide (GaAs) and light-emitting crystal, etched from a substrate. Shambat and his colleagues have been working on similar devices for computing applications. His breakthrough came when he was able to peel the nanobeams off the substrate and glue them to fiber-optic cable with which he steers the probe into the cell. A thin, electrically insulating coating of alumina and zirconia encapsulates the device, making it nontoxic and rugged.

In one finding the authors describe as stunning, they loaded nanobeams into cells and watched as the cells grew, migrated, 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 means that researchers can study living cells over long periods, which is not possible with existing detection techniques. "We tracked one cell for eight days," said Shambat.

1. G. Shambat et al., Nano Lett., doi:10.1021/nl304602d (Feb. 6, 2013).

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