A novel nano-sized optical fiber, about 100 times thinner than a human hair, is sensitive enough to detect forces down to 160 femtonewtons (fN) (about ten trillion times smaller than a newton) when placed in a solution containing live Helicobacter pylori bacteria, i.e. swimming bacteria found in the gut. In cultures of beating heart muscle cells from mice, the nanofiber demonstrated the ability to detect sounds down to -30 decibels — a level 1,000 times below the limit of the human ear. The compact Nanofiber Optic Force Transducer (NOFT) uses near-field plasmon-dielectric interactions to measure local forces with a sensitivity of <200 fN.
This is an artist's illustration of nano-optical fibers detecting femtonewton-scale forces produced by swimming bacteria. Courtesy of Rhett S. Miller/UC Regents.
The device, developed by researchers from the University of California, San Diego, is made from an extremely thin fiber of tin dioxide, coated with a thin layer of polyethylene glycol and studded with gold nanoparticles.
To use the device, researchers dip the nano-optical fiber into a solution of live cells, send a beam of light down the fiber and analyze the light signals it sends out. As light travels down the nanofiber, it interacts with the gold nanoparticles, which scatter the light as signals that can be seen with a conventional microscope. The intensity of the light signals changes when the fiber is placed in the live-cell solution. Based on their intensity, the signals indicate how much force or sound the fiber is picking up from the surrounding cells.
Forces and sound waves from the cells impact the gold nanoparticles, pushing the nanoparticles into the polymer layer that separates them from the fiber's surface. When the nanoparticles are pushed closer to the fiber they are able to interact more robustly with the light coming down the fiber, thus increasing the intensity of the light signals. The researchers calibrated the device so the signal intensities could be matched to different levels of force or sound.
“We're not just able to pick up these small forces and sounds, we can quantify them using this device. This is a new tool for high resolution nanomechanical probing,” professor Donald Sirbuly said.
The polymer layer that coats the nanofiber acts like a spring mattress that’s sensitive enough to be compressed to different thicknesses by the faint forces and sound waves produced by the cells. Sirbuly says the polymer layer can be tuned: If researchers want to measure larger forces, they can use a stiffer coating. For increased sensitivity, they can use a softer polymer like a hydrogel.
According to the researchers, the optical nanofiber is at least ten times more sensitive than an atomic force microscope (AFM). While AFMs are bulky, in contrast the nanofiber is only several hundred nanometers in diameter.
“It's a mini AFM with the sensitivity of an optical tweezer,” Sirbuly said.
A variety of molecular force probes, including quantum dots, fluorescent pairs and molecular rotors, have been designed to measure intracellular stresses. However, fluorescence-based techniques can have short operating times due to photo-instability; and it can be challenging to quantify the forces with high spatial and mechanical resolution.
Future applications for the NOFT device could include detecting the presence and activity of a single bacterium; monitoring bonds forming and breaking; sensing changes in a cell’s mechanical behavior that might signal it becoming cancerous or being attacked by a virus; or as a mini stethoscope to monitor cellular acoustics in vivo.
“This work could open up new doors to track small interactions and changes that couldn’t be tracked before,” said Sirbuly.
Going forward, the researchers plan to use the nanofibers to measure bio-activity and the mechanical behavior of single cells. Plans also include improving the fibers’ “listening” capabilities to create ultra-sensitive biological stethoscopes, and tuning their acoustic response to develop new imaging techniques.
The research was published in Nature Photonics (doi: 10.1038/nphoton.2017.74).