A tiny “force probe” that can measure sub-piconewton forces when inserted directly into liquid media has been created by researchers in the US. The team says that it used the probe to detect the tiny forces associated with swimming bacteria and heart-muscle cells. The researchers suggest that the technique could be used to create miniature stethoscopes. A leading biophysicist, however, says more work must be done on characterizing the device before he is convinced of its efficacy.
Sensing and manipulating tiny forces is crucial to numerous areas of science. Scientists have therefore developed several techniques to do this – including the atomic force microscope (AFM). An AFM uses a very sharp tip attached to a flexible cantilever. The tip pushes against or pulls an object, while measuring the forces involved. This involves measuring the cantilever deflection – usually by reflecting light from the cantilever. Although the tip itself can be as small as one atom, the rest of the measurement system is much larger and this can make it difficult to map the forces in a tiny object such as a living cell.
Now, Donald Sirbuly of the University of California, San Diego, and colleagues have taken a different approach by detecting the forces on tiny optical fibres. Their probe comprises tin-dioxide fibres around 100 times thinner than a human hair that are coated with the highly compressible polymer polyethylene glycol. They then deposited gold nanoparticles on the polymer layer. When white light travels down a fibre, some of the electromagnetic energy leaks laterally. This “evanescent” light couples to the gold nanoparticles and then scatters into the surroundings.
The coupling between each nanoparticle and the waveguide – and therefore the strength of the scattering – is extremely sensitive to the positions of the nanoparticles. “Any time a force or sound wave hits these particles, they move,” explains Sirbuly, “and we can track that simply by looking at the optical scattering signals.”
The researchers calibrated their “nanofibre optic force transducer” (NOFT) by pressing on it with an AFM and measuring how the scattering signals varied with applied force. They reckon it is sensitive to forces as small as 160 fN – which they say is at least 10 times smaller than the sensitivity of an AFM.
To test the NOFT, they tried to measure the forces at work in a solution of living bacteria – finding them significantly greater than in a similar solution of dead bacteria. Then, they placed the device about 100 μm from mouse heart cells in a dish and resolved beating frequencies between 1–3 Hz. The researchers now want to explore the signals from other types of tissue: “The idea of having a really small stethoscope is certainly interesting,” Sirbuly says: “It would be interesting to see if we can detect differences in the acoustic signatures of bio-organisms.” On the more fundamental side, he says NOFTs might be useful to measure the mechanical signals cells produce as they undergo changes to, for example, diseased states.
Biophysicist Vincent Croquette of Ecole Normale Supérieure in Paris agrees that NOFTs could have potential where very small force sensors are required, but believes the paper describing the probe does not properly demonstrate this. He notes a detector’s sensitivity is defined by the smallest signal distinguishable from noise, and, without the noise spectrum of the probe, he says the figure of 160 fN is difficult to interpret.
He also says the NOFT needs proper calibration: “The classic test is to pull on a DNA molecule, which has a force-extension curve that is extremely well known,” he says. “So it’s perfectly suited to test a sensor for forces in the range of 200 fN. Everyone calibrates sensors with a DNA molecule these days, because it’s so reproducible it’s become a standard. Why don’t they choose a classical, canonical example to specify their sensitivity?” He adds: “They have done a good job of making a sensor, but a pretty bad job of showing that their sensor is good.”
The NOFT is described in Nature Photonics.