Instrument drift is the bane of experimental science; the more sensitive the instrument, the more important it becomes to stop the sample moving. Even the tiniest influence of air currents or temperature instabilities can affect sensitive measurements, and experimentalists have gone to extreme lengths to eliminate these - vibration isolated labs, acoustic shielding, even performing experiments in a helium atmosphere. Some of the smallest length scales probed in biology are the Angstrom-sized steps of molecular motors and enzymes; the seminal experiments here worked around drift by measuring the displacement between two optical traps. As most of the drift was common to both traps, a differential measurement was able to cancel it out and reveal the sub-nanometre motion.

Many biological experiments, however, cannot be isolated from the sample cell - optical trapping assays performed on a functionalised coverslip, for example, or imaging techniques such as atomic force microscopy or optical superresolution. In this Optics Express article, Walder and co-workers have taken the dual-trap idea and turned it around; instead of simply taking a differential measurement with two lasers, they use a feedback loop and a piezo stage to lock the sample position to one of the lasers. The other laser can then be used for position detection, and the resulting drift depends only on instabilities between the two lasers - orders of magnitude better than the drift of the sample relative to the instrument.

Despite the elegant simplicity of the idea, implementing such a system requires phenomenal attention to detail. The NIST-based team used stablilised diode lasers, coupled through the same single mode fibre to ensure they started with the same spatial position. Great care was taken to keep areas of the system where the beams were separate to an absolute minimum so that any drift in the system was common to both, and lock-in detection was used to allow a single photodiod to measure both beams - again minimising sources of drift not common to both beams.

The resulting system's performance is impressive - Angstrom-scale stability over minutes and nanometre-sized drift over hours. As the reduction in drift no longer depends on performing experiments between two optical traps, it becomes possible to apply this technique to a wide range of experiments; surface-based assays, atomic force microscopy or even localisation-based superresolution techniques like PALM/STORM. As we probe ever deeper into the structure of cells and proteins, instrument designs such as this one will enable us to reach the increasingly stringent requirements for stability.

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