Twisting and Stretching
Single Molecules
Adding a twist to DNA
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A new design for a microscope with ultra-low drift.

Nanomanipulation experiments will typically analyze the behavior of a protein acting on a DNA molecule for times ranging from below one second up to several days. During this time the apparatus will track nanometer changes in the conformation of the DNA molecule. One of the great obstacles to nanomanipulation is microscope drift which pollutes the enzyme signal. Standard microscopes have not been designed to observe small objects for long times and certainly not to record their position with nanometer accuracy. Most of the time mechanical drift is induced by temperature changes, and most microscope manufacturers do not even supply the drift amplitude caused by a temperature change of one degree celsius. It turns out to be quite large, typically 1 μm per degree Celsius, thus a change of one 1/100 C is enough to simulate a 10 nm change of extension. Of course one can stabilize the temperature of the room but it is a difficult proposition to achieve a regulation with 1/100 C in accuracy.

At PicoTwist, we have therefore built our magnetic tweezer around a new kind of microscope in which thermal drifts have been minimized. The PicoTwist microscope is based on a 100x oil immersion microscope objective which is placed in a compact metallic housing with the sample placed on top. The design automatically compensates thermal drifts of the various parts. The focus position of the objective is driven to nanometer resolution by a feedback loop piezo translator. Finallly, the objective and sample holder are temperature-regulated with a stability better than 1/100 C. This has several advantages:

Drift of microscopes over 20 minutes Comparison of the drift in focus position for a standard commercial microscope and the PicoTwist design placed in the same room and thus experiencing the same thermal environement.
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For further information please contact picotwist.