Abstract: The subject invention concerns methods for interrogating a surface using scanning ion conductance microscopy (SICM). In one embodiment, a method of the invention comprises the steps of: a) repeatedly bringing a SICM probe into proximity with the surface at discrete, spaced locations in a region of the surface and measuring surface height at each location; b) estimating surface roughness or other characteristic for the region based upon the surface height measurements; and c) repeatedly bringing the probe into proximity with the surface at discrete, spaced locations in the region, the number and location of which is based upon the estimated surface roughness or other characteristic in the region, and obtaining an image of the region with a resolution adapted to the surface roughness or other characteristic.

Abstract: The present invention is based on the realization that the bonds between a target molecule, or a target molecule attached to a particle, and a surface, can be ruptured by mechanically oscillating the surface at increasing amplitude, leading to detachment of the target molecule or particle from the surface. The required acceleration, and hence force, will depend on a variety of factors, including the mass of the molecule or particle, the nature of the bond to the surface and the geometric shape or size of the target molecule or particle. The present invention may therefore be used to separate or to size different target molecules, or to detect their presence.

Abstract: An apparatus for separating an analyte from a mixture or for detecting an analyte or for determining the affinity, or a property related to affinity, between binding partners is described. The apparatus comprises: a) a surface having the analyte or one of the binding partners immobilised thereon, in use; b) a transducer for oscillating the surface; c) a controller connected to the transducer for varying the amplitude and/or frequency of the oscillation to cause a dissociation event; and. d) an analyser connected to the transducer for detecting an oscillation of the transducer due to the dissociation event. The controller includes an oscillator connected in a resonant circuit with the transducer such that the transducer oscillates at two frequencies simultaneously, one of these causing the transducer to oscillate the surface and the other being supplied as an output to the analyser.

Abstract: An apparatus for oscillating a surface is described. The apparatus comprises an oscillator circuit having: a) a piezoelectric crystal connected to the surface; b) a variable frequency generator for generating a driving signal which is supplied to the crystal to cause the crystal to oscillate, thereby causing the surface to oscillate; and, c) an analyser for monitoring the phase shift between the voltage across the crystal and the current flowing through it and, in response generating an adjustment signal which relates to the difference between the oscillation frequency and a resonant frequency of the crystal, the variable frequency generator being responsive to the adjustment signal to vary the frequency of the driving signal to cause the crystal to oscillate at the resonant frequency.