Abstract: A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising 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: A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising 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: A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising 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: A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising 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 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: Provided herein is a method of determining a sequence of a target polynucleotide. The method can include the steps of a) providing a device including an array of relatively short polynucleotides and relatively long polynucleotides immobilised on a surface of a solid support, wherein the relatively long polynucleotides are fragments of the target polynucleotide and wherein the relatively long polynucleotides are separated by a distance of at least 10 nm, whereby parts of the relatively long polynucleotides that extend beyond the relatively short polynucleotides can be individually optically resolved; and b) determining the sequence of the target polynucleotide by detecting incorporation of nucleotides into strands complementary to the relatively long polynucleotide fragments using fluorescent labels associated with the incorporated nucleotides. Also provided is system for determining a sequence of a target polynucleotide. The system can include means for carrying out steps a) and b) of the above method.

Abstract: The subject invention pertains to a method for the production of an array of molecules immobilised on a substrate, comprising the deposition of the molecules from a micropipette containing them, onto the substrate, in a liquid environment, wherein the distance of the micropipette from the substrate is controlled in response to the ion current in the liquid. This method is particularly suitable for the deposition of biological molecules. The subject invention also pertains to an array of biological molecules deposited on a substrate.

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: The invention is directed to a method for analysing genome wide variation in an individual. The method comprises randomly fragmenting the individual's genome and generating sequence reads of multiple bases on all fragments of the individual's genome, aligning the sequence reads generated with a known genomic reference sequence, and analysing variations between the sequence reads derived from the individual's genome and the known genomic reference sequence.

Abstract: The subject invention pertains to a method for determining the affinity between binding partners, or a property of one of the binding partners dependent on the affinity, comprising the steps of: (i) contacting the binding partners, one of which is immobilised on a surface; (ii) oscillating the surface at increasing amplitude; and (iii) detecting a dissociation event. An analogous method can be used to separate a target analyte from a composition. The subject invention also pertains to an apparatus for determining the affinity between binding partners, and comprises: a surface (10) having one binding partner (16) immobilised thereon; means for oscillating the surface at increasing amplitude; and means (14, 15) for detecting a dissociation event.

Abstract: The present invention pertains to an apparatus for imaging an object, comprising a probe via which an assay component may be delivered; a sensor to detect ion current; and means for controlling the position of the probe relative to the object in response to the ion current. Such apparatus can be used to image live cells, without affecting them, in solution, e.g., using light, wherein the distance between probe and cell is less than the wavelength of light.

Abstract: The subject invention pertains to a method for the production of an array of molecules immobilised on a substrate, comprising the deposition of the molecules from a micropipette containing them, onto the substrate, in a liquid environment, wherein the distance of the micropipette from the substrate is controlled in response to the ion current in the liquid. This method is particularly suitable for the deposition of biological molecules. The subject invention also pertains to an array of biological molecules deposited on a substrate.

Abstract: The present invention concerns a method for determining the identity of one or more single nucleotide polymorphisms (SNP) in a genome, comprising: (i) fragmenting a sample genome; (ii) contacting the fragments with an excess of a plurality of different oligonucleotide primers under conditions that permit a primer to form a duplex with a complementary region on a fragment, each primer having a predetermined sequence complementary to a sequence on the genome that is proximal to a putative SNP site, and the resulting duplexes being immobilised on a solid support; (iii) carrying out the sequencing reaction(s) and detecting the incorporation of bases onto the oligonucleotide primers to extend the primers to at least the SNP site; and (iv) comparing the resulting sequences to those of the reference one or more SNPs.

Abstract: A device comprising an array of molecules immobilised on a solid surface is disclosed, wherein the array has a surface density which allows each molecule to be individually resolved, e.g. by optical microscopy. Therefore, the arrays of the present invention consist of single molecules are more spatially distinct than the arrays of the prior art.

Abstract: A device comprising an array of molecules immobilised on a solid surface is disclosed, wherein the array has a high density of relatively short molecules and relatively long polynucleotides immobilised on the surface of a solid support, wherein the polynucleotides are at a density that permits individual resolution of those parts thereof that extend beyond the relatively short molecules.

Abstract: A device comprising an array of molecules immobilised on a solid surface is disclosed, wherein the array has a surface density which allows each molecule to be individually resolved, e.g. by optical microscopy. Therefore, the arrays of the present invention consist of single molecules are more spatially distinct than the arrays of the prior art.

Abstract: The subject invention pertains to a method for determining the affinity between binding partners or a property of one of the binding partners dependent on the affinity, comprising the step of:

Abstract: A device comprising an array of molecules immobilised on a solid surface is disclosed, wherein the array has a surface density which allows each molecule to be individually resolved, e.g. by optical microscopy. Therefore, the arrays of the present invention consist of single molecules are more spatially distinct than the arrays of the prior art.

Abstract: A method for determining the affinity between binding partners, or a property of one of the binding partners dependent on the affinity, comprising the steps of: (i) contacting the binding partners, one of which is immobilised on a surface; (ii) oscillating the surface at increasing amplitude; and (iii) detecting a dissociation event. An analogous method can be used to separate a target analyte from a composition. The subject invention also pertains to an apparatus for determining the affinity between binding partners, and comprises: a surface (10) having one binding partner (16) immobilised thereon; means for oscillating the surface at increasing amplitude; and a device (14, 15) for detecting a dissociation event.