Abstract: The invention relates to methods, kits and systems for determining an analyte in a liquid sample as well as the use thereof for concentration analysis and screening purposes. In one method, a specific binding partner to the analyte is permitted to compete with a conjugate containing the analyte or an analyte analogue for the binding to free analyte. The conjugate also contains a component that specifically binds to a solid support so that reacted and unreacted conjugate are bound thereto when the reaction solution is contacted with the solid support. The amount of analyte is then determined by measuring by a label-free mass-detection technique, such as surface plasmon resonance, the amount of binding partner immobilized on the solid support via the reacted conjugate. This is made possible by the binding partner having a considerably greater mass than the conjugate. Variants of this method are also disclosed.

Abstract: Methods for capturing analytes associated with surface-bound ligands are disclosed. The methods involve eluting analytes from surface-bound ligands with a first liquid to generate free analytes, and capturing the free analytes with a solid capturing material within the first liquid to generate a first liquid containing captured analytes. The first liquid may be a flowing liquid or a non-flowing liquid, and the surface to which the surface-bound ligand is attached may be a sensing surface, such as a biosensor, or a non-sensing surface. The captured analytes may be further consolidated at a location removed from the surface-bound ligand, eluted from the solid capturing material with a second liquid, and used for subsequent analysis or procedures.

Abstract: A method of examining thin layer structures on a surface for differences in respect of optical thickness, which method comprises the steps of: irradiating the surface with light so that the light is internally or externally reflected at the surface; imaging the reflected light on a first two-dimensional detector; sequentially or continuously scanning the incident angle and/or wavelength of the light over an angular and/or wavelength range; measuring the intensities of light reflected from different parts of the surface and impinging on different parts of the detector, at at least a number of incident angles and/or wavelengths, the intensity of light reflected from each part of the surface for each angle and/or wavelength depending on the optical thickness of the thin layer structure thereon; and determining from the detected light intensities at the different light incident angles and/or wavelengths an optical thickness image of the thin layer structures on the surface.

Abstract: A method of operating an analytical flow cell device comprising an elongate flow cell having a first end and a second end, at least two ports at the first end and at least one port at the second end, comprises introducing a laminar flow of a first fluid at the first end of the flow cell, and a laminar counter flow of a second fluid at the second end. Each fluid flow is discharged at the first end or the second end, and the position of the interface between the first and second fluids in the longitudinal direction of the flow cell is adjusted by controlling the relative flow rates of the first and second fluids. Also disclosed are a method of analyzing a fluid sample for an analyte, a method of sensitizing a sensing surface, and a method of contacting a sensing surface with a test fluid.

Abstract: Methods for capturing analytes associated with surface-bound ligands are disclosed. The methods involve eluting analytes from surface-bound ligands with a first liquid to generate free analytes, and capturing the free analytes with a solid capturing material within the first liquid to generate a first liquid containing captured analytes. The first liquid may be a flowing liquid or a non-flowing liquid, and the surface to which the surface-bound ligand is attached may be a sensing surface, such as a biosensor, or a non-sensing surface. The captured analytes may be further consolidated at a location removed from the surface-bound ligand, eluted from the solid capturing material with a second liquid, and used for subsequent analysis or procedures.

Abstract: A method of examining thin layer structures on a surface for differences in respect of optical thickness, which method comprises the steps of: irradiating the surface with light so that the light is internally or externally reflected at the surface; imaging the reflected light on a first two-dimensional detector; sequentially or continuously scanning the incident angle and/or wavelength of the light over an angular and/or wavelength range; measuring the intensities of light reflected from different parts of the surface and impinging on different parts of the detector, at at least a number of incident angles and/or wavelengths, the intensity of light reflected from each part of the surface for each angle and/or wavelength depending on the optical thickness of the thin layer structure thereon; and determining from the detected light intensities at the different light incident angles and/or wavelengths an optical thickness image of the thin layer structures on the surface.

Abstract: The present invention relates to a method of preparing a substrate surface supporting a lipid film membrane structure, which method comprises the steps of contacting a substrate surface with an aqueous liquid containing detergent/lipid mixed micelles to adhere detergent/lipid mixed micelles to the substrate surface, and then contacting the substrate surface having detergent/lipid mixed micelles adhered thereto with an aqueous liquid substantially free from detergent to elute the detergent molecules from the adhered mixed micelles and make the remaining lipid molecules assemble into a lipid film membrane structure on the substrate surface. The invention also relates to a substrate supporting a lipid film membrane structure as prepared by the method, the use of a substrate supporting a lipid film membrane structure as prepared by the method for molecular interaction studies, and a substrate surface for use in the method.

Abstract: An optical apparatus for total internal reflection spectroscopy comprises: a transparent body having an internally reflective surface; at least one source of electromagnetic radiation for providing at least one beam of collimated electromagnetic radiation; optical scanning means for directing the beam or beams to the transparent body so that the radiation is internally reflected at the reflective surface, and sequentially or continuously scanning the incident angle of the radiation over an angular range; at least one detector for detecting electromagnetic radiation exiting the transparent body, and means for counteracting variation of the irradiance in the illuminated area of the surface during the angular scan, or the effect of such variation on the reflected beam or beams. An optical apparatus for examining thin layer structures on a surface for differences in respect of optical thickness and/or refractive index, and a method for total internal reflection spectroscopy are also disclosed.

Abstract: The present invention discloses a valve integrally associated with a microfluidic transport assembly that is useful for regulating the flow of a liquid sample through an analytical instrument such as, for example, a biosensor.

Abstract: Surface regeneration of affinity biosensors and characterization of biomolecules associated therewith by multivariate technique employing cocktails of regeneration agents to optimize regeneration of biosensor surface and/or characterize biomolecules associated therewith. Kits and stock solutions for use in the context of this invention, as well as associated computer algorithms are also disclosed.

Abstract: A method of determining the binding of an oligonucleotide probe to a test nucleic acid sequence comprises the steps of: (a) providing the test nucleic acid sequence in single-stranded form, (b) contacting the test nucleic acid sequence under hybridizing conditions with a solution containing an oligonucleotide probe which is complementary to a defined portion of a standard nucleic acid sequence, (c) immobilizing to a solid support a nucleic acid fragment at least part of which is complementary to said oligonucleotide probe, (d) contacting the solution from step (b) with said solid support, and (e) determining the amount of binding of oligonucleotide probe present in said solution to its complementary nucleic acid fragment on the second solid support, said amount being inversely related to the amount of binding of the oligonucleotide probe to the test nucleic acid sequence.

Abstract: Methods and devices are provided for controlling a fluid flow over a sensing surface within a flow cell. The methods employ laminar flow techniques to position a fluid flow over one or more discrete sensing areas on the sensing surface of the flow cell. Such methods permit selective sensitization of the discrete sensing areas, and provide selective contact of the discrete sensing areas with a sample fluid flow. Immobilization of a ligand upon the discrete sensing area, followed by selective contact with an analyte contained within the sample fluid flow, allows analysis by a wide variety of techniques. Sensitized sensing surfaces, and sensor devices and systems are also provided.

Abstract: Methods and kits are disclosed for detecting betalactam-containing compounds in a sample, and typically liquid products intended for human consumption such as milk. Betalactam-containing compounds include the class of betalactam antibiotics which may be present as undesired contaminates of milk. The methods involves contacting the sample with a D,D-carboxypeptidase and a substrate having a carboxyterminal D-alanine-D-alanine to form a reaction mixture, wherein the D,D-carboxypeptidase is capable of cleaving the terminal D-alanine from the substrate to yield a cleaved substrate. In an optional step, the reaction mixture is further contacted with a ligand specific to the cleaved substrate or substrate. The cleaved substrate or substrate of the reaction mixture, or the ligand specific to the cleaved substrate or substrate, is then captured by a surface-bound binding partner, with the amount of captured material being indicative to the amount of betalactam-containing compound in the sample.

Abstract: A method of determining affinity and kinetic properties for the solution interaction between an analyte and a binding partner therefor, which method comprises: (a) mixing a solution of said analyte with a solution of said binding partner, contacting the resulting reaction solution with (i) immobilised binding partner, or analogue, for said analyte, and/or (ii) immobilised analyte, or analogue, and monitoring the binding of said analyte and/or binding partner in said reaction solution to the respective immobilised species to determine the variation with time of the concentration of free analyte and/or binding partner in said solution; and/or (b) contacting a solution of the reaction complex of said analyte and a binding partner therefor with (i) immobilised binding partner, or analogue, and/or (ii) immobilised analyte, or analogue, and monitoring the binding of said analyte and/or binding partner in said reaction complex solution to the respective immobilised species to determine the variation with time of the

Abstract: The invention relates to a method of analysing a chemical or physical interaction taking place in a film layer at an optical sensor surface when the film layer is contacted with a fluid sample containing a species capable of interacting with the film layer, wherein the interaction is monitored by determination of the refractive index of the film layer through a light-intensity signal producing technique by measuring the relationship between a parameter of the incident and/or reflected light and one of the minimum, the maximum and the centroid of the light intensity signal curve.

Abstract: Systems and methods for reversibly and controllably flowing a first and second fluid adjacent to one or more discrete sensing surfaces of a biosensor are disclosed herein. The systems utilize a flow-cell conduit adapted to flow the first and second fluids in either a first or second flow direction and in a manner such that the first and second fluids separately contact the one or more discrete sensing surfaces of the biosensor. The flow-cell conduit is operatively connected to both a two-fluid conduit and a single-fluid conduit via a valveless juncture. The system also comprises a selector valve for reversing the flow direction of the fluid within the flow-cell conduit.

Abstract: A method of analysing nucleic acid sequences comprises measuring by surface sensitive detection technique the binding interaction between a first nucleic acid sequence and a second nucleic acid sequence, one of the first and second nucleic acid sequences being immobilized to a solid phase surface, to determine the affinity or an affinity related parameter for the binding reaction as indicative of the extent of complementary between the first and second nucleic acid sequences. The method is characterized in that the measurement of the binding interaction is performed at annealing conditions adjusted such that the dissociation rate constant for the binding interaction corresponding to full complementarity between the first and second nucleic acid sequences is greater than about 10.sup.- per second, thereby permitting equilibrium for the interaction to be rapidly attained.

Abstract: Disclosed is apparatus for detecting the presence of an analyte of interest in a sample, comprising an immobilised binding partner comprising a solid support and a reversibly binding receptor which is capable of binding to the analyte of interest thereby causing a measurable change in a property of the immobilised partner, and detection means for detecting the measurable change and a method for detecting the presence of an analyte of interest.