Analytical apparatus

Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is inorganic

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356426, 356427, 356428, 385 12, 385129, 385130, 422 50, 422 55, 422 58, 422 8205, 422 8211, 4352871, 4352872, 4352887, 435808, 436164, 436165, 436518, 436535, 436805, G01N 33543, G01N 33552

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active

057704627

DESCRIPTION:

BRIEF SUMMARY
This invention relates to analytical apparatus for the qualitative or quantitative determination of chemical or biochemical species or their interactions.
Many devices for the automatic determination of biochemical analytes in solution have been proposed in recent years. Typically, such devices (biosensors) include a sensitised coating layer which is located in the evanescent region of a resonant field. Detection of the analyte typically utilizes optical techniques such as, for example, surface plasmon resonance (SPR), and is based on changes in the thickness and/or refractive index of the coating layer resulting from interaction of that layer with the analyte. This causes a change, eg in the angular position of the resonance.
Other optical biosensors include a waveguide in which a beam of light is propagated. The optical characteristics of the device are influenced by changes occurring at the surface of the waveguide. One form of optical biosensor is based on frustrated total reflection. The principles of frustrated total reflection (FTR) are well known; the technique is 2167-2173!. An FTR device for use in immunoassay is disclosed in European Patent Application No 0205236A and comprises a cavity layer bounded on one side by the sample under investigation and on the other side by a spacer layer which in turn is mounted on a substrate. The substrate-spacer layer interface is irradiated with monochromatic radiation such that total reflection occurs, the associated evanescent field penetrating through the spacer layer. If the thickness of the spacer layer is correct and the incident parallel wave vector matches one of the resonant mode propagation constants, the total reflection is frustrated and radiation is coupled into the cavity layer. The cavity layer must be composed of material which has a higher refractive index than the spacer layer and which is transparent at the wavelength of the incident radiation.
In all such devices, problems can occur due to thermal effects. For accurate results it is vital to ensure that the sample reaches good equilibration with the surroundings and that comparative measurements are carried out at constant temperatures. In addition, inhomogeneities or transport phenomena occurring within the sample may lead to difficulties.
There has now been devised an analytical apparatus which overcomes or substantially mitigates the above-mentioned disadvantages.
According to the invention, there is provided an analytical apparatus comprising a biosensor device, a sample chamber adjacent the biosensor device, a stirrer extending into the sample chamber, and means for causing the stirrer to move within the sample chamber.
The apparatus according to the invention is advantageous primarily in that the motor-driven stirrer provides virtually instantaneous homogeneity and uniformity of the samples, in terms of both composition and temperature. This enables a larger area of sensitised coating to be used, which in turn leads to higher sensitivity. The apparatus offers significant advantages compared to known systems in which the sample chamber is a flow cell into which the sample is pumped, since in such systems the reaction kinetics are strongly dependent upon, and often adversely influenced by, the flow hydrodynamics.
The apparatus according to the invention is useful in the qualitative or quantitative determination of an analyte species in a sample or their interactions. The apparatus may be used not only for the determination of the presence and/or concentration of a particular molecular species, but also to monitor any process in which the molecular species interacts with the surface of the biosensor or with other molecular species at or in the vicinity of the surface. For example, the parameter under investigation may be the binding affinity of a molecular species with the biosensor surface.
Generally, the stirrer will comprise an elongate stirrer shaft. The shaft may terminate at a point within the sample chamber which, in use, lies within the sample fluid. Alternatively, the shaft may b

REFERENCES:
patent: 5051551 (1991-09-01), Doyle
patent: 5085759 (1992-02-01), Harker
patent: 5170056 (1992-12-01), Berard et al.
Wu et al., "Growth of a wetting layer in a flowing binary-liquid mixture at bulk coexistence", The American Physical Society, vol. 36 (8), Oct. 15, 1987, pp. 3975-3983.

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