| 摘要 |
The invention provides improved methods and devices for the detection and identification in a sample of one or more target molecules which bind to pro be molecules, particularly to nucleic acid probe molecules. The improved method is based on contacting the sample with a surface that is coated with one or more gradients of probe molecules, particularly nucleic acid or nucleic acid analog probe molecules that serve to bind target molecules in the sample, particularly nucleic acids having sequences that are complementary or partially complementary to one or more probe molecules. A probe gradient generated on the surface is formed by the variation of a physical, structura l or functional property of the probes on the surface. The gradients is generated, e.g., by varying density of probe molecules bound to the surface, by varying probe sequence length, by varying probe sequence, by varying prob e sequence type, by varying the orientational structure of probes, and by varying the concentration of label associated with probes. Determination of the location, speed and/or extent of hybridisation of a nucleic acid on such a gradient surface is useful to identify target molecules bound to probes and/ or to quantitatively measure the amount of the target in a sample. Hybridisatio n of target molecules toa gradient of nucleic acid probe can be examined as a function of time and/or hybridisation conditions (e.g., temperature, salt concentration, etc.) The method and devices of this invention employ gradien t surfaces to bind to one or more target molecules, particularly nucleic acids (or target sequences) in a sample, detecting their presence in the sample an d quantitating the amount of one or more of such targets in a sample.
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