Abstract: A method and apparatus of interrogating an addressable array unit, which includes a substrate, a light reflecting layer on a front side of the substrate, and a plurality of features on a front side of the array. The method may include, for each of multiple features, illuminating the feature simultaneously with reflected and non-reflected interrogating light. A light emitted from respective features is detected. Either or both, constructive interference of interrogating light at the features, or constructive interference of light emitted from the features, can be obtained to allow lowering of light power from the source, enhanced signal, or reduced noise, or combinations of the foregoing. High depth discrimination may also be obtained without the need for a confocal detection system with conventional pinhole.

Abstract: A computational method and system for predicting the hybridization potential for two polymers. A probe/target interaction matrix is prepared to contain indications of all possible probe/target subunit interaction stabilities. The probe/target interaction matrix is analyzed to create a list of possible single-fragment hybridizations. A graph is then generated with vertices representing fragments, and edges representing possible loops in one or both of the probe and target sequences that allow the pair of fragments interconnected by the edge to coexist within a multi-fragment cross-hybridization. Finally, the graph is analyzed to construct a list of all possible single-fragment and multi-fragment cross-hybridizations possible between the probe molecule and the target molecule. The different hybridizations are scored and sorted by score.

Abstract: Methods and reagents are disclosed which satisfy the need for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of natural and mass-modified oligonucleotide precursors having a high level of coverage and mass number complexity. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of natural and mass-modified oligonucleotide precursors and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis, generally via MALDI-TOF. The enzymatic assay may be a polymerase extension assay or a ligase assay. The kits for carrying out the methods of the invention are also disclosed.

Abstract: A CCD array imager adapted for use as a spatial noise discriminator in confocal scanning microscopy comprises a parallel (vertical) register with a horizontal unmasked imaging row of pixels in tandem with a masked storage array, a serial (horizontal) register for readout, and a means for synchronizing image acquisition in the unmasked row with vertical charge shifting in the storage array such that images are mapped to on-diagonal pixels of the storage array whereas noise is mapped to off-diagonal pixels.

Abstract: A CCD array imager adapted for use as a spatial noise discriminator in confocal scanning microscopy comprises a parallel (vertical) register with a horizontal unmasked imaging row of pixels in tandem with a masked storage array, a serial (horizontal) register for readout, and a means for synchronizing image acquisition in the unmasked row with vertical charge shifting in the storage array such that images are mapped to on-diagonal pixels of the storage array whereas noise is mapped to off-diagonal pixels.

Abstract: A technique for making precise spectrophotometric measurements illuminates a sample with two or more modulated light sources at two or more, typically closely spaced, wavelengths. Light from the sources is combined, homogenized, and directed to the sample, and the light from the sample is collected and detected by a photodetector. The optical output powers of two sources are modulated with the same periodicity and with a reversed amplitude. Variations in the concentrations of species in the sample affect the modulation amplitude representing the sum of the optical powers from two sources in such a way as to produce an output signal. That output signal, based on an electrical component varying with a periodicity at the fundamental frequency, provides a measure of the difference in the transmissions (or other optical properties) of the sample at the two wavelengths. Feedback methods, such as null-point detection, provide stable, sensitive measurements.