Abstract: A novel and efficient single pot synthetic schemes are disclosed for preparing modified nucleotides, nucleotide analogs, nucleotide polyphosphates, and nucleotide polyphosphate analogs. The novel method is used to prepare nucleotides, nucleotide analogs, nucleotide polyphosphates, and nucleotide polyphosphate analogs having non-persistent or persistent and non-persistent modifications. Novel biomolecular reactions are also disclosed using the novel modified biomolecules disclosed herein.

Abstract: An apparatus and method based on the apparatus is disclosed for automated single molecule or molecular assemblage detection via light irradiation and detection of transient FRET between a donor or acceptor bound to an immobilized single molecule or molecular assemblage and a corresponding acceptor or donor associated with, covalently bonded to, a reagent, where the donor or acceptor associated with the reagent is transiently in FRET proximity to the acceptor or donor associated with the immobilized molecule or molecular assemblage.

Abstract: An apparatus and method based on the apparatus is disclosed for detecting and monitoring chemical and/or bio-chemical reactions or interactions at the single molecule level, where detection and monitoring is improved by moving the viewing field of the detector in a controlled manner. The motion of the moving frame is accomplished either through software in the detector system or is accomplished by moving the reacting system. The motion is controlled and is either linear, circular or elliptical. The motion provides for improved site identification or mapping, improved event detection and monitoring, improved signal recognition and improved noise reduction.

Abstract: Modified nucleotides are disclosed for use in single molecule sequencing, methods for making the modified nucleotides and method for using the modified nucleotides. Linkers for making the modified nucleotide are also disclosed.

Abstract: Support surfaces are disclosed that are designed to support molecules or molecular assemblies immobilized thereon so that the molecules or molecular assemblies can be observed in single molecule detections systems, where the support surfaces have reduced background and the fluorescent labels associated with the immobilized molecules or molecular assemblies have longer active lifetimes prior to permanent photo-bleaching or deactivation and have improve fluorescence properties and where the surfaces have more uniform fluorescent properties.

Abstract: A sequencing methodology is disclosed that allows a single DNA or RNA molecule or portion thereof to be sequenced directly and in substantially real time. The methodology involves engineering a polymerase and/or dNTPs with atomic and/or molecular tags that have a detectable property that is monitored by a detection system.

Abstract: Nucleotide triphosphate probes containing a molecular and/or atomic tag on a a ? and/or ? phosphate group and/or a base moiety having a detectable property are disclosed, and kits and method for using the tagged nucleotides in sequencing reactions and various assay. Also, phosphate and polyphosphate molecular fidelity altering agents are disclosed.