Abstract: The present disclosure relates to methods and constructs for single molecule electronic sequencing of template nucleic acids. The constructs are molecular sensor complexes which comprise a processive nucleic acid processing enzyme localized to a nanopore. Conformational changes in the enzyme induced by single nucleic acid processing events are transduced into electric signals by the nanopore, which are used to identify individual nucleotides.

Abstract: Embodiments of the present invention include processing steps and subsystems, within automated-biopolymer-synthesis systems and within other automated systems for organic-chemistry-based processing, for removing reagent solutions and solvents from reaction chambers following various synthetic reaction steps and washing steps undertaken during biopolymer synthesis. Embodiments of the present invention employ any of various different types of liquid-absorbing materials to wick, or remove by capillary action, liquids from reaction chambers. Wicking-based methods and subcomponents of the present invention remove significantly greater fractions of solutions from reaction chambers than conventional methods and subsystems and, in addition, are mechanically simpler and produce fewer deleterious side effects than currently used methods and subsystems.

Abstract: Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.

Abstract: Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.

Abstract: Embodiments of the present invention include processing steps and subsystems, within automated-biopolymer-synthesis systems and within other automated systems for organic-chemistry-based processing, for removing reagent solutions and solvents from reaction chambers following various synthetic reaction steps and washing steps undertaken during biopolymer synthesis. Embodiments of the present invention employ any of various different types of liquid-absorbing materials to wick, or remove by capillary action, liquids from reaction chambers. Wicking-based methods and subcomponents of the present invention remove significantly greater fractions of solutions from reaction chambers than conventional methods and subsystems and, in addition, are mechanically simpler and produce fewer deleterious side effects than currently used methods and subsystems.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: Methods and systems for automated polynucleotide synthesis design are provided. Example embodiments provide an Automated Polynucleotide Synthesis Design System (“APSDS”), which automatically generates a synthesis design for a designated target sequence specification. In one embodiment, the APSDS comprises a synthesis design engine, user interface support, a synthesis rules data repository, and a synthesis data repository. The APSDS automatically generates a synthesis design by receiving a target sequence(s) specification, generating a potential synthesis design, evaluating the potential design against synthesis rules, and when the evaluation indicates that the potential design is not successful according to the synthesis rules, adjusting the design to generate a new potential synthesis design and repeating the process of evaluating and adjusting until a potential synthesis design is found that satisfies the synthesis rules or until no solution is found.

Abstract: Tags and linkers specifically designed for a wide variety of nucleic acid reactions are disclosed, which are suitable for a wide variety of nucleic acid reactions wherein separation of nucleic acid molecules based upon size is required.

Abstract: Methods are provided for detecting the binding of a first member to a second member of a ligand pair, comprising the steps of (a) combining a set of first tagged members with a biological sample which may contain one or more second members, under conditions, and for a time sufficient to permit binding of a first member to a second member, wherein said tag is correlative with a particular first member and detectable by non-fluorescent spectrometry, or potentiometry, (b) separating bound first and second members from unbound members, (c) cleaving the tag from the tagged first member, and (d) detecting the tag by non-fluorescent spectrometry, or potentiometry, and therefrom detecting the binding of the first member to the second member.

Abstract: The synthesis of novel diketopiperazines, their use in inhibiting cellular events such as those involving NFK-&agr;, NFK-&bgr; and in the treatment of inflammation events, a combinatorial library of diverse diketopiperazines and process for their synthesis as a library and as individual compounds. In particular novel diketopiperazines are disclosed including their synthesis and use in cellular events such as activation of the transcription factor, nuclear factor, TNF-&agr;, TNF-&bgr; and also apoptosis.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: Synthetic oligonucleotides, such as synthetic DNA, often contain sequence errors due to synthetic failures (e.g., side products and/or truncated products). Methods are provided herein for improving the sequence fidelity of synthetic double-stranded oligonucleotides by separative depletion of synthetic failures. Separation is effected by utilization of methodologies in a preparative mode under denaturing conditions. A preferred use of the methods relates to gene synthesis.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: Tags and linkers specifically designed for a wide variety of nucleic acid reactions are disclosed, which are suitable for a wide variety of nucleic acid reactions wherein separation of nucleic acid molecules based upon size is required.

Abstract: Methods are provided for detecting the binding of a first member to a second member of a ligand pair, comprising the steps of (a) combining a set of first tagged members with a biological sample which may contain one or more second members, under conditions, and for a time sufficient to permit binding of a first member to a second member, wherein said tag is correlative with a particular first member and detectable by non-fluorescent spectrometry, or potentiometry, (b) separating bound first and second members from unbound members, (c) cleaving the tag from the tagged first member, and (d) detecting the tag by non-fluorescent spectrometry, or potentiometry, and therefrom detecting the binding of the first member to the second member .

Abstract: The synthesis of novel diketopiperazines, their use in inhibiting cellular events such as those involving NFK-&agr;, NFK-&bgr; and in the treatment of inflammation events, a combinatorial library of diverse diketopiperazines and process for their synthesis as a library and as individual compounds. In particular novel diketopiperazines are disclosed including their synthesis and use in cellular events such as activation of the transcription factor, nuclear factor, TNF-&agr;, TNF-&bgr; and also apoptosis.

Abstract: A method and system for correlating characteristics (e.g., type of nucleotide) of biomolecules (e.g., DNA) to molecular tags with unique molecular weights that are associated with the biomolecule. In one embodiment. the molecular tags are applied to primers used when synthesizing the biomolecule. The system initially receives a mapping of each characteristic of the biomolecules to the corresponding molecular weight of the molecular tag. The system also receives an indication of the molecular weights detected when analyzing the biomolecules to which the molecular tags have been associated. For each molecular weight detected, the system determines based on the received mapping the characteristic corresponding to the detected molecular weight. The system then indicates that the analyzed biomolecule has the determined characteristic.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides a oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes.