Abstract: A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

Abstract: This invention provides novel high density memory devices that are electrically addressable permitting effective reading and writing, that provide a high memory density (e.g., 1015 bits/cm3), that provide a high degree of fault tolerance, and that are amenable to efficient chemical synthesis and chip fabrication. The devices are intrinsically latchable, defect tolerant, and support destructive or non-destructive read cycles. In a preferred embodiment, the device comprises a fixed electrode electrically coupled to a storage medium comprising a storage molecule comprising a first subunit and a second subunit wherein the first and second subunits are tightly coupled such that oxidation of the first subunit alters the oxidation potential(s) of the second subunit rendering the oxidation potential(s) of the second unit different and distinguishable from the oxidation potentials of the first subunit.

Abstract: Methods of recombining nucleic acids, including homologous nucleic acids, are provided. Families of gene shuffling oligonucleotides and their use in recombination procedures, as well as polymerase and ligase mediated recombination methods are also provided.

Abstract: Assay devices, kits, and methods for detection of one or more analytes in a sample are provided. The assay device features the controlled release of reagents and hence is particularly suitable for binding assays such as immunoassays. The assay device achieves greater sensitivity than conventional rapid test assays, leading to stronger visual signals than those produced by conventional devices, easier interpretation of results, and reduced occurrence of indeterminate results. The device can be used for detecting analyte in a variety of biological samples without the need for conventional sample filtration techniques, and thus is suitable for use by untrained personnel without specialized equipment. In addition, the device can be used to simultaneously analyze a number of analytes using a single sample.

Abstract: The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.

Abstract: An apparatus for analyzing a plurality of compounds is used in conjunction with microfluidic devices for performing high throughput screening assays. A conveyor system delivers libraries of compounds to a microfluidic device which accesses the compounds in order to screen large numbers of different compounds for their effects on a variety of chemical and biochemical systems.

Abstract: Multiphasic microfluidic apparatus for performing product fluid manipulation and separation in a single continuous unit are provided. Related methods, kits, and compositions are also provided.

Abstract: The present invention provides for an isolated A-type substance having a structure identical to an A-type substance obtained from human liver or placenta, which is a cyclical containing carbohydrate comprising Zn2+ and related compositions.

Abstract: Methods of performing fast polymerase mediated reactions are provided. These reactions can be used in an inefficient fashion in the cycles of the polymerase mediated reactions to produce product at a much faster rate than conventional polymerase mediated reaction methods. Integrated systems for performing these methods are also provided.

Abstract: Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.

Abstract: A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

Abstract: The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: A sample preparation method is disclosed for volatilization and mass spectrometric analysis of nonvolatile high molecular weight molecules. Photoabsorbing molecules having significant sublimation rates at room temperature under vacuum, and preferably containing hydroxy functionalities, are disclosed for use as matrices in matrix-assisted laser desorption/ionization mass spectrometry. The samples are typically cooled in the mass spectrometer to temperatures significantly below room temperature.

Abstract: This invention provides a novel intracellular recycling free cholesterol pathway whose activity is required for cell division. The pathway provides the cholesterol needed for cell division prior to separation of daughter cells (mitosis). The new pathway offers several targets from pharmaceutical intervention, either via small molecules (such as sterol analogs) or by molecular engineering (preventing the cell from accumulating cholesterol by promoting free cholesterol efflux by transfection of caveolin cDNA).

Abstract: The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

Abstract: Microfluidic devices are provided for the performance of chemical and biochemical analyses, syntheses and detection. The devices of the invention combine precise fluidic control systems with microfabricated polymeric substrates to provide accurate, low cost miniaturized analytical devices that have broad applications in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields.

Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.