Abstract: Disclosed are methods, compositions and devices for screening a protein library for proteins having a desired activity, such as capable of catalyzing the formation of a bond between two reactants. In an exemplary embodiments, a plurality of proteins are expressed in vitro from a plurality of nucleic acids, the plurality of proteins are exposed with two single stranded oligonucleotides having complementary sequences, each oligonucleotide having a reactant and a fluorophore, the fluorescence of the protein-reactant-oligonucleotide-fluorophore complexes is detected and the complexes showing detectable fluorescence energy transfer are isolated, thereby isolating proteins having the desired enzymatic activity.

Abstract: Methods of obtaining sequence information about target polynucleotide having a predefined sequence are disclosed. The methods include sequencing by ligation and sequencing by polymerase.

Abstract: A novel subtype of type A botulinum neurotoxin (BoNT/A) is disclosed in the application. Methods to purify the neurotoxin as well as uses thereof are also disclosed.

Abstract: Methods and apparatus relate to the synthesis of high fidelity polynucleotides and to the reduction of sequence errors generated during synthesis of nucleic acids on a solid support. Specifically, design of support-bound template oligonucleotides is disclosed. Assembly methods include cycles of annealing, stringent wash and extension of polynucleotides comprising a sequence region complementary to immobilized template oligonucleotides. The error free synthetic nucleic acids generated therefrom can be used for a variety of applications, including synthesis of biofuels and value-added pharmaceutical products.

Abstract: Aspects of the invention relate to methods, compositions and algorithms for designing and producing a target nucleic acid. The method can include: (1) providing a plurality of blunt-end double-stranded nucleic acid fragments having a restriction enzyme recognition sequence at both ends thereof; (2) producing via enzymatic digestion a plurality of cohesive-end double-stranded nucleic acid fragments each having two different and non-complementary overhangs; (3) ligating the plurality of cohesive-end double-stranded nucleic acid fragments with a ligase; and (4) forming a linear arrangement of the plurality of cohesive-end double-stranded nucleic acid fragments, wherein the unique arrangement comprises the target nucleic acid.

Abstract: In exemplary implementations of this invention, a photoelectrode includes a semiconductor for photocarrier generation, and a catalyst layer for altering the reaction rate in an adjacent electrolyte. The catalyst layer covers part of the semiconductor. The thickness of the catalyst layer is less than 60% of its minority carrier diffusion distance. If the photoelectrode is a photoanode, it has an OEP that is more than the potential of the valance band edge but less than the potential of the Fermi level of the semiconductor. If it is a photocathode, it has an RHE potential that is less than the potential of the conduction band edge but more than the potential of the Fermi level of the semiconductor. The absolute value of difference (OEP minus potential of valence band edge, or RHE potential minus potential of conduction band edge) is greater than zero and less than or equal to 0.2V.

Abstract: Methods and devices relate to the isolation of nucleic acids of interest from within a population of nucleic acids such as libraries of nucleic acid sequences.

Abstract: Methods and compositions are provided for manipulating the genome of host cell to produce at least one exogenous gene product. Also provided are methods and composition for producing a programmable cell comprising a plurality of exogenous genes, wherein each exogenous gene is under the control of a disrupted regulatory sequence and wherein the disrupted regulatory sequences are restored by in vivo recombination. Preferably, the gene of interest is under the control of a genetically altered promoter which sequence recombination effects the expression of the exogenous gene(s).

Abstract: Methods and devices are provided for manipulating droplets on a support using surface tension properties, moving the droplets along a predetermined path and merging two droplets together enabling a number of chemical reactions. Disclosed are methods for controlling the droplets volumes. Disclosed are methods and devices for synthesizing at least one oligonucleotide having a predefined sequence. Disclosed are methods and devices for synthesizing and/or assembling at least one polynucleotide product having a predefined sequence from a plurality of different oligonucleotides having a predefined sequence.

Abstract: Methods and apparatus relate to reduction of sequence errors generated during synthesis of nucleic acids on a microarray chip. The error reduction can include synthesis of complementary stands (to template strands), using a short universal primer complementary to the template strands and polymerase. Heteroduplex can be formed be melting and re-annealing complementary stands and template strands. The heteroduplexes containing a mismatch can be recognized and cleaved by a mismatch endonuclease. The mismatch-containing cleaved heteroduplexes can be removed from the microarray chip using a global buffer exchange. The error free synthetic nucleic acids generated therefrom can be used for a variety of applications, including synthesis of biofuels and value-added pharmaceutical products.

Abstract: An all-additive apparatus for direct fabrication of nanometer-scale planar and multilayer structures that performs “pick-and-place” retrieval and deposition of materials comprises a tip and a controller and transport mechanism configured for causing the tip to acquire a transferable material and deposit at least a portion of the acquired transferable material at a predetermined location onto a substrate, without the use of a bridging medium, in order to directly assemble a structure. The tip may be submillimeter-scale, may comprise a plurality of sub-tips disposed in a predetermined arrangement, and/or may mechanically vibrate. Mechanical vibration of the tip may be monitored. The tip may acquire the transferable material from a reservoir. The assembled structure may be cured on the substrate.

Abstract: Disclosed are devices and methods to synthesize polynucleotides and libraries of polynucleotides such as libraries of oligonucleotides. In exemplary embodiments, the device includes a support having a plurality of features. Each feature contains a plurality of oligonucleotides. Within each feature, each of the plurality of oligonucleotides includes an identical predetermined subunit sequence of X nucleosides and a degenerate sequence of Y nucleosides. A predetermined combination of a subset of the features can be used to produce a polynucleotide having a predetermined sequence of Z nucleosides.

Abstract: An all-additive method for direct fabrication of nanometer-scale planar and multilayer structures comprises the steps of acquiring a transferable material with a submillimeter-scale tip, depositing at least a portion of the acquired first transferable material at a predetermined location onto a substrate without a bridging medium, and repeating to create a structure using the transferable material.

Abstract: A novel subtype of type A botulinum neurotoxin (BoNT/A) is disclosed in the application. Methods to purify the neurotoxin as well as uses thereof are also disclosed.

Abstract: Disclosed are methods for synthesizing and/or assembling at least one polynucleotide product having a predefined sequence from a plurality of different oligonucleotides. In exemplary embodiments, the methods involve synthesis and/or amplification of different oligonucleotides immobilized on a solid support, release of synthesized/amplified oligonucleotides in solution to form droplets, recognition and removal of error-containing oligonucleotides, moving or combining two droplets to allow hybridization and/or ligation between two different oligonucleotides, and further chain extension reaction following hybridization and/or ligation to hierarchically generate desired length of polynucleotide products.

Abstract: Systems and methods are provided to evaluate a search engine using search results retrieved from a plurality of different search engines. For example, a controller can randomly distribute a set of pre-formulated queries to a plurality of computers to query the search engines at random times to obtain search results and combine the search results to evaluate the completeness of a query result provided by a particular search engine. The controller may simulate the random queries from users using a set of computers and may reduce the burden on the search engines by spreading out the query activities over a period of time, such as a month.

Abstract: A touch-sensitive system, and apparatus, and method of operation of the apparatus, are provided. In one embodiment, the apparatus includes a light source module configured to emit light; and a deformable waveguide coupled to the light source module and configured to transmit the light or a deflected version of the light at a situs at which pressure external to the deformable waveguide is applied. The deformable waveguide may also be illuminated by the light. The apparatus may also include one or more sensors configured to detect information indicative of the light or the deflected version of the light at the situs, and output a signal in response to the detected information.

Abstract: Methods of obtaining sequence information about target oligonucleotides by repetitive single molecule hybridization are disclosed. The methods include exposing a target oligonucleotide to one or more copies of a test oligonucleotide; measuring hybridization; dehybridizing the test oligonucleotide; and repeating until the information content from the hybridization trials equals or exceeds the information content of the target oligonucleotide.

Abstract: Systems and methods are described for carrying out fusion reactions by changing either the Coulombic energy barrier or the reaction cross section or both. Such systems and methods are useful for creating fusion reactions which exceed energy breakeven (Q>1) and which have a relatively low cost and compact size.

Abstract: A molecular shuttle device comprises two or more molecular subunits connected to form a molecular chain, with the subunits defining binding positions along the molecular chain, and a shuttle capable of binding at each of the binding positions, wherein the shuttle moves between binding positions in response to one or more input signals which interact with the molecular subunits. In some embodiments the one or more input signals comprise an input signal sequence that interacts with the molecular chain and the shuttle moves between binding positions in response to the input sequence.