Abstract: A microfluidic emulsion droplet generation system and methods of use thereof are provided. The system may include a microfluidic substrate having a flow path configured and arranged for emulsion droplet generation, at least one textured surface in the flow path configured and arranged for inducing surface-mediated coalescence of emulsion droplets; and at least one channel junction in the flow path for emulsion droplet formation.

Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.

Abstract: The systems and methods described herein relate to a high-throughput flow apparatus. The apparatus is used with an array of wells, and is configured to impart a predetermined shear stress on cells cultured within each of the wells of the array of wells. The apparatus includes a plurality of mechanical tips. The plurality of mechanical tips each includes a head with a hemispheroid shape. The apparatus also includes a motor associated with at least one of plurality of mechanical tips. The motor is configured to drive the plurality of mechanical tips to impart the shear stress pattern in each of the wells.

Abstract: Disclosed is a spotter device and methods for the formation of microassays, biochips, biosensors, and cell cultures. The spotter may be used to deposit highly concentrated spots of protein or other materials on a microarray slide, wafer, or other surface. It may also be used to perform various chemistry steps on the same spots. The spotter increases the surface density of substances at each spot by directing a flow the desired substance (or a solution thereof) over the spot area until surface saturation is accomplished. The spotter may be loaded by well plate handling equipment. The spotter uses wells, microfluidic conduits, and orifices to deposit proteins, other biomolecules, or chemicals on a spot on, a separate surface. Each orifice is connected to two wells via microconduits. When the spotter contacts a surface, a seal is formed between the orifices and the surface. The same or different substances may be flowed across each orifice. Any number of orifices may be incorporated into a spotter.

Abstract: Patterned material depositions are formed on a surface of a substrate following filling each of one or more dispersions between each of spaces bounded by a stencil or a pair of patterned barriers on the surface of the substrate. Each dispersion comprises at least one liquid continuous medium and at least one dispersed material. Each patterned material deposition encompasses at least one dispersed material and is formed by evaporating the liquid continuous medium from the dispersion. Patterned material depositions may have multilayer structures. Systems include methods and device.

Abstract: Provided herein are methods, compositions, and kits for assays, many of which involve amplification reactions such as digital PCR or droplet digital PCR. The assays may be used for such applications as sequencing, copy number variation analysis, and others. In some cases, the assays involve subdividing a sample into multiple partitions (e.g., droplets) and merging the partitions with other partitions that comprise adaptors with barcodes.

Abstract: An object is to provide a highly effective segmented process apparatus for a microplate using a standard microplate without increasing the scale of the apparatus, as well as a method for processing a microplate. The apparatus includes: a predetermined microplate provided with a number of wells are set in array; one or more nozzle heads provided with a number of nozzles set in array; a suction and ejection mechanism for sucking and ejecting a gas via the nozzles; and a moving means which allows relative movement between the microplate and the nozzle heads, wherein tips of all of the nozzles provided on each nozzle head are provided in such a manner that the tips can be inserted into the wells in a portion of the microplate all together, and the row intervals and column intervals of the nozzles in array are respectively same as the row intervals and column intervals of the wells in array.

Abstract: The present patent application introduces methods for generating mixture compound libraries from a drug lead. The mixture compound libraries are then screened for the discovery of modified drug lead compounds which possess desired improved drug properties. The process utilizes a non-selective reaction to modify the drug lead compound structure. Compared to existing methods of modifying a drug lead compound, this new method can modify more structural positions of a drug lead compound. As a consequence, there will be greater probability of finding a product with improved drug properties.

Abstract: A system is provided that can include: a plurality of retainment regions, where each retainment region is adapted to retain a respective type of an oligonucleotide supported on a respective support; a mixture retainment region; a handling device; a control unit adapted to control the handling device; and a separating unit adapted to simultaneously separate different supported oligonucleotides from their respective supports. A method is provided that can include: pooling together a plurality of supported oligonucleotides to form a mixture; and simultaneously separating the oligonucleotides of the supported oligonucleotides in the mixture from their supports.

Abstract: The present invention relates to a method of producing a set of MHC molecules, and more precisely to a method of producing a set of MHC molecules which differ in their peptide bound in the binding groove. The method allows for parallel and rapid synthesis of different MHC molecules at high yields for each molecule.

Abstract: Lipid multilayer structures are formed by evaporating a solvent from each of a plurality of lipid solutions thereby form the lipid multilayer structures. Each lipid solution comprises the solvent and one or more lipids. Each lipid multilayer structure is a microstructure comprising one or more lipids.

Abstract: A method for production of a chemical library is provided, where the method involves: reacting, in a single vessel, a) a plurality, x, of aldehydes and/or ketones; and b) either (i) a plurality, y, of nucleophiles, (ii) a plurality, z, of electrophiles or both (i) and (ii); in the presence of c) a cascade catalyst capable of catalyzing reaction between said plurality of aldehydes and/or ketones and said plurality of nucleophiles, said plurality of electrophiles or both; to obtain a mixture of x-y ?-nucleophile substituted aldehydes and/or ketones, x•z ?-electrophile substituted aldehydes and/or ketones or x•y•z ?-nucleophile substituted, ?-electrophile substituted aldehydes and/or ketones; and the chemical libraries thus produced.

Abstract: A multi-port liquid bridge (1) adds aqueous phase droplets (10) in an enveloping oil phase carrier liquid (11) to a draft channel (4, 6). A chamber (3) links four ports, and it is permanently full of oil (11) when in use. Oil phase is fed in a draft flow from an inlet port (4) and exits through a draft exit port (6) and a compensating flow port (7). The oil carrier and the sample droplets (3) (“aqueous phase”) flow through the inlet port (5) with an equivalent fluid flow subtracted through the compensating port (7). The ports of the bridge (1) are formed by the ends of capillaries held in position in plastics housings. The phases are density matched to create an environment where gravitational forces are negligible. This results in droplets (10) adopting spherical forms when suspended from capillary tube tips. Furthermore, the equality of mass flow is equal to the equality of volume flow.

Abstract: According to various embodiments, a method is provided that comprises washing an array of DNA-coated beads on a substrate, with a wash solution to remove stacked beads from the substrate. The wash solution can include inert solid beads in a carrier. The DNA-coated beads can have an average diameter and the solid beads in the wash solution can have an average diameter that is at least twice the diameter of the DNA-coated beads. The washing can form dislodged DNA-coated beads and a monolayer of DNA-coated beads. In some embodiments, first beads for forming an array are contacted with a poly(ethylene glycol) (PEG) solution comprising a PEG having a molecular weight of about 350 Da or less. In some embodiments, slides for forming bead arrays are provided as are systems for imaging the same.

Abstract: The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Abstract: A novel N-acetyl-5-N,4-O-carbonyl-protected dibutyl sialyl phosphate donor for sialylation of both primary and sterically hindered secondary acceptors to prepare sialosides with high yield and ?-selectivity is disclosed. Methods for making disaccharide building blocks comprising ?(2?3), ?(2?6), ?(2?8), ?(2?8)/?(2?9) alternate, and ?(2?9) sialosides are provided. methods for one-pot synthesis of complex sialosides are disclosed. Libraries of sialosides and methods for using the libraries for detection and receptor binding analysis of surface glycoproteins or pathogens and cancer cells are disclosed. Methods for distinguishing between hemagglutinin (HA) from various strains of influenza are provided.

Abstract: Provided are a method and a device for synthesizing proteins from DNA molecules captured in microchambers, whereby the distance between microchambers can be shortened, thereby allowing the density of arrays to be increased. Microchambers (32) are arranged at a high density. A DNA solution (34) which has been diluted so as to capture one DNA molecule on average is enclosed in the microchambers (32). Then, mRNA is synthesized using one DNA molecule on average as a template. Based on this mRNA, a protein (37) is extracellularly synthesized.

Abstract: A method for producing libraries of structurally and stereochemically diverse molecules that can be screened for biological or chemical activity. A library of 91 heterocyclic compounds composed of 16 distinct scaffolds was synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis to illustrate the methods. Three compounds inhibiting migration of human breast cancer cells are identified from the library.

Abstract: Provided are methods and compositions for the generation of broad size distributions of polynucleic acid fragments from larger polynucleic acids. The invention provides unbiased polynucleic acid fragments, i.e. fragments representative of all portions of the larger polynucleic acids. The methods are amendable to automation and are cost-effective. The methods comprise contacting the polynucleic acid sample with a reducing agent and a transition metal in a solvent to form a mixture. An exemplified reducing agent is sodium ascorbate, and an exemplified transition metal is copper.

Abstract: The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.

Abstract: The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

Abstract: Rapid and specific detection of biological cells and biomolecules is important to biological assays across diverse fields including genomics, proteomics, diagnoses, and pathological studies. Microarrays and microfluidics increasingly dominate such detection techniques due to the ability to perform significant numbers of tests with limited sample volumes. A snap chip assembly is provided for the transfer of a microarray of reagents within semi-spherical liquid droplets on a transfer chip to a target assay microarray on an assay chip following assembly of the two chips and physical contact of the droplets with the target array. Reagents in nanolitre quantities are spotted on both chips and selectively transferred as liquid droplets between transfer chip and assay chip within the contact areas. Using the snap chip structure the inventors performed immunoassays with colocalization of capture and detection antibodies with 10 targets and bead-in-gel droplet microarrays with 9 targets in the low pg/ml regime.

Abstract: The present invention relates to a plurality of isotopically labeled compounds (“tag isotopomers”) and individual labeled compounds, which are useful for labeling samples of analytes, such as biological compounds. The present invention further relates to methods of labeling and quantifying analytes using these tag isotopomers.

Abstract: The present invention discloses metal (III) complex of a biuret-amide based macrocyclic ligand as green catalysts that exhibit both excellent reactivity for the activation of H2O2 and high stability at low pH and high ionic strength. The invention also provides macrocyclic biuret amide based ligand for designing of functional peroxidase mimics. Further, the present invention discloses synthesis of said metal (III) complex of a biuret-amide based macrocyclic ligand.

Abstract: A method of preparing a protein chip by gelation of a sol composition. In the method, a mixture of specific silicate monomers, such as SolB1, SolB2 and SolB3, SolBH, and a mixture of SolBS, distilled water and a detector protein are mixed sequentially, so that the gelation rate of the sol composition can be delayed, thus inducing the stable gelation of the composition. Also, the biochip can be fabricated in a simple and easy manner by dispensing the sol composition by hand using an arrayer or a tool such as a pipette. In addition, a uniform biochip can be prepared by dispensing the sol composition, solution I (SolBH) and solution II (a mixture of buffer, SolBS, distilled water and a detector protein) sequentially onto a substrate without needing a conventional pretreatment process such as mixing.

Abstract: The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.

Abstract: The present invention provides compositions comprising a ligand-nucleic acid nanostructure that promote tumor cell-specific killing and methods of using the compositions. Specially, the invention provides aptamer-nucleic acid nanostructures for treating tumors in a mammal. The methods of making the compositions are also provided.

Abstract: Methods for making a combinatorial antibody library from human germline segments are provided. Also provided are libraries of nucleic acid molecules compiled from germline segments encoding VL chains and libraries of nucleic acid molecules encoding VH chains, and resulting antibody libraries. The libraries are provided as addressable libraries. Methods for screening antibody libraries against a target protein antigen, and the identified or selected antibodies are provided.

Abstract: Systems, including apparatus and methods, for synthesis of oligomers in arrays.

Abstract: Libraries of nanoparticles comprising therapeutic agents and/or imaging agents are disclosed, as well as methods of making, customizing, and using such libraries of nanoparticles.

Abstract: The present invention is generally related to systems and methods for producing a plurality of droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, the fluidic droplets may be rigidified to form rigidified droplets (e.g., gel droplets). In certain embodiments, the droplets may undergo a phase change (e.g., from rigidified droplets to fluidized droplets), as discussed more herein. In some cases, a species may be added internally to a droplet by exposing the droplet to a fluid comprising a plurality of species.

Abstract: An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: Methods, kits, systems, and multilayer transfer media for transferring a substance to and from an array are disclosed herein. Also disclosed herein are methods of detecting a substance that has been transferred to an array.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. A composition is provided that comprises an array of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. The inventive arrays are generated by: providing a solid support functionalized with a selected chemical moiety capable of interacting with a chemical compound to form an attachment and delivering compounds to the solid support having a density of at least 1000 spots per cm2. The present invention also provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

Abstract: System, including apparatus and methods, for forming an array of emulsions. The system may comprise a plate including an array of emulsion production units. Each unit may include at least one first input well, a second input well, and an output well connected to the first and second input wells by channels that form a droplet generator. The system also may comprise a vacuum or pressure source configured to be connected operatively to wells of the plate to form a pressure drop between the input wells and the output well of each unit that is capable of driving a first fluid and a second fluid from respective first and second input wells of such unit and through the droplet generator, for collection as an emulsion in the output well of such unit.

Abstract: Novel thiol-terminated bent-core liquid crystals (LCs) are used to decorate gold nanoparticles. Thioacetate or xanthate/xanthogenate functional groups are used to effect the attachment of the LCs to the gold nanoparticles. Such bent-core decorated nanoparticles may be dissolved in bent-core liquid crystal host media to provide polarizable systems which respond quickly to applied electric fields and exhibit other interesting and useful optical and electro-optic behaviour.

Abstract: A sensing platform includes: a plurality of metal nanoparticles; a plurality of aggregate inducers each comprising first and second functional groups different from each other, and the first functional group of the aggregate inducers being in contact with the metal nanoparticles; and a plurality of recognition molecules for binding the metal nanoparticles and for interacting with a target to recognize the target, wherein the second functional group of the aggregate inducers is free from being in contact with the metal nanoparticles, and is used to induce the metal nanoparticles to aggregate after the recognition molecules interact with the target.

Abstract: An object is to provide a highly effective segmented process apparatus for a microplate using a standard microplate without increasing the scale of the apparatus, as well as a method for processing a microplate. The apparatus includes: a predetermined microplate provided with a number of wells are set in array; one or more nozzle heads provided with a number of nozzles set in array; a suction and ejection mechanism for sucking and ejecting a gas via the nozzles; and a moving means which allows relative movement between the microplate and the nozzle heads, wherein tips of all of the nozzles provided on each nozzle head are provided in such a manner that the tips can be inserted into the wells in a portion of the microplate all together, and the row intervals and column intervals of the nozzles in array are respectively same as the row intervals and column intervals of the wells in array.

Abstract: The invention pertains, at least in part, to a method for forming an ordered structure of amphiphilic molecules, such as proteins. The method includes contacting a population of amphiphilic molecules with a interface; compressing said population laterally to an appropriate pressure, such that an ordered structure at the interface is formed. The invention also pertains to the two- and three-dimensional ordered structures that are formed using the planar membrane compression method of the invention.

Abstract: Method for monitoring and controlling a combinatorial process are presenting including: receiving a substrate; executing the combinatorial process, wherein the combinatorial process includes an in-line chemical preparation; analyzing the in-line chemical preparation for conformance with a corresponding in-line chemical preparation parameter using an in-line chemical analysis; and if the in-line chemical preparation is out of conformance with the corresponding in-line chemical preparation parameter, adjusting the in-line chemical preparation to conform with the corresponding in-line chemical preparation parameter utilizing a replenishing chemical preparation. In some embodiments, methods further include: performing a post-chemical mechanical planarization (CMP) clean before executing the combinatorial process, wherein the combinatorial process is a pre-clean; and depositing a capping layer after the pre-clean.

Abstract: A probe array substrate suitable for forming a probe array that has high packing density, that can hold sufficient amounts of probe molecules, and that has little variation in the amounts of probe molecules. A plurality of arrayed probe-holding portions are defined by recesses, and isolating grooves are formed between the adjacent probe-holding portions to prevent probe solutions introduced into the probe-holding portions from spreading to adjacent probe-holding portions. Inner surfaces of the probe-holding portions are made hydrophilic, whereas inner surfaces of the isolating grooves are made hydrophobic. Liquid-introducing protrusions are formed in the probe-holding portions.

Abstract: Methods for use in the synthesis and identification of molecules which bind to a target component of a biological system or modulate the activity of a target are described.

Abstract: Methods and apparatus for the fluid delivery and removal of micron scale structures that increase the efficiency of such fluid delivery and removal. An exemplary method for fluid delivery of a micron scale structure includes providing a silicon device that comprises a plurality of wells. Each of the wells includes a bottom wall, a side wall, a top opening and a plurality of protrusions that extend into the interior of the well. A plurality of micron scale structures are delivered into the wells using a fluid. The fluid is then removed from the wells, whereby spaces between the protrusions facilitate flow and removal of the fluid. The protrusions then retain the plurality of micron scale structures in the wells.

Abstract: A method of producing a particle array is disclosed, comprising allowing monodisperse particles to be arrayed in an aqueous medium containing a monomer to form a colloidal crystal exhibiting a structural color and then polymerizing the monomer to form a polymer.

Abstract: Various methods, such as a method of detecting SNPs, involving (a) introducing onto a droplet actuator a solution comprising genomic DNA, extension oligos and suspension array beads; (b) dispensing on the droplet actuator one bead per droplet; (c) cleaving DNA from the bead in each droplet; (d) amplifying the cleaved DNA; (e) detecting SNP signals and barcode signals from the amplified DNA.

Abstract: This application provides a high throughput method of making nanoparticles is provided that utilizes plates comprising wells (e.g., 96-well plates).

Abstract: The invention provides coding compositions comprising mixtures of coding oligonucleotides and methods of using such compositions to code samples. The compositions and methods are useful for identifying, verifying, or authenticating any type of sample, whether the sample is biological or non-biological.

Abstract: The invention provides a porous biological assay substrate suitable for detecting at least one analyte in a biological sample fluid. The substrate comprises one or more capture probes able to each specifically bind one target analyte. The average concentration of the capture probes in pores with a size larger than the O50 of the substrate pore size distribution is at least equal to the average concentration of the capture probes in pores with a size smaller than the O50. The substrate thereby shows improved binding efficiency. The invention also relates to a method and device for producing the biological assay substrate, and to a method for examining analyte fluids using the substrate.

Abstract: A method of sorting beads on a droplet actuator.

Abstract: A combinatorial library includes a gelcast substrate defining a plurality of cavities in at least one surface thereof; and a plurality of gelcast test materials in the cavities, at least two of the test materials differing from the substrate in at least one compositional characteristic, the two test materials differing from each other in at least one compositional characteristic.