Abstract: Methods and kits for the diagnosis of illnesses related to protocadherin 19 (PCDH19) protein deficiency or altered PCDH19 protein function are provided, as well as methods and kits for the identification of a predisposition to such illnesses and methods of screening subjects to identify carriers of such illnesses and methods and kits for the therapeutic or prophylactic treatment of PCDH19 deficiency or altered PCDH19 protein function. Further, nucleotide and amino acid sequences corresponding to a complete PCDH19 open reading frame (ORF), mutant sequences encoding non-functional PCDH19 mRNA or altered PCDH19 mRNA are described along with transformed cells and non-human transgenic animals comprising wild-type or mutant PCDH19 ORF nucleotide sequences.

Abstract: Quantitative methods for optimizing the permeabilization of cellular tissues for spatial transcriptomics are provided. Also provided is an instrument for quantitatively optimizing the permeabilization of cellular tissues used for spatial transcriptomics.

Abstract: In some aspects, the present disclosure provides methods for forming ligation products comprising single-stranded polynucleotides without the need for enriching the single-stranded polynucleotides. Ligation products formed by various aspects of the present disclosure can be useful for various applications, including but not limited to sequence analysis. In some embodiments, the ligation products comprise cell-free polynucleotides. In some aspects, the present disclosure provides reaction mixtures, kits and complexes consistent with the methods herein.

Abstract: The present invention features antisense oligonucleotides (AONs) for the treatment of diseases and disorders associated with the deleterious effects of transposable element insertion (e.g., long interspersed nuclear element-i (LINE-1), Arthrobacter luteus element (Alu), short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR-Alu) or (SVA), or endogenous retrovirus (ERV). In one aspect, the invention provides one or more antisense oligonucleotides complementary to a transposable element present in an intronic sequence within a gene. In another aspect, the invention provides a method for treating a subject having a genetic disorder associated with the insertion of a transposable element, the method involving administering to the subject one or more antisense oligonucleotides of any aspect delineated herein.

Abstract: This disclosure provides methods and systems for single-cell analysis, including single-cell transcriptome analysis, of target cells without microfluidic devices. The disclosed methods involve the use of template particles to template the formation of monodisperse droplets to generally capture a single target cell from a population of cells in an encapsulation, derive a plurality of distinct mRNA molecules from the single target cell, and quantify the distinct mRNA molecules to generate an expression profile.

Abstract: Provided herein is technology relating to predicting a subject's resistance or responsiveness to a decitabine based therapy and particularly, but not exclusively, to methods, compositions, and related uses for predicting a subject's resistance or responsiveness to a decitabine based therapy wherein the subject is diagnosed with chronic myelomonocytic leukemia.

Abstract: In an example, a flow cell includes a substrate, a selectively removable porous molecular network on the substrate and defining exposed substrate regions, and sequencing surface chemistry on at least some of the exposed regions. The sequencing surface chemistry is selected from the group consisting of i) an activated pad, a polymer layer attached to the activated pad, and a primer attached to the polymer layer; or ii) a nanostructure and an enzyme attached to the nanostructure.

Abstract: Disclosed herein are gene signature sets expressed by kidney allograft recipients prior to transplant that determine the risk for acute rejection (AR) post-transplant and methods of using the gene signature sets for identifying renal allograft recipients at risk for acute rejection. Also disclosed herein are kits for use in the invention which comprise primer pairs for the gene signature sets.

Abstract: Implementations of a method for seeding sequence libraries on a surface of a sequencing flow cell that allow for spatial segregation of the libraries on the surface are provided. The spatial segregation can be used to index sequence reads from individual sequencing libraries to increase efficiency of subsequent data analysis. In some examples, hydrogel beads containing encapsulated sequencing libraries are captured on a sequencing flow cell and degraded in the presence of a liquid diffusion barrier to allow for the spatial segregation and seeding of the sequencing libraries on the surface of the flow cell. Additionally, examples of systems, methods and compositions are provided relating to flow cell devices configured for nucleic acid library preparation and single cell sequencing. Some examples include flow cell devices having a hydrogel with genetic material disposed therein, and which is retained within the hydrogel during nucleic acid processing.

Abstract: Provided herein are systems and methods for assays. In particular, provided herein are systems and methods for performing high throughput immunoassays. Embodiments of the present disclosure provide multiplex capable LSPR immunoassays that meet a need for rapid (e.g., near real time), accurate immunoassays (e.g. for use in beside diagnostics). The LSPR assays are as accurate as existing ELISA assays but provide the advantage of increased speed and multiplex capability. In addition, the LSPR immunoassays are able to analyze small volumes of complex patient samples (e.g., serum).

Abstract: The invention provides compositions and methods for assembling a DNA molecule having a desired sequence. The methods involve contacting a DNA polymerase, dNTPs, and a plurality of pairs of oligonucleotides. The oligonucleotides of a pair have a portion of the desired sequence, and an internal sequence that overlaps and is complementary to an internal sequence of the other oligonucleotide of the pair, and, when arranged in order, they have at least a portion of the desired sequence. The oligonucleotides also have a 3? or a 5? primer binding sequence having a binding site for a primer. The oligonucleotides that correspond to the end oligonucleotides of the desired sequence also have a universal 3? flanking sequence and a universal 5? flanking sequence, respectively.

Abstract: A high-throughput combinatorial materials experimental apparatus for in-situ synthesis and real-time characterization includes a composition spread device to prepare continuous or discrete composition distribution as precursor of the high-throughput experimental samples library, a low temperature diffusion mixing device to thoroughly mix the composition spread in the thickness direction through diffusion at a relatively low temperature to form an amorphous precursor, and an integrated synthesis-characterization unit for heat treatment of the material library precursor in either a parallel or point-by-point scanning mode at different thermodynamic conditions for phase formation and to characterize features or properties of the materials of interest in an in-situ and real-time manner. The integrated synthesis-characterization unit includes a chamber maintained at desired vacuum and atmosphere, a micro-heating source, an excitation source, a signal collector, and a sample holder.

Abstract: Provided herein is technology relating to depositing and/or placing a macromolecule at a desired site for an assay and particularly, but not exclusively, to methods and systems for transporting a macromolecule such as a protein, a nucleic acid, or a protein:nucleic acid complex to an assay site, such as the bottom of a nanopore, a nanowell, or a zero mode waveguide.

Abstract: Provided are a gas separation membrane which has a resin layer containing a compound having a siloxane bond, in which the resin layer containing a compound having a siloxane bond satisfies Expressions 1 and 2, and at least one of gas permeability or gas separation selectivity is high under high pressure; a method of producing a gas separation membrane; a gas separation membrane module; and a gas separator. 0.9?A/B?0.55??Expression 1 B?1.7??Expression 2 In the expressions, A represents an O/Si ratio that is a ratio of the number of oxygen atoms relative to the number of silicon atoms contained in the resin layer containing a compound having a siloxane bond at a depth of 10 nm from the surface of the resin layer containing a compound having a siloxane bond, and B represents an O/Si ratio that is a ratio of the number of oxygen atoms relative to the number of silicon atoms in the surface of the resin layer containing a compound having a siloxane bond.

Abstract: Apparatus and methods for using a flow cell array are provided herein. A method includes determining placement of one or more reaction sites on a first component; providing a material for the one or more reaction sites in one or more surface channels of the first component; connecting the first component to a second component to form an array, wherein the one or more surface channels of the first component connect the one or more reaction sites with one or more vias, and wherein the second component comprises the one or more vias connected to multiple sub-surface channels; and aligning the one or more surface channels of the first component with the one or more vias of the second component to form a connection between the first component and the second component.

Abstract: Embodiments of the present disclosure provide a multistage procedure for treatment of biological samples (e.g., living cells with membranes, and the like) with a substance (e.g., a drug, DNA, RNA, plasmids, and other biomolecules or materials) to achieve more efficacious intracellular delivery and transfection.

Abstract: Provided herein are apparatuses and methods for fragmenting nucleic acids or disrupting cells. For example, some embodiments provide a disposable microfluidic device designed to position a sample to be in direct contact with a high frequency vibrating element that emits an ultrasonic frequency into the sample such that the vibrational energy transduced into the sample results in fragmenting nucleic acids or disrupting cells.

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.

Abstract: A multilayer well device includes a first substrate comprising an array of wells having a first pattern disposed therein and a second substrate comprising an array of wells having a second pattern, complementary to the first pattern disposed therein, wherein the second substrate is secured adjacent to a face of the first substrate. A common channel is interposed between the array of wells of the respective first and second substrates and is coupled to an inlet and an outlet.

Abstract: The invention provides a method of printing, onto a substrate (12), an array (14) of spots of reagent compositions for use in a chemical and/or biochemical analysis. The method includes displacing an array of reagent composition containing capillary tubes (22) arranged alongside one another from an inoperative position to an operative position in which open ends of the capillary tubes (22) simultaneously impinge against a substrate and thereafter displacing the array of tubes (22) from the operative position back to the inoperative position. The invention extends to a printing apparatus (10), a method of printing a layered array of spots of reagent compositions, a method of introducing reagent compositions into the tubes, a reagent introducing device for introducing reagent compositions into the tubes and a printing installation which includes the printing apparatus (10) and the reagent introducing device.

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.

Abstract: The present invention describes microplates with arrays of wells containing magnetic inserts in the form of disks, cylinders or otherwise shaped materials with apertures in the centre for optical interrogation of the contacting solution. These inserts are capable of capturing ferro- and paramagnetic nano- and microparticles. The subject microplates find use in a variety of applications, including clinical and environmental assays, high throughput screening for genomics, proteomics and pharmaceutical applications, point-of-care in vitro diagnostics, molecular genetic analysis and nucleic acid diagnostics, cell separations, and bioresearch generally and high-throughput screening of materials for separation and catalysis.

Abstract: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.

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: A system for inserting reagent or macrobeads into bores of a sample plate is disclosed comprising an insertion device arranged to retain one or more reagent or macrobeads by means of a vacuum whilst inserting the reagent or macrobeads into bores of the sample plate.

Abstract: A method of making an assay device comprising providing micro-elements in the form of micro-particles or micro-length tube detection elements and thereafter with an automated tool, picking and placing the micro-elements into open-sided microfluidic channels in a body.

Abstract: The present invention relates to methods for producing an oligonucleotide on a solid substrate surface and methods for using the same. Some aspects of the invention provide methods for selecting a single DNA molecule reproducibily with an atomic force microscope (AFM).

Abstract: A reactor assembly having a plurality of reaction chambers defined therein is provided. The reactor assembly includes a fluid flow module that provides a pressurized control flow of fluid from an open container. In another embodiment, the reactor block includes a plurality of passageways defined over a surface of a substrate to accommodate the combinatorial processing in order to obtain multiple data points from a single substrate.

Abstract: Fc domains and CH3 domains are disclosed that bind the neonatal Fc (FcRn) receptor and are at least 99% monomeric. Monomeric Fc domain molecules and CH3 domain molecules are disclosed herein that include a monomeric Fc domain or a monomeric CH3 domain and an effector molecule. In some embodiments, the monomeric Fc or monomeric CH3 domain include amino acid substitutions and/or CDR insertions in the beta strands such that they specifically bind an antigen. Methods for using these monomeric Fc domains, monomeric CH3 domains, monomeric Fc domain molecules and CH3 domain molecules are also provided.

Abstract: Discrete microstructures of predefined size and shape are prepared using sol-gel phase-reversible hydrogel templates. An aqueous solution of hydrogel-forming material is covered onto a microfabricated silicon wafer master template having predefined microfeatures, such as pillars. A hydrogel template is formed, usually by lowering the temperature, and the formed hydrogel template is peeled away from the silicon master template. The wells of predefined size and shape on the hydrogel template are filled with a solution or a paste of a water-insoluble polymer, and the solvent is removed to form solid structures. The formed microstructures are released from the hydrogel template by simply melting the hydrogel template in water. The microstructures are collected by centrifugation. The microstructures fabricated by this method exhibit pre-defined size and shape that exactly correspond to the microwells of the hydrogel template.

Abstract: A liquid dispenser for a microfluidic assay system is described. The dispenser includes at least one transfer pin for transferring a microfluidic sample of liquid to a target receptacle. A pin tip at one end of the transfer pin is structured to cooperate with an opening in the target receptacle. The tip uses a high voltage potential to transfer the sample from the pin to the receptacle.

Abstract: Methods, compositions, systems, apparatus, and kits are provided for depositing samples onto surfaces. The samples can include one or more particles, and the surface can include one or more reaction chambers. In some embodiments, the depositing can include the use of companion particles in combination with sample particles.

Abstract: To provide a means and a method of quickly sampling a tissue fragment from a plant tissue, quickly preserving a gene expression state within the tissue fragment, and comprehensively analyzing the gene expression state. The present invention relates to a method of sampling a plant tissue section, comprising: inserting a first gel layer into a needle; arranging a plant tissue on a second gel layer; and passing the needle through the plant tissue together with the second gel layer, and sampling a section of the plant tissue in the needle.

Abstract: Methods are described for phototransferring a compound from a first surface to a second surface. Compounds are described with photocleavable linkers. Compounds attached to a first surface through a photocleavable linker are put in proximity (or contact) with a second surface, and then phototransferred to the second surface upon exposure to electromagnetic radiation. Illuminating the compound with radiation photocleaves the compound from the first surface and transfers the compound to the second surface.

Abstract: Methods and compositions for determining the nucleic acid sequence of polynucleotides that are at least 1500 nucleotides in length are provided.

Abstract: The present invention relates to methods and arrays for use in high resolution imaging of individual nucleic acid molecules and chromatin fragments, including native chromatin fragments. In one aspect, the present invention relates to a chromatin array that includes a transfer platform having a support and a transfer surface layered on the support. The chromatin array also includes a plurality of elongated individual native chromatin fragments coupled to the transfer surface in an orderly pattern suitable for high resolution imaging of the plurality of native chromatin fragments. The native chromatin fragments of the chromatin array include both DNA and histones.

Abstract: A process for making a micro-array. The process comprises the step of depositing a population of microbeads on a substrate having at least one fiducial. The population being comprised of at least two sub-populations, preferably multiple sub-populations, each comprising a known active agent capable of specific binding with at least one target analyte. The said subpopulations are deposited sequentially and at discrete periods of each other. The process also comprises the step of making images of the substrate after deposition of each subpopulation. The images are then compared using the fiducial as a reference to thereby determine the location of each microbead and to identify the subpopulation, and its known active agent, based on differences between each image. Also disclosed in a system for using the microarray.

Abstract: The present invention is to provide a base for use in the amplification of a nucleic acid, which makes it possible to accurately and effectively amplify and detect a plurality of target nucleic acid sequences that are subjects for detection. A base for use in the amplification of a nucleic acid according to the present invention is a base in which a hydrophilic gel is held and which has arrayed plural zones, and the zones contain different kinds of primer or the like for amplifying nucleic acids.

Abstract: A platform for biological assays includes a base substrate providing structural support to the platform, at least one surface of the base substrate coated with position markers, a first deformable layer positioned on top of the base substrate, and a second deformable layer positioned on top of the first deformable layer, the second deformable layer embedded with deformation markers.

Abstract: Disclosed herein are methods of immobilizing a particle which comprise focusing the flow of a sample fluid containing the particle into a virtual channel which flows towards an unoccupied hydrodynamic trap in a microfluidic channel such that the particle flows into the hydrodynamic trap and becomes immobilized therein. Also disclosed are microfluidic devices which comprise at least one microchannel having at least one hydrodynamic trap, at least one focusing fluid inlet, said focusing fluid inlet is upstream of the hydrodynamic trap such that a focusing fluid introduced therein results in a virtual channel of a sample fluid when present which preferentially flows toward the hydrodynamic trap.

Abstract: Described herein are kits and components thereof used for a multiplexed analysis of a set of cytokines.

Abstract: The present invention relates to single cell array micro-chips and fabrication, electrical measurement and electroporation method thereof. The single cell array microchip comprises a substrate (1), a plurality of positioning electrodes (2) formed in an array, a plurality of measuring electrode-pairs (3) formed in an array, and a micro sample pool (4). The invention integrates cell array positioning with electrical measurement and electroporation for living cells, which is characteristic of label-free and noninvasive methods to manipulate, position particles/cells as well as further measure their electrical parameters. Therefore, single-cell-array positioning and multi-mode in-situ real-time measurement can be realized for intensive analysis. Since the positioned cells are immobile, the precision of the electrical measurement of cells is effectively improved, so is the efficiency of electroporation with lower cell mortality rate.

Abstract: The present invention relates to a method for absolute quantification of polypeptides.

Abstract: The subject matter relates to relates to a one-bead-one-sequence composition, a library of tagged chemicals comprising a plurality of one-bead-one-sequence compositions, a method for identifying a candidate molecule from a library of tagged chemicals, and a composition produced by a process, all as described herein.

Abstract: A method of preparing a species-specific phosphorylation site peptide array for a target organism comprising: a) selecting a plurality of known non-target organism (NTO) phosphorylation site sequences and cognate known NTO phosphorylation polypeptide sequences from one or more NTO, each of the known NTO phosphorylation site sequences comprising at least 5 residues and less than 30 residues; b) identifying a matching target organism (TO) phosphorylation site sequence and cognate TO phosphorylation polypeptide sequence for one or more of the known NTO phosphorylation site sequences; c) determining the matching TO phosphorylation site sequences that correspond to orthologue polypeptides of the cognate known NTO phosphorylation polypeptide sequences; d) selecting the matching TO phosphorylation site sequences determined to correspond to orthologue polypeptides for inclusion on the array; wherein the matching TO phosphorylation site sequences that correspond to orthologue polypeptides are determined by calculating

Abstract: The present application pertains to products and methods related to the ability of short nucleotide oligomers to bind the tertiary or globular structure of nucleic acids. This application discloses libraries of short oligomers and methods for using these libraries.

Abstract: An apparatus, method and sensor apparatus for determining a spatial positioning of loading equipment is disclosed. The loading equipment has an operating implement for loading a payload, the operating implement being coupled to a support for movement relative to the support. The apparatus includes an orientation sensor disposed on the support and being operable to produce an orientation signal representing an orientation of the support. The apparatus also includes a displacement sensor operable to produce a displacement signal representing a displacement of the operating implement relative to the support. The apparatus further includes a processor circuit operably configured to receive the orientation signal and the displacement signal, use a kinematic model of the loading equipment to compute a spatial positioning of the loading equipment, and produce an output signal representing the spatial positioning.

Abstract: The instant invention comprises a process for the solid phase synthesis of directed epitope peptide mixtures useful in the treatment and diagnosis of protein conformational disorders, such process defined by a set of rules regarding the identity and the frequency of occurrence of amino acids that substitute a base or native amino acid of a known epitope. The resulting composition is a mixture of related peptides for therapeutic use. The invention also pertains to the process of generating antibodies using the directed epitope peptide mixtures as the antigens, and antibodies generated by such process, useful in the treatment and diagnostics of the said protein conformational disorder.

Abstract: The present invention provides kits and assay methods for the early detection of pathogens, precise identification of the etiologic agent, and improved disease surveillance. More specifically, the present invention discloses an immunoassay leading to the rapid and simultaneous detection of antibodies to a wide range of infectious pathogens in biological fluids of infected patients. This immunoassay involves the covalent and oriented coupling of fusion proteins comprising an AGT enzyme and a viral antigen on an identifiable solid support (e.g. fluorescent microspheres), said support being previously coated with an AGT substrate. This coupling is mediated by the irreversible reaction of the AGT enzyme on its substrate. The thus obtained antigen-coupled microspheres show enhanced capture of specific antibodies as compared to antigen-coupled microspheres produced by standard amine coupling procedures.

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.