Abstract: System, including methods and apparatus, for detection of spaced droplets.

Abstract: The present invention provides methods and systems for discretized, combinatorial processing of regions of a substrate such as for the discovery, implementation, optimization, and qualification of new materials, processes, and process sequence integration schemes used in integrated circuit fabrication. A substrate having an array of differentially processed regions thereon is processed by delivering materials to or modifying regions of the substrate.

Abstract: There is provided a biochip stamping device. The biochip stamping device includes a stamping jig in which a first biochip is aligned; an inverting mechanism vertically inverting a second biochip; and a movement mechanism transferring the vertically inverted second biochip on the stamping jig to combine the first biochip and the second biochip.

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: Embodiments of the invention are directed to a one-bead-two-compound method for the creation of encoded cyclic peptoid libraries. This scheme is useful for the creation of cyclic peptoid microarrays since only the cyclic peptoid, not the linear encoding molecule, contains an attachment residue and thus can be spotted onto an activated substrate.

Abstract: The present disclosure provides apparatuses, systems, and methods involving a spotter for depositing a substance on a submerged surface. The spotter comprises an outlet cavity defined at least in part by a spotting orifice, a first opening, and a second opening. The spotter also comprises a first conduit fluidly coupled to the first opening and a second conduit fluidly coupled to the second opening. The spotter is adapted so that fluid flowing through the first conduit and the second conduit is communicated among the first opening, the second opening, and a submerged deposition surface when the sealing orifice is sealed against the submerged deposition surface to form a deposition spot on the submerged deposition surface. The submerged deposition surface is within a liquid such that the liquid covers the deposition spot upon removal of the orifice from the deposition surface.

Abstract: The present invention provides methods and systems for analyzing mammalian transcriptomes, particularly, for low abundant transcripts, and with the use of high throughput technologies. Heptamer primers and sequence tags generated by the iterative randomized algorithm, as well as the sequencing-library generation system for amplifying and synthesis-based sequencing low abundant transcripts using the heptamer primers are also provided. The present invention further provides the use of the invention system and method for identifying key embryological lineage specific transcripts that anticipate differentiation of specific cell types.

Abstract: The present invention relates to a microfluidic array platform comprising a substrate and two layers between which one membrane is sandwiched, wherein a plurality of cell culture wells are constructed in the top layer and one or more microfluidic channels for oxygen scavenging reactions or/and oxygen generating reactions to control the oxygen tensions are constructed in the bottom player. The microfluidic array platform is capable of simultaneously performing cell culture under different oxygen tensions and compatible with existing cell incubators and high-throughput instruments for cost-effective setup and straightforward operation.

Abstract: Disclosed are compositions, devices, and methods for loading molecules of interest onto a substrate by contacting beads having molecules of interest attached to them with the substrate, for example by providing a field that brings the beads into proximity or contact with the substrate and moves the beads with respect to the substrate. Such molecules of interest can be deposited onto substrates for single-molecule analysis.

Abstract: The present invention relates to a system for producing a nucleic acid molecule imaging array for use in high resolution imaging of individual nucleic acid molecules. The system includes a micro/nanostructured capture array having a hydrophobic surface having topographical features effective to assist in capillary-based trapping and elongation of individual nucleic acid molecules. The system also includes a transfer platform having a support and a hydrophobic substrate layered on the support. The transfer platform is effective to receive and capture, through solvent mediation, the trapped and elongated individual nucleic acid molecules from the micro/nanostructured capture array. The present invention also relates to a nucleic acid molecule imaging array, a transfer platform for use in preparing a nucleic acid molecule array, and a kit for producing a nucleic acid molecule imaging array for use in high resolution imaging of individual nucleic acid molecules.

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: A system and method for programming DNAzymes to be utilized as programmable drugs, which are active only in the presence of specific input combinations and/or certain conditions.

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: The embodiments describe methods for controlling the particles generated when cleaning and drying a wafer in a spin rinse dryer (SRD) module. In some embodiments, the substrate surface is cooled by dispensing deionized (DI) water across the surface of the substrate, while the substrate rests on the SRD chuck. In addition, a method for controlling the particles generated when sleeves in a processing module or SRD contact a substrate surface during a clamping operation or when the sleeves are removed from the substrate surface is provided. A bottom edge or lip of the sleeves and/or the surface of the wafer contacting the sleeve is wetted during clamping/unclamping operations. Alternatively, the substrate may be wetted prior to clamping/unclamping operations.

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: The present invention discloses the integration of programmable microfluidic circuits to achieve practical applications to process biochemical and chemical reactions and to integrate these reactions. In some embodiments workflows for biochemical reactions or chemical workflows are combined. Microvalves such as programmable microfluidic circuit with Y valves and flow through valves are disclosed. In some embodiments microvalves of the present invention are used for mixing fluids, which may be part of an integrated process. These processes include mixing samples and moving reactions to an edge or reservoir for modular microfluidics, use of capture regions, and injection into analytical devices on separate devices. In some embodiments star and nested star designs, or bead capture by change of cross sectional area of a channel in a microvalve are used. Movement of samples between temperature zones are further disclosed using fixed temperature and movement of the samples by micropumps.

Abstract: In a method and system for forming concentrated volumes of microbeads, a polymer solution and/or suspension includes a polymer dissolved and/or dispersed in a medium. Streams of a focusing fluid and of the polymer solution and/or suspension flow towards a fluid bath, and into intersection with one another, so as to focus the polymer solution and/or suspension. The polymer solution and/or suspension stream forms microbeads in the fluid bath Some of the focusing fluid is drawn from the fluid bath, so as to concentrate the microbeads in the fluid bath. The system includes a flow focusing apparatus and a liquid-containing cell. The focusing apparatus includes polymer and focusing nozzles. The cell contains the fluid bath and has an outlet port, through which the focusing fluid is drawn.

Abstract: The invention relates to a device and a method for the generation of molecular microarrays. The invention relates therefore to a universal approach for the generation of protein microarrays, DNA microarrays and RNA microarrays (in general nucleic acid microarrays), by production of an output molecule from a template molecule microarray via enzymatic or chemical processes and transfer of the output molecule onto the desired molecular microarray.

Abstract: Patterned SAM arrays and methods of preparing patterned SAM arrays are disclosed. Advantageously, the methods used to prepare the patterned SAM arrays allow for controlling SAM spot-to-spot conditions such as ligand identity and ligand density, which allows for preparing a wide range of SAM spots in a single array format. Additionally, the patterned SAM arrays of the present disclosure support the culture of a range of cell types. The patterned SAM arrays offer the ability to rapidly screen substrate components for influencing cell attachment, spreading, proliferation, migration, and differentiation.

Abstract: An interface is provided for storing microfluidic samples in a nanoliter sample chip. A fluid access structure provides a fluid access region to a selected subset of sample wells from an array of sample wells. A fluid introduction mechanism introduces a sample fluid to the fluid access region so that the sample wells in the selected subset are populated with the sample fluid without the unselected sample wells being populated with the sample fluid.

Abstract: Disclosed herein is a microarray cell chip. The microarray cell chip includes an upper substrate that has biomatrices encapsulating biomaterials formed on one surface thereof and through holes penetrating from one surface to the other surface thereof and a lower substrate that is coupled with the upper substrate and is provided with wells storing reagents supplied to the biomatrices. The microarray cell chip according to the present invention can smoothly transfer the culture media and the reagents to the biomaterials embedded in the biomatrices through the diffusion and simply separate the upper substrate from the lower substrate, thereby improving the easiness of washing. Therefore, the present invention provides an environment similar to the bio environment, thereby making it possible to increase accuracy of an experiment.

Abstract: A method and an apparatus for genome assembly are provided.

Abstract: The present invention provides integrated sample preparation systems and stabilized enzyme mixtures. In particular, the present invention provides microfluidic cards configured for processing a sample and generating DNA libraries that are suitable for use in sequencing methods (e.g., next generation sequencing methods) or other suitable nucleic acid analysis methods. The present invention also provides stabilized enzyme mixtures containing an enzyme (e.g., an enzyme used in whole genome amplification), BSA, and a sugar. Such enzyme mixtures may be lyophilized and stored at room temperature without significant loss of enzyme activity for months.

Abstract: A spotter that includes a plurality of spotting heads, each of the plurality of spotting heads having a discharging portion at a tip portion, the plurality of spotting heads form an m×n array (m, n>1) with m spotting heads arranged lengthwise and n spotting heads arranged crosswise; and a pitch varying mechanism configured to vary an array pitch of the plurality of spotting heads arrayed in a lengthwise direction and an array pitch of the plurality of spotting heads arrayed in a crosswise direction.

Abstract: Described microfluidic technology focused on: 1) direct integration of microfluidic devices with solidified liquid tissue samples, 2) subordination of architectural and operational principles of microfluidic devices specific tissue structure and needs and/or 3) on-chip sample acquisition integrated with the detection measurement within the same device. In contrast to conventional methods of off-chip sample prep and subsequent insertion into a detection device, new applications are possible on solidified liquid or solid tissue samples, such as in situ PCR.

Abstract: Systems and methods of screening biomarkers in bodily fluids. According to at least one embodiment of the system for analyzing stabilizing agents of the present disclosure, the system comprises a detection platform comprising a plurality of detection sites each capable of receiving a diagnostic marker, a stabilization agent, and a detection agent. The system, in at least one embodiment, further comprises a detection device capable of determining a binding characteristic between the detection agent and the diagnostic marker in the detection sites. Further, the system may also be able to compare the binding characteristic among a plurality of detection markers to order the level of effect of the stabilizing agents assayed on the binding characteristic between the detection agent and the diagnostic agent.

Abstract: A cell capture system including an array, an inlet manifold, and an outlet manifold. The array includes a plurality of parallel pores, each pore including a chamber and a pore channel, an inlet channel fluidly connected to the chambers of the pores; an outlet channel fluidly connected to the pore channels of the pores. The inlet manifold is fluidly connected to the inlet channel, and the outlet channel is fluidly connected to the outlet channel. A cell removal tool is also disclosed, wherein the cell removal tool is configured to remove a captured cell from a pore chamber.

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

Abstract: The disclosure generally relates to compositions and methods for the production of nucleic acid molecules. In some aspects, the invention allows for the microscale generation of nucleic acid molecules, optionally followed by assembly of these nucleic acid molecules into larger molecules. In some aspects, the invention allows for efficient production of nucleic acid molecules (e.g., large nucleic acid molecules such as genomes).

Abstract: A microarray comprises a carrier substrate and a plurality of immobilization particles configured to immobilize capture molecules. Each immobilization particle comprises a first sub-section bonded to the carrier substrate and a second sub-section which is exposed.

Abstract: There is provided a bio-chip including a first substrate including a first recess formed in a first end surface thereof; and a second substrate including a first coupling pillar inserted into the first recess and a second coupling pillar in contact with a second end surface opposed to the first end surface.

Abstract: The invention provides systems and methods for improved peptide screening library design. In some implementations the systems and methods utilize screening data relating to a plurality of peptides used in a peptide screen against a target molecule to construct a consensus binding sequence alignment using least a subset of the plurality of peptides. For one or more positions of the sequence alignment an observed distance matrix is constructed, the matrix describing a distance between the relative binding activity of pairwise comparisons of each amino acid in a given position. The observed distance matrix is then compared to a plurality of molecular field-based amino acid substitution matrices so as to identify one or more preferred amino acids for use in the design of novel predicted binding peptide sequences for a subsequent peptide screen.

Abstract: An object of the invention is to provide a metal nanoparticle array structure in which metal nanoparticle arrays are firmly bonded to the substrate thereof via chemical bonding or the like and in which the coverage with the metal nanoparticle arrays is high. The problem can be solved by using a metal nanoparticle array structure 10 that comprises a substrate 1, a immobilizing layer 2 formed on one surface 1a of the substrate 1, and metal nanoparticle arrays 3 formed on one surface 2a of the immobilizing layer 2, wherein the metal nanoparticle arrays 3 are so arrayed that multiple metal nanoparticles 4 can be at regular intervals and the metal nanoparticles 4 are bonded to each other via the modifying part 5 arranged on a surface thereof while the metal nanoparticles 4 are immobilized on one surface 2a of the immobilizing layer 2 via chemical bonds.

Abstract: Provided are systems and methods for generating context-specific, field based amino acid substitution matrices. In some implementations, the systems and methods utilize a set of characteristics including sequence length, sequence, variable position, backbone conformation, sidechain conformation, and charge and/or ionization state to construct a number of instantiated virtual peptide variants that vary an amino acid at the variable position. Molecular fields are then calculated for each instantiated variant. The fields for each variant are then compared to one another in a pairwise fashion. Values representing the similarity of the fields resulting from the comparison are then assembled into an amino acid substitution matrix.

Abstract: A slotted pin tool, a delivery system containing the pin tool, a substrate for use in the system and methods using the pin tool and system are provided. The slotted pin tool contains a plurality of pins having slotted ends designed to fit around each loci of material deposited on a surface, such as a microarray, without contacting any of the deposited material. Sample is delivered by contacting the pin tool with the surface; the amount delivered is proportional to the velocity of the pin tool as it contacts the surface or the velocity of the liquid when movement of the pin is halted.

Abstract: An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

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: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

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: A device is provided for the controlled sampling of fluid into a well formed within an upper surface, in which the well may be filled under dynamic wetting conditions by contacting a droplet on the upper surface with the top of the well. Wetting is supported by the increased hydrophilicity of the upper surface relative to that of the well side wall. The relative difference in hydrophilicity may be achieved by providing an upper surface with greater roughness than the side wall, effectively amplifying the hydrophilicity of the upper surface relative to that of the side wall. Wells are preferably formed in an unpolished surface of a siliconwafer, and can achieve a stable film with micron depth and an aspect ratio in excess of 100.

Abstract: The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and/or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.

Abstract: A silicon structure has a substrate, a first layer formed on a surface of the substrate, and a fibrous film formed on a surface of the first layer. The first layer and the fibrous film are silicon compounds made of the same elements, and the first layer and the fibrous film are directly bonded together.

Abstract: Disclosed are compositions, devices, and methods for loading molecules of interest onto a substrate by contacting beads having molecules of interest attached to them with the substrate, for example by providing a field that brings the beads into proximity or contact with the substrate and moves the beads with respect to the substrate. Such molecules of interest can be deposited onto substrates for single-molecule analysis.

Abstract: The present invention relates to a method for making arrays or patterns comprising hydrophilic areas and hydrophobic background surrounding the hydrophilic areas, methods of cultivating cells using these arrays or patterns, and uses of these arrays or patterns in cell cultivation methods, e.g. for cell patterning, cell screenings, cell transfection and cell co-culturing.

Abstract: Systems and methods for the detection of biomarkers. In at least one embodiment of a microarray system of the present disclosure, the microarray system comprises a microarray product comprising at least 100 diagnostic markers/cm2, a microarray identifier, and a stabilizing agent, a control microarray product comprising a first specific binding pair member that binds to a first detectable label, and a processor for providing information regarding the identification and concentration of markers on the microarray based on the identity of the array provided by the microarray identifier.

Abstract: An apparatus for forming a surface reservoir to hold a sample for a desirable period of time is described. The apparatus contains a platform, a solid surface disposed onto the platform, and an assembly of a bottomless vessel mounted on the solid surface. Also described is an apparatus that forms an array of surface reservoirs on a solid surface when multiple bottomless vessels are used, which can be used for high throughput applications. The apparatus can be used in applications on a solid surface, such as immunohistochemistry (IHC), oligo synthesis, peptide synthesis, ELISA, DNA array, peptide array, protein array, antibody array, tissue array, cell culturing, etc.

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: An apparatus of manufacturing a microarray biochip including a spinning platen, at least one carrier and at least one substrate is provided. The carrier is disposed on the spinning platen and includes at least one micro-channel having an input terminal and an output terminal. The substrate is attached on the output terminal of the micro-channel of the carrier. A method of manufacturing a microarray biochip with said apparatus is also provided. A sample is injected into the micro-channel through the input or the output terminal. The spinning platen is powered-on to provide a centrifugal force to the carrier, such that the sample is flowed toward the output terminal from the input terminal, and then is immobilized on the surface of the substrate.

Abstract: The invention is directed to enzyme immobilization compositions comprising: one or more enzymes, a humectant, an acrylic-based monomer, a water-soluble organic photo-initiator and a water-soluble acrylic-based cross-linker in a substantially homogeneous aqueous mixture. The invention is also directed to methods for forming sensors comprising such compositions and to apparati for forming arrays of immobilized layers on an array of sensors by dispensing such compositions onto a substrate.