Abstract: A fluidic device (10) is described. The fluidic device (10) comprises the first part (110) and the second part (120). The first part (110) comprises a first inlet (111) and a first outlet (112), mutually spaced apart. The second part (120) comprises a first chamber (121) arranged to contain a predetermined first amount A1 of a first fluid F1 therein and a first wall portion (122) arranged to contain, at least in part, the first fluid F1 in the first chamber (121). The fluidic device (10) is arrangeable in a first configuration, wherein the first part (110) is fluidically isolated from the first chamber (121). The fluidic device (10) is arrangeable in a second configuration, wherein the first inlet (111) and the first outlet (112) are fluidically coupled via the first chamber (121), whereby increasing a first pressure P1 in the first chamber (121) via the first inlet (111) urges at least a part of the predetermined first amount A1 of the first fluid F1 through the first outlet (112).

Abstract: A mask structure for a deposition device includes first segments and second segments. The first segments are arranged in a direction surrounding a central axis and separated from one another. The second segments are disposed above the first segments. Each of the second segments overlaps two of the first segments adjacent to each other in a vertical direction parallel to an extending direction of the central axis. A deposition device includes a process chamber, a stage, and the mask structure. The stage is at least partially disposed in the process chamber and includes a holding structure of a substrate. The mask structure is disposed in the process chamber, located over the stage, and covers a peripheral region of the substrate to be held on the stage. An operation method of the deposition device includes horizontally adjusting positions of the first segments and the second segments respectively between different deposition processes.

Abstract: An apparatus includes a flow cell body, a plurality of electrodes, an integrated circuit, and an imaging assembly. The flow cell body defines one or more flow channels and a plurality of wells. Each flow channel is configured to receive a flow of fluid. Each well is fluidically coupled with the corresponding flow channel. Each well is configured to contain at least one polynucleotide. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are operable to effect writing of polynucleotides in the corresponding wells. The integrated circuit is operable to drive selective deposition or activation of selected nucleotides to attach to polynucleotides in the wells to thereby generate polynucleotides representing machine-written data in the wells. The imaging assembly is operable to capture images indicative of one or more nucleotides in a polynucleotide.

Abstract: The present disclosure provides a semiconductor device. The semiconductor device includes a substrate, a pair of walls and a conductive layer. The pair of walls, disposed on the substrate, are configured to define a recess therebetween to receive a liquid. The conductive layer is disposed above the substrate, and has a resistance, wherein the resistance is correlated with a surface tension of the liquid in the recess.

Abstract: The invention relates to a method and system for generating droplets of an aqueous solution on a microfluidic chip with an air continuous phase. Specifically, the droplet generator according to the present invention is integrated into a microfluidic chip to generate and introduce droplets of an aqueous solution into the microfluidic chip. The droplets travelling in a network of chip channels may be captured in on-chip traps in a manner defined by hydrodynamic resistances of chip channels. A biological reaction may be performed on a droplet trapped on the microfluidic chip.

Abstract: A case for containing a plurality of biological samples contains a base, a substrate and a cover. The substrate is attached to the base and comprises a plurality of reaction regions configured to receive one or more biological samples. The cover comprises an inner surface and is configured to be attached to the base such that the base and cover together provide a cavity containing the substrate. The inner surface includes a central area and a recessed area disposed about the central area. The central area is configured to cover the reaction regions, while the recessed area is offset from the central area in a direction normal to the inner surface.

Abstract: A thin film with multiple binding functionality can be prepared on an electrode surface via consecutive electroreduction of two or more aryl-onium salts with different functional groups. This versatile and simple method for forming multifunctional surfaces provides an effective means for immobilization of diverse molecules at close proximities. The multifunctional thin film has applications in bioelectronics, molecular electronics, clinical diagnostics, and chemical and biological sensing.

Abstract: A wafer having a plurality of dies (also called array chips) on the wafer, the die having an electrode to generate a deprotecting reagent, a working electrode to electrochemically synthesize a material, a confinement electrode adjacent to the working electrode to confine reactive reagents, and a die pad, wherein die pads of the plurality of dies are interconnected on the wafer to electrochemically synthesize the material in parallel on a plurality of working electrodes is disclosed. Also, a method for wafer-scale manufacturing of a plurality of dies and a method for electrochemically synthesizing a material in parallel on a plurality of dies on a wafer are disclosed.

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 present invention describes a method and devices for the simultaneous detection, recovery identification and counting of a plurality of microorganisms consisting in providing mixtures of nutrients specially selected from those that curtail the lag phase of growth in bacteria and moulds and which, together with fluorescent enzymatic, chromogenic or bioluminescent markers and other nutrient components or growth inhibitors, are embedded in three-dimensional structures or natural or artificial clays or ceramics with cavities of different dimensions and forms and specific surface areas of between 2×103 and 6×108 m2/m3.

Abstract: The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors.

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: A method and an array filling system for loading a plurality of disparate sample containers, the sample containers comprising an integral structure. Each receptacle is characterized by a hydrophilic surface, and the receptacles are separated by a hydrophobic surface. The system has a liquid transfer device capable of holding liquid and adapted for motion to cause sequential communication of liquid held in the liquid transfer device with successive receptacles of the array by dragging the liquid across the hydrophobic surface.

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 present invention provides methods for rapidly screening and measuring the ligand binding affinity of in vitro selected peptides to the cognate and off-target proteins. This general strategy is amenable to high throughput analysis because the peptides are synthesized by cell-free translation, as opposed to solid-phase synthesis required by traditional assays, and affinities can be readily measured in standard formats.

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 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: 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 sample loader for loading a liquid sample into a plurality of reaction sites within a substrate is provided. The sample loader includes a first blade, and a second blade coupled to the first blade. The sample loader further comprises a flow path between the first blade and second blade configured to dispense a liquid sample to a substrate including a plurality of reaction sites. Further, in various embodiments the liquid sample has an advancing contact angle of 85+/?15 degrees with the first and second blade. Furthermore, loading of the liquid sample dispensed from the flow path to the plurality of reaction sites may be based on capillary action.

Abstract: Sample processing droplet actuators, systems and methods are provided. According to one embodiment, a stamping device including a droplet microactuator is provided and includes: (a) a first plate including a path or network of control electrodes for transporting droplets on a surface thereof; (b) a second plate mounted in a substantially parallel orientation with respect to the first plate providing an interior volume between the plates, the second plate including one or more stamping ports for transporting some portion or all of a droplet from the interior volume to an exterior location; (c) a port for introducing fluid into the interior volume between the plates; and (d) a path or network of reference electrodes corresponding to the path or network of control electrodes. Associated systems and methods including the stamping device are also provided.

Abstract: Provided is a microarray platform for the culture of cells atop combinatorial matrix mixtures; enabling the study of differentiation in response to a multitude of microenvironments in parallel.

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: An apparatus for biological reactions is provided. The apparatus includes a substrate and a plurality of reaction sites within the substrate. A surface of the substrate is configured to have a first hydrophilicity and each surface of the plurality of reaction sites is configured to have a second hydrophilicity to load a substantial number of reaction sites with a sample volume. The sample volume of each loaded reaction site is substantially confined to its respective reaction site. The sample volume is configured to undergo a biological reaction within the reaction site.

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: Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation apparatus described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation apparatus can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation apparatus can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation apparatus can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device.

Abstract: Methods and systems for processing a first solution on a respective primary area of a device with a plurality of primary areas and a plurality of secondary areas are described. A method includes providing the device and dispensing a second solution to a respective secondary area of one or more secondary areas adjacent to the respective primary area, thereby mixing the first solution on the respective secondary area and the second solution on the respective primary area. The method also includes removing at least a portion of the mixed solution.

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: Novel and improved systems and methods for high speed arraying, hybridization, quantitative development and/or assaying are provided. Some embodiments provide a web based arraying format. Some other embodiments provide a sheet based arraying format. Some embodiments use a drop on drop assaying or hybridization mode. In some embodiments, a substantially inert substrate is utilized. In some other embodiments, an interactive substrate is utilized.

Abstract: Microfluidic system, including methods and apparatus, for processing fluid, such as by droplet generation. In some embodiments, the system may include a well and a channel component attached to the well. The channel component may include (a) a body, (b) an input tube (a “fluid pickup”) projecting from a bottom surface of the body and having an open bottom end disposed in the input well, (c) a microchannel, and (d) a passage extending through the input tube and the body and connecting the well to the microchannel. The system may be configured to receive a sample-containing fluid in the well and retain the sample-containing fluid below a top end of the passage, until a pressure differential is created that drives at least a portion of the sample-containing fluid from the well via the passage and through the microchannel.

Abstract: Methods, devices and systems for handling sample liquids, encapsulating liquids and magnetic particles are disclosed.

Abstract: A substrate, which is useful for performing biological, chemical and diagnostic assays, and a method for preparing the substrate are provided. The substrate has an upper surface with a coating disposed thereon. The coating comprises a charged polymer, a non-ionic polyether, and a silicate compound. The substrate can increase capture phase binding and reduce non-specific binding of biomolecules for a biological microarray.

Abstract: The present invention provides a system for receiving biological sequence information and activating the synthesis of a biological entity. The system has a receiving unit for receiving a signal encoding biological sequence information transmitted from a transmitting unit. The transmitting unit can be present at a remote location from the receiving unit. The system also has an assembly unit connected to the receiving unit, and the assembly unit assembles the biological entity according to the biological sequence information. Thus, according to the present invention biological sequence information can be digitally transmitted to a remote location and the information converted into a biological entity, for example a protein useful as a vaccine, immediately upon being received by the receiving unit and without further human intervention after preparing the system for receipt of the information.

Abstract: A multi-well manifold assembly and method for reducing cross-contamination in continuous synthesis reactions in channels of microfluidic devices, for example oligonucleotide synthesis.

Abstract: The present teachings provide a fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension control valves can be disposed in fluid communication with the first manifold and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

Abstract: The present invention relates to methods and devices for amplifying nucleic acid, and, in particular, amplifying so as to generate products on a surface without the use of emulsions. In a preferred embodiment, a plurality of groups of amplified product are generated on the surface, each group positioned in different (typically predetermined) locations on said surface so as to create an array.

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: 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 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.