Abstract: The present invention relates to a method of pooling samples to be analyzed for a categorical variable, wherein the analysis involves a quantitative measurement of an analyte, said method of pooling samples comprising providing a pool of n samples wherein the amount of individual samples in the pool is such that the analytes in the samples are present in a molar ratio of x0:x1:x2:x(n?1), and wherein x is equal to a positive value other than 1 representing the pooling factor.

Abstract: Provided is a substrate that is used to produce a microarray, wherein the substrate includes; a fiducial mark disposed on the substrate, and a probe immobilization region disposed on the substrate, wherein a surface of the first fiducial mark is a hydrophobic and a probe immobilization compound is immobilized on the probe immobilization region.

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: The invention provides an ink jet device and method for producing a biological assay substrate (41) by releasing a plurality of substances onto the substrate (41) The device comprises at least a print head and a plurality of substance containers (60, 61, 62) connectable thereto, and mounting means (55) for the containers, whereby at least part of the containers (60, 61, 62) is provided with identification means (63) The device further comprises reading means to read information contained in the identification means (63).

Abstract: Provided herein are methods and apparatuses for transfecting a cell with a compound of interest by stressing the cell, e.g. with shear stress. The compound of interest may be nucleic acids, proteins, molecules, nanoparticles, drugs, etc., or any combination thereof. Methods of printing cells with an inkjet printing device are also provided, wherein at least a portion of viable cells (preferably at least 1%) are transfected with a compound of interest. Preferably, at least 25% of the cells are viable after printing. In addition, methods of forming an array of viable cells are provided wherein at least a portion of the viable printed cells (preferably at least 1%) are transfected with at least one compound of interest.

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

Abstract: To provide a magnetic particle parallel processing apparatus permitting repeated use of a container, and a method of magnetic particle parallel processing permitting repeated use of a container, with which the rate of repeated use of a container is enhanced to thereby achieve a saving in the working space and a saving in the working time. The apparatus comprises: at least one reaction container; a liquid disposal tank; a reagent etc.

Abstract: A device for positioning at least one cell in at least one addressable position, the device comprising a substrate formed with at least one addressable pore and at least one channel embedded in the substrate and being in fluid communication with the at least one pore. The at least one pore and the at least one channel are designed and constructed such that an under-pressure formed in the at least one channel results in vacuum adherence of the at least one cell onto the at least one pore, such that a single cell is vacuum adhered onto a single pore. In one embodiment, the substrate is a non-conductive substrate and is further formed with one or more electrode structures, where each of the electrode structures is positioned in one of the pores. In an additional embodiment the device is designed locatable onto an organ, such as a brain.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. Such methods can include labeling a library of compounds by emulsifying aqueous solutions of the compounds and aqueous solutions of unique liquid labels on a microfluidic device, which includes a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate such that a continuous channel is provided for flow of immiscible fluids, whereby each compound is labeled with a unique liquid label, pooling the labeled emulsions, coalescing the labeled emulsions with emulsions containing a specific cell or enzyme, thereby forming a nanoreactor, screening the nanoreactors for a desirable reaction between the contents of the nanoreactor, and decoding the liquid label, thereby identifying a single compound from a library of compounds.

Abstract: A biochip substrate which is free from cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same. A biochip substrate on which multiple valleys for immobilizing biological substances are formed so as to prevent cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same are provided. Moreover, it is found out that a desired binding in a target molecule contained in a test sample occurs at a detectable level in a solution system even in the case where a valley have such a small capacity as 1 nL to 10 nL.

Abstract: The disclosure provides methods and devices for rapidly assembling high density biomolecular arrays.

Abstract: The present invention generally relates to systems and methods for mixing and dispensing a sample droplet from a microfluidic system, such as a liquid bridge system. In certain embodiments, the invention provides systems for mixing and dispensing sample droplets, including a sample acquisition stage, a device for mixing sample droplets to form sample droplets wrapped in an immiscible carrier fluid, a dispensing port, and at least one channel connecting the stage, the droplet mixing device, and the port, in which the system is configured to establish a siphoning effect for dispensing the droplets.

Abstract: Individual temperature control in multiple reactions performed simultaneously in a spatial array such as a multi-well plate is achieved by thermoelectric modules with individual control, with each module supplying heat to or drawing heat from a single region within the array, the region containing either a single reaction vessel or a group of reaction vessels.

Abstract: [Task] A process of fabricating a tissue array block; a process of fabricating a tissue array sheet; a tissue array block; a tissue array chip; a system of fabricating a tissue array block; and a system of fabricating a tissue array sheet are proposed, in which the tissue array block can be fabricated even in the case of that having a small thickness, is little affected by tissue hardness and, when having been processed into a tissue array chip, does not suffer any defect in a piece of tissue or at a site of interests, enables the collection of pieces of tissue from a dispersed area, also enables the establishment of positional relationship between the inside of a tissue piece and the inside of a tissue block, and scarcely affects the utilization of the tissue block remaining after collecting the pieces of tissue. [Solving Means] A tissue block B1 is sliced to fabricate roll-shaped pieces of tissue t2. Then, the roll-shaped tissue pieces t2 are inserted into a base block B2 to give a tissue array block B3.

Abstract: A heat block assembly and an organic compound synthesizing apparatus using the heat block assembly are provided. The heat block assembly includes one or more heat blocks provided with grooves in which reaction containers are inserted, and a temperature adjustor for adjusting the temperature of the heat block.

Abstract: The present invention relates to an apparatus 1 for transferring cells 2 suspended in a fluid 3 from the fluid 3 to a substrate 17. The apparatus 1 comprises a transfer device 8 having an exterior surface 9, an interior cavity 10, and a plurality of passages 11 each having a first end 12 at the exterior surface 9 and a second end 13 in fluid 5 communication with the cavity 10 and each having a diameter corresponding to a predefined size of the cells 2 to be transferred. The apparatus further comprises a pressure regulating device 14 capable of regulating a pressure in the cavity 10 so as to establish a pressure difference between the first and second ends 12, 13 of each passage 11, a container 4 for containing the fluid 3, and a flow device 7 capable of causing the fluid 3 to flow across the 10 exterior surface 9 when in contact with the fluid 3.

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: The present invention generally relates to methods of constructing liquid bridges and methods of forming predetermined combinations of samples using liquid bridges.

Abstract: A method and device are presented for modifying parameters of a solid material. This is implemented by applying radiation, such as photon flux and/or charged particle beam and/or heat, to at least a region of the material, and controlling at least one parameter of the applied radiation, thereby modifying a wettability property of the material within the irradiated region(s) thereof in a reversible manner.

Abstract: A method for determining oxidation stability for a plurality of different lubricating oil composition samples is provided. The methods can advantageously be optimized using combinatorial chemistry, in which a database of combinations of lubricating oil compositions is generated. As market conditions vary and/or product requirements or customer specifications change, conditions suitable for forming desired products can be identified with little or no downtime.

Abstract: The present invention comprises systems and devices for isothermal amplification of polynucleotide sequences to produce DNA cluster arrays.

Abstract: An apparatus that accelerates the determination of NN free energy of binding estimates for a large number of DNA oligomers using reconfigurable hardware and applies it to the design of high quality DNA code word libraries. The invention provides a reconfigurable hardware accelerator and method for implementing a nearest-neighbor based free energy calculation. The invention further provides a method to produce the maximum weight of the 2-stem common subsequence of two DNA oligonucleotides. In practice, the present invention comprises a general purpose microprocessor or computer, a hardware accelerator, and a software program.

Abstract: In situ nucleic acid synthesis compositions are provided. The compositions include a solvent; and at least one of: a viscosity modifier; and a surface tension modifier. During use, the compositions further include one of a phosphoramidite and an activator. Also provide are methods of using the compositions, e.g., in the synthesis of nucleic acid arrays, and systems kits for practicing the methods.

Abstract: Materials and Methods for photodirected synthesis of oligonucleotide arrays on a solid substrate by photodirected synthesis are disclosed which employ a film formed from (i) a photoacid generator that on photolysis generates acid that is capable of directly removing the protecting group of the linker molecules or oligonucleotides and (ii) a polymer substantially lacking electronegative heteroatoms that are capable of hydrogen bonding with photogenerated acid. Methods of synthesizing an oligomer arrays are also described that use a film that restricts diffusion of reactants and products on the substrate during synthesis of the array and which includes a precursor of a deprotecting reagent. The method involves removing one or more of the non-required products of the deprotection reaction from the reactive array elements at which they are produced during the reaction, in order to displace the deprotection reaction towards completion.

Abstract: Systems for filling sample array by droplet dragging are provided. One aspect of the invention provides an array filling system for filling a platen having a platen surface and an array of receptacles, the receptacles having an internal surface and the receptacles separated by the platen surface, the system comprising: a liquid transfer device capable of holding liquid; and a controller configured to position the liquid transfer device in proximity to the platen surface and to move the liquid transfer device across the surface and over the receptacles to be filled so as to cause sequential communication of liquid in the liquid transfer device with the interior surface of each receptacle.

Abstract: At each lattice point of pantographs, a capillary is held perpendicular to the pantograph lattice. The pantograph includes: rings to serve as lattice points; and shafts linking the rings with one another. Each of the capillaries is supported by the two rings. The shafts are free to rotate about an intersection. The ring is fixed to the capillary, but the ring is a movable ring being moveable freely up and down in the axial direction of the capillary in conjunction with the pantograph. The lattice distance can be determined accomplished by moving up or down the movable ring at an arbitrarily-chosen lattice point in a pantograph. Accordingly, all the capillaries move in parallel to one another, and the ends of all the capillaries always stay within a single plane.

Abstract: The invention relates to processes and devices for the controlled fabrication of nanostructures from starting components that have high fidelity recognition properties and multiple binding groups. In one embodiment, the invention relates to the formation of nanostructures using controlled sequential addition of nanocomponents at regular intervials via sequential formation of binding pairs or other chemical binding reactions.

Abstract: A method for determining storage stability for a plurality of fluid lubricant samples of different compositions is provided. Each sample includes one or more lubricating oil additives, or a combination of one or more lubricant base oils and one or more lubricating oil additives. The methods can advantageously be optimized using combinatorial chemistry, in which a database of combinations of lubricating oil additives or lubricating oil compositions containing such additives are generated. As market conditions vary and/or product requirements or customer specifications change, conditions suitable for forming desired products can be identified with little or no downtime.

Abstract: The invention relates to a printer device for producing biological test arrays by depositing an array of biofluids onto a substrate. The invention further relates to the use of such a device in the production of biological test arrays. The invention also relates to a method for producing a biological test array. The invention moreover relates to a biological test array. The method according to the invention is failure-proof, and results in biological test arrays of superior quality.

Abstract: An acoustic wave transducer substrate is provided, the substrate having a surface with a plurality of growth promotion sites for promoting the accumulation of polypeptide molecules at said sites. The growth-promotion sites are preferably for promoting fibril formation. The invention also provides a method of screening a candidate compound for an effect on fibril growth, including the steps of: providing an acoustic wave transducer substrate having a surface with a plurality of growth promotion sites for promoting the accumulation of polypeptide molecules at said sites; causing oscillation of the substrate; contacting the substrate surface with a sample fluid comprising polypeptide molecules and a candidate compound; and measuring one or more parameters of the substrate oscillation to monitor the accumulation of said polypeptide molecules of interest in the presence and absence of said candidate compound.

Abstract: The invention relates to a heated reaction chamber for processing a biochip and to a method for controlling said reaction chamber. The heated reaction chamber for processing a biochip comprises a chamber wall, constituted by a flexible circuit board (10), a circuit path (10.3) being configured on the flexible circuit board (10) and being used as the heating device. The use of a flexible circuit board as the wall of a reaction chamber allows for a low thermal capacity of the reaction chamber in the area of the heating device, thereby allowing the chamber to be heated up quickly.

Abstract: A method of ex situ fabrication of at least one biochip, the method being of the type consisting in projecting onto a substrate a microvolume of reagent comprising at least one probe diluted in a suitable solvent so as to form, after the solvent has been eliminated, a spot comprising said probe, the method consisting in using a microprojection device comprising at least one tank in which the reagent is stored, and at least one source of gas under pressure put into communication with the tank, and in projecting the microvolume of reagent through an ejection nozzle under drive from the pressure exerted by the gas on the reagent.

Abstract: An apparatus for producing a probe carrier in which ambient humidity for a plurality of nozzles of a liquid ejection device for ejecting droplets of solutions containing probes to the surface of a carrier is controlled to 50% or more, preferably 60% or more. A part of solution supply passages to the plurality of nozzles is constructed from gas permeable membranes permitting gas-liquid separation under reduced pressure. These gas permeable membrane portions are gathered and altogether placed under reduced pressure to remove air bubbles from the respective solutions supplied to the plural nozzles and decrease the amount of a dissolved gas, which causes air bubbles to be generated.

Abstract: A system for directly printing a variety of chemicals, including very large molecules on the substrate, includes a channel of nanometric dimension movable with respect to a substrate on which printing is to occur or a substrate movable with respect to the channel. Precision contact of the end aperture, or tip, of the channel with the surface deposits the chemical on the surface. Precision contact can be made by normal force atomic force microscopy or by other techniques that allow controlled contact or near contact with the surface on which the chemical is to be written with fine precision. Multiple channels with multiple orifices may be provided. The channel is connected to a suitable separation device such as a high performance liquid chromatograph and the chemicals are delivered through a probe orifice onto a substrate.

Abstract: Liquid delivery apparatus and methods, in particular for the production of high-density arrays, wherein a partial drop of liquid is deposited from a capillary (1) onto a substrate (12), the capillary (1) and substrate (12) being capable of x, y and z movements relative to one another under the control of a translation mechanism.

Abstract: Disclosed are methods permitting colonies of nucleic acids produced by amplifying them in an immobilized medium to be visualized with a homogeneous fluorescence detection system which is introduced into the medium before amplification. No post-amplification steps, such as opening the gel, blotting, hybridization, and removal of unbound substrates, dyes, or probes are needed, and the growing molecular colonies can be monitored in real time. Also disclosed are methods for quantitative in situ assays of nucleic acids contained in individual cells or in tissue fragments. The methods are conveniently executed using a disposable transparent chamber containing dry matrix of the medium and equipped by inlet and outlet ports that serve for filling the chamber with a solution comprising components of amplification and detection systems, said solution being absorbed by said matrix to swell all over the inner volume of said chamber.

Abstract: The present invention is directed to devices and methods for molecular association, particularly to devices and methods for hybridization of nucleic acids utilizing temperature gradients and imaging thereof. In one aspect, a molecular hybridization system generally includes a substrate having a plurality of molecular probes attached thereto, the plurality of probes being generally present in multiple copies arranged in localized formations on the surface of the substrate. The molecular hybridization system further generally includes a chamber that encloses the plurality of molecular probes such that a fluid containing sample may be applied and kept in contact with the substrate having the probes thereon. The molecular hybridization system also includes a temperature affecting system that generally produces at least one desired temperature on the surface of the substrate and in the adjacent fluid within the chamber.

Abstract: Methods for electrochemically synthesizing polymers are provided in which a cleavable linker is coupled to the surface of at least one electrode of an array of electrodes on a substrate and a polymer coupled to the cleavable linker is synthesized through a series of monomer addition cycles. Polymers that are synthesized include nucleic acids and peptides. Cleavable linkers include linkers that can be cleaved under conditions such as reducing, oxidizing, acidic, and or basic conditions. Additionally, provided are devices that comprise an array of individually addressable electrodes having surface-attached cleavable linker molecules.

Abstract: The present invention relates to a spot pin (2) including: a liquid holding portion (21) including a tubular portion and defining a liquid holding space (27) for holding a liquid; and an upper limit position definition portion positioned in a middle of the liquid holding portion (21) in an axial direction and defining the upper limit position of the liquid held in the liquid holding portion (21). The upper limit position definition portion has one or a plurality of outside air communication holes (24) communicated with the liquid holding space (27) and opened in the circumferential surface of the liquid holding portion (21).

Abstract: Provided are systems for arrays for assaying various biomolecules and other compounds in a microtiter plate format. The wells are designed so as to contain subwells to facilitate fluid communication between subwells and to allow for efficient human or robotic manipulation of samples and assay of binding or other interactions of components within the wells.

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: An object of the present invention is to provide a probe array having partitioned array regions with uniform surface chemical properties. The probe array of the present invention includes a substrate having a plurality of partitioned array regions where many probes are immobilized and a separator attached to the substrate and including partitions partitioning the array regions. The above object can be achieved by attaching the separator including the partitions capable of partitioning instead of forming hydrophobic regions on a surface of the substrate by printing or chemical treatment.

Abstract: Arrays and substrates comprising a material, in particular capture agents and/or detectable targets, attached to the substrates along substantially parallel lines forming a barcoded pattern and related methods and systems.

Abstract: This invention provides improved components (e.g. array “pins”, print head, substrate platen, print head platen, and the like) for microarray printing devices as well as microarray printing devices incorporating such components. In one embodiment, this invention provides a microarray print head comprising a plurality of glass or quartz spotting capillaries disposed in a support that maintains a fixed spacing between the spotting capillaries and that permits the spotting capillaries to move in a direction parallel to the long axis of the capillaries.

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: Provided are a programmable mask for promptly fabricating a biomolecule or polymer array having high density, an apparatus for fabricating a biomolecule or polymer array including the mask, a method of fabricating a biomolecule or polymer array using the programmable mask and a photochemical synthesis apparatus.

Abstract: A fast, multiplexed PCR system is described that can rapidly generate amplified nucleic acid products, for example, a full STR profile, from a target nucleic acid. Such systems include, for example, microfluidic biochips and a custom built thermal cycler, which are also described. The resulting STR profiles can satisfy forensic guidelines for signal strength, inter-loci peak height balance, heterozygous peak height ratio, incomplete non-template nucleotide addition, and stutter.

Abstract: Method and systems that provide improved handling and/or culturing and/or assaying of cells, chemically active beads, or similar materials in microfluidic systems and microfluidic culture arrays.

Abstract: An apparatus for use in fabricating structures and depositing materials from tips to surfaces for patterning in direct-write mode, providing ability to travel macroscopic distances and yet provide for nanoscale patterning. Useful in small scale fabrication and nanolithography. The instrument can be compact and used on a laboratory bench or desktop. An apparatus comprising: at least one multi-axis assembly comprising a plurality of nanopositioning stages, at least one pen assembly, wherein the pen assembly and the multi-axis assembly are adapted for delivery of material from the pen assembly to a substrate which is positioned by the multi-axis assembly, at least one viewing assembly, at least one controller. Nanopositioning by piezoelectric methods and devices and motors is particularly useful. The apparatus can include integrated environmental chambers and housings, as well as ink reservoirs for materials to be delivered. The viewing assembly can be a microscope with a long working distance.

Abstract: The invention provides methods and apparatuses that utilize mass spectrometry for preparation of a surface to have catalytic activity through molecular soft-landing of mass selected ions. Mass spectrometry is used to generate combinations of atoms in a particular geometrical arrangement, and ion soft-landing selects this molecular entity or combination of entities and gently deposits the entity or combination intact onto a surface.