Abstract: Systems and methods for determining therapeutic potential. In at least one embodiment of a system of the present disclosure, the system comprises a detection platform, a computer processor and a database. The processor, in at least one embodiment of a method of the present disclosure, has and executes a software program operational to determine a binding characteristic of the detection agent and a stabilized diagnostic marker in each of the plurality of detection sites on the platform, compare the binding characteristic, and determining the stabilizing agent with the greatest effect on the binding characteristic between the detection agent and the diagnostic marker. Further, at least one embodiment of a system for determining the therapeutic potential of a therapeutic compound of the present disclosure is able to generate a binding record using the compared binding characteristics, and deliver the binding record to a recipient.

Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time- resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Abstract: Apparatus and methods for forming self-assembly arrays of substances, such as nanoparticles, on a substrate are disclosed. The apparatus may include a substrate supporting a liquid composition including the substance and a solvent, and a removable micro-mold placed over the substrate and the liquid composition. To form the self assembly arrays of the substance, the solvent may be evaporated through at least one evaporation channel formed between the micro-mold and the substrate. The evaporation channel may be adjustable by subjecting the micro-mold to a positive pressure.

Abstract: An integrated instrument for oligonucleotide synthesis and PCR, and a system and method thereof are disclosed. The integrated instrument is basically composed of two independent modules. The first module is a unit for chemical de novo synthesis of oligonucleotides such as oligonucleotide primers and/or oligonucleotide hybridization probes. The second module is a unit for performing an analytical polymerase chain reaction amplification in real time, i.e. a qPCR. The two modules are operatively linked to each other in such a way that a user can load a nucleic sample to be analyzed into the integrated instrument and perform a PCR reaction by programming the instrument without a previous external synthesis of oligonucleotide amplification primers.

Abstract: An enhanced microplate and retention device for selectively retaining tube inserts within the microplate. A dynamic microplate having a selectable number of interchangeable microwells.

Abstract: A multiple cuvette strip comprises a plurality of wells and a reversible interlocking device. The well strips can be reversibly interlocked to other well strips to form a sample holder system. One embodiment of a well strip comprises a flange and a slot to form a reversible interlocking device.

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: The present invention describes microfluidic devices that provide novel fluidic structures to facilitate the separation of fluids into isolated, pico-liter sized compartments for performing multiplexing chemical and biological reactions. Applications of the novel devices including biomolecule synthesis, polynucleotide amplification, and binding assays are also disclosed.

Abstract: Combinatorial processing including stirring is described, including defining multiple regions of a substrate, processing the multiple regions of the substrate in a combinatorial manner, introducing a fluid into a first aperture at a first end of a body to dispense the fluid out of a second aperture at a second end of the body and into one of the multiple regions, and agitating the fluid using an impeller at a second end of the body to facilitate interaction of the fluid with a surface of the substrate.

Abstract: A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31), downstream from the nozzles (22), sweeps the common chamber (31) of toxic fumes emitted by the reagents.

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: To provide an autoanalyzer for analyzing a sugar chain contained in a biological sample, in particular, serum. Namely, it is intended to provide a method of analyzing a sugar chain in a sample, which comprises the following steps: A) the sugar chain-releasing step of releasing the sugar chain in the sample; B) the detection sample-preparing step of preparing the released sugar chain for detection; and, in the case of conducting mass spectrometry using a plate, C) the step of forming a plate for the mass spectrometry having the captured sugar chain dotted thereon which comprises the step of providing the tagged sugar chain sample solution obtained in the step B) on a collection plate; and, if required, the step of conducting an operation in a solid phase support-enclosed plate to form the plate for mass spectrometry; and D) the step of analyzing the sugar chain to be assayed.

Abstract: Three-dimensional cellular arrays, methods of making three-dimensional cellular arrays, and methods of identifying agents using the arrays are disclosed.

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

Abstract: A system, including method and apparatus, for forming an array of emulsions. The system may include a plate providing an array of emulsion production units each configured to produce a separate emulsion and each including a set of wells interconnected by channels that intersect to form a site of droplet generation. Each set of wells, in turn, may include (1) at least one first input well to receive a continuous phase, (2) a second input well to receive a dispersed phase, and (3) an output well configured to receive from the site of droplet generation an emulsion of droplets of the dispersed phase disposed in the continuous phase.

Abstract: A method of fabricating a device comprising an array of test locations defined on a substrate with each test location comprising one or more identical oligonucleotides affixed to the substrate.

Abstract: Improved nanolithography components, systems, and methods are described herein. The systems and methods generally employ a resistively heated atomic force microscope tip to thermally induce a chemical change in a surface. In addition, certain polymeric compositions are also disclosed.

Abstract: The present invention relates to a method of manufacturing a patterned substrate for culturing cells, comprising the steps of: (1) preparing a substrate; (2) forming a first plasma polymer layer by integrating a first precursor material using a plasma on the substrate; (3) placing a shadow mask having a predetermined pattern on the first plasma polymer layer; and (4) forming a second patterned plasma polymer layer by integrating a second precursor material using a plasma.

Abstract: A method for immobilizing a target material on a substrate includes applying a voltage across a first solution including the target material in contact with a surface of a film including a pore disposed therein, a second solution in contact with an opposite surface of the film, and a substrate disposed facing the opposite surface of the film, moving the target material from the first solution, through the pore of the film into the second solution, and immobilizing the target material on the substrate.

Abstract: A method and a system for selecting a set of FISH probe oligonucleotide sequences from a plurality of overlapping tiled candidate FISH probe oligonucleotide sequences are provided. A composition that includes FISH probes with sequences from the set of FISH probe oligonucleotide sequences is also provided.

Abstract: The disclosure relates to a method of generating a diverse set of variants to screen improved and novel properties within the variant population, a system for creating the diverse set of variants, and the variant peptides.

Abstract: A method, device and system for hybridizing a target oligonucleotide to at least one array comprising a plurality of mixing beads are provided. A target solution is mixed by agitating the mixing beads while the target oligonucleotides are hybridizing to the complementary probes on the array. In another embodiment, a permeable barrier contains the mixing beads, thereby preventing them from contacting the array surface.

Abstract: The present invention provides a system, comprising at least one reactor array, comprising at least two reactor vessels (2) a connecting member for fixating the at least two reactor vessels relative to each other (4, 5) at least one reactor block (18) comprising a heating block (20) for heating the reactor vessels (2) the heating block (20) comprising at least two reactor channels for receiving the at least two reactor vessels (2) wherein the heating block (20) is constructed of a material having a thermal expansion coefficient <=1×10e?5 K-I (at 293K). In an embodiment the heating block is substantially entirely constructed of graphite.

Abstract: A system for thermal cycling a plurality of samples. The system includes a case having a fluid-tight cavity defining an interior volume. A microfluidic array is disposed in the interior volume, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces. A thermal cycler having at least one thermally controlled surface is adapted to thermally contact the case.

Abstract: There is disclosed an acoustic device for manipulation of fluid samples including fluid samples comprising particles characterised in that it comprises a flexible member, a sound wave generator for generating a sound wave and a sound wave coupler for coupling the sound wave from the generator into the flexible member, in which the device, flexible member and the coupler are adapted to excite a predetermined acoustic mode of pure resonant vibration in the flexible member at a predetermined frequency of the sound wave.

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: Transfecting biology cells with nucleic acid molecules (DNA, siRNA) is an essential prerequisite in elucidating how genes function in complex cellular context and how their activities could be modulated for therapeutic intervention. Traditionally studies are carried out on a low throughput gene-by-gene scale, which has created a huge bottleneck in functional genomic study and drug discovery. Development of high-throughput cell transfection technology will permit functional analysis of massive number of genes and how their activities could be modulated by chemical or biological entities inside cells. This invention describes design, construction of device and apparatus for high throughput effective cell transfection. Procedures and protocols for using the device and apparatus are also described in the application. Novel methods of using the device in cell-based assays are also disclosed.

Abstract: An immobilizing device for biological material comprises a rigid support (12) carrying a substrate layer (20, 20?) of polymer having biological immobilizing properties, e.g. for amino and nucleic acids. Substantially solid ultra-thin substrate layers (20?) having a thickness less than about 5 micron, preferably between about 0.1 and 0.5 micron, and microporous, ultra-thin substrate layers (20?) having a thickness less than about 5 micron, preferably less than 3 micron, 2 or 1 micron are shown, which may be segmented by isolating moats M. The substrate layer is on a microscope slide (302), round disc (122), bio-cassette, at the bottom of a well of a multiwell plate, and as a coating inside a tube. Fluorescence or luminescence intensity and geometric calibration spots (420) are shown. Reading is enhanced by the intensity calibration spots (420) to enable normalization of readings under uneven illumination conditions, as when reading by dark field, side illumination mode.

Abstract: Transfecting biology cells with nucleic acid molecules (DNA, siRNA) is an essential prerequisite in elucidating how genes function in complex cellular context and how their activities could be modulated for therapeutic intervention. Traditionally studies are carried out on a low throughput gene-by-gene scale, which has created a huge bottleneck in functional genomic study and drug discovery. Development of high-throughput cell transfection technology will permit functional analysis of massive number of genes and how their activities could be modulated by chemical or biological entities inside cells. This invention describes design, construction of device and apparatus for high throughput effective cell transfection. Procedures and protocols for using the device and apparatus are also described in the application. Novel methods of using the device in cell-based assays are also disclosed.

Abstract: Novel processes are disclosed 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. In one embodiment, two substrates are processed simultaneously in a reaction chamber, wherein the substrates are facing each other and in contact with a monomer solution. In a further embodiment, multiple rotating flow cells are used in combination with a photolysis equipment to synthesize wafers.

Abstract: A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.

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

Abstract: Methods for forming cell arrays of multiple cell samples arranged substantially in a monolayer on a single substrate particularly suited for diagnostic analysis are disclosed. The cell arrays are formed with a high-speed dispensing apparatus capable of dispensing small volumes in precise, complex patterns. Also disclosed are substrates upon which cell arrays may be formed, and methods for conducting diagnostic analyses on the formed cell arrays.

Abstract: Methods for synthesizing chain molecules on particles in a multi-stream laminar flow, microfluidic reaction cells in which the methods can be carried out, and microfluidic systems incorporating the microfluidic reaction cells are provided. The methods, cells and systems are well suited for the rapid, large-scale production of chain biomolecules, such as oligonucleotides, in parallel.

Abstract: Systems and methods for using the same to obtain a chemical array layout are provided. Also provided are computer program products for executing the subject methods.

Abstract: The present disclosure provides apparatus, systems and method for detecting separately and substantially simultaneously light emissions from a plurality of localized light-emitting analytes. A system according to exemplary embodiments of the present disclosure comprises a sample holder having structures formed thereon for spatially separating and constraining a plurality of light-emitting analytes each having a single nucleic acid molecule or a single nucleic acid polymerizing enzyme, a light source configured to illuminate the sample holder, an optical assembly configured to collect and detect separately and substantially simultaneously light emissions associated with the plurality of light emitting analytes. The system may further include a computer system configured to analyze the light emissions to determine the structures or properties of a target nucleic acid molecule associated with each analyte.

Abstract: A printing device for fabricating hydrogel based microarrays by a nanostamping process is provided. Features of a preferred printing device include: maintaing consistent temperature profile during contact; reproducible temperature profile during separation; constant and uniform pressure profile during contact; and parallelism tolerance during conditions where the gimbal is slightly offset.

Abstract: Methods and apparatuses for selecting and arranging clinically relevant chromosomal loci allow an exemplary diagnostic array to simultaneously test for numerous genetic alterations that occur in many different parts of the human genome. Clinically irrelevant or ineffective loci are eliminated. One implementation increases reliability and accuracy by dividing the base-pair sequence of each chromosomal locus into segments and then assigning nucleic acid clones for comparative genomic hybridization to each different segment. The segments may overlap for increased resolution and control. Clones representing segments that are adjacent on a native chromosome are placed in non-adjacent target areas of the array to avoid interfering hybridization reactions. Arrangement motifs within an array may be redundantly repeated for high availability and increased reliability and accuracy of results. Techniques, hardware, software, logic engines, loci collections, and diagnostic arrays are described.

Abstract: The present disclosure provides apparatuses, systems, and methods involving a spotter apparatus for depositing a substance from a carrier fluid onto a deposition surface in an ordered array, the spotter apparatus comprising a loading surface including a first well and a second well; and a different outlet surface, including a first opening and a second opening, where a first microconduit fluidly couples the first well with the first opening and a second microconduit fluidly couples the second well with the second opening. An overlay is sealed to the outlet surface and penetrated by a deposition channel that is situated to communicate carrier fluid among the first opening, the second opening, and the deposition surface when the overlay is pressed against the deposition surface.

Abstract: A method for manufacturing synthetic genes and combinatorial DNA and protein libraries, termed here Divide and Conquer-DNA synthesis (D&C-DNA synthesis) method. The method can be used in a systematic and automated way to synthesize any long DNA molecule and, more generally, any combinatorial molecular library having the mathematical property of being a regular set of strings. The D&C-DNA synthesis method is an algorithm design paradigm that works by recursively breaking down a problem into two or more sub-problems of the same type. The division of long DNA sequences is done in silico. The assembly of the sequence is done in vitro. The D&C-DNA synthesis method protocol consists of a tree, in which each node represents an intermediate sequence. The internal nodes are created in elongation reactions from their daughter nodes, and the leaves are synthesized directly. After each elongation only one DNA strand passes to the next level in the tree until receiving the final product.

Abstract: The embodiments of the invention relate to a system and method for making a biomolecule microarray comprising a spacer attachment module adapted to attach a linker to a substrate surface of the biomolecule microarray, a coupling module adapted to couple a molecule to the linker, the molecule being capable of forming a peptide bond and containing a protecting group that prevents the formation of the peptide bond, and a deprotection module adapted to create deprotection of the protecting group with a radiation exposure of about 1-50 mJ/cm2.

Abstract: The invention relates to a carrier comprising at least one substrate, which has a coating in at least certain regions produced from individual modules by plasma polymerisation, and the coating has one or more free spaces in at least certain regions for accommodating at least one solution containing a biological sample.

Abstract: A method for immobilizing biological polymers such as DNA or proteins, on a solid support, by ionocovalent bond, for making biochips, and the resulting chips obtained by the method.

Abstract: Fluidic conduits, which can be used in microarraying systems, dip pen nanolithography systems, fluidic circuits, and microfluidic systems, are disclosed that use channel spring probes that include at least one capillary channel. Formed from spring beams (e.g., stressy metal beams) that curve away from the substrate when released, channels can either be integrated into the spring beams or formed on the spring beams. Capillary forces produced by the narrow channels allow liquid to be gathered, held, and dispensed by the channel spring probes. Because the channel spring beams can be produced using conventional semiconductor processes, significant design flexibility and cost efficiencies can be achieved.

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.