Abstract: According to the present invention there is provided an assembly comprising, a needle unit comprising n hollow needles wherein n is greater than one, and wherein each hollow needle can receive a respective sample fluid; a flow cell unit comprising m flow cells wherein m is greater than one, each flow cell having an input and an output, and a test surface on which ligands can be provided located between the input, and output; a means for consecutively moving sample fluids, from each of said n hollow needles respectively, into all said m flow cells, so that said sample fluids flow consecutively through the same flow cells. There is further provided a corresponding method of screening a sample fluid for molecules which can bind to predefined ligands.

Abstract: In one example, a flow cell includes a plurality of inlet ports sized to receive a flow of reagent from one of a plurality of reagents into the flow cell. An outlet port of the flow cell is sized to pass each flow of reagent out of the flow cell. A flow channel of the flow cell is positioned between, and in fluid communication with, each inlet port and the outlet port. The flow channel includes a manifold section and a detection section. The manifold section has a plurality of manifold branches in fluid communication with a common line, wherein each branch is connected to one of each inlet port. The detection section is in fluid communication with the common line and the outlet port. The detection section is operable to perform a plurality of different chemical reactions between the plurality of reagents and analytes positioned in the detection section.

Abstract: Methods and devices for a stacked nanofluidic sensor are described. The stacked nanofluidic sensor and methods for forming a nanosheet stack of at least two alternating layers of a first nanosheet material and a second nanosheet material on a substrate. Additionally, a gate structure is formed on the nanosheet stack. Further, nanofluidic channels are formed within the gate structure, including removing each layer of the first nanosheet material within the gate structure to form a channel configured to receive a nanofluidic sample.

Abstract: Methods and devices for a stacked nanofluidic sensor are described. The stacked nanofluidic sensor and methods for forming a nanosheet stack of at least two alternating layers of a first nanosheet material and a second nanosheet material on a substrate. Additionally, a gate structure is formed on the nanosheet stack. Further, nanofluidic channels are formed within the gate structure, including removing each layer of the first nanosheet material within the gate structure to form a channel configured to receive a nanofluidic sample.

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: 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: Described herein is a digital microfluidic droplet generator (DMDG) and a microfluidic platform for processing material introduced into the DMDG. The combination is particularly suited for hydrogen/deuterium exchange and mass spectrometer (HDX-MS) processing and analysis of membrane proteins.

Abstract: Compositions, methods and kits are disclosed for high-sensitivity single molecule digital counting by the stochastic labeling of a collection of identical molecules by attachment of a diverse set of labels. Each copy of a molecule randomly chooses from a non-depleting reservoir of diverse labels. Detection may be by a variety of methods including hybridization based or sequencing. Molecules that would otherwise be identical in information content can be labeled to create a separately detectable product that is unique or approximately unique in a collection. This stochastic transformation relaxes the problem of counting molecules from one of locating and identifying identical molecules to a series of binary digital questions detecting whether preprogrammed labels are present. The methods may be used, for example, to estimate the number of separate molecules of a given type or types within a sample.

Abstract: Fluid-based no-moving part logic devices are constructed from complex sequences of micro- and nanofluidic channels, on-demand bubble/droplet modulators and generators for programming the devices, and micro- and nanofluidic droplet/bubble memory elements for storage and retrieval of biological or chemical elements. The input sequence of bubbles/droplets encodes information, with the output being another sequence of bubbles/droplets or on-chip chemical synthesis. For performing a set of reactions/tasks or process control, the modulators can be used to program the device by producing a precisely timed sequence of bubbles/droplets, resulting in a cascade of logic operations within the micro- or nanofluidic channel sequence, utilizing the generated droplets/bubbles as a control. The devices are based on the principle of minimum energy interfaces formed between the two fluid phases enclosed inside precise channel geometries.

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: A biochip for the integration of all steps in a complex process from the insertion of a sample to the generation of a result, performed without operator intervention includes microfluidic and macrofluidic features that are acted on by instrument subsystems in a series of scripted processing steps. Methods for fabricating these complex biochips of high feature density by injection molding are also provided.

Abstract: Methods for non-random loading of single analyte molecules into array structures are provided. The methods allow for distribution of a population of target molecules into a plurality of size confined regions such as wells. Sizing moieties are linked to individual target molecules. The sizing moieties are of sufficient size, relative to the size-confined reaction or observation regions, such that only a selected number of sizing moieties will fit into the size confined regions. The confined regions and the sizing moieties or target molecules comprise a selected charge that allow for controlling the loading of the sizing moities.

Abstract: A system and method for isolating cells, comprising: a substrate having a broad surface; an array comprising a set of wells defined at the broad surface of the substrate, each well including: a base surface, an open surface directly opposing the base surface, defined at the broad surface of the substrate, and configured to receive one of a single cell and a single cluster of cells from a direction perpendicular to the broad surface of the substrate, and a set of channels that fluidly couple each well to at least one adjacent well; wherein the set of wells includes an interior subset and an exterior subset fluidly coupled to and surrounding the interior subset by way of the set of channels; and a fluid delivery module surrounding the array and fluidly coupled to each well in the set of wells.

Abstract: Methods, systems, and computer programs for designing probes or primers for nucleic acid sequencing, generating libraries of nucleic acid sequences, and mapping genomic sequences are provided herein,

Abstract: The present disclosure discloses a method to prepare a supra-monolayer nanopattern and its uses.

Abstract: Provided are a novel antibiotic preparation method and platform system based on the method, belonging to a novel drug development method. The method is based on a fixed structural formula: F—R, wherein F is an effect area, and R is an identification area. At the prior art level, the present invention can quickly develop a specific novel antibiotic for most pathogenic microorganisms or biological cells. Also provided is a platform for implementing the method, ensuring that the novel antibiotic is developed in an efficient streamlined process.

Abstract: The present invention provides a method and system for determining whether a genomic abnormality exists. The method for determining whether a genomic abnormality exists includes the steps of: separating fetal nucleated red blood cells from a sample from a pregnant woman; sequencing at least a part of the genome of the nucleated red blood cells, so as to obtain a sequencing result; and on the basis of the sequencing result, determining whether a genomic abnormality exists in the nucleated red blood cells.

Abstract: A vacuum assist apparatus can comprise a microplate. The microplate can comprise a first surface and an opposing second surface. A plurality of wells can be formed in the first surface of the microplate. Each of the plurality of wells can be sized to receive an assay therein. A support base can comprise a fluid passage. The microplate can be positioned adjacent and in contact with the support base. A pressure device, in fluid communication with the fluid passage, can exert a vacuum within the fluid passage to actively retain the microplate in the contact with the support base.

Abstract: Apparatus, systems, and methods for detecting, screening and sampling of cells are disclosed.

Abstract: System, including methods and apparatus, for spacing droplets from each other and for detection of spaced droplets.

Abstract: Device to detect at least an analyte, comprising a transparent substrate (2), having a first surface (3) with which a light source (7) is associated, and a second surface (4) on which a plurality of biological protein probes (12) are disposed, a layer (6) of polymer being interposed between said second surface (4) and said biological protein probes (12). A marker (fluorophore) is associated with said analyte, having determinate characteristics of fluorescence and/or phosphorescence correlated to the emission wavelength of the light source (7). Said light source (7) is suitable to emit a light radiation in a range of wavelengths equal to 400-550 nm, inside which range the absorption peak of said marker (fluorophore) used is comprised. The value of the distance (“s”) between the wavelength corresponding to the absorption peak of the marker (fluorophore) and the wavelength corresponding to the emission peak of fluorescence (phosphorescence) is comprised between 25 and 150 nm.

Abstract: A microfluidic chip automatic system includes a microfluidic chip platform and an optical platform. The microfluidic chip platform includes a microfluidic chip, a fluid source, a gas source, and a controller. A time sequence of charging a high pressure gas from the gas source into the microfluidic chip and discharging the high pressure gas from the microfluidic chip is controlled by the controller through plural solenoid valves. The optical platform includes a light source, plural lenses, a digital micromirror device, a grating device and a reflective mirror. A light beam provided by the light source is guided to the microfluidic chip. The digital micromirror device includes plural micromirrors. The optical switching states of the micromirrors are controlled by a computer, so that a position of the microfluidic chip to carry out a photochemical reaction is correspondingly controlled.

Abstract: Assay plate assemblies are disclosed. The assemblies include an assay plate that has a top side, a bottom side, and at least one well accessible from the top side of the plate. The well includes a side surface and a bottom surface, with at least one secondary container protruding through the bottom surface and into an interior volume of the well. The assemblies further include a dispenser plate that is adapted to be positioned adjacent to the top side of the assay plate. The dispenser is further configured to provide one or more reagents to one or more secondary containers of at least one well of the assay plate.

Abstract: This disclosure provides methods, devices and systems for using a stamp to enhance selectivity between surface layers of a substrate, and to facilitate functionalizing selected layers. An array of flat stamps may be used to concurrently stamp multiple regions of a substrate to transfer one or more substances to the topmost layer or layers of the substrate. If desired, the affected regions of the substrate may be isolated from each other through the use of a reactor plate that, when clamped to the substrate's surface, forms reaction wells in the area of stamping. The stamp area can, if desired, be configured for stamping the substrate after the reactor plate has been fitted, with the individual stamps sized and arranged in a manner that permits stamping within each reaction well.

Abstract: The invention relates to a silane compound including a cycloalkyne functionality, to a method for functionalising a solid substrate, and to the solid substrate thus produced. The silane compound of the invention corresponds to the formula X-E-A-Z where X is a silyl group, E is an organic spacer group, A is a single bond or a —CONH—, —NHCO—, —OCH2CONH—, —NHCOCH2O—, —O— or —S— group, and Z is a cycloalkyne or heterocycloalkyne with at least 8 members. The invention is particularly suitable for use in the field of medicine.

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: 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: A microfluidic device is described that has a slug mixing arrangement. A reaction well has an input flow channel with a first valve near the reaction well, and a second valve further from the reaction well. A fluid source is connected to the segment in between the two valves. A second fluid source is connected behind the second valve. The channel between the two valves receives the first fluid by blind filling when the two valves are closed. The reaction well receives the first fluid followed by the second fluid when the first and second valves are open.

Abstract: In a multiplexed assay, each molecule of a plurality of molecules is attached to a support matrix particle with a substrate adapted for attachment and/or synthesis of molecules. A spectrally-encoded identifier embodied in a photochemical medium is embedded or encased within the substrate to uniquely identify the molecule attached to the substrate. The molecules are exposed to one or more processing conditions, and then placed within the path of an optical detector adapted to read the spectrally-encoded identifier and measure biochemical activity on each support matrix particle. The measured biochemical activity is associated with the unique identity of the support matrix particle and, hence, with the molecule attached to the particle.

Abstract: A valved microfluidics device, microfluidics cell-culture device and system incorporating the devices are disclosed. The valved microfluidics device includes a substrate, a microchannel through which liquid can be moved from one station to another within the device, and a pneumatic microvalve adapted to be switched between open and closed states to control the flow of fluid through a microchannel. The microvalve is formed of three flexible membranes, one of which is responsive to pneumatic pressure applied to the valve and the other two of which deform to produce a more sealable channel cross-section. The cell culture device provides valving to allow controlled loading of cells into the individual well of the device, and exchange of cell-culture components in the wells.

Abstract: This invention relates to a kit and a method for the collection and analysis of complex protein mixtures. More particularly, the invention relates to a kit comprising a single barrel filtration well or a multi-well filtration plate wherein each well comprises an upper filtration zone; a lower filtration zone; a conical flow director zone; and, an elution tip, wherein the upper filtration zone and the lower filtration zone are separated by a retainer ring disposed within the lower filtration zone. The upper filtration zone comprises an upper collection zone, a sponge zone, and a deep bed filtration zone; and, the lower filtration zone comprises the retainer ring, a supported hydrophilic membrane and a lower bed filtration media. When used with an array of selected buffer solutions, the multi-well filtration plate can provide accurate, automated, high-throughput protein analysis by affinity chromatography.

Abstract: The present invention discloses a polymerase chain reaction (PCR) method, a PCR droplet device and a PCR droplet device array. The steps of the method comprise that a liquid comprising an analyzer is dropped on the heating coil disposed on the droplet device to form a droplet, then dropping a hydrophobic solution to prevent the droplet from evaporating. When an electric current or a voltage is supplied through at least one conducting wire to heat the heating coil, the inside of the droplet can generate buoyancy to drive the analyzer to move to the top of the inside of the droplet. Subsequently, the analyzer is moved to a periphery of the inside of the droplet so as to form a thermal cycle. Therefore the template is amplified by recycling the thermal cycle.

Abstract: Methods of isolating at least one cell of interest, methods of making fixed arrays, arrays comprising a glass substrate bonded to a patterned siloxane structure having inlets, outlets and microchannels, array kits, and methods of making microfluidic apparati are provided in the present application.

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: Systems, methods, and devices are provided for assessing DNA damage and repair in cells by measuring DNA migration under electrophoresis. In one exemplary embodiment, a microarray configured to hold cells in a predetermined spatial relationship is employed to improve accuracy, speed, and reliability of such measurements. In another embodiment, a self-contained cassette having a matrix material disposed therein can be used to create a substantially uniform environment for analyzing DNA damage and repair. Fluid can be circulated through the cell to assist in creating spatial patterns on the matrix material, or alternatively, the matrix material can already include a microarray pattern disposed thereon. Various methods and systems that take advantage of such microarrays and cassettes are also provided.

Abstract: The invention provides methods and apparatus for characterizing complex polymeric mixture of interest. Candidate solutions are eliminated from a solution space using one or more experimental measurements of a polymeric mixture of interest. The elimination step can be repeated one or more times using different experimental measurements produced by various chemical and physical protocols, so that the remaining candidate solutions converge to describe the actual polymeric mixture under investigation. Once the composition of the complex polymeric mixture has been characterized, the information thus generated can be used to facilitate, for example, the manufacture of a bio-equivalent of the complex polymeric mixture.

Abstract: Carriers or holders for holding microfluidic devices are provided. Some of the carriers that are provided include a hydration control device and/or a source of controlled fluid pressure to facilitate use of the carrier in conducting various types of analyses.

Abstract: A biosensor comprising an electrically conductive substrate coated with a modified chitosan biopolymer that has been electrodeposited on the substrate, wherein said modified chitosan biopolymer comprises at least one vesicle binding molecule. The biosensor is manufactured by a method where a modified chitosan biopolymer is electrodeposited on a substrate. The method is also used to manufacture a modified chitosan biopolymer film by electrodeposition of the chitosan on the substrate and later removing the film from the substrate after electrodeposition. The resulting film can be used in bandages to treat various types of wounds. The biosensor can also be used to detect various analytes in samples.

Abstract: Methods and reagents for site-selective functionalization of peptides and proteins. The methods most generally involve the reaction of a thioester with hydrazine. Reagents include bifunctional reagents of formula: H2N—NH—CH2-M-L-FG and salts thereof where M is a single bond or a chemical group carrying a non-bonding electron pair, such as —C(O)NR?—, where R? is H, or an alkyl or aryl group; L is an optional linker group as described above; and FG is a functional group having reactivity that is orthongonal to that of the hydrazine group. FG can, among others, be an azide, alkenyl, alkynyl, nitrile (—CN) or triazole group and is preferably an azide group (—N3). Methods and reagents can, for example, be combined with intein-mediated protein splicing to link proteins or fragments thereof to various chemical species or to a surface.

Abstract: The present invention relates to novel iminecalixarene derivatives, method of preparation thereof, and self-assembled monolayer prepared by the method, fixing method of oligo-DNA by using the self-assembled monolayer, and oligo-DNA chip prepared by the method. Also, the present invention relates to novel aminocalixarene derivatives, method of preparation thereof, and self-assembled monolayer prepared by the method, fixing method of oligo-DNA wherein the oligo-DNA is voluntarily fixed by molecular recognition on said self-assembled monolayer in a liquid phase, and oligo-DNA chip prepared by the method.

Abstract: Provided is a method for determining one or more kinetic parameters of binding between a first binding member and a second binding member. The method includes adsorbing the first binding member to a surface at a plurality of microspots. The second binding member is then presented to the first binding member at each of the microspots, there being a plurality of combinations of first binding member surface density and second binding member concentration among the plurality of microspots. Data indicative of a binding reaction between the first of microspots are then obtained and analyzed so as to obtain one or more kinetic parameters of the binding between the first and second binding members. Also provided is a system for carrying out the method. A method for localizing a molecular species at microspots on a surface, and a probe array produced by the method are also provided.

Abstract: A sequencing method is presented in which a biomolecule is hybridized with a specially chosen pool of different probes of known sequence which can be electrically distinguished. The different probe types are tagged such that they can be distinguished from each other in a Hybridization Assisted Nanopore Sequencing (HANS) detection system, and their relative positions on the biomolecule can be determined as the biomolecule passes through a pore or channel. The methods eliminate, resolve, or greatly reduce ambiguities encountered in previous sequencing methods.

Abstract: A method for carrying out nucleic acid amplification, includes providing a reaction chamber (31), accommodating an array (36) of nucleic acid probes (37) at respective locations, for hybridizing to respective target nucleic acids; and introducing a solution (50) into the reaction chamber (31), wherein the solution (50) contains primers, capable of binding to target nucleic acids, nucleotides, nucleic acid extending enzymes and a sample including nucleic acids. The a structure of the nucleic acid probes (37) and of the primers so that a hybridization temperature (TH) of the probes (37) is higher than an annealing temperature (TA) of the primers, whereby hybridization and annealing take place in respective separate temperature ranges (RH, RA).

Abstract: The present invention relates among others 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: Multiplex binding assay assemblies are disclosed. The assemblies generally include at least one assay bar that includes a top side, a bottom side, and at least one well accessible from the top side of the assay bar. Each well includes a side surface, a bottom surface, an open top end, and at least one secondary container, with each secondary container including a capillary tube that (i) begins at a location within an interior volume of the well and (ii) ends at a location beneath the bottom surface of the assay bar. The assemblies further include a dispenser bar that is adapted to be positioned adjacent to the top side of the assay bar, which includes one or more reservoirs that are configured to provide one or more reagents to the at least one secondary container located in each well of the assay bar.

Abstract: The present invention relates to microfluidic chips and their use in SELEX. The microfluidic chip preferably includes a reaction chamber that contains a high surface area material that contains target. One preferred high surface area material is a sol-gel derived material. Methods of making the microfluidic chips are described herein, as are uses of these devices to select aptamers against the target.

Abstract: The invention relates to a method for the detection and characterization of a toxinogenic Clostridium difficile strain in a sample, wherein the following steps are performed, (i) a sample is provided for, (ii) in a multiplex PCR assay, (iii) the sample is analyzed with respect to the presence or absence of the cytotoxin tcdB gene, (iv) the sample is analyzed with respect to the presence or absence of one or more of the following deletions in the tcdC gene: (a) an 18 bp deletion in SEQ ID NO. 1 from nucleotide 330 to nucleotide 347, (b) a 36 bp deletion in SEQ ID NO. 1 from nucleotide (301) to nucleotide (336), (c) a 39 bp deletion in SEQ ID NO. 1 from nucleotide (341) to nucleotide (370), (d) a 54 bp deletion in SEQ ID NO. 1 from nucleotide (313) to nucleotide (366) and (e) a single nucleotide deletion at position 117 of SEQ ID NO. 1. The invention also relates to respective kits and primers and probes.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. In particularly preferred embodiments, these compounds are attached to the solid support through a covalent interaction.

Abstract: An apparatus for dispensing reagents and loading oligonucleotide spotting devices, the apparatus having a plurality of reagent vials, each with a droplet dispenser, a plurality of oligonucleotide vials, each with a droplet dispenser, a mounting surface for detachably mounting a microfluidic device for movement relative to the reagent vials, and detachably mounting an oligonucleotide spotting device, and, a control processor for operative control of the reagent vials and oligonucleotide vials and movement of the mounting surface relative to the reagent vials and oligonucleotide vials, wherein, the control processor is configured to activate any of the droplet dispensers, move the microfluidic device into registration with the reagent vials and move the oligonucleotide spotting device into registration with the oligonucleotide vials.

Abstract: A test module for amplifying DNA and RNA, the test module having an outer casing with receptacle for receiving a sample containing genetic material including DNA and RNA, a plurality of reagent reservoirs containing reagents for addition to the sample, a first nucleic acid amplification section for amplifying at least some of the genetic material, and, a second nucleic acid amplification section for amplifying at least some of the genetic material in parallel with the first nucleic acid amplification section.