Abstract: The present invention is directed to optical bio-discs, methods, and optical disc drives for clinical diagnostics. The present invention is further directed to methods for determining the quantity of a specific type of blood cell in a biological sample including on-disc sample preparation and processing, providing a pre-processed sample onto a capture zone, removing portions of the sample that are not bound in the capture zone, and counting bound cells. Also disclosed are fluidic circuits for processing blood samples for use in a cluster designation marker assay in the optical bio-disc.

Abstract: The invention relates to a device for containing, reacting and measuring, and a method of containing, reacting and measuring, and provides a device for containing, reacting and measuring, and a method of containing, reacting and measuring which is also able to effectively and quickly perform the reaction processing, measuring and identification.

Abstract: Diagnostic devices are disclosed which contain porous material. The porous material preferably comprises silica and alumina. Chemical and/or biological molecules can be bound to the porous material in high concentrations while both having high accessibility to molecules in solution, and retaining their natural conformation. Such diagnostic devices may be used for a wide array of assays including protein (e.g. ELISA) and nucleic acid (e.g. hybridization on chips or beads) detection and/or quantification methods.

Abstract: This invention provides solid phase specific binding lateral flow assay methods, devices and kits for quantitating high and low molecular weight analytes. The methods and devices of the invention employ labelled reagents which are either analyte analogs or complementary specific binding pair members for the analyte and a novel arrangement of capture zones comprising immobilized specific binding substances for either the analyte or the labelled reagent to effect bound from unbound labelled reagent as a function of analyte concentration. The capture zones are disposed on a non-bibulous matrix defining a flow path from a sample receiving zone to the capture zone. The devices of this invention also include multilane flow paths and multiple capture zones to quantitate analyte.

Abstract: The present invention relates to optical bio-disc systems and related methods and to immobilizing receptor molecules. When a sample is injected into a fluidic circuit, the target agent binds to a capture probe bound in a capture zone. A signal is generated from tags attached to a reporter probe that has specific affinity to the target agent. The assays and methods of the present invention are implemented on an optical bio-disc. The optical bio-disc includes a flow channel having capture zones and in fluid communications with a mixing chamber, and a peripheral waste reservoir. The optical bio-disc is implemented on an optical bio-disc that has information encoding format such as CD. An disc drive assembly is employed to rotate the optical bio-disc, read and process any encoded information, and analyze the samples in the flow channel of the optical bio-disc.

Abstract: An immunochemical assay device for determining the presence of NT-proBNP alone or conjunctively with Cardiac Troponin I comprising a base member, an array disposed on the base member, and at least one assay indicia zone. The array comprises (i) a reservoir pad to receive sample liquid, (ii) a wicking membrane, and (iii) at least one filter zone interposed between the wicking membrane and the reservoir pad. The filter zone being operable to permit passage of any specific immunocomplex to the wicking membrane while impeding passage of larger components.

Abstract: A conductive compound of formula (I) below, an electrode coated with the conductive compound, a sensor including the electrode, and a target molecule detection method using the sensor are provided: wherein Y is a carbonyl or —NH—; R is one of H, OH, a leaving group, and a probe group; l is an integer from 3 to 6; m is an integer from 1 to 4; and n is an integer from 0 to 3.

Abstract: A method for selectively combining multiple membranes for assembly into test strips (such as visual blood glucose test strips with side-by-side membranes). The method includes first measuring a plurality of color parameters (e.g., L*, a* and b*color parameters) associated with membrane samples from at least two membrane lots. Next, response characteristics (e.g., blood glucose response levels) are simulated for a speculative test strip that includes, for purposes of the simulation, combined multiple membranes tentatively selected from the at least two membrane lots. The simulated response characteristics are based on the measured plurality of color parameters of the tentative selection of combined multiple membranes. Optionally, the simulated response characteristics can also be based on simulated color parameters of the tentative selection of combined multiple membranes.

Abstract: Methods for the detection and/or quantification of a biological material in a sample. The method includes the steps of liquefying the sample (if necessary) and pouring the liquefied sample into the incubation vessel. The incubation vessel has a generally flat horizontal surface and the surface is divided into at least one incubation site. Each incubation site is adapted to hold an aliquot of liquid and is sized and shaped, and formed of a suitable material, to hold the aliquot within the well by surface tension. Any excess liquid from the liquefied sample is poured from the surface of the incubation vessel. The method then involves incubating that incubation vessel until the presence or absence of the biological material is determined. The presence of air bubbles can be dramatically reduced by the presence of a surface acting agent in the liquid sample deposited on the device surface.

Abstract: An on-spot selectively activated hydrophobic slide/microarray. The preparation method relates to a hydrophobic copolymer prepared by blending, grafting or co-polymerization of a hydrophobic material and a compound bearing a functional group protected by a protecting group, wherein the functional group is imide or cyclic amide, and the protecting group is a photo acid group such as a tosyloxy group. The hydrophobic copolymer coated on a substrate is then subjected to selective photolithographical activation so that the slide will have functional active copolymer spots separated by inactive copolymers. The resulting slide is suitable for the preparation of high-density and high-efficiency bio-chip/microarray.

Abstract: A microfluidic system is provided that includes a substrate, a first microchannel disposed in the substrate for providing a reactant to a reaction zone, a second microchannel disposed in the substrate, and a third microchannel disposed in the substrate, the third microchannel providing fluid communication between the first and second microchannels. The system also typically includes first and second electrodes, positioned at opposite ends of the second microchannel, for providing an electric field within the second microchannel. In operation, when the reactant is in the reaction zone, a reaction product is produced having a net electric charge different from the electric charge of the reactant.

Abstract: A biosensor is provided with an area in which a reagent having bleaching action is carried in a state where it can be dissolved, at least in a part of a sample application area to which an inspection target solution is applied or the downstream of the sample application area in the direction of the inspection target solution permeating, in a development layer. In the so-constituted biosensor, a colored component in the inspection target solution can be faded by the bleaching reagent, so that the color in parts other than a reactive area is reduced in consequence, whereby a visual judgment is possible and a more accurate measurement result in which a reading error by a measuring device is extremely suppressed can be obtained.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: An immunochemical assay device for determining the presence of NT-proBNP alone or conjunctively with Cardiac Troponin I comprising a base member, an array disposed on the base member, and at least one assay indicia zone. The array comprises (i) a reservoir pad to receive sample liquid, (ii) a wicking membrane, and (iii) at least one filter zone interposed between the wicking membrane and the reservoir pad. The filter zone being operable to permit passage of any specific immunocomplex to the wicking membrane while impeding passage of larger components.

Abstract: An analytical test device useful for example in pregnancy testing, comprises a hollow casing (500) constructed of moisture-impervious solid material, such as plastics materials, containing a dry porous carrier (510) which communicates indirectly with the exterior of the casing via a bibulous sample receiving member (506) which protrudes from the casing such that a liquid test sample can be applied to the receiving member and permeate therefrom to the porous carrier, the carrier containing in a first zone a labelled specific binding reagent is freely mobile within the porous carrier when in the moist state, and in a second zone spatially distinct from the first zone unlabelled specific binding reagent for the same analyte which unlabelled reagent is permanently immobilised on the carrier material and is therefore not mobile in the moist state, the two zones being arranged such that liquid sample applied to the porous carrier can permeate via the first zone into the second zone, and the device incorporating mea

Abstract: A method and device for carrying out immunoassays in which non analyte specific binding of heterophilic antibodies to a labeled antibody in a capture region produces an incorrect measure of the amount of an analyte attached to the antibody. Immunoglobulin from the same animal source as the labeled antibody is added to the sample fluid to prevent non-specific binding of the heterophilic antibodies in the capture region. One part of specific binding pair is added to said antibody or its label capable of binding to a second part of the binding pair immobilized in a control region downstream of said capture region for trapping the portion of the labeled anti-body which is not bound to the analyte. Preferably said binding pair is biotin/avidin or fluoroscein/anti-fluoroscein.

Abstract: An on-spot selectively activated hydrophobic slide/microarray. The preparation method relates to a hydrophobic copolymer prepared by blending, grafting or co-polymerization of a hydrophobic material and a compound bearing a functional group protected by a protecting group, wherein the functional group is imide or cyclic amide, and the protecting group is a photo acid group such as a tosyloxy group. The hydrophobic copolymer coated on a substrate is then subjected to selective photolithographical activation so that the slide will have functional active copolymer spots separated by inactive copolymers. The resulting slide is suitable for the preparation of high-density and high-efficiency bio-chip/microarray.

Abstract: Methods for chromatographically separating materials, including the separation of materials in kinase or phosphatase assays, in microfluidic devices under positive or negative fluid pressure. Devices and integrated systems for performing chromatographic separations are also provided.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: A method for detecting a substance, comprising developing a developing liquid through a test region up to a reference region, and a detection device for use therein, wherein the reference region comprises a metal compound other than an alkali metal salt, and the developing liquid that reaches the reference region contains a label that can be accumulated in the reference region. The label is preferably a colored particle, and is preferably bound to an antibody or an antigen.

Abstract: A simple easy to manufacture analytical device capable of performing membrane based immunoassays on batch of samples within 3 to 10 minutes wherein the method permits focused application of samples, costly labeled immunoassay and signal amplification reagents, said device includes an antibody-immobilized micro porous membrane, breadth corner layer of which is directly attached to a semi-rigid liquid-impervious body with water insoluble adhesive; absorbent body is provided separately and is not attached to analytical device during manufacture, absorbent body is wetted and is placed proximal to the lower surface of the membrane thereby forming networks of capillary channels with the absorbent body; flow of samples or reagents is always kept downwards and focused without application of any force to the absorbent body and the use of disposable adsorbent body permits stepwise addition of signal amplification reagents for ultra sensitive detection of diagnostically important molecules by visual examination of the m

Abstract: Optical bio-discs for biochemical analysis, bio-disc analysis systems and biochemical analysis methods are described herein. In one embodiment, the bio-disc includes a sample analysis circuit that includes a separation membrane for separating an investigational feature of a sample. The bio-disc also includes a conjugate release pad, and an analysis membrane containing analysis zones that may be analyzed for the presence of analytes. An analysis method includes providing a sample to a separation membrane in a bio-disc, separating an investigational feature from the sample using a separation membrane, mixing reagents that include signal elements for detecting an analyte with the investigational feature so as to form a reagent-investigational feature mixture and capturing an analyte with a signal element bound thereto in an analysis zone on an analysis membrane.

Abstract: An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over the dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments.

Abstract: A method for quantitatively assaying one or more target molecules in a sample uses a nucleic acid aptamer that is specific for each target molecule. A quantitative replicative procedure is used to determine a quantity of aptamer specific for each molecule.

Abstract: A test device (20) for detecting human blood includes a strip (22) having an introduction station (24), a test station (26), and a control station (28) disposed in spaced apart relationship. The test sample introduction station (24) has labeled antihuman Hb antibodies, the test station (26) has immobilized antihuman Hb antibodies, and the control station has immobilized polyclonal antibodies. A test sample (500) is deposited at the introduction station (24). If human hemoglobin is present in the test sample (500), a colored line will appear at the test station (26) and at the control station (28). If no human hemoglobin is present in the test sample (500), a colored line will only appear at the control station (28).

Abstract: The present invention is a method for selectively removing objects from a surface utilizing a probe. The probe is scanned over the surface utilizing a greater and greater relative amount of force so that a certain number of the objects are removed from the surface. The force required to remove the objects from the surface can be calculated utilizing Hook's law and the spring constant of the probe. After removal of the objects that have a relatively weaker binding affinity with the surface, the remaining objects can be harvested, characterized, and subjected to further study.

Abstract: An assay device and method are provided which allow the determination of the presence or absence of at least one analyte in a test sample, while providing specific identification of the test subject. The assay device includes a reaction medium having at least one reaction zone and at least one control zone, which is capable of providing a pattern suitable for identifying the test subject. The pattern suitable for identifying the test subject is preferably a fingerprint. In a preferred embodiment of the invention, the reaction zone and the control zone include at least one member of a ligand/receptor pair.

Abstract: This invention provides a novel Cryptosporidium parvum protein disulfide isomerase polypeptide, and nucleic acids that encode this polypeptide. The invention also provides methods, reagents, and kits that are useful for diagnosing infection by Cryptosporidium parvum. The methods are based on the discovery of binding agents, including recombinant polyclonal antibodies, that bind to the protein disulfide isomerase polypeptide of C. parvum.

Abstract: An improved multi-layered diagnostic sanitary test strip for receiving a heterogenous fluid, such as whole blood, to test for presence and/or amount of a suspected analyte in the fluid by facilitating a color change in the strip corresponding to the amount of the analyte in the fluid, wherein the test strip includes fluid volume control dams to prevent spillage of the fluid from the strip and a chemical reagent solution that facilitates end-point testing.

Abstract: Method and device for magnetic detection of binding of biological molecules on a biochip in which a magnetoresistive sensor device measures an areal density of magnetic nanoparticles on a micro-array, the magnetic nanoparticles being directly or indirectly coupled to a target sample. The magnetoresistive sensor device includes a substrate having attached thereto binding sites able to selectively bind the target sample, and a magnetoresistive sensor for detecting the magnetic field of the nanoparticles coupled to the target sample. The magnetoresistive sensor includes a plurality of magnetoresistive sensing elements, the width and length dimensions of which are at least a factor 10 or more, preferably a factor 100 or more larger than the diameter of the nanoparticles.

Abstract: The invention provides an improved test cell for detecting the presence of an analyte in a liquid sample. The device has an elongate casing defining a liquid sample inlet, a reservoir volume, a test volume, and a window through the casing at the test volume. Disposed within the cell is a sample absorbent, a novel biphasic substrate and a reservoir, together capable of transporting an aqueous solution within the casing along a flow path extending from the sample inlet through the test volume and into the reservoir volume. The invention further comprises a method for detecting the presence of an analyte in a liquid sample using the device and a biphasic chromatographic material for carrying out the method.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: Substrates for producing a DNA library are produced by immobilizing DNA onto a suitable substrate having excellent thermal conductivity. A surface of the substrate is chemically modified with a radical having a terminal polar radical. DNA can be amplified by the PCR method in a short period of time using substrates of the present invention onto which DNA is immobilized.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: The method of the invention is directed to the novel use of a diffusion chamber within which previously “uncultivatible” microorganisms can be isolated. Rather than attempting to replicate the natural environment of an unknown microorganism, the method of the invention provides for exposing dividing microorganisms to all the components of the original environment while simultaneously containing the resulting colonies so that they can be isolated. The method of the invention can take advantage of the recognition that the preponderance of difficult-to-grow microorganisms do not form colonies visible to the naked eye. Therefore, these organisms must be isolated under a compound microscope as “microcolonies.” In addition, methods according to the invention permit the isolation of novel microorganisms capable of growing in artificial media only in co-culture in the presence of a companion microorganism.

Abstract: The invention concerns a method for quantitative or qualitative determination of an analyte or its interaction or reaction kinetics in a system with at least two different phases, comprising the step of taking at least one measurement signal from at least one of the phases, whereby the different phases are present in parallel when taking the signal and whereby each measurement signal is attributed to one of at least two phases. In addition, the invention concerns a sample carrier, in particular for use in the method constituting the invention with one or more wells. The sample carrier is characterized by the fact that at least a portion of the sample carrier at least in the range of one or more wells is coated with fluorescence-quenching material.

Abstract: The invention concerns an analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of capillary liquid transport which has a sample application opening at one end and a vent opening at the other end of the channel capable of capillary liquid transport, wherein the channel capable of capillary liquid transport is formed at least partially by the carrier and the detection element and extends in the direction of capillary transport from the sample application opening at least to the edge of the detection test element that is nearest to the vent opening and wherein a notch is located in one of the surfaces forming the channel capable of capillary liquid transport at the edge of the test element forming the sample application opening so that one side of the edge of the test element forming the sample application opening is at least partially discontinuous and the surface opposite to the notch is exposed.

Abstract: Devices and methods are disclosed for containing and processing samples on the surface of supports. Biopolymer features are attached to the surfaces of the supports. A device in accordance with the invention comprises a housing and a support confined by the housing. The housing comprises a well having walls and at least one wall extending from the edge of the well. The height of the walls of the well is at least great enough, and the design of the at least one wall is such, that liquid contained in the well is not drawn out of the well to any substantial degree by surface tension or small movements or small mechanical vibrations. In one embodiment, the at least one wall is designed such that corners thereof are curved or are distant from the edge of the well to substantially eliminate wicking of liquid from the well. Also disclosed are methods for mixing materials on the surface of a support. A sample is incubated with the surface of the support of the aforementioned device.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: Novel magnetic assay methods and systems. According to a preferred embodiment, a chromatographic medium, which preferably comprises a test strip, is provided that is designed to be contacted with a test solution having activated magnetic particles such that the solution flows bilaterally thereacross. A magnetic field, generated by a magnet or electromagnet, is selectively applied to the medium which causes the charged particles to become substantially bound at a site on the medium specified by the position of the magnet, to thus form a captured line or zone. In one preferred embodiment, the magnetic field is applied at the site on the medium at which the test solution is contacted. The degree of magnetic force applied to the membrane may be selectively adjusted to vary the width or surface area of the capture line or zone.

Abstract: A self contained diagnostic test device is provided for use in the collection and detection of a biological specimen or the like. The device comprises a tubular swab and reagent dispensing cap component for receiving specimens. The reagent dispensing cap component includes barrel, reagent chamber, and results window subcomponents, and delivers one or more selected reagents to a specimen testing chamber for contacting the collected specimen, upon the rotation of the reagent chamber component.

Abstract: An improved multi-layered diagnostic sanitary test strip for receiving a heterogenous fluid, such as whole blood, to test for presence and/or amount of a suspected analyte in the fluid by facilitating a color change in the strip corresponding to the amount of the analyte in the fluid, wherein the test strip includes fluid volume control dams to prevent spillage of the fluid from the strip and a chemical reagent solution that facilitates end-point testing.

Abstract: An automated microfluidic system that includes a cartridge reservoir part, a cartridge, a compressed-air storage tank, a buffer storage tank, and a reader is provided. The automated microfluidic system that detects a particular protein in a biological sample by enzyme-linked immunosorbent assay (ELISA) can automate a series of assaying processes, beginning with sample injection and ending with detection, with a simple structure, thereby allowing for convenient and quick detection of a particular protein in a biological sample without requiring skillful, elaborate manipulations by an operator.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semicylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method has patches of capture molecules, each specific for a different analyte disposed adjacently within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers, which in turn are coupled to the waveguide surface or to a nonspecific binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers, the selective irradiation involving a mask, a laser light source, or the like.

Abstract: Disclosed is a testing device and methods for the identification of an analyte of interest in a sample. In a preferred embodiment, the testing device includes a front panel having at least one sample application aperture; a rear panel having at least one solvent application aperture; a sample collection matrix disposed between the rear panel and the front panel, the sample collection matrix being in communication with the sample and solvent application apertures of the front and rear panels; and at least one insertable test strip containing a reagent enabling detection of the analyte of interest.

Abstract: The present invention provides a method for determining expression levels of one or a multiplicity of target proteins in a tissue or cell sample.

Abstract: The invention discloses an on-spot hydrophilic enhanced slide/microarray. The preparation method relates to a hydrophobic copolymer prepared by blending, grafting or co-polymerization of a hydrophobic material and a compound bearing functional groups such as anhydride, imide, cyclic amide, and cyclic ester, and application of the hydrophobic copolymer onto an organic or inorganic substrate. The resulting slide has the properties of on-spot hydrophilic/hydrophobic dynamic conversion, as well as on-spot hydrophilic enhancement for the preparation of high-density and high-efficiency bio-chip/microarray.

Abstract: The optical sensor contains an optical waveguide (1) with a substrate (104), waveguiding material (105), a cover medium (106) and a waveguide grating structure (101-103). By means of a light source (2), light can be emitted to the waveguide grating structure (101-103) from the substrate side and/or from the cover medium side. (101-103). With means of detection (11), at least two differing light proportions (7-10) radiated from the waveguide (1) can be detected. For carrying out a measurement, the waveguide can be immovably fixed relative to the light source (2) and the means of detection (11). The waveguide grating structure (101-103) itself consists of one or several waveguide grating structure units (101-103), which if so required can be equipped with (bio-)chemo-sensitive layers. The sensor permits the generation of absolute measuring signals.

Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide polymerization reaction. The devices comprise a substrate microfabricated to define a sample inlet port and a mesoscale flow system, which extends from the inlet port. The mesoscale flow system includes a polynucleotide polymerization reaction chamber in fluid communication with the inlet port which is provided with reagents required for polymerization and amplification of a preselected polynucleotide. In one embodiment the devices may be utilized to implement a polymerase chain reaction (PCR) in the reaction chamber (PCR chamber).

Abstract: A device for analyzing immunoassays with a liquid assay medium includes a vessel for holding the assay medium. The vessel has a base comprised of a solid body having a first side wall and a top surface forming a boundary surface of the solid body. First reaction agents are dissolved in the assay medium in the vessel and are labeled with a luminophore or different luminophores and second reaction agents are bonded to the boundary surface within a boundary layer of the assay medium. A transmitter for emitting light rays is arranged so that the light rays are coupled into the base of the vessel via the first side wall and conducted at the total reflection angle to the boundary surface so that luminophore-labeled first reaction agents that are bonded to the second reaction agents are optically excited by at least some of the light rays and emit fluorescent and/or phosphorescent rays. A receiver is positioned for quantitatively detecting the fluorescent rays and/or phosphorescent rays.