Abstract: A chemical sensor having a field-effect transistor as an electronic transducer and used for the analysis of specific constituents in a liquid, the chemical sensor comprising means which permits an externally supplied sample solution to reach a chemical receptor of said chemical sensor but substantially prevents external light from reaching said field effect transistor.

Abstract: Methods and devices for separating bound label from unbound label within an assay mixture and for predispensing assay reactants in self-contained assay vessels, as well as a method for detecting the presence and/or amount of an analyte within a fluid sample, and a reusable detection vessel for use therein and with specific binding assays in general are disclosed. Significant to the separation of bound label from unbound label is the use of a cushion comprising generally one primary layer and in some cases one or more secondary layers.

Abstract: Nuclear magnetic resonance imaging of animal or human tissue is enhanced when a paramagnetic pyrophosphate compound is administered intraveneously as a contrast agent. The contrast agent is particularly useful in magnetic resonance imaging of area of tissue calcification, such as acute myocardial infarctions. Specific localization of paramagnetic pyrophosphate in ischemic and necrotic muscle cells at the periphery of a myocardial infarction makes accurate localization and sizing of the central infarct and peri-infarct zones possible.

Abstract: Nitroxide contrast agents for MRI have a long useful life and can be administered in low concentration doses. Such agents include nitroxide-doped liposomes that encapsulate an oxidant and large molecules having surfaces covered with persistent nitroxide free radicals.

Abstract: This invention is a method for obtaining improved NMR images of the uterine cavity and fallopian tubes comprising imjecting a physiologically acceptable solution of a chelate of a parmagnetic material into the uterus under sufficient pressure to cause the solution to pass through the fallopian tubes and obtaining an enhanced NMR image of the tissue surrounding the fallopian tubes. The chelates and the injection solutions thereof do not include carbohydrate groups or other compounds which might support growth of Staphylococcus aureus or other pathological miroorganisms in the peritoneal cavity.Kits including contrast medium and non-metallic uterine balloon catheters suitable for use with NMRI procedures are also included within the scope of this invention.

Abstract: Ferromagnetic particles, conveniently embedded in or coated by a biotolerable polymer and held in dispersion in a physiologically acceptable dispersion medium, may be used as contrast agents in nmr imaging for the production of images suitable for use in diagnosis. Unlike paramagnetic nmr contrast agents, ferromagnetic nmr contrast agents give particularly good contrast in the T.sub.2 dependent images.

Abstract: Devices and methods are provided for making a plurality of determinations of the local (site-specific) redox state of a liquid system, by employing a photoresponsive element, which can be independently irradiated at different sites to provide independently detectable signals.

Abstract: A method of imaging a tumor by magnetic resonance imaging (MRI) of liver and/or spleen is provided which employes microspheres composed of a biodegradeable matrix material with a particulate superparamagnetic contrast agent therein. The microspheres have diameters of less than 1.5 microns, and the ferromagnetic contrast agent, such as magnetite, has a particle size below 300 Angstroms. The superparamagnetic microspheres when administered intravenously segregate through the reticuloendothelial system in the liver and spleen where they reduce the T.sub.2 relaxation time to obtain improved MR imaging. In the T.sub.2 or mixed T.sub.1 and T.sub.2 images obtained by the MRI examination, the normal liver and spleen tissues appear dark and the tumor appears light with distinct margins therebetween.

Abstract: A method for detecting a first member of a specific binding pair in a sample, the first member being capable of forming a complex with a second member of the specific binding pair, includes immobilizing the second member on a surface of a piezoelectric oscillator, determining a first vibrational frequency of the oscillator on which the second member has been immobilized, contacting the surface of the oscillator on which the second member has been immobilized with the sample under conditions permitting formation of the complex, and with a particle under conditions permitting binding of the particle with the first member, mass coupling the bound particle with the oscillator, and determining a second vibrational frequency of the oscillator with which the particle has been mass coupled, the difference between the first vibrational frequency and the second vibrational frequency providing a measure of the quantity of the first member in the sample.

Abstract: The invention relates to acino-fetal differentiation proteins associated with cancer of the pancreas, these proteins being mannoside-containing glycoproteins of average apparent molecular mass chosen from: 120 KD, 94 KD and 58 KD.The invention also relates to a method for preparing these proteins, an antiserum against these proteins and the method for preparation thereof, monoclonal antibodies against these proteins and the method for preparation thereof, and compositions for diagnostic or therapeutic use containing these proteins or antibodies.

Abstract: The present invention discloses an assay for nucleic acid which comprises the steps of;(a) providing a probe material comprising;(i) a sequence of nucleic acids complementary to a given target sequence and,(ii) a first ligand chemically linked thereto and capable of a specific binding reaction with an antiligand;(b) contacting the said probe material with an assay system comprising:(i) a suitable mediator, enzyme, substrate system capable of transferring charge to an electrode surface when the enzyme is catalytically active, and;(ii) a second ligand chemically linked to one of said mediator, enzyme or substrate, wherein the second ligand is capable of a competitive binding reaction with the antiligand, and;(iii) the said antiligand, Whereby the said first ligand competes with the said second ligand in a specific binding reaction with the antiligand, and;(c) contacting the above system with a solution suspected of containing the said target sequence whereby the binding of any of the said target sequence presen

Abstract: Charged, stable, organic nitroxides, e.g., charged by a quaternary ammonium or a Bronsted acid group, are useful as NMR image enhancing agents for cerebrospinal fluid.

Abstract: Electrochemical detection of mediator level is employed in a method of assay using a redox enzyme and redox substrate to detect conversion to an effective mediator by an assay enzyme label of a compound which is non-mediating under the assay conditions.

Abstract: The disclosure is directed to compounds of the formula: ##STR1## wherein n=0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 may be the sam e or different and are selected from the group consisting of hydrogen and lower alkyl and hydroxy lower alkyl groups containing between 1 and 6 carbon atoms. Complexes of iron(II), iron(III), manganese(II), manganese(III), gadolinium(III), chromium(III), cobalt(II), and nickel(II) and such compounds are useful for enhancing magnetic resonance images of body organs and tissues. Illustrative complexes include (N,N"-bis[N-(2,3-dihydroxypropyl) carbamoylmethyl]diethylenetriamine-N,N',N"-triaceto)-iron(III), (N,N"-bis[N-(2,3-dihydroxypropyl)carbamoylmethyl]diethylenetriamine-N,N',N "-triaceto)manganese(II), (N,N"-bis[N-(2,3-dihydroxypropyl) )carbamoylmethyl]diethylenetriamine-N,N',N"-triaceto)gadolinium(III) and (N,N'-bis[N-(2,3-dihydroxypropyl)-carbamoylmethyl]ethylenediamine-N,N'-dia ceto)manganese(II).

Abstract: An apparatus for detecting the presence and/or measuring the concentration of an analyte in the fluid medium is disclosed. The apparatus relies on biospecific binding between a biochemical binding system and the analyte to change the dielectric properties of a capacitive affinity sensor. The biological affinity sensor is optimized by: (1) adjusting the thickness and dielectric properties of a passivation layer to generally match the impedance of the biological binding system; and (2) minimize the double layer capacitance so that bulk capacitance changes associated with the biological binding system are maximized.

Abstract: A saccharide matrix containing chelating agents. In a preferred embodiment the chelating agents, for example, EDTA or DTPA, bind metals having at least one unpaired electron. Such compositions are useful for enhancing the contrast of Magnetic Resonance images.

Abstract: A diagnostic site-specific imaging reagent in the form of a receptor and an indicating means selectively binds to a specific cell membrane-associated antigen of a blood platelet that is in a stimulated active state but does not substantially bind to a platelet that is in a non-stimulated resting state. In particular, prelabelled monoclonal antibodies and polyclonal antibodies are prepared that bind and image thrombospondin when it is cell membrane-associated on a thrombin-stimulated platelet, thereby providing means for detecting and discriminating between a stimulated active blood platelet and a non-stimulated resting blood platelet.

Abstract: Disclosed is a process and device for facilitating the differentiation of particles in a medium. The particles, which belong to at least two different groups of particles, are enclosed in a chamber bounded by electrodes which produce a rotating electrical field. A means for producing two rotating electrical fields having opposite directions of rotation and variable rotational frequency is provided to be attached to the electrodes. The particles exposed to the rotating electrical field forces with opposite directions of rotation can be differentiated on the basis of their rotational behavior.

Abstract: A method is disclosed for detecting the occurrence of a binding or complex-forming reaction between specific substances by utilizing the binding reaction to complete an electrical circuit, and then measuring a change in the electrical state of this circuit. In a preferred embodiment, a layer of antigen is coated onto a non-conductive base between a pair of electrically conductive layers superposed on the base. Antibodies which react with the foregoing antigen are treated so that they become bound to fine electrically conductive, metallic particles. The electrically conductive particles having antibody bound thereto are then added to the antigen layer deposited on the base and allowed to react therewith. Electrically conductive particles are thereby bound to the base due to the binding reaction between the antigen and antibody to thereby form aggregates of electrically conductive particles which bridge the electrically conductive layers and complete the circuit.

Abstract: Disclosed herein is a method for examining cells, comprising subjecting the cells to an antigen-antibody reaction treatment, then measuring a pattern of the electrophoretic mobility of the cells and comparing the electrophoretic property of the cells under examination with the electrophoretic property of standard cells.

Abstract: In its broadest aspect, the present invention provides a method of assaying a ligand in a sample which comprises contacting the sample with a predetermined quantity of a specific binding partner to the ligand, said specific binding partner being immobilized on the effective gate electrode of a field effect transistor, and determining whether (and, if desired, the extent to which) an appropriate transistor characteristic is changed as a result of complex formation between the ligand and the specific binding partner.

Abstract: This invention introduces a new class of devices for detecting the presence of biological molecules. The construction principle of the device involves the direct introduction of small monomers of macromolecules into the surface layer of a semiconductor, for example by doping at the gate-area of a field effect transistor (or any other similar suitable electronic device, also on carbon basis). There are a few biological monomers which pair specifically enough for a selective measurement, such as nucleotides (or portions thereof, e.g. adenine, thymine, guanine, cytosine and uracil). This invention leads to substantial improvement of biosensors, as there should be: Better signal to noise ratio, and options for: reading of nucleotide sequences, better process control, and new synthesis possibilities (e.g. modified Merrifield Synthesis). The invention also offers the potential to construct cybernetic systems and true biochips.

Abstract: Immunological fluorometric assay method, wherein an antigen (1) attached to magnetic particles (3) reacts in a liquid with an antibody (2) present in the sample and with an antibody (4) marked with a fluorescent substance. After the reaction, the particles are pulled by means of a magnetic field through a second (6) liquid layer onto the bottom of the measurement vessel, whereupon the particles are excited, and emitted radiation is collected through the wall of the vessel.

Abstract: A method and apparatus for assaying a species in a biological sample fluid. The apparatus comprises an SAW device (1) comprising a slab (2) of piezoelectric material on the upper surface (5) of which is formed an input transducer (3) and an output transducer (4). A source of RF energy is applied to the input transducer to generate a surface acoustic wave. Applied to the surface (5) is a thin layer (8) of a material capable of binding a species to be assayed. The sample (13) to be tested is applied to the top of the layer (8). A collimated light beam (1) from a source (9) is applied to the thin film from underneath the slab (2) and is collected by a photodetector (12). When the slab (2) is energized, the vibration sets up an effective diffraction grating which is coupled to the thin film and acts to diffract the light beam (10) applied to it. The energy in the diffracted beam, as measured by the photodetector ( 12), is indicative of the progress and result of the reaction between the layer 8 and the sample.

Abstract: In the NMR imaging of a subject comprising administering to such subject a composition containing an image-modifying effective amount of an image enhancer, permitting the enhancer to move through the subject, and after a time interval taking an NMR image of the subject, the improvement which comprises employing as said enhancer a complex of an oxamine and a polyvalent paramagnetic metal, e.g. ferrioxamine. Novel complexes of trihydroxamic acids, optionally N-acylated, with polyvalent metals other than iron, are also described.

Abstract: A sensor and method for performing immunoassays using surface acoustic waves on a piezoelectric crystal is provided. A specific antigen or antibody is bonded to the surface of the piezoelectric crystal and its resonant frequency in a blank solution is determined. The sensor is then exposed to a test solution containing an antigen or antibody corresponding to the substance bonded to the surface of the crystal. As the antigen and antibody react, the resonant frequency of the crystal is altered. This change can be correlated to determine the amount of antigen or antibody in the test solution. A nonreactive reference sensor can also be used to compensate for any nonselective adsorption.

Abstract: An improvement in NMR imaging techniques is disclosed, whereby the image is "shadowed" to intensify and contrast the image generated by the NMR sensitive nuclei, as a consequence of the introduction to the examined locus, e.g., human tissue of ferromagnetic, diamagnetic or paramagnetic particles. The intensified and clarified image is itself diagnostically valuable, in accordance with art recognized methods but also provides an improved information base for establishing and controlling treatment modes, especially in determining spatial density and distribution of particles by comparing standard and enhanced images. According to a preferred embodiment, metabolizable particles are employed, whereby the change and rate of change with metabolic time can be imaged, compared, and correlated with various metabolic diseases or malignant states.

Abstract: Fluorometric immunological assay method in which an antigen is attached onto magnetic particles, which are, for the time of measurement, pulled against the wall of the measurement vessel by means of the magnetic field. The magnetic particles adhering to the vessel walls are irradiated and the resultant emitted fluorescence is measured.

Abstract: Cross-linked hydrogel materials in the swollen state exhibit a range of nuclear magnetic resonance spin density values, spin-lattice or longitudinal relaxation (T.sub.1) values, and spin-spin or transverse relaxation (T.sub.2) values embracing that of the spectrum of values associated with animal and human tissues, thereby rendering such materials useful in nuclear magnetic resonance tomography equipment contrast determinations in physiological imaging and, as to those cross-linked hydrogel materials having T.sub.1 and T.sub.2 values substantially shorter than the surrounding tissue, such materials are useful as image contrast agents, for example, in the gastro-intestinal tract.

Abstract: An enteral contrast medium useful for proton nuclear spin tomography contains at least one physiologically compatible paramagnetic compound in combination with a physiologically compatible, osmotically active substance, as well as a physiologically compatible base/buffer or buffer mixture with a pH value of 3 to 8, and, optionally, also a viscosity-raising material, all dissolved or suspended in water. It is excellently suitable for enhancing contrast in imaging, e.g., of the gastrointestinal tract by nuclear spin tomography.

Abstract: Very stable, polymer-based electrochemical devices, formed by polymerization of thiophene or a derivative such as 3-methylthiophene which is durable in an aqueous electrolyte over a wide pH range, which respond rapidly to chemical or electrical signals, are disclosed. In one embodiment, the device functions as an extremely sensitive sensor which measures changes in chemical concentration or pH. For example, a poly-3-methylthiophene-based device is sensitive to as little as 8.times.10.sup.-16 moles of an oxidant which reversibly interacts with the polymer, including gas phase oxidants such as I.sub.2. In a variation of the polymer-based device, a catalyst such as a noble metal or an enzyme, is dispersed on or within the conducting polymer matrix so that the device is responsive to chemicals such as H.sub.2 and O.sub.2 which the polymer would otherwise respond very slowly to.

Abstract: Methods, apparatus and sensors are described for detection of specific ligands in a fluid sample by measuring ligand-specific changes in the bulk electrical conductance (or resistance) of a fixed test volume, with antiligand or ligand localized in or near that volume.

Abstract: Devices and methods are provided for making a plurality of determinations of the local (site-specific) redox state of a liquid system, by employing a photoresponsive element, which can be independently irradiated at different sites to provide independently detectable signals.

Abstract: An aqueous system for testing magnetizable articles is provided by a water based slurry of magnetic particles including a corrosion inhibitor, surface tension adjusting agent, an antifoam agent, a viscosity adjustment element, and a buffering element to assist in the corrosion resistance.

Abstract: Homologs of Diester-DTPA-Paramagnetic compounds (such as dimethyl acetyl diethylene triamine triacetic acid) provide excellent contrast agents for magnetic resonance imaging (MRI). The magnetic dipole generated by the unpaired electron within the paramagnetic (PM) atom, causes a local reduction in the bulk magnetic field of the MRI system. The resulting shorting of the T1 (spin lattice) relaxation time in the local hydrogen protons within the area of interest, causes an intense "free induction signal" and a corresponding modulation in the collected scanning data. The tissue or organ of interest appears on the MRI display highlighted in white. Background tissue is displayed as darker or lower intensity greys. The ester homologs replace two carboxylic acids to form functional ester groups on the DTPA chelator. The homologs cause the Diester-DTPA-PM contrast agents to go into solution readily, and promotes organ selectivity.

Abstract: Homologs of Diamide-DTPA-Paramagnetic compounds (such as diamido acetyl diethylene triamine triacetic acid) provide excellent contrast agents for magnetic resonance (MR) imaging. The magnetic dipole generated by the unpaired electron within the paramagnetic (PM) atom, causes a local reduction in the bulk magnetic field of the MR system. The resulting shorting of the T1 (spin lattice) relaxation time in the local hydrogen protons within the area of interest, causes an intense "free induction signal" and a corresponding modulation in the collected scanning data. The tissue or organ of interest appears on the MR display highlighted in white. Background tissue is displayed as darker or lower intensity greys. A surface highlighted image of the small and large intestine may be obtained by venous injection of the diamide contrast agent. The contrast agent is formed by replacing two carboxylic acids on the DTPA chelator with functional amide groups.

Abstract: A method for detecting or removing a substance in a medium is presented. Magnetic material, particularly magnetic bacteria or magnetic particles contained therein, are treated to render them receptive to binding or attachment to the substance sought to be detected or removed. Following binding or attachment to the treated magnetic material, the medium is subjected to a magnetic field, which results in removal of the magnetic material and the substance bound or attached thereto.

Abstract: A method of magnetic resonance imaging (MRI) of liver and/or spleen is provided employing encapsulated contrast agents in the form of microspheres having a biodegradeable matrix with the paramagnetic/ferromagnetic contrast agent dispersed therein. Ferromagnetic contrast agents such as magnetite are preferred. Ferromagnetic microspheres when administered intravenously segregate through the reticuloendothelial system in the liver and spleen where they reduce the T.sub.2 relaxation time to obtain improved MR imaging.

Abstract: Stable lipid-protein membranes are prepared by providing a medium of dissolved and emulsified lipids and dissolved proteins. The medium is applied to an orifice formed in a sheet of material in sufficient volume to provide sufficient lipid and protein to form a membrane across the orifice, which membrane comprises a bimolecular lipid layer with protein molecules interspersed therein. The medium is allowed to dry in the presence of air, and the lipid and protein molecules arrange themselves to form the membrane. The protein is selected to be specifically reactive with a particular chemical substance or a narrow class of chemical substances. When the membrane is exposed to a substance with which the membrane proteins react, a physical characteristic of the membranes is altered. Detection of a change in such membrane characteristic confirms the presence of the substance.

Abstract: A biologically active substance is incorporated in a unitary body with a magnetically responsive material for carrying out diffusion testing. These may be, microbiological, immunological, serological and other biochemical examinations. The body is applied against a substrate or medium by application of an external magnetic field and a reaction region is produced at the site of the body and is measured by means of a reader. In order to insure deposit of the body on the substrate a predetermined location and corresponding reading of the reaction region at such location, the support for the substrate and the dispenser and rear are provided with suitable releasable coupling and orienting devices such that the dispenser and reader can be respectively engaged and oriented on the support in predetermined secured positions.

Abstract: An improved imaging technique involving nuclear magnetic resonance. Known drug or neurotransmitter receptor ligands are covalently bound to magnetic resonance image enhancing spin label compounds, such as sterically hindered free radical nitroxide compounds, with the resulting adduct being administered to a patient, and thereafter when the ligand is bound to specific receptor sites in the soft tissue such as the brain, regional tissue area is assessed with nuclear magnetic resonance, allowing diagnostic discrimination.

Abstract: Chelates of gadolinium with 1,4,7-triazacyclononane-N,N',N"-triacetate; 1,4,7,10-tetrazacyclododecane-N,N',N'"tetraacetate; and 1,5,9-triazacyclododecane-N,N',N"-triacetate are useful as NMR contrast agents.

Abstract: Water soluble, substantially nontoxic salts of compounds of the formula:CF.sub.3 Rwherein R is --SO.sub.3 H, --SO.sub.2 NH.sub.2 or --PO.sub.3 H.sub.2, are useful for obtaining fluorine magnetic resonance images of body organs and tissues. Illustrative salts of such compounds include sodium trifluoromethane sulfonate, N-methylglucaminium trifluoromethanesulfonate and N-methylglucaminium trifluoromethanesulfonamide.

Abstract: The Ferrioxamine (FOM) family of chelates and amide homologs thereof provide excellent contrast agents for magnetic resonance (MR) imaging. The magnetic dipole generated by unpaired electrons within the paramagnetic Fe(III) atoms, cause a local reduction in the bulk magnetic field Bz of the MR system. The resulting shorting of the T1 (spin lattice) relaxation time in the local hydrogen protons within the area of interest, causes an intense "free induction signal" and a corresponding modulation in the collected scanning data. The contrast agent within the tissue or organ of interest causes the tissue to appear on the MR display as a high intensity or white area. Background tissue is displayed as darker or lower intensity greys.FOM does not penetrate the blood-brain-barrier under normal circumstances; and is therefore useful in detecting the extravasation of arterial blood in the extravascular space during cerebral hemorrhaging and in the endema fluid surrounding tumors.

Abstract: A stabilized, lipid membrane-based device is provided. This device includes a plurality of membrane-forming lipids, and a support for stabilizing the lipid membrane. Each membrane-forming lipid includes a long chain through which the lipid is anchored to a binding site on the support, and another long chain unattached to the support. The support binding sites are spaced apart from one another to provide the lipid membrane with an appropriate molecular packing density.Also provided is a process for determining the concentration of a selected chemical species in an aqueous electrolytic solution, using an electrochemical cell formed from a lipid membrane-based device in accordance with the present invention. This process includes the step of applying across the lipid membrane of the device an electrical potential difference to produce an analytical signal based upon an increase in membrane ion permeability.

Abstract: Disclosed is a process and device for facilitating the differentiation of particles in a medium. The particles are exposed to a rotating electrical field of variable rotational frequency. By providing a means for adjusting the frequency of the rotating fields, the particles can be caused to rotate in different directions thereby facilitating differentiation of particles belonging to different groups of particles. An apparatus for implementing this process includes at least three electrodes which are arranged so as to form a space therebetween. A device for producing a rotating field of variable rotational frequency is connected to the electrodes.

Abstract: A process is provided for the preparation of magnetic particles to which a wide variety of molecules may be coupled. The magnetic particles can be dispersed in aqueous media without rapid settling and conveniently reclaimed from media with a magnetic field. Preferred particles do not become magnetic after application of a magnetic field and can be redispersed and reused. The magnetic particles are useful in biological systems involving separations.

Abstract: Disclosed is a process and device for determining which cells of a suspension containing cells of the same species and genus are secreting cellular substances. Such determinations are made by exposing the cells to rotating electrical field forces of variable rotational speed and differentiating the cells secreting the cellular substances from the other cells by means of their rotational behavior which differs from that of the other cells.

Abstract: Contrast media compositions for nuclear magnetic resonance (NMR) imaging of the gastrointestinal system are provided for oral or rectal administration. The compositions comprise aqueous suspensions of particles of an NMR contrast agent, the particles being very finely-divided and providing in their outer surfaces a substantially water-insoluble paramagnetic compound. Suspending and/or wetting agents may be included to maintain the contrast agent particles in a dispersed, suspended condition for the oral or rectal administration. Buffering agents may also be included to maintain the pH of the suspension in a pH range protecting the insolubility of the paramagnetic compound.

Abstract: A field emission chemical sensor for specific detection of a chemical entity in a sample includes a closed chamber enclosing two field emission electrode sets, each field emission electrode set comprising (a) an electron emitter electrode from which field emission electrons can be emitted when an effective voltage is connected to the electrode set; and (b) a collector electrode which will capture said electrons emitted from said emitter electrode. One of the electrode sets is passive to the chemical entity and the other is active thereto and has an active emitter electrode which will bind the chemical entity when contacted therewith.