Abstract: Method for integrating isotope dilution analysis with chromatography. One embodiment of the invention includes a liquid chromatographic column, a radiochemical detector, an eluent that contains an additive at saturation and a radiochemically labeled derivative of the analyte to be determined. When the analyte, which is not radioactive, is injected, its movement through the column occurs more slowly than the movement of the radioactive derivative situated on the column outside the analyte band. As a result, radioactivity enters the analyte band and isotope dilution occurs. The distribution of radioactivity within the band is used to determine the amount of analyte injected.

Abstract: Nucleic acid fragments labelled by radio isotape migrate at speeds that increase as the molecular weights decrease in a migration path served with a potential at both ends thereof. The migration path is constituted by a pipe-shaped gel support such as a glass tube. A ring-shaped scintillator is provided at a middle portion of the migration path to circumscribe the gel support, and whereby the beta rays are detected. A window may be formed in the glass tube at a portion opposed to the scintillator, so that the beta rays are not attenuated by the glass.

Abstract: A device is disclosed for use in a chromatographic system wherein a component of a mixture is paritioned between a liquid phase and an immobile phase. The device is comprised of a chromatographic material. In the chromatographic system the component traverses at least a portion of the chromatographic material. The device generally has at least one longitudinal edge substantially corresponding to the direction of traverse of the component. The longitudinal edge includes means for controlling the shape of the front of the traversing component.

Abstract: A device is disclosed for use in a chromatographic system wherein a component of a mixture is partitioned between a liquid phase and an immobile phase. The device comprises at least one strip of a bibulous material. In the chromatographic system the component traverses at least a portion of the strip. The strip generally has a longitudinal edge substantially corresponding to the direction of traverse of the component. The longitudinal edge has the characteristic of substantially the same rate of traversal by the component along this edge when compared to the rate of traversal of the component along the body of the strip. The strips are prepared from a sheet of a bibulous material by non-deformative or non-compressive cutting of the sheet. The preferred cutting means is a laser beam.

Abstract: A stirrer for biochemical reactions comprising a magnetically permeable vessel for containing a solution of biochemically reacting substances, at least one magnetic bead placed in the vessel, and a magnetic device which is installed outside the vessel and generates an oscillating magnetic field acting on the bead. The stirrer is advantageous for stirring the solution of biochemically reacting substances for biochemical reactions without direct contact.

Abstract: The invention relates to an apparatus for carrying out analyses comprising at least one incubation step and at least one separation step for separating a liquid phase from a phase, which is insoluble in said liquid phase. The apparatus comprises a plurality of reaction vessels (2), making it possible to simultaneously carry out similar working sequences with reaction mixtures in the separate reaction vessels, each of which has a porous bottom (3) connected to a separate chamber (8), the reaction vessels being able to retain the reaction mixture during the incubation steps. According to the invention, there is provided a pressure regulating system, which creates a higher relative pressure in the chambers (8) than in the reaction vessels (2). This pressure difference prevents leakage from the reaction vessels to the chambers.

Abstract: There is presented a novel immunological element suitable for an immunological assay of an antigen according to the so called two antibody method, which element having two separate sheets, one being a sheet for reaction in which the reaction for formation of antigen-antibody bounds is carried out and the antigen-antibody bounds formed are immobilized, the other being a F receptor sheet in which unreacted free labelled antigen is transferred at a controlled rate to be received for analysis. This element enables separation between the bounds and the free labelled antigen by a simple operation without cumbersome separation procedures and is also excellent in storability.

Abstract: A ligand is dissociated from a binder specific for the ligand by directing a beam of ultrasound at the complex of ligand and binder. The procedure may be employed in a solid phase assay to separate a labeled form of ligand, employed as a tracer, from a binder supported on a solid support.

Abstract: Microencapsulation of solid phase scintillators in gels selectively permeable to diffusible radioactive label. These encapsulated scintillators are used to monitor the concentration of radioactive-tagged subtances in fluid systems.

Abstract: Method and apparatus for use in the diagnostic analysis of a liquid specimen through binding assays. The apparatus includes a rigid body having an elongated, shallow well formed in it, with a plurality of elongated strips, preferably in the form of cotton threads, stretched across the well in spaced relationship and generally perpendicular to the well's longitudinal axis. Each thread is coated with a separate binding conjugate such as an antigen or allergen. A cover plate that includes a thin plastic layer and an overlaying thin metallic layer covers the well to form an enclosed chamber having a specific volume. The metallic layer includes a separate elongated aperture in alignment with each coated thread. A liquid specimen is introduced into the chamber through one of two ports, for incubation with the coated threads, after which the specimen is removed and the reaction that occurred on each thread is determined.

Abstract: Method and apparatus for use in accurately measuring the binding reactions occurring between a predetermined class of components in a liquid specimen and their corresponding binding conjugates coated on separate test regions of a carrier. The carrier further includes a reference region that is uncoated, and the carrier is adapted for simultaneous contact of all of its regions with the liquid specimen. Any resulting binding reaction on each test region indicates both specific binding to the coated component as well as non-specific binding, and any resulting binding reaction on the reference region indicates merely non-specific binding. The measurements for the test regions are all reduced by an amount determined in accordance with the measurement for the reference region, to reduce the effects of non-specific binding on those measurements and thereby provide accurate measurements of the specific binding on each coated component.

Abstract: An apparatus for transferring beads employed in a radioimmunoassay is disclosed. The apparatus comprises a receptacle tray 30, test tube rack 48 and plurality of test tubes 42. The receptacle tray 30 contains an array of wells 32, which may be marked individually with indicia such as numerals and colors, and two alignment holes 34 and 35. The test tube rack 48 contains an array of columns 51 in a pattern corresponding to that of the wells 32 on tray 30. Test tube rack 48 also contains two alignment pins 52 and 53 for insertion into alignment holes 34, 35. Each of the test tubes 42 are generally cylindrical but have a gradually increasing diameter from bottom to top so that they can be inserted into rack columns 51 with a friction fit.

Abstract: Novel activated polyamide polymer container or test tube means and a method for the determination of ligand or analyte content in aqueous samples, are provided. The surfaces of the container tubes are specially activated thermally during their manufacture by injection molding thereby avoiding the need for subsequent coating of the tubes, e.g., with antibody, for binding assay procedures.

Abstract: A device for handling and washing beads. The device is attachable to a test tube rack and includes a frame, a containing slide, and a capture slide. By manipulating the slides in various combinations of positions the beads may be added to, removed from, or separately washed apart from test tubes in the rack. Complete and easy washing of the beads may thus be accomplished.

Abstract: Method and apparatus are provided for carrying out multiple simultaneous transfers of fluid. The method and apparatus are particularly directed toward immunoassays wherein immunologically active compounds, such as antigens and haptens, are detected through their associated antibodies. The device relies on the ability to transfer fluids, such as biological samples and reagents, between a reservoir and an associated receptacle. By providing a receptacle having a port at its lower end and which is otherwise hermetically sealed, such fluid transfer can be effected by immersing the port beneath the surface of the fluid in the reservoir and manipulating the pressure on the remaining surface area outside the port. The transfer of biological fluids at positive pressure provides enhanced fluids flow characteristics, particularly reduction or elimination of the tendency of these fluids to froth or bubble.

Abstract: A multiple component binding assay system, and related methods of making and using it, having a plurality of coated filaments mounted at their opposite ends on a support, in a predetermined spaced relationship, for simultaneously screening a liquid test sample for a plurality of components. The system is particularly suitable for screening the sample for IgE class antibodies specific for certain allergens. The filaments are preferably cotton threads, each thread binding a different allergen through a covalent bond. The support, which is preferably cut away adjacent the mid-portion of each filament to reduce background interference, is composed of a plastic or other water insoluble material, permitting inexpensive and relatively simple manufacture. After any IgE class antibodies present in the liquid sample have reacted with the corresponding allergens coated on the filaments, they are detected using second antibodies labeled with radioactive, fluorescent or enzymatic tracers.

Abstract: A method and device for assaying a test substance utilizing a primary absorbent substance for selectively allowing only a quantity of an analytical reagent proportional to the quantity of test substance to pass therethrough when test substance and analytical reagent are contacted with the primary absorbent. An analytical absorbent is disposed in a series of zones for sequentially absorbing the analytical reagent which passes through the primary absorbent so that detection of the last zone of absorbed analytical reagent indicates the quantity of test substance. The method comprises passing test substance and analytical reagent through the primary absorbent and then the analytical absorbent followed by detection of the last zone in which analytical reagent is absorbed. The device comprises a funnel with the primary absorbent therein for directing the test substance and analytical reagent to a narrow tube holding the analytical absorbent.

Abstract: Attenuator compositions useful as reagents in an improved internal sample attenuator counting method for radioimmunoassays are described. These compositions comprise an attenuator material that have a high capacity to absorb emitted radiation from a radioligand of the radioimmunoassay and are combined with an immunologically reactive material which interacts with components of the radioimmunoassay or combined with an absorbent of the free radiolabelled component to separate bound from free radioligand.

Abstract: A test device for determining a characteristic of a sample, particularly for determining substances in fluid samples. The device comprises a strip element which is composed of a material capable of transporting a developing fluid therealong by capillarity and which has a portion at a predetermined location on the strip element for receiving the test sample and portions at predetermined locations on the strip element incorporated with reagent means for providing a detectable response sensitive to the characteristic under determination. The beginning end portion of the strip element is immersed in the developing fluid which, as a result, traverses the length on the strip element, thereby promoting appropriate contact between the test sample and the reagent means resulting in the disposition of a detectable response at a predetermined location on the strip element, which response is a function of the characteristic under determination.

Abstract: Method of concentrating a low-concentration element in a solution and removing other, high-concentration elements, using an ion exchange resin specific to the element to be concentrated.The resin is disposed in a mini-column less than 3 mm in diameter into which the solution is made to pass, the elution of the element from the resin is carried out by using a very small volume of elution liquid.The invention applies to quantitative analysis by emission spectrum in an inductive plasma, and in this case the whole of the small volume of elution liquid, previously nebulized, is simultaneously supplied to the plasma.

Abstract: A charcoal coated solid support of regular geometric form can be employed as an adsorbent device in a variety of biochemical assays to adsorb selected components for separation and easy removal from an assay medium.

Abstract: A device useful in the performance of a variety of immunologic and biochemical assays which comprises a container enclosing a solid phase reagent with an adsorbent and a retaining means for prohibiting the removal of said solid phase reagent is disclosed. The device is particularly well adapted to perform heterogeneous immunoassays and to permit processing large numbers of said immunoassays by facilitating the separation of assay medium from the solid phase reagents.

Abstract: A process for preparing a derivative of an hydroxyl bearing substrate by reacting an hydroxyl bearing substrate with oxirane bearing molecules to produce an oxirane ring bearing substrate; and reacting the oxirane ring with a substituted primary aromatic amine selected from primary aromatic amine alcohols and primary aromatic amine thiols. Among the compositions so produced is a stable modified hydroxyl bearing substrate or hydroxyl bearing sheet having covalently bonded thereto primary aromatic amines which can be diazotized. The diazotized substrate selectively, covalently binds proteins, polypeptides, peptides, nucleic acids, RNA, single stranded DNA, and nucleic acid hybrids.

Abstract: An apparatus useful in expediting the performance of immunochemical determinations which require the complete separation of a solid phase or precipitate from a liquid phase is disclosed. In particular, this apparatus features a test tube rack and cooperating retaining means for spanning said rack and tubes whereby inversion results in a rapid and uniform removal of the liquid contents of each tube while retaining the precipitate or solid phase.

Abstract: In an arrangement for carrying out a radioimmunological method of determining both antigens and antibodies by examining samples of human body liquids by forming an antigen/antibody-complex with a radioactively labelled antibody, a micro-titer-plate is provided with recesses for accommodating a solution of said radioactively labelled antibody and to the sample to be examined. Carriers, in the form of elongated elements secured to a holding band, are loaded with unlabelled antigen and are contacted with the sample by being inserted in the recesses of the micro-titer-plate. The carrier is washed, and the radioactivity of the carrier is measured.

Abstract: Automated radioassay in which a serum is diluted and pre-incubated in the presence of a radioactive labeled ligand, such as an antigen, and a binder, such as an antibody, specific to the ligand. The pre-incubated mixture is flowed through a chamber containing binder specific to the ligand supported on a solid support, and the labeled and unlabeled ligand not bound to the binder in pre-incubation are bound to the receptor on flow through the chamber. An eluting solution is flowed through the chamber to release the ligand bound to the binder in the chamber for reuse thereof. By counting the radioactivity of one or both of the fraction which flows through the chamber or which is subsequently released therefrom the quantity of a specific ligand in the serum may be assayed.

Abstract: Test device for determining a characteristic of a sample, particularly for determining substances in fluid samples. The device comprises a strip element which is composed of a material capable of transporting a developing fluid therealong by capillarity and which has a portion at a predetermined location on the strip element for receiving the test sample and portions at predetermined locations on the strip element incorporated with reagent means for providing a detectable response sensitive to the characteristic under determination. The beginning end portion of the strip element is immersed in the developing fluid which, as a result, traverses the length of the strip element, thereby promoting appropriate contact between the test sample and the reagent means resulting in the disposition of a detectable response at a predetermined location on the strip element, which response is a function of the characteristic under determination.

Abstract: Method and apparatus for the processing of fluid materials, particularly in the preparation of samples for radioactive isotope tracer studies by combustion of starting materials containing such isotope tracers. The sample is burned in a combustion chamber which tapers upwardly and inwardly above the sample receptacle so as to approximate the shape of the flame of a burning sample, and the combustion products are continuously exhausted from the combustion chamber and passed through a heat exchanger which condenses the condensable vapors in the combustion products. The condensed vapors are then separated from the gases, and the gases are passed into a reaction column if there is a radioactive isotope tracer remaining in gas form.

Abstract: A coated bead, a gripper for rotatably engaging the bead, a carrier for carrying at least one gripper, test tray bearing at least one reaction chamber and an agitator for agitating the carrier in relation to the test tray are disclosed.

Abstract: A method and solid phase matrix is disclosed which has special utility for use in conjunction with automatic pipetting apparatus for conducting reactions at a liquid-solid interface. A reaction component is fixed on the surface of the solid phase matrix which is wetted by a liquid phase containing a freely diffusing, mobile component. The matrix is comprised of a support surface to which are attached a plurality of inwardly projecting fins. The innermost extension of the fins defines a centrally located well into which an automatic pipetting apparatus may be inserted. The method may be used for qualitative or quantitative determinations of the mobile component contained in a liquid which wets the solid phase matrix.

Abstract: An immobilized immunoadsorbent for use in immunoassay and radioimmunoassay procedures includes, in a preferred form, a mass of superficially porous refractory particles having a water insoluble polymer, such as dextran, bonded thereto. The polymer in turn has bonded to it, by covalent bonds, antibodies capable of binding a specific antigen thereto and stoichiometrically releasing the bound antigen by the use of a rinsing solution which does not adversely affect the binding of the antibody to the polymer. Preferably, each of the porous particles includes an impervious core which has joined thereto sufficient layers of microparticles to form an outer porous coating on the core. Methods of forming such an immunoadsorbent and for using the same and structure for supporting the same.

Abstract: Apparatus for treating samples comprising a sample holding element; a wash trough removably positioned over the sample holding element; transfer tubes or conduits in sample receiving contact with the sample holding element, extending through the wash trough to a transfer head positioned over a vacuum manifold which elements, in combination, deliver sample from the sample holding element directly to a plurality of filter discs in said vacuum manifold means. A cutter block is positioned between the transfer head and manifold. The apparatus is designed and arranged so that the cutter block will simultaneously cut and position a plurality of filter paper discs on said filter discs. A plurality of individual samples can be treated rapidly while minimizing the amount of filter paper used with assurance of quantitative sample transfer.

Abstract: A method and apparatus for measuring thyroid function by means of measuring the up-take of a radioactive tracer on a resin involves causing the mixing of resin with tracer for predetermined periods and preferably by a means which causes agitation of the resin in the tracer-containing sample to be tested. Also disclosed is an apparatus useful for handling multiple samples to be tested.

Abstract: A process and apparatus for pulse labelling protein material for high sensitivitiy sequence analysis of protein material by Edman degradation technique comprising an isolated, auxiliary unit for storing a radioactive coupling reagent together with tubes, valves and controls for interrupting the Edman process, for pumping a measure of radioactive coupling reagent into the reaction vessel, a timer for controlling duration of contact between the radioactive reagent, and the protein material to maximize the coupling reaction therebetween, and thereafter reactivating the Edman process to admit nonradioactive coupling reagent to the vessel and to drive the coupling reaction to completion.

Abstract: Adsorption columns are provided which can be utilized in radioimmunoassay systems, such as those involving the separation of antibody-antigen complexes from free antigens. The preparation of the columns includes the treatment of retaining substrate material to render it hydrophilic, preparation and degassing of the separation material and loading the column.

Abstract: An automated immunoassay apparatus which provides: time controlled incubation of a multiplicity of sample solutions, each of which comprise a mixture of (a) a sample, possibly containing an antigen or antibody intended to be assayed; (b) a solution of a known concentration of a tagged antigen or tagged antibody; and when assaying for antigen, optionally; (c) a solution of a known titer of an antibody reactable with said antigen;Isolation of incubated samples from additional sample solutions introduced into said apparatus for assay, whereby the system is isolated at a first predetermined signal from a timing device, and whereby the system is reconnected at a second predetermined signal from the timing device, wherein the second predetermined time period is set so as to enable sufficient time to complete a measurement of the amount of tagged material before the next incubated sample arrives in the detector for the next sequential measurement.

Abstract: A system for the automated analysis of large numbers of liquid samples, in which a multiplicity of sample tubes are loaded in racks into a cassette and the loaded cassette is transferred from station to station, with operations of sample insertion, dilution, reagent addition and withdrawal for filtering being performed at successive stations. At each station there is a separate processing module adapted to receive the cassette, each module including the apparatus necessary for performing one of the abovementioned operations on each individual sample tube when it is located at a particular operational location in the cassette. Each module also has members for shifting the racks in the cassette in such manner that all tubes pass through the operational location in turn while strictly maintaining the same order of sequence throughout the operations.