Abstract: An immunodiagnostic reagent consists of magnetic balls covered with a substance binding specifically to a substance to be detected in suspension in a suitable liquid. The magnetic balls consist of an organic matrix enclosing a magnetic charge and having a magnetizable material mass/non-magnetizable material mass ratio between 60 and 70%.

Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided. Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n is at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3.sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2).sub.p wherein p is an integer between 1 and 5.

Abstract: An assay for the identification of neutralizing botulinum antibodies in sera is provided which includes the steps of separating non-sodium dodecyl sulfate, non-trypsinized complex botulinum toxin in an arylamide gel by electrophoresis, the separation occurring on a basis of botulinum toxin protein size and charge. Thereafter, the separated protein is electrophoretically transferred onto a solid support, the transferred separated protein being bound to the solid support at spaced apart sites. Remaining sites on the solid support not occupied by bound protein are blocked and the solid support and bound protein are contacted with a sera sample containing an antibody directed against botulinum toxin. The contacted solid support is then exposed to a second antibody capable of reacting to produce an insoluble colored substrate of intensity relative to a quantity of antibodies present. Finally, the second antibody is reacted to produce the insoluble colored substrate which is visually identified.

Abstract: A surface of specific reactivity is formed by adsorbing a modified block polymeric surfactant of the Pluronic-type, i.e., containing pendant poly(ethylene oxide) blocks attached at an end to poly(propylene oxide) center blocks and with specifically reactive groups at the unattached ends of the poly(ethylene oxide) blocks, upon a hydrophobic surface.

Abstract: Device for capturing a target molecule for the purpose of detecting it and/or assaying it, including a solid support on which is immobilized a ligand, the ligand being provided in the form of a conjugate resulting from the covalent coupling of a polymer with a plurality of molecules of the ligand. The polymer is an N-vinylpyrrolidone copolymer, and the conjugate is immobilized on the solid support by adsorption.When the ligand is capable of forming a complex with the target, the device is specific for a given target. When the device comprises, in addition, a bifunctional reagent capable of forming a complex, on the one hand, with the ligand and, on the other hand, with the target, the support on which the ligand is immobilized constitutes a universal capturing system.

Abstract: The invention relates to a method of detection, a sensor and a test-kit which find application in immunological detection (e.g., immunoassay). The invention provides, inter alia, a method of detection, suitable for use in immunological detection of an entity, which method includes the use of a secondary species (as defined in the specification), the use of a first detectable species, and the use of a second detectable species. The method may include, for example, the use of a primary species, a secondary species, a first detectable species and a second detectable species. The primary species may be, for example, an antibody or a ligand. The secondary species may be, for example, an auxiliary species such as an auxiliary binder or an auxiliary ligand, or a species which has a part which is an auxiliary function. The entity to be detected may be an analyte species as such or may be an entity which carries or includes analytes species.

Abstract: An assay method comprising the step of binding a second substance to a first substance immobilized to a solid phase surface, the first substance being either a ligand or a species bound directly or indirectly thereto. The method is characterized in that the solid phase surface having the first substance immobilized thereto exhibits and electric charge, and that the reaction for binding the second substance to the first substance is performed at an ionic strength below 100 mM, and at such pH conditions that the electric charge of the second substance is opposite to that of the solid phase surface so that the second substance is electrostatically attracted by the solid phase surface to be concentrated thereto.

Abstract: A chemical linking agent is formed of a di- or higher functional photoactivatable compound having at least one group that is charged under the conditions of use in order to provide improved water solubility. The linking agent contains two or more photoreactive groups in order to allow the agent to be used as a cross-linking agent in aqueous systems. The charged group can be provided by a radical that includes one or more salts of organic acids, onium compounds, or protonated amines, (and optionally one or more additional photoreactive groups) and the photoreactive groups can be provided by two or more radicals that include an aryl ketone. The onium compound can provide a quaternary ammonium, sulfonium or phosphonium group.

Abstract: A dry immunoassay analytical element, for assaying a ligand is disclosed. The element comprises, in the following order, (a) a layer containing a labeled ligand, (b) a bead spreading layer, c) a cross-linked hydrophilic polymer layer and d) a support; wherein(i) a fixed concentration of an immobilized receptor for the labeled ligand is located in a zone at the interface of layers (b) and (c); and(ii) the receptors are immobilized by being covalently bonded to polymeric beads that are smaller than the beads in layer (c).

Abstract: The present invention relates to an optical solid-phase biosensor for the detection of molecules which can be labelled with a fluorescent dye for the identification of substances in solution, for which there exists a biomolecule (receptor) which specifically recognises these and is chemically bonded to the uppermost layer of one or more layers of polyions on the surface of the sensor, by measurement of the Forster transfer between another dye molecule which is bonded in one of the uppermost layers of the sensor, and the said dye molecule.

Abstract: The present invention is drawn to an immunoassay capable of the rapid detection of a variety of test substances that may be present in a test sample. One feature of the invention is that extraction or isolation of the test substance occurs simultaneously with the formation of the primary antigen-test substance complex. The primary antigen-test substance complex is then captured in a solid phase format having a plurality of interstitial spaces which facilitate rapid and efficient detection. The immunoassay of the present invention works over a wide range of environmental conditions and is simple enough to be used in the absence of laboratory facilities.

Abstract: The present invention provides a method of detecting an analyte in a sample the method comprising adding a sample suspected of containing the analyte to a membrane comprising a closely packed array of self-assembling amphiphilic molecules, the membrane including a plurality of ion channels selected from the group consisting of peptides capable of forming helices and aggregates thereof, podands cryptands and coronands, a first receptor moiety reactive with the analyte being attached to the ion channel at an end thereof, the first receptor moiety being such that it normally exists in a first state, but when bound to the analyte exists in a second state, said change of state of the first receptor moiety causing a change in the ability of ions to pass through the ion channel, the first receptor moiety being selected from the group consisting of antigens, peptides, antibodies (e.g.

Abstract: SLO peptide antigens are described. These peptide antigens are suitable for the determination of SLO antibodies, as immunogens for the production of antibodies against SLO and as vaccines for the production of vaccines against SLO.

Abstract: A method and apparatus for carrying out affinity purification of a ligate. The method comprising, (a) providing a ligate containing liquid to a first side of at least one porous hollow fiber membrane with a ligand immobilized thereto that binds and separates the ligate from the liquid, (b) withdrawing a first portion of the liquid from the first side of the porous hollow fiber membrane, (c) recirculating the first portion of liquid to the first side of the porous hollow fiber membrane, (d) repeating steps (a) to (c) until a majority of the liquid has flowed through the porous hollow fiber membrane, and (e) providing an elution solution to one side of the porous hollow fiber membrane under a pressure sufficient to cause the elution solution to flow into and through the membrane to effect disassociation of any ligate-ligand bonds wherein any ligate bound to the ligand is eluted with the elution solution.

Abstract: Insoluble supports are prepared which possess high surface areas and efficiently dispersed isocyanate groups. These reactive supports are useful for covalently binding proteins which preferably are enzymes and provide catalysts for conducting organic reactions.

Abstract: Polyolefin particles are chemically modified by oxidation to provide a large surface area and high loading. The particles result in low back pressure in column systems, and are economical to manufacture. The particles are useful as supports in a wide range of applications including general organic as well as biopolymer synthesis, library methods, purification processes and enzyme mediated processes. In a preferred embodiment, polyethylene or polypropylene particles are oxidized in a solution containing trifluoroacetic acid or trifluoromethane sulfonic acid, chromium trioxide and sulfuric acid to provide the particles with a chemically reactive irregular surface and open channels that extend below the surface and up to essentially the length of the radius of the particles resulting in increased surface area and decreased density. The particles have pendant functional groups produced by the oxidation and/or by subsequent chemical reaction.

Abstract: The present invention provides a method of identifying immunocompromised individuals who are at high risk for development of cryptococcosis, comprising the step of measuring the levels of IgG antibody to glucuronoxylomannan in the sera of said individuals. Also provided are various methods of detecting antibody to glucuronoxylomannan in sera and a kit for assaying the presence of antibody to glucuronoxylomannan in the sera of immunocompromised individuals.

Abstract: An assay system for detecting the binding of a mobile reactant to an immobilized reactant on an assay plate. The assay plate includes a substrate having an assay spot deposited thereon. The assay spot includes the immobilized reactant. In the present invention, a carrier dye is included in the assay spot, the amount of the carrier dye indicating the amount of the immobilized reactant that is present in the assay spot. In the preferred embodiment of the present invention, the assay spot is generated by depositing liquid on the assay plate at a location corresponding to the assay spot. The carrier dye is dissolved in the liquid and remains after the liquid evaporates. The amount of carrier dye in each spot may be measured spectroscopically and provides a means for identifying defective assay plates.

Abstract: Heterofunctional crosslinking agents are used to produce a device for detecting a target polynucleotide. Synthetic single stranded capture and detector polynucleotides are covalently immobilized to plastic surfaces by novel heterofunctional reagents. The capture and detector polynucleotides are covalently attached through a synthetic region of amine-bearing nucleotides that interact with reactive moieties on the heterofunctional crosslinker. The regions of the capture and detector polynucleotides that can hybridize a diagnostically important target polynucleotide are protected from binding to a solid phase support by intrastrand pairing. This system provides monolayers of immobilized polynucleotides with precise orientation and unimpaired diagnostic coding regions.

Abstract: A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials.

Abstract: A trifunctional conjugate is providing having three chemical moieties attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moieties. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second tridentate member to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.

Abstract: The instant invention provides a highly fluorescent conjugate which is useful in specific binding assays, and which comprises a specific binding member bound to a fluorescent polymer. The fluorescent polymer comprises a backbone polymer having multiple signal generating groups immobilized thereon and, optionally, cyclodextrin moieties in association with the polymer. Also provided is a novel process for creating 6-cyclodextrin monoaldehyde.

Abstract: A biosensor detector method for detecting biological targets, using specific binding, or hybridization techniques coupled with enzymatic amplification and the mass sensing capability of a piezoelectric oscillator. An optical biosensor is also contemplated.

Abstract: A method for separation of a mixture of biological entities into at least three distinct, subpopulations. Different antibodies are provided, with each antibody bound to a solid support in a unique manner such that by a manipulation of the physical or chemical environment, the bonds between the antibodies and the solid supports can be selectively broken. The mixed population of cells is incubated with the antibodies. The cells are magnetically separated from a test medium and collected in a monolayer upon a collection surface. Then by manipulation of the physicochemical environment, specific linkages can be broken and desired cell subpopulations released from the collection surface. This method has medically significant diagnostic and therapeutic applications, as entire cell types can be separated from non-malignant medically vital cell types. Cancer can be diagnosed, staged, and monitored. Genetic analysis from maternal blood, CVS, or amniocentesis samples is possible.

Abstract: The present invention is directed to methods for using reagents to generate and stabilize thiols derived from thiol precursors in order to permit more effective reactions with thiol-reactive substances such as liposomes, proteins and antibodies. These methods provide greatly improved conjugates for utilization in various in vivo and in vitro applications.

Abstract: A method combining the techniques of immunoaffinity separation and continuous flow centrifugal separation is provided for selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture. The heterogeneous cell mixture is intimately contacted to promote binding thereto by particles having attached a substance that actively binds to a specific desired type of cell out of the cell mixture. The particles are selected so that the sedimentation velocity of the particle/cell conjugate differs sufficiently from those of other cells in the cell mixture to allow its separation by means of a continuous flow cell separator.

Abstract: Gelatin and aminodextran coated polymer core particles useful in immunoassays and methods of making the same are disclosed. The preparation of aminodextrans having varying amounts of amine groups is also described, as is a method of crosslinking gelatin and aminodextran without the use of a stabilizer.

Abstract: Method for optimizing an optical assay device for an analyte, including the steps of: providing a substrate having a chosen thickness of an optically active layer thereon; providing an attachment layer of a chosen thickness on the optical coating; providing a receptive layer of a chosen thickness for the analyte, wherein at least one of the thicknesses of the optically active layer, attachment layer and receptive layer is varied to provide a plurality of thicknesses of that layer; contacting analyte with the receptive layer under conditions in which an increase in mass on the receptive layer results; and determining the optical thickness of the layer.

Abstract: The invention is directed to monoclonal antibodies, their fragments, single chains and polypeptide mimics of their hypervariable regions which immunoreact with bare small moieties such as metallic cations the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: An aqueous colloidal dispersion for diagnostic or immunodiagnostic tests, comprising non-polymer nuclei surrounded by a hydrophilic copolymer that contains functional groups, a method for the detection of a specifically binding substance or immunochemically active component in a test fluid, and test kit containing the aqueous colloidal dispersion.

Abstract: A method for forming an optical device for detecting the presence or amount of an analyte of interest comprising a substrate which supports an optically active layer, an attachment layer provided on the optically active layer, and a receptive layer specific the analyte provided on the attachment layer. The method comprises forming the optically active layer with a chosen refractive index on the substrate by curing the optically active layer on the substrate at a controlled temperature or for a controlled length of time and subsequently providing the attachment and receptive layers on the optically active layer.

Abstract: A biosensor for use in a surface plasmon resonance (SPR) System includes a transparent substrate layer, a thin metallic film on the substrate, and an ultrathin organic layer of a material which is polyanionic and adsorbs on the metallic film, and a layer of polylysine on this polyanionic material. In one embodiment, there is an outer layer on the polylysine which binds with a specific desired analyte.

Abstract: Methods and derivatized supports which are useful in solid-phase synthesis of peptides, oligonucleotides or other small organic molecules as well as arrays of ligands. The methods provide means to control the functional site density on a solid support. Some of the derivatized supports are polymer-coated or glycan-coated. Other methods for regenerating the surface of a used ligand array are also provided.

Abstract: Bioelectronic sensors are provided employing a thin surfactant polymeric electrically conducting layer to which may be bound members of specific binding pairs. Binding of an analyte or a reagent to the specific binding pair member layer may change the electrical, optical, or structural properties of the layer for measurement of analyte. The change in the polymeric layer provides for a sensitive measurement.

Abstract: An immunoassay process is provided for the detection of a target antigen in a fluid sample where an admixture of the target antigen and a labeled capture reagent against the target antigen is contacted by a solid polymeric carrier having bound to a portion of its surface a capture reagent against the target antigen and visual determination of a change in color of the bound labeled reaction product on the surface of the solid carrier member serves to readily detect the presence of the target antigen.

Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

Abstract: Fluorescent latices, well suited for a wide variety of analytical techniques, comprise polymer particles having at least one hydrophobic fluorochrome encapsulated therein, notably at least one condensed polyaromatic compound or derivative thereof, or a tetraphenylporphine and/or organometallic complex thereof, and have a detection threshold for fluorescence which is less than or equal to 10.sup.-12 mol of particles per liter of latex.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micromachining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific microlocations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: A method of measuring the ambient concentration in a fluid, especially a body fluid, of an analyte, such as a hormone or other biologically active material, whose concentration in the fluid is dependent on thedilution of the fluid is disclosed. The fluid is contacted with a trace amount of a binding agent, such as an antibody, specific for the analyte, the proportional occupancy of binding sites on the binding agent is determined and from that figure the analyte concentration is estimated without the need to measure accurately beforehand the volume of the fluid or fluid sample being tested. It is therefore possible to design a concentration-measuring device for insertion into a body fluid of a living creature for in situ measurement of concentration.

Abstract: A method of detecting or determining a sequence of amino acids which is antigenically active within a known amino acid sequence of a protein or portion thereof comprises the steps of: synthesising a plurality of peptides, each of said peptides comprising a sequence of a plurality of amino acids which corresponds to a sequence within the known amino acid sequence, and the said peptides having overlapping amino acid sequences; contacting each of said peptides with antibody against the protein or portion of interest; and detecting or determining the presence or absence of an antigen-antibody reaction between each of said peptides and said antibody to indicate whether or not said peptide has antigenic activity.

Abstract: A method of binding aggregated immunoglobulin or immune complexes comprising contacting them with modified forms of C-reactive protein. The method may be employed for diagnostic and therapeutic purposes and to deplete fluids of aggregated immunoglobulin or immune complexes. Further, a method of reducing the levels of immune complexes in a mammal comprising administering modified-CRP to the mammal, and a method of binding immunoglobulins comprising contacting them with modified C-reactive protein. Also, a method of binding aggregated immunoglobulin or immune complexes comprising contacting them with antibody to neo-CRP, and a method of modifying C-reactive protein. Finally, a test kit for detecting or quantitating immune complexes and a device for removing aggregated immunoglobulin or immune complexes from fluids are disclosed.

Abstract: Membrane for use in the detection of an analyte having a closely packed array of self-assembling amphiphilic molecules and a plurality of ionophores. First and second ligands are attached to an end of the ionophores adjacent the surface of the membrane. The membrane is such that the binding of the first ligand to its specific binding partner prevents the flow of ions across the membrane via the ionophores. In addition, the binding of the second ligand to its specific binding partner prevents the binding of the first ligand to its specific binding partner.

Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide amplification reaction. The devices are provided with a substrate microfabricated to include a polynucleotide amplification reaction chamber, having at least one cross-sectional dimension of about 0.1 to 1000 .mu.m. The device also includes at least one port in fluid communication with the reaction chamber, for introducing a sample to the chamber, for venting the chamber when necessary, and, optionally, for removing products or waste material from the device. The reaction chamber may be provided with reagents required for amplification of a preselected polynucleotide. The device also may include means for thermally regulating the contents of the reaction chamber, to amplify a preselected polynucleotide. Preferably, the reaction chamber is fabricated with a high surface to volume ratio, to facilitate thermal regulation.

Abstract: The invention relates to an aqueous suspension for diagnostic or immunodiagnostic tests, comprising non-polymer nuclei surrounded by a hydrophilic copolymer that contains functional groups, and also to a method for the preparation of this suspension. The method involves adding a monomer mixture to a colloidal dispersion of non-polymer particles, the monomer mixture being so chosen that the resultant copolymer has a charge of identical sign to that of the original dispersion. The invention also relates to a method for the detection of a specifically binding substance or immunochemically active component in a test fluid, and to a reagent and a test kit to be used when employing said detection methods.

Abstract: For the detection of proteins containing phosphorylated tyrosine the sample of a body fluid is incubated with at least two receptors R.sub.1 and R.sub.2 whereby a change in signal is produced by binding of at least the receptors R.sub.1 and R.sub.2 with the substance to be detected in the sample solution and in which in each case one of the two receptors contains an antibody or its derivative capable of specifically binding to the protein to be detected and the other receptor contains an antibody or its derivative capable of specifically binding to phosphorylated tyrosine and the signal change caused by the binding is determined in the sample.

Abstract: The present invention relates to an homogeneous immunoassay system for the determination of an antibody or an antigen in a sample which consists of an interferometric signal emitted from an infrared source, a waveguide coated with an antibody or an antigen and having at least one region immersed in an aqueous sample, whereby the corresponding antigen or antibody can be complexed on the surface of the waveguide, a detector adapted to measure the interferometric signal after its propagation through the waveguide, and a measuring device to take the Fourier transform of the interferometric signal for determining the degree of attenuation of the interferometric signal at a wavelength corresponding to an absorption characteristic of an infrared label incorporated into the antigen-antibody complex, whereby determining the concentration of antigen or antibody in the sample.

Abstract: The invention relates to methods for labeling or detecting one or more target materials using surface coated fluorescent microparticles with unique characteristics. The unique microparticles used to practice the invention have at least two components: an external substance or coating that is selective for each target material and an internal mixture of multiple fluorescent dyes. The mixture of dyes is a series of two or more fluorescent dyes having overlapping excitation and emission spectra allowing efficient energy transfer from the excitation wavelength of the first dye in the series, transfer through the dyes in the series and re-emitted as an optical signal at the emission wavelength of last dye in the series, resulting in a desired effective Stokes shift for the microparticle that is controlled through selection of appropriate dyes. The unique microparticles are combined with a sample thought to contain the target material(s), so that the microparticles label the target materials.

Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.

Abstract: An improved surface plasmon resonance detector, capable of recovering a desired eluted ligate, permits the isolation and characterization of novel ligates and ligands.