Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Abstract: A method is described for performing an affinity assay comprising contacting a sample to be assayed for the presence of an analyte with a dry reagent containing the analyte (hapten, antigen, antibody, receptor, or complementary polynucleotide) bound to a reaction cascade initiator, an antibody or other binding pair partner reactive with said analyte, and magnetic particles, to form an assay mixture in a reaction chamber, incubating the assay mixture, applying an oscillating or moving static magnetic field to the assay mixture, activating the reaction cascade initiator to initiate a reaction cascade, monitoring the response of the magnetic particles to the oscillating or moving static magnetic field to provide a time varying signal, and determining the analyte concentration of the sample by analysis of the time varying signal, as well as a kit for performing the assay and a diagnostic system for performing the assay.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent 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 non-specific-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: A method and apparatus for identifying molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. Each test site includes a probe formed therein to bond with an associated target molecular structure. An electrical signal is applied to the test site and the electrical properties of the test sites are detected to determine which probes have bonded to an associated target molecular structure.

Abstract: Disclosed is an apparatus designed to be used for enriching specific cell types from cell mixtures. The apparatus includes a centrifugable device that includes a constriction defining a lower region and a defined cell separation medium. The constriction prevents mixing between the upper and lower portions of the device. Also disclosed are methods that use precisely defined cell separation media to isolate specific cells from cell mixtures, including CD34.sup.+ hematopoietic progenitor cells from blood or bone marrow, nucleated fetal cells from maternal blood, specific tumor cells, dendritic cells, natural killer cells, and natural suppressor cells from various body fluids, and for enrichment or depletion of T cell lymphocytes. Also disclosed is a density adjusted cell separation technique used to augment the above apparatus and enrichment methods. The apparatus and enrichment methods are useful in various diagnostic and therapeutic regimens.

Abstract: A disposable diagnostic assay device and method for its use are provided. The device comprises a sample addition port in fluid communication with at least one main channel. The main channel comprises, in the direction of fluid flow, a main reagent area in fluid communication with an incubation area and a waste area. In fluid communication with the main channel is at least one side reagent channel. The side reagent channels comprise, in the direction of fluid flow, a liquid addition port and a side reagent area in fluid communication with the main channel at a region of the main channel upstream from the incubation area. Agitation means may be included in the at least one of the main and side reagent areas and/or the incubation area. Capillary valves may be located at various positions along the main and side reagent channels upstream from the incubation area, providing for control over fluid flow through the device.

Abstract: Red blood cells are removed from whole blood or a fraction thereof by contacting whole blood with a combination of an agglutinating agent and nucleating particles to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma which is substantially free of red blood cells is further passed through a filter that optionally contains an additional agglutinating agent. Flow-delay means may be provided to return the fluid sample in contact with a regard for a predetermined time.

Abstract: The invention pertains to dipstick immunoassay devices. The device comprises a base member and a single, combined sample contact zone and test zone, wherein the test zone incorporates the use of symbols to detect analytes in a sample of biological fluid. A first immunological component, an anti-immunoglobulin capable of binding to an enzyme-labeled antibody, is immobilized in a control indicia portion. A second immunological component, capable of specifically binding to a target analyte which is bound to the enzyme-labeled antibody to form a sandwich complex, is immobilized in a test indicia portion. The enzyme-labeled antibody produces a visual color differential between a control indicia portion and a non-indicia portion in the test zone upon contact with a substrate.

Abstract: Red blood cells are removed from whole blood or a fraction thereof by contacting whole blood with a combination of an agglutinating agent and nucleating particles to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma which is substantially free of red blood cells is further passed through a filter that optionally contains an additional agglutinating agent.

Abstract: A metod is proposed of obtaining a chemical interaction between at least one reagent trapped in sol-gel glass by doping it with the reagent(s), and diffusible solutes or components in an adjacent liquid or gas phase. The reagents, the solutes or the components can be any organic or inorganic compounds or materials of biological origins including enzymes. The doped sol-gel glass in various forms may be useful as analytical test, chromatographic medium, sensor, catalyst or biocatalyst, electrode or enzyme electrode, or other detection device.

Abstract: The present invention relates to methods of enriching breast tumor cells from a patient's body fluids. In particular, it relates to the use of a cell-trap centrifugation tube containing a specific density gradient solution adjusted to a specific density to enrich for breast tumor cells from a cell mixture. The tube allows the desired cell population to be collected by decantation after centrifugation to minimize cell loss and maximize efficiency. In addition, the method can be further simplified by density-adjusted cell sorting which uses cell type-specific binding agents such as antibodies and lectins linked to carrier particles to impart a different density to the non-tumor or tumor cell populations allowing the breast tumor cells to be separated from the non-tumor cells in a more convenient manner.

Abstract: A chromatographic assay device for detection and/or determination of an analyte in a competitive immunoassay gives a semiquantitative or quantitative indication of analyte concentration in a single assay device while also giving a positive indication that flow has occurred properly through the device. In one form, the device comprises: (1) a first opposable component including a sample preparation zone and an absorber; and (2) a second opposable component including a first chromatographic medium with capture and detection zones, a second chromatographic medium with a comparison zone, and a comparison label. In another form, the second opposable component includes one chromatographic medium with capture, detection, and control zones. Test kits incorporating the devices and methods for their use are also disclosed.

Abstract: The present invention relates to methods of enriching fetal cells from maternal body fluids. In particular, it relates to the use of a cell-trap centrifugation tube containing a gradient solution adjusted to a specific density to enrich for fetal nucleated red blood cells from maternal blood. The tube allows the desired cell population to be collected by decantation after centrifugation to minimize cell loss and maximize efficiency. In addition, the method can be further simplified by density-adjusted cell sorting which uses cell type-specific binding agents such as antibodies and lectins linked to carrier particles to impart a different density to undesired cell populations allowing the fetal cells to be separated during centrifugation in a more convenient manner. The rapid fetal cell enrichment method described herein has a wide range of applications, including but not limited to, gender determination and prenatal diagnosis of genetic diseases without the use of invasive procedures.

Abstract: The present invention is a sample preparation system and method that can be used with all types of analyte materials, that produces homogeneously deposited crystals across a sample surface, and that lends itself to automation. In this system and method, analyte crystallization is caused by lyophilization. A homogeneous analyte/solvent mixture is placed on a sample surface. The mixture is frozen, then the solvent is sublimated through the application of a vacuum. A homogenous distribution of analyte crystals across the sample surface results.

Abstract: A method of marking a liquid and subsequently detecting that the liquid has been marked, which method comprises: adding to the liquid an additive comprising a plurality of particles in an amount no greater than 1 part weight of particles per 10.sup.6 parts weight liquid, the particles comprising signal means to aid their detection and not being visible in the liquid to the naked eye; sampling a portion of the liquid containing said additive, and detecting the presence of particles in the liquid, with the proviso that said signal means does not consist solely of a nucleic acid tag.

Abstract: Disclosed are materials and methods for detecting biomolecules in samples employing transponders having memory elements associated with particle(s) used as a solid phase in art assay, and information pertinent to the assay is encoded on the transponder memory elements. A dedicated read/write device is used remotely to encode or remotely to read the information encoded on the transponder memory elements. The invention can be used in direct or competitive ELISA-type assays, or in multiplex assays for the simultaneous assay of several analytes.

Abstract: In a method of assaying for an analyte in a fluid sample, the presence of the analyte is detected by determining the resulting change in refractive index at a solid optical surface in contact with the sample, which change is caused by the analyte involving or influencing the binding or release of a refractive index enhancing species to or from, respectively, the optical surface, the refractive index of the refractive index enhancing species varying with wavelength. According to the invention, the determination comprises determining the variation with wavelength of the resulting change of refractive index, caused by the variation of refractive index with wavelength of the refractive index enhancing species, for a number of discrete wavelengths or for a continuous range of wavelengths. This variation is representative of the amount of analyte.

Abstract: An optical system which may be a component of apparatus for assaying a fluid sample with radiation is capable of exciting fluorescence in fluorescent material and includes a totally internally reflecting, unitary elongated substrate transmissive to both the excitation radiation and to the fluorescence. The fluorescent material includes at least a moiety of an antibody-antigen complex that includes a tag that will provide the fluorescence when excited by an evanescent wave generated by the excitation radiation. The substrate includes an elongated fiber and an integral lens formed to guide the optical radiation into the fiber within the bounds of a critical angle to assure total internal reflectance. A hollow elongated enclosure is disposed concentrically about and spaced from the fiber so as to provide an interspace of capillary dimensions.

Abstract: New and useful methods of producing stabilized enzyme antibody conjugates are disclosed which are particularly useful in forming multi-layer immunoassay test devices. In particular, the invention concerns the formation of a manganese ion and enzyme-antibody conjugate in aqueous solution and drying the solution to produce a dry stabilized enzyme-antibody conjugate. Further, this stabilized enzyme-antibody conjugate can be formed on a continuous web and dried in a heat tunnel. This continuous manufacturing process allows for the more efficient production of multi-layer test strips.

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: A system for biomolecular separation and detection of a molecular species includes a solid state laser detector having a sample channel therein. The presence of a molecular species is indicated by a frequency shift in the laser's output, which is detected by optical heterodyning the laser's output with the output of a reference laser. The interior of the sample channel is optionally coated with a ligand for binding the molecular species of interest. The system involves preprocessing a sample by electroosmotic separation in channels that are lithographically formed in a two-dimensional planar substrate. Molecular separation is also accomplished in a nanostructural molecular sieve comprising spaced apart posts defining narrow channels therebetween.

Abstract: Disclosed are devices and methods for analyzing a fluid cell containing sample. The devices are composed of a solid substrate, microfabricated to define at least one sample inlet port and a mesoscale flow system. The mesoscale flow system includes a sample flow channel, extending from the inlet port, and a cell handling region for treating cells disposed in fluid communication with the flow channel. The devices may further include a component for inducing flow of cells in the sample through the flow system. In one embodiment, the cell-handling region may include a cell lysis component to enable the lysis of cells in the sample, prior to, e.g., the detection of an intracellular component in the cell sample. In another embodiment, the cell handling region may have a cell capture region, with binding sites which reversibly bind to a specific population of cells in the cell sample, to permit the isolation of the specific cell population from the sample.

Abstract: An instrument configured and arranged to detect a change in thickness or refractive index of a thin film substrate. A method for optimizing the instrument and a method for detecting a change in thickness or refractive index of a thin film substrate.

Abstract: The present invention relates to a process for determining complexes of .alpha.-1-antichymotrypsin and cathepsin G in a sample comprising adsorbing the cathepsin G portion of the complex to a solid phase coated with non-specific binding protein or gelatin, and detecting the .alpha.-1 portion of the complex with a detectably labelled anti-.alpha.-1-antichymotrypsin antibody. A diagnostic kit comprising the solid phase coated with non-specific binding protein or gelatin and the labelled anti-.alpha.-1-antichymotrypsin antibody is also provided.

Abstract: A method for improving measurement precision in an optical biosensor assay for a ligand in a sample is described. The method involves referencing the assay with an artificially raised background level by the labelling of the optical waveguide with an appropriate reference reagent. Devices for use in such a method are also described.

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: The present invention relates to an enzyme reagent ticket for conducting diagnostic or serological tests. More particularly, the present invention relates to an enzyme reagent device which allows for a low-cost, disposable, rapid and convenient system for use in the determination of various components in test fluids, and to a diagnostic kit including the device according to the present invention for conducting certain immunochemical, diagnostic or serological testing.

Abstract: Immunoassay methods employing capillary containers are provided. The immunoassays may be competitive or sandwich immunoassays, where fluorescently labeled conjugates are used. Sample suspected of containing analyte is combined with fluorescently labeled conjugate, as well as any additional reactants which may be required. At least a portion of the incubated sample is placed in a capillary container. The capillary container has, on at least one region of its inner surface, a binding member capable of complexing with the fluorescently labeled conjugate, either directly or indirectly. Fluorescently labeled conjugate not complexed to binding member is then washed from the capillary container. The complexed fluorescently labeled conjugate is detected by irradiating the capillary and measuring the emitted signal. The intensity of the emitted signal is indicative of the presence of analyte in the sample.

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: Diagnostic and therapeutic compositions which comprise the .alpha.Gal(1-4).beta.Gal subunit are described. These compositions permit the rapid diagnosis and treatment of enteric infections caused by E. coli that produce shiga-like toxins (SLT).

Abstract: Tightly focused beams of laser light are used as "optical tweezers" to trap and manipulate polarizable objects such as microspheres of glass or latex with diameters on the order of 4.5 .mu.m. When analytes are allowed to adhere to the microspheres, small quantities of these analytes can be manipulated, thus allowing their detection and quantitation even when amounts and concentrations of the analytes are extremely small. Illustrative examples include measuring the strength needed to break antibody-antigen bonds and the detection of DNA sequences.

Abstract: A process using hydrothermally synthesized porous kaolinite as a carrier for use in a bioreactor. A carrier-biocatalyst composite body for use in a bioreactor, includes the synthesized kaolinite as a carrier and a biocatalyst fixed onto the synthesized kaoline. A bioreactor system includes a bioreactor vessel, and such a carrier-biocatalyst composite body placed in the bioreactor vessel.

Abstract: A method for the qualitative or quantitative determination of an analyte in a test sample wherein a labelled reagent is caused to be immobilized in bound form on a solid phase to provide an indication of the presence or quantity of the analyte in the sample is disclosed and is characterized in that the labelled reagent comprises a gold sol bound to a substance capable of specifically binding to said analyte or to a specific binding partner therefor, at least 75% by weight of the gold particles of the gold sol having a mean diameter of less than 5 nanometers.

Abstract: A process is disclosed which makes possible the isolation of the luminal endothelial cell membrane from associated tissue. It is particularly applicable to vasculature, but broadly is applicable to all tissue cavities which are accessible from adjacent perfusable lumens. The method involves the identification of characteristic molecules (primarily proteins and lipids) associated with the luminal surface of the any endothelial membrane in situ by utilizing a novel membrane-isolation scheme to separate the endothelium from associated tissue. The normal form of that tissue of interest and diseased and/or dysfunctional forms (such as tumors) can then be examined comparatively in order to identify proteins highly enriched and/or unique for normal and abnormal endothelia. This in turn permits the production of antibodies to the proteins of interest in order to develop probes specific for the abnormal tissue, such as vasculature of a tumor.

Abstract: Magnetic porous inorganic siliceous materials having a particle size of about 1 to about 200 microns useful as solid supports in various chromatography, immunoassays, synthesis and other separation and purification procedures as disclosed.

Abstract: A method is described for performing an affinity assay comprising contacting a sample to be assayed for the presence of an analyte with a dry reagent containing the analyte (hapten, antigen, antibody, receptor, or complementary polynucleotide) bound to a reaction cascade initiator, an antibody or other binding pair partner reactive with said analyte, and magnetic particles, to form an assay mixture in a reaction chamber, incubating the assay mixture, applying an oscillating or moving static magnetic field to the assay mixture, activating the reaction cascade initiator to initiate a reaction cascade, monitoring the response of the magnetic particles to the oscillating or moving static magnetic field to provide a time varying signal, and determining the analyte concentration of the sample by analysis of the time varying signal, as well as a kit for performing the assay and a diagnostic system for performing the assay.

Abstract: Polysaccharide derivative molecules are crosslinked exclusively among themselves on a support such as silica gel with the use of a polyfunctional crosslinking agent to immobilize the polysaccharide derivative on the support. The separating agent for optical isomers produced by the method has a high solvent resistance and, therefore, is most suitable as a separating agent for optical resolution.

Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on or in its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. The preferred plate embodiment employs an HPMP wink of porous polyolefin removably received in holes in the plate. A unique multi-slot block assembly is used to prepare the ASPCLs.

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: A probe system for monitoring chemical activity of a target chemical in an environment has first and second marker compounds each bonded to a common substrate to keep the respective markers in physical proximity. The first marker is a chemical that has a maximum emission intensity at a first wavelength, and it is chemically shielded from the environment being studied. The second marker is a chemical that, when in a first state, has a maximum emission intensity at a second wavelength different from the first wavelength and which, in a second state, does not have a maximum emission intensity at the second wavelength. The second marker is convertible between said states through chemical reaction with the target chemical. The common substrate is a carrier particle, the first marker being impregnated within the carrier particle and the second marker being chemically bonded to the exterior surface of the carrier particle.

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: A method of assaying for an analyte in a fluid sample comprises detecting the presence of the analyte by determining the resulting change in refractive index at a solid optical surface in contact with the sample, which change is caused by the analyte involving or influencing the binding or release of a refractive index-enhancing species to or from, respectively, the optical surface. Determination is performed with light having a wavelength at or near the maximum of the negative derivative of the absorptivity with respect to wavelength of the refractive index-enhancing species to obtain maximum sensitivity.

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

Abstract: A dye is covalently bound to a polymeric film, especially a polyhydric polymer, for assays and other purposes. The dye may be one which, when it comes into contact with hydrogen peroxide, changes color to indicate the presence of hydrogen peroxide. This dyed film may be used in qualitative or quantitative assays. This method chemically immobilizes dyes on support matrices with much higher yields of immobilized dye than has heretofore been possible. The covalently immobilized dye may be immobilized on solid matrix particles and combined with a free-flowing dye component to form a two component dye system. By combining a dyed film-former with a film-opener, the amount of dye available for assay is greatly enhanced. This provides a dye system which can be used to detect and measure quantitatively, accurately and precisely high levels of hydrogen peroxide. These high levels of hydrogen peroxide may result from the enzyme-mediated decomposition of various analytes from undiluted whole blood samples.

Abstract: A method of characterizing a macromolecule by studying its interactions with ligands comprises the determination of the mutual influence of ligand interactions by, after the macromolecule has interacted with at least one ligand, contacting the macromolecule with at least one additional ligand, either the macromolecule or the additional ligand or ligands having been bound to a sensor surface, determining interaction by detecting a consequential change in the physico-chemical properties of the sensor surface, and on the basis of the determined mutual dependence between the ligand interactions discriminating between epitopes of the macromolecule and mapping their relative positions.

Abstract: A system for assaying a fluid sample, typically employing a fluorescent tag, the system comprising a lens capable of focussing both excitation and fluorescent radiation, a fluid-flow conducting conduit being provided in the lens extending transversely of the optical axis of and through the focal region of the latter. One or more mechanical screens are disposed adjacent to the focal region in the conduit to arrest passage of beads as a function of bead diameter. The beads, precoated with at least a moiety of a ligand/conjugate complex, e.g. a specific-binding ligand, are preferably substantially transparent to both the excitation and fluorescent radiation.

Abstract: Device for detecting the presence or amount of an analyte of interest, comprising a reflective solid, optical support and a label capable of generating fluorescent signal upon excitation with a suitable light source wherein said support comprises an attachment layer comprising a chemical selected from the group consisting of dendrimers, star polymers, molecular self-assembling polymers, polymeric siloxanes, and film forming latexes wherein the support provides an enhanced level of exciting photons to the immobilized fluorescent label compound, and wherein the support also increases the capture of fluorescent signal.

Abstract: Method for producing an optical assay device having a substrate and one or more optical layers, an attachment layer and a receptive layer, including the step of spin coating an anti-reflective layer or an attachment layer.

Abstract: Packing materials for liquid chromatographic or catalytic columns are prepared by contacting a porous protein-adsorptive particulate or membranous support, such as a porous silica particulate support, with an aqueous solution into which a protein has been dissolved to form a saturated coating of protein on the external surfaces of the porous protein-adsorptive support, removing excess protein that remains in solution by washing, and, then crosslinking the protein in the coating. The result is a packing material which resists further adsorption by many different proteins but which continues to provide the adsorptive or catalytic properties of the groups on the internal surfaces of the porous protein-adsorptive support for separations, analysis, or alteration of small molecules. The packing material of the present invention is particularly useful in HPLC or solid phase extraction columns for direct injection drug analysis in plasma, serum, and urine.

Abstract: Method for detecting the presence or amount of an analyte of interest in a sample by providing a substrate having an optically active surface exhibiting a first color in response to light impinging thereon, and exhibiting a second color comprising a combination of wavelengths of light different from the first color or comprising an intensity of at least one wavelength of light different from the first color, in response to the light when the analyte is present on the surface in an amount selected from any one of 0.1 nM, 0.1 ng/ml, 50 fg, 2.times.10.sup.3 organisms comprising the analyte; and contacting the optically active surface with a sample potentially comprising the analyte of interest under conditions in which the analyte can interact with the optically active surface to cause the optically active surface to exhibit the second color when the analyte is present.