Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces which are electronically excited for use in electrochemiluminescence based tests. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use in flat panel displays and multiply specific testing procedures.

Abstract: A molecular sensing apparatus comprises a first electrode (10), a second electrode (12), a first molecule (20), a second molecule (22), and a third molecule (34). The first molecule (20) has a first chain of nucleic bases (30) and a first group (24). The first group (24) is bound to the first electrode (10). The second molecule (22) has a second chain of nucleic bases (32) and a second group (26). The second group (26) is bound to the second electrode (12). The third molecule (34) is bound to the first molecule (20) and the second molecule (22). A method which uses the molecular sensing apparatus is disclosed.

Abstract: Disclosed is a sensor for sensing the presence of an analyte component without relying on redox mediators. This sensor includes (a) a plurality of conductive polymer strands each having at least a first end and a second end and each aligned in a substantially common orientation; (b) a plurality of molecular recognition headgroups having an affinity for the analyte component and being attached to the first ends of the conductive polymer strands; and (c) an electrode substrate attached to the conductive polymer strands at the second ends. The electrode substrate is capable of reporting to an electronic circuit reception of mobile charge carriers (electrons or holes) from the conductive polymer strands. The electrode substrate may be a photovoltaic diode.Also disclosed is method of forming a sensor capable of sensing the presence of an analyte component. This method includes (a) contacting a sensor substrate (e.g.

Abstract: A binding of a molecule with a molecular receptor at a binding site is sensed using a magnetoresistive member proximate to the binding site. A magnetic field associated with the molecule acts to modify an electrical characteristic of the magnetoresistive member when the molecule binds with the molecular receptor. The magnetic field is produced by a magnetic member, such as a magnetic bead, attached to the molecule. Preferably, the magnetoresistive member is integrated with a substrate which supports the binding site. A readout device, such as a thin-film transistor, can also be integrated on the substrate to provide a signal indicative of a binding event.

Abstract: A system and method for handling magnetic particles, as in an immunoassay. A remover having a magnetic body and covering sleeve is inserted in a vessel containing magnetic particles and a liquid. The remover is moved up and down with the particles adhered to agitate the liquid and improve adherence of the particles.

Abstract: The invention relates to a process for magnetorelaxometric quantitative detection of analytes in liquid and solid phases, compounds for magnetorelaxometric detection, and their use in analysis and immunomagnetography.

Abstract: The present invention relates, in general, to a protein that regulates programmed cell death and, in particular, to the pro-apoptotic protein, Bax, which forms channels in lipid membranes. The invention further relates to methods of identifying agonists and antagonists of Bax channel formation and/or activity and thereby agents that can be used therapeutically to promote or inhibit cell death.

Abstract: The invention relates to a method for separating magnetic particles from a composition in a vessel. In the method, particles are first concentrated on the wall of the vessel and collected from this area by using a separation means (1) to which the magnetic particles adhere. In this way, particles can be collected efficiently. The invention can be used in different applications especially in the fields of biotechnology, biochemistry, and biomedicine.

Abstract: Assay methods utilizing the response of a magnetically responsive reagent to the influence of a magnetic field to qualitatively or quantitatively measure binding between specific binding pair members. According to the invention, the presence of an analyte mediates whether or not the magnetically responsive reagent binds to a mobile solid phase reagent. The extent of binding will modulate the response of the magnetically responsive reagent or that of the mobile solid phase reagent, or both, to the influence of a magnetic field. Hence, by measuring the response to the magnetic field of the magnetically responsive reagent, or that of the mobile solid phase reagent, the presence or amount of analyte contained in a test sample can accurately be determined. The invention utilizes various devices to carry out the assay methods described.

Abstract: A method and a system for correction a patient's biological fluid containing various low-, medium- and high-molecular toxins. The biological fluid substantially continuously flows through an extracorporeal flow line interconnected between an outlet and an inlet means attached to first and second locations, respectively, on a patient's body. A substantially small amount of the biological fluid containing various xenobiotics occupies the flow line at any given time as compared to a whole amount of the biological fluid contained in the patient's body. The biological fluid containing the various toxins is mixed with a predetermined amount of magneto-conductive particles capable of adsorbing the various toxins. An obtained mixture of the biological fluid with the particles passes through a magnetic field effect region and substantially all of the magneto-conductive particles are retained therein. Particle-free biological fluid is then returned into the patient's body through the inlet means.

Abstract: A molecular detection device including a support member (36) and a plurality of molecular receptors (34) arranged at a plurality of sites of the support member (36). In a first aspect, the molecular receptors (34) are arranged in accordance with a mapping selected from the group consisting of a random mapping and a pseudorandom mapping. In a second aspect, data associated with the mapping is written to a member associated with the support member (36). In a third aspect, the molecular receptors (34) includes a first plurality of molecular receptors germane to an application and at least one molecular receptor extraneous to the application.

Abstract: A biosensor apparatus for detecting a binding event between a ligand and receptor. The apparatus includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having ligands attached to the exposed monolayer surface. Binding of a receptor to the monolayer-bound ligand, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer. In one embodiment, the monolayers have a coil--coil heterodimer embedded therein, one subunit of which is attached to the substrate, and the second of which carries the ligand at the monolayer surface.

Abstract: A method and system for optically assaying a substance in a sample using a sensing system having a diffraction grating sensor. A system and method are described that expose the sensor with a light beam at near normal angles of incidence and quantitatively measure the concentration of targeted substance by determining the angular separation between resulting anomaly angles. The present invention also contemplates a system and method that quantitatively measure the concentration of targeted substance by determining the wavelength separation between resulting anomaly wavelengths. Advantages of the present invention include increased sensitivity and less susceptibility to system drifts due to mechanical motion and thermal changes than conventional diffraction grating sensors.

Abstract: An elcctrobiochemical system for the determination of the presence and optionally concentration of an analyte in a liquid medium, the system comprising an electrode having immobilized thereon a member of a recognition pair, the other member of said pair being said analyte, the presence of said analyte in the medium resulting in formation of a pair complex, being a complex between said immobilized member and said analyte; the system further comprising redox molecules capable of changing their redox state by accepting electrons from or donating electrons to the electrode; the formation of the pair complex on the electrode bringing a change in the electrical response of the system, whereby the presence and optionally the concentration of said analyte in the medium can be determined.

Abstract: In accordance with a first aspect, a binding assay comprises a machine-readable storage medium which supports a molecular receptor (22). In accordance with a second aspect, a support member (50) supports first (22) and second (24) molecular receptors and first (26) and second (28) data identifying the molecular receptors (22,24). In accordance with a third aspect, a support member has a first annular portion (106) to support molecular receptors and a second annular portion (108) to support machine-readable data identifying the plurality of molecular receptors.

Abstract: A process for the qualitative and/or quantitative determination of an analyte in a sample. The process includes providing a sample containing an analyte of interest in a liquid phase, providing at least one reagent having super-paramagnetic reactive metal particles linked to a substance that binds to the analyte, contacting the sample and the reagent to allow binding of the analyte in the sample and the reagent, applying a magnetic field to the mixture of sample and reagent, and detecting the presence of the analyte in the sample. The device includes a support for the sample and reagent, means for contacting the sample and reagent, magnetic means for confining and separating the analyte from the other components of the sample, and detection means for qualitative and/or quantitative measurement of the analyte.

Abstract: The invention provides a sensor for detecting an analyte comprising a support for a bioreceptor or biomimic and a detection means, wherein the support can retain a bioreceptor or biomimic and the support and the bioreceptor or biomimic and the detection means can be arranged such that when the sensor is placed in a medium containing a substrate, the substrate contacts the bioreceptor or biomimic and reacts to generate a response which is detectable by the detection means and which is relatable to the concentration of the analyte, and the support comprises a non-volatile organic liquid.

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: Electrode membrane combinations for use in biosensors to detect analytes in a sample and methods for making and storing same are disclosed. In one aspect, a method is provided for producing a first layer electrode membrane comprising:(1) Forming a solution containing Linker Lipid A, the disulfide of mercaptoacetic acid (MAAD) or similar molecule, linker Gramicidin B, membrane spanning lipid C (MSL-C) and membrane spanning lipid D (MSL-D) or other suitable linker molecules and other ion channel combinations;(2) Contacting an electrode containing a clean gold surface with the solution, the disulfide containing components in the solution thus adsorbing onto the gold surface of the electrode;(3) Rinsing the electrode with a suitable organic solvent; and(4) Removing the excess organic solvent used for rinsing.

Abstract: Graphitic nanotubes, which include tubular fullerenes (commonly called "buckytubes") and fibrils, which are functionalized by chemical substitution, are used as solid supports in electrogenerated chemiluminescence assays. The graphitic nanotubes are chemically modified with functional group biomolecules prior to use in an assay. Association of electrochemiluminescent ruthenium complexes with the functional group biomolecule-modified nanotubes permits detection of molecules including nucleic acids, antigens, enzymes, and enzyme substrates by multiple formats.

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: Disclosed is an assay for determining the presence of at least one analyte in a sample, which involves the steps of: (a) mixing the sample and predetermined amounts of first test microparticles having disposed thereon a binding molecule which binds a first analyte, and inert reference microparticles to form a reaction mixture, and to allow for the first binding molecule to bind the first analyte; b) counting the numbers of the non-reacted first test microparticles and the reference microparticles; and (c) comparing the number of non-reacted first test microparticles to the reference microparticles to thereby establish a first test value so that the presence of the first analyte in the sample may be determined. In a preferred embodiment, the first test value is compared to a control value for a non-reactive sample, and a change value is calculated therefrom.

Abstract: Luminescent chemical reagents that include complexes of rare earth metals with ligands such as aromatic heterocyclic nitrogen-containing compounds and semi-aromatic oxygen-containing compounds are used to detect small quantities of complex substances such as pharmaceuticals, metabolites, and microorganisms in complex sample mixtures.

Abstract: The present disclosure is directed to a novel apparatus and novel methods for the separation, characterization, and manipulation of matter. In particular, the invention combines the use of frequency-dependent dielectric and conductive properties of particulate matter and solubilized matter with the properties of a suspending medium to discriminate and separate such matter. The apparatus includes a chamber having at least one spiral electrode element. Matter is separated in the chamber by a dielectrophoretic (DEP) force caused by the energized electrode or electrodes.

Abstract: The invention relates to a device including a substrate and at least one biologically active substance bound to at least a part of the surface of this substrate, which is obtained by simultaneous or sequential reaction of said substrate and of said substance with a bifunctional coupling agent in which one of the functional groups is capable of being photoactivated and generates carbenes and is used to bind the coupling agent to the inorganic substrate and the other functional group is used to bind the coupling agent to the biologically active substance, in which said substrate is a covalent inorganic nitride.

Abstract: A system for assaying a fluid sample for one or more types of analytes, which employs at least one class of finely divided polystyrene spheroidal particles, each class being limited to a predetermined specific narrow range of particle diameters, the particles of each such class being coated with a specific reactant unique for that class. After the coated particles are mixed with the sample to specifically react to form conjugates of the particles and any of the analyte present, the mixture is irradiated with bursts of ultrasound swept over a range of frequencies resonant to the expected conjugate sizes. The presence of the conjugates and therefore the analyte is detected directly by measuring any selective absorption or scattering of waves of frequencies to which the conjugates are resonant.

Abstract: The invention concerns a binding matrix containing a carrier material with an oxidic surface and a solid phase reactant covalently bound thereto via anchor groups which is capable of binding to at least one free reaction partner, which is characterized in that the solid phase reactant forms a diluted and essentially laterally homogeneous binding layer on the surface of the carrier material and that the anchor groups are silane groups and are linked to the solid phase reactant via a spacer molecule.

Abstract: A sensor format is based on impedance analysis of polymer coatings of electrodes. A detectable signal is produced by the effect of a reactive or catalytic species at or very near the polymer coated electrode. The reactive or catalytic species directly or indirectly effects a reaction with the polymer layers, whereby the polymer layer becomes porous and thus causes a measurable change in electrical properties of the electrode surface.

Abstract: The new membrane biosensors consist of a solid A as a support, a lipid bilayer B as a membrane, spacers C incorporated between A and B and a receptor D embedded in the lipid bilayer. The new membrane biosensors are characterized in particular by their spacer C, which consists of a molecule of ethanolamine which forms an ester bond to the phosphatide group of the lipid bilayer B, an oligopeptide in helical or pleated sheet structure formed from 4-20 C.sub.2 -C.sub.10 -.alpha.-amino acids and a reactive group which enters into a chemical or physicochemical bond with the support A.

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

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

Abstract: A species such as a microorganism, e.g. Legionella, Giardia or Cryptosporidium, is captured by first attracting plastic coated magneticbeads or other magnetically attractable particles to a solid support such as stainless steel mesh, which particles have a selective affinity for the species, e.g. by virtue of an antibody coating, and contacting a sample containing the species with the particles on the solid support. The beads bearing the captured species may be released by reduction of the magnetic attraction of the support for the beads, e.g. by turning off an electromagnet used to magnetize the support.

Abstract: A chemical sensor includes a patterned layer having discrete sections, a -dimensional detector array, and a two-dimensional lens array that focuses an optical signal from the patterned layer onto the two dimensional detector array. Typically, the two-dimensional detector array is a charge-coupled device array and the lens array is a graded index of refraction lens array. The chemical sensor maintains good resolution throughout its field of view.

Abstract: A piezoelectric biosensor substrate useful for immobilizing biomolecules in an oriented manner on the surface of a piezoelectric sensor has a ladder polymer of polyacrylonitrile. To make the substrate, a solution of an organic polymer, preferably polyacrylonitrile, is applied to the surface of a piezoelectric sensor. The organic polymer is modifying by heating the polymer in a controlled fashion in air such that a ladder polymer is produced which, in turn, forms the attachment point for the biomolecules comprising the piezoelectric biosensor.

Abstract: A method for determining an analyte in a sample which includes: providing the sample in liquid phase, the analyte of which has a ligand having at least one anti-ligand specific recognition site; providing at least one reagent containing metal particles, in suspension in liquid phase and non-separable from the liquid phase by a magnetic or electromagnetic force, each particle containing a metal core to which at least one anti-ligand is fixed directly or indirectly; contacting the sample and the at least one reagent in order to obtain metal clusters; placing the metal clusters in a magnetic field generated by a magnetic or magnetic field generating sensor in order to assemble the metal clusters; and detecting the assembled metal clusters to obtain a signal representative of the mass of metal in the clusters, which is correlated with the quantity of analyte present in the sample initially. A device for determining an analyte in a sample by the above process is also included.

Abstract: Methods are disclosed for separating a component of interest from a mixture containing the component of interest and other components. The method comprises contacting a first liquid medium containing the component of interest and other components with a second liquid medium that is of different density than and/or of different viscosity than the first liquid medium. The contact is carried out in such a way that mixing of the media is minimized or avoided. The component of interest is bound to magnetic particles. The contacted first liquid medium and second liquid medium are subjected to a magnetic field gradient to allow the magnetic particles to migrate into the second liquid medium and separation of the component of interest from other components is realized. Also disclosed are assays employing the present method. Kits for carrying out the present method and assays are also disclosed.

Abstract: A method and apparatus for separating solid supports formed of magnetic particles on which immunocomplexes are bound, from a liquid phase includes a reaction container containing a fluid in which magnetic particles having immunocomplex bound thereon are suspended. The reaction container is positioned at a flock forming station, where the fluid is subjected to an alternate current magnetic field having a temporally varying intensity by an electromagnetic. The magnetic particles are flocculated with each other due to the application of such varying magnetic field to form a multiplicity of flocks. A stronger magnetic field then is applied to the resulting contents in the reaction container by a permanent magnet. The flocks are magnetically fixed on the inner wall surface of the reaction container by the action of the stronger magnetic field.

Abstract: A bilayer lipid membrane (BLM) sensor comprising (1) a gold recording surface, (2) a first lipid layer which is an imperfect layer of a thiolipid which comprises the residue of two phospholipid molecules linked to each end of a disulphide (--S--S--) group, each through an oxyethylene (--O--CH.sub.2 --CH.sub.2) chain which is short enough to allow the thiolipid to become anchored to the gold surface by self-assembly, but long enough to trap an aqueous layer between the gold surface and the bottom of the thiolipid layer, said thiolipid being attached to the gold surface and said imperfect layer being completed by a phospholipid which provides an unattached fluid phase at room temperature, and (3) a second lipid layer of phospholipid. The sensor is especially useful for measuring changes in electrical resistance and/or capacity when it is prepared to contain a receptor protein and an analyte containing an agonist to the receptor is contacted with the bilayer.

Abstract: A method of determining the affinity and kinetic properties of low molecular weight ligands for their interaction with a common receptor comprises the steps of immobilizing the receptor on a sensing structure, mixing in known proportions each ligand with a ligand analogue the response of which on the sensing structure is substantially higher than that of the low molecular weight ligands, contacting each mixture with the sensing structure and measuring the response, and comparing the response of each mixture with that of the ligand analogue alone, the distortion of the ligand analogue response being representative of the affinity and kinetic properties of the ligand.

Abstract: The present invention relates to the use of paramagnetic materials, such as lanthanide chelates, as contrast agents in magnetometric analysis, especially imaging. The invention is particularly directed to structural and functional diagnosis or imaging.

Abstract: A chemical moiety is disclosed which comprises a chemical, biochemicals, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organo-metallic compounds. Methods are disclosed for detecting low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photo-luminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.

Abstract: A cuvette based testing device for use in testing or otherwise analyzing a fluid sample. A cuvette is provided that defines at least one conduit, wherein the fluid sample is introduced into the various conduits. Reagents are disposed within the conduits that are intended to be mixed with the fluid sample. The fluid sample is drawn into the conduits by the force of a pneumatic pump. As the fluid sample contacts the various reagents, the reagents mix with the sample. Mixing is further conducted by moving the fluid sample back and forth across an obstruction in the conduit. The obstruction causes turbulent flow in the fluid sample, thereby mixing the sample with any reagent also present. The conduit is preferably transparent. The fluid sample is brought to a point in the cuvette where it is disposed below a detector. The detector is used to measure a characteristic of the fluid sample such as optical density, nephelometry, fluorescence, chemical luminescence, photoemittions or the like.

Abstract: The present invention provides a general purpose specific binding assay method which has the advantages of highly accurate and quick measurements which exclude the effects of various factors that decrease reliability of the measured values, such as non-specific reactants in test samples, assay conditions and inactivation and the like changes in the activity of reagents. The present invention is further drawn to a specific binding assay device suitable for the practice thereof.

Abstract: A chemical sensor includes a thin film transistor with a gate positioned on one side. An insulating layer is positioned on the opposite side and an indicator film is positioned on the insulating layer in generally opposed relationship to the gate. Induced charge in the indicator film caused by a biological or chemical species changes the channel current in the transistor. A potential on the gate is then used to null out the resulting change in channel current. The potential used to null out the current change is an extremely sensitive measure of the induced charge.

Abstract: A chemical moiety is disclosed which comprises a chemical, biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organometallic compounds. Methods are disclosed for detecting low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.

Abstract: Improved magnetic separators, devices and methods for magnetic separation procedures are provided. The improved separation devices contain matrices which provide uniform pores or channels that reduce the entrapment of air or non-target substances, and decrease the loss of target substances due to mechanical disruption. Target cells, from various systems and organs, or other target biological substances are labeled in conjunction with a suitable specific binding member, and isolated using the devices and methods of the present invention. In its simplest form, the cell separation system of the present invention has two main components: a magnetic separator and a cell separation reagent. A more complex separation device includes fluid passages, collection and storage containers and the separation column. The fluid circuitry can be constructed with integrated valves, or the valves may be applied externally to the fluid pathways.

Abstract: Polymers comprising a ligand containing a carboxylic acid group, optionally at least one ion of an element of the atomic numbers 21-29, 42, 44 or 57-83 as well as optionally cations of inorganic and/or organic bases, amino acids or amino acid amides are valuable complexing agents and complexes for diagnosis.

Abstract: A new class of magnetic resonance (MR) contrast agents are described whose in vivo biodistribution is based upon the ability of certain cells to recognize and internalize macromolecules, including the MR contrast agents of the present invention, via a process which substantially involves receptor mediated endocytosis. The RME-type MR contrast agents described herein comprised of biodegradable superparamagnetic metal oxides associated with a variety of macromolecular species, including but not limited to, serum proteins, hormones, asialoglycoproteins, galactose-terminal species, polysaccharides, arabinogalactan, or conjugates of these molecules with other polymeric substances such as a poly(organosilane) and dextran. One of the advantages of these MR contrast agents is that they may be selectively directed to those cells which bear receptors for a particular macromolecule or ligand and are capable of undergoing receptor mediated endocytosis.

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: There is disclosed an apparatus for the determination of a trace amount of an analyte substance or organism. A substrate solution is brought into contact with a small diameter tube which has captured, at least on its inner surface, a trace amount of an analyte substance or organism. The trace amount has the ability to change the pH of the substrate solution.