Abstract: A mixture of two different kinds of particles having distinctive, different properties is employed for determining the presence of a select protein in, or the absence of a select protein from, a solution. The first kind of particle provides a property facilitating separation, while the second kind of particle provides a property facilitating detection. The particles are coated with the same protein, a protein able to interact specifically with the select protein.

Abstract: In carrying out an immunological reaction or diagnostic test, an immunologically inert organic compound of sufficient quantity is added to an aqueous medium containing an immunologically reactive antigen. A substrate is then treated with the aqueous medium and on the surface thereof is formed, by adsorption, a monomolecular layer of the reactive antigen molecules separated from each other to distances of several hundred Angstrom by the inert organic molecules. Subsequent immersion of the coated substrate in aqueous media alternately containing an immunologically reactive antibody specific to the antigen, and then again containing the reactive antigen, forms a multimolecular immunologically complexed film on the substrate.

Abstract: Method and apparatus for the detection of antibodies and antigens based upon the effect that any arbitrary antigen will adsorb onto a substrate in a monomolecular layer only, but that a corresponding specific antibody for such arbitrary antigen will bond thereto to form a bimolecular layer on the substrate. A first layer of antigen is adsorbed onto a substrate and the coated substrate is then exposed to a solution suspected of containing the specific antibody of interest. The substrate is then examined to determine whether a monomolecular or bimolecular layer is adhering thereon. Optical, including visual, electrical, and chemical means for examining the coated substrate are disclosed. The method can be reversed by replacing the antigen in each step above with its specifically reacting antibody and by replacing the antibody with its specific antigen.

Abstract: A monomolecular layer of first biological particles is absorbed on the surface of a non-reactive substrate. The coated substrate is exposed to a solution suspected of containing second biological particles specific to the first biological particles. Next, the coated substrate is subjected to a tagging step, following which it is exposed to a cleaving agent solution which cleaves the bond between the first and second biological particles. The used cleaving agent solution is then examined by a tag-sensing instrument following possible concentration thereof for determining whether tag-bearing second particles have been removed. The tags may, for example, be radioactive, fluorescent, etc. A supplement is described, wherein the coated substrate is studied with a tag-sensing instrument before and after exposure of the coated substrate to the cleaving agent solution to help provide said determination.

Abstract: Small magnetic particles are used to provide large and widely-distributed surface area for separating a select protein from a solution to enable detection thereof when present in low concentrations. The particles are coated with a protein that will interact specifically with the select protein.

Abstract: The detection of immunologically reactive biological particles such as viruses, bacteria and other cells is obtained by detection of the occurrence of an immunological reaction on a substrate between the particle to be detected and its tagged antibody. A first immmunologically reactive biological particle is adsorbed onto the surface of the substrate in a particular monomolecular layer pattern, and the substrate is then exposed to a solution suspected of containing select particles to be detected which are specific to the first particle. Finally, the substrate is exposed to a medium containing tagged antibodies to the particle to be detected, and the pattern substrate surface is monitored for the presence of the tags by searching with a tag-sensing instrument for the particular pattern.

Abstract: Devices for the detection of biological particles, particularly proteins. Such devices comprise a non-transparent surface of metal (solid metal or a non-transparent coating of metal on some different substrate) covered with a thin transparent first layer of dielectric material, which in turn has a transparent second layer of metal adhered over the outer surface thereof, the transparent layer preferably being in the form of metal globules or metal islets. The detection device as provided to the user will usually have a monomolecular layer of biological particles applied over at least a portion of the transparent layer of metal. Interference of light is obtained useful in distinguishing between monomolecular layers and multi-molecular layers with the unaided eye, when the non-transparent surface metal reflects light relatively poorly and is at least approximately matched to the light reflecting ability of the dielectric material forming the transparent layer thereover.

Abstract: A monomolecular layer of first biological particles is adsorbed on the surface of a substrate fabricated of virtually any nonreactive solid material, the coated substrate is then exposed to a solution suspected of containing second biological particles specific to the first biological particles, next a porous, opaque layer of nonreactive third particles is formed in the coated substrate, and then the coated substrate is exposed to a cleaving agent solution which cleaves the bond between the first and second biological particles. A visual examination of the coated substrate surface clearly indicates to the naked eye or examination by suitable instrument whether the suspect solution contains the second biological particles by determining whether the opaque layer is complete or a portion common to the second biological particles, has been removed.

Abstract: A method and apparatus for optically detecting complexing of molecules in solution with surface-bound enzymes comprises slowly varying, in periodic fashion, the surface electrical potential so as to vary correspondingly the pH of the solution at the enzymatic sites through a range in which the Michaelis constant exhibits a relatively large change with pH variation. The potential is also oscillated over a smaller voltage range at a higher frequency. Phase sensitive detection of the output signal of an ellipsometer directed onto the surface provides a signal proportional to the concentration of complexing molecules.

Abstract: Small magnetic particles coated with an antibody layer are used to provide large and widely-distributed surface area for sorting out and separating select viruses, bacteria and other cells from multi-cell, bacteria or virus populations.

Abstract: The area of a bimolecular layer formed on a metallized slide is related to the concentration of second immunologically reactive biological particles forming the second layer. The slide initially has adsorbed thereon a first monomolecular layer of first immunologically reactive biological particles specific to the second particles. A second slide is placed on top of the monomolecular layer coated slide and a moistened region between the two slides is exposed to a solution of the second biological particles to form the second monomolecular layer. The biomolecular layer is visible with good contrast to the unaided eye.

Abstract: A thin layer of gel on a metallized solid surface has two or more wells formed through the gel which are subsequently filled with specimens of first and second solutions suspected of respectively containing first and second immunologically reactive biological particles specific to each other. The specmens are allowed to diffuse in the gel, and presence of the first and second biological particles in the solutions forms a complexed protein precipitate line on the metallized solid surface corresponding to the region of intersection of the two diffused specimens and which is visible with good contrast to the unaided eye without the need for staining the gel and provides a durable record of the immunological reaction which forms the precipitate.

Abstract: A metallized solid substrate is covered with a moistened porous paper, and specimens of first and second solutions suspected of respectively containing first and second immunologically reactive biological particles specific to each other are applied to selected areas of the paper and allowed to diffuse therein. Presence of the first and second biological particles in the solutions is indicated with high sensitivity by formation of a complexed protein precipitate line on the metallized substrate along the region of intersection of the two diffused particles and which is visible with good contrast to the unaided eye.

Abstract: A metallized slide has adsorbed thereon a first monomolecular layer of particular first immunologically reactive biological particles and is covered with a suitable moisture holding medium. A test solution is then applied along a first edge of the slide, a solution containing second immunologically reactive biological particles specific to the first particles is applied along an edge perpendicular to the first edge, or midway along the slide, and the biological particles in the two solutions diffuse toward each other. The slope or distance from the first edge of a precipitation line formed on the metallized slide at the intersection of the diffused first and second biological particles is related to the concentration of the first particles in the test solution.