Substrates for Isolating, Reacting and Microscopically Analyzing Materials
6 Assignments
0 Petitions
Accused Products
Abstract
An immobilizing device for biological material comprises a rigid support (12) carrying a substrate layer (20, 20′) of polymer having biological immobilizing properties, e.g. for amino and nucleic acids. Substantially solid ultra-thin substrate layers (20′) having a thickness less than about 5 micron, preferably between about 0.1 and 0.5 micron, and micro-porous, ultra-thin substrate layers (20′) having a thickness less than about 5 micron, preferably less than 3 micron, 2 or 1 micron are shown, which may be segmented by isolating moats M. The substrate layer is on a microscope slide (302), round disc (122), bio-cassette, at the bottom of a well of a multiwell plate, and as a coating inside a tube. Fluorescence or luminescence intensity and geometric calibration spots (420) are shown. Reading is enhanced by the intensity calibration spots (420) to enable normalization of readings under uneven illumination conditions, as when reading by dark field, side illumination mode. The reference spots are shown being printed simultaneously with printing an array of biological spots or with the same equipment. Methods of forming layers of the device include controlled drawing from a bath of coating composition and drying, and spinning of C-D shaped substrates. Post-forming treatment is shown by corona treatment and radiation. Adherent metal oxides (14), silica-based materials and other materials are used to unite layers of the composite. In multiwell plates the oxide promotes joining of a bottom plate (95, 95′) and upper, well-defining structure (94) of dissimilar material. The oxides (14) also provide beneficial opacity to prevent light entering the glass support, for applying potential to the substrate, etc.
-
Citations
73 Claims
-
1-50. -50. (canceled)
-
51. An arrangement of members that provides multiple wells for reacting bio-materials and enables their analysis, the arrangement comprising:
- a bottom member comprised of a rigid support, a polymer substrate layer lying over an upwardly directed side of the rigid support, the substrate layer having thickness less than about 5 micron and having an upwardly exposed surface that has biological immobilizing properties, the polymer substrate layer being of dissimilar material to that of the rigid support, there being between the polymer substrate layer and the rigid support at least one adhesion-promoting intervening layer adherently joined at its oppositely directed sides to substance of said bottom member; and
a bottomless well-defining member at least temporarily engaged upon the bottom member to define multiple wells for reacting fluids in respective wells with bio-material immobilized on the polymer substrate layer at the bottoms of the wells. - View Dependent Claims (52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)
- a bottom member comprised of a rigid support, a polymer substrate layer lying over an upwardly directed side of the rigid support, the substrate layer having thickness less than about 5 micron and having an upwardly exposed surface that has biological immobilizing properties, the polymer substrate layer being of dissimilar material to that of the rigid support, there being between the polymer substrate layer and the rigid support at least one adhesion-promoting intervening layer adherently joined at its oppositely directed sides to substance of said bottom member; and
- 67. A multi-well plate device for immobilizing biological material in which the bottom portion of the device comprises a polymer substrate layer having biological immobilizing properties for protein or nucleic acid, the substrate layer supported on a rigid support and having an outer deposit-receiving region exposed to receive the biological materiel, wherein the substrate layer has thickness less than about 5 micron, the bottom portion of the multi-well plate device being sufficiently transparent to enable transmission of fluorescence excitation light across the bottom portion to fluorescently labeled bio-material immobilized on the surface of the substrate layer and transmission of fluorescent radiation from the labeled bio-material across the bottom portion to an objective of a detection system.
-
69. A bottom member for a multi-well plate, the bottom member comprised of a rigid support, a polymer substrate layer lying over an upwardly directed side of the rigid support, the substrate layer being ultra-thin with a thickness less than about 5 micron, and having an upwardly exposed surface that has biological immobilizing properties, the polymer substrate layer being of dissimilar material to that of the rigid support, there being between the polymer substrate layer and the rigid support at least one adhesion-promoting intervening layer adherently joined at its oppositely directed sides to substance of said bottom member, the rigid support, the adherently joined intervening layer and the substrate layer of the bottom member being sufficiently transparent to enable transmission of fluorescence excitation light across the bottom member to fluorescently labeled bio-material immobilized on the surface of the substrate layer and transmission of fluorescent radiation from the labeled bio-material across the bottom member to an objective of a detection system.
Specification