Back to results
US 2006/0134606 A1Published application
Substrates for isolating reacting and microscopically analiyzing materials
AssigneeDecision Biomarkers, Inc.
InventorJean Montagu
Life of this patent
Estimating the term…
Loading patent…
Loading patent…
AssigneeDecision Biomarkers, Inc.
InventorJean Montagu
Estimating the term…
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 multi-well 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.
A device for immobilizing biological material comprising a polymer substrate layer 20, 20′, 20″ having biological immobilizing properties preferably for protein or nucleic acid, the substrate layer deposited on a rigid support 12, and having an outer deposit-receiving region exposed to receive the biological material, wherein the substrate layer is ultra-thin, having a thickness tut less than about 5 micron.
The device of any of the foregoing claims wherein the deposit-receiving region of said substrate layer 20, 20′, 20″ is in a surface-treated state for enhanced adhesion of deposits of biological material thereon, preferably the surface treatment being that provided by a corona treater 122.
The device of any of the foregoing claims, wherein at least one intervening layer 14, 14′, 112 lies between said rigid support 12 and said ultra-thin polymer substrate layer 20, 20′, 20″, said intervening layer adherently joined on each of its oppositely directed faces to substance of said device.
The device of any of the foregoing claims wherein a surface of one of the constituents of said device, prior to being united with a next constituent layer of the device, is in a surface-treated state for enhanced adhesion of that surface to said next constituent layer.
The device of any of the foregoing claims wherein the substrate layer 20, 20′, 20″ is adapted to receive a deposit of biological material 420 and to be temporarily engaged by an object adjacent the deposit, as by an elastomeric gasket 430, wherein the substrate layer is interrupted so that adherence of the substrate to the removed object does not disrupt the array, preferably an intervening adhesion promoting layer 14′ beneath said substrate layer being interrupted such that a substrate layer 20″ applied thereto is disrupted, for example by moat M, FIGS. 23, 24, formed by a gap in a pattern of a metal oxide adhesion promoting intervening layer 14′.
The device of any of the foregoing claims constructed for use in microscopy, wherein an outer surface of the substrate layer 20, 20′, 20″ is constructed to receive deposits of biological material thereon in position exposed for direct illumination and inspection from the exterior.
A device for immobilizing biological material comprising a polymer substrate layer 20, 20′, 20″ having biological immobilizing properties preferably for protein or nucleic acid, the substrate layer deposited on a rigid support 12, and having an outer deposit-receiving region exposed to receive biological material, wherein the rigid support defines a straight support surface e.g., planar or cylindrical, and said substrate layer is a drawn coating applied directly or indirectly to the rigid member in the direction of said straight surface, preferably drawn substantially according to FIG. 14, preferably there being at least one intervening layer 14, 14′, 112, which lies between said rigid support 12 and said ultra-thin polymer substrate layer 20, 20′, 20″, said intervening layer adherently joined on each of its oppositely directed faces to substance of said device and preferably wherein immediately adjacent materials on opposite sides of a said intervening layer 14, 14′, 112 are not as adhesively compatible with each other as each is with said intervening layer.
A device for immobilizing biological material comprising a polymer substrate layer 20, 20′, 20″ having biological immobilizing properties preferably for protein or nucleic acid, the substrate layer deposited on a rigid support 12, and having an outer deposit-receiving region exposed to receive biological material, wherein at least one intervening layer 14, 14′, 112 lies between said rigid support and said polymer substrate layer, said intervening layer adherently joined to substance of said device on each of its oppositely directed faces and wherein a said intervening layer 14, 14′, 112 is at least partially opaque to radiation employed to stimulate emission from the biological material, limiting or preventing transmission of radiation from said rigid support, preferably wherein immediately adjacent materials on opposite sides of a said intervening layer 14, 14′, 112 are not as adhesively compatible with each other as each is with said intervening layer.
A device for immobilizing biological material comprising a polymer substrate layer 20, 20′, 20″ having biological immobilizing properties preferably for protein or nucleic acid, the substrate layer deposited on a rigid support 12, and having an outer deposit-receiving region exposed to receive biological material, wherein at least one intervening layer 14, 14′, 112 lies between said rigid support and said polymer substrate layer, said intervening layer adherently joined to substance of said device on each of its oppositely directed faces, preferably immediately adjacent materials on opposite sides of a said intervening layer 14, 14′, 112 are not as adhesively compatible with each other as each is with said intervening layer, and said intervening layer comprising an electrically conductive layer, for instance, wherein the electrically conductive layer is associated with at least one electrical terminal and the conductive layer and said electrical terminal are constructed and arranged to provide a potential to the receiving surface of said device to promote binding or rejection of material exposed to said outer deposit-receiving surface of said substrate layer.
A device for immobilizing biological material comprising a polymer substrate layer 20, 20′, 20″ having biological immobilizing properties preferably for protein or nucleic acid, the substrate layer deposited on a rigid support 12, and having an outer deposit-receiving region exposed to receive biological material, wherein the deposit-receiving region of said substrate layer is in a surface-treated state for enhanced adhesion of deposits of biological material thereon, e.g. the surface treatment being that provided by a corona treater 122.
The device of any of the foregoing claims, wherein said substrate layer 20′, 20″ is substantially solid, preferably having a thickness less than about 5 micron, preferably less than 3, 2 or 1 micron and in preferred embodiments between about 0.1 and 0.5 micron.
The device of any of the foregoing claims, wherein said rigid support 12 is a microscope slide 10, preferably a frosted microscope slide (see FIG. 7A), preferably a blank frosted glass slide, preferably said microscope slide coated with a metal oxide to which is adhered a drawn coating, as by the process shown in FIG. 13.
The device of any of the foregoing claims including a localized reference deposit 420, FIG. 11 or FIG. 23 of stable fluorescent material, preferably characterized by a broad fluorescence spectrum, e.g. polyimide, and preferably disposed on said device in position to be read by an optical instrument such as a microscope or CCD sensor for quality control of production of the device, or as an intensity calibrator during reading of fluorescence of substance deposited on said substrate layer 20, 20′, 20″.
The device of any of the foregoing claims, wherein said support 12 is selected from the group consisting of glass, fused quartz, silicon, plastic, PMMA or polystyrene, or for those claims not requiring transparency, of ceramic or a metal such as gold, aluminum or silver.
A method of forming the device of any of the foregoing claims including applying directly or indirectly to said rigid support a fluid containing said polymer of said substrate layer under conditions to form said substrate layer, preferably by drawing the rigid support from a bath of coating composition.
The method of claim 50 wherein the reading is accomplished with a CCD sensor.
Dependencies are inferred from the claim text.