Abstract: Novel coumarin derivatives comprising a coumarin moiety linked to a non-nucleosidic backbone moiety are disclosed. The resulting molecules are typically used as photoactivate crosslinking groups when incorporated into polynucleotides as replacements for one or more of the complementary nucleoside bases present in probes used in procedures involving nucleic acid hybridization reactions.

Abstract: Methods and compositions are provided for detecting nucleic acid sequences. Probes comprising a crosslinking agent are combined with a sample which may comprise a target sequence which is complementary to the probe. Hybridization is allowed to occur between complementary sequences. The crosslinking agent is activated. Covalent bonds are formed between the probe and the target sequence if they are hybridized to one another. The crosslinked nucleic acids can then be detected to indicate the presence of the target sequence. Also provided are kits comprising reagents.

Abstract: Improved methods for in situ hybridization assays of cellular and subcellular systems and tissue sections, and immobilization-based assay techniques such as Northern blotting, Southern blotting, dot blots, and the like, and assay techniques wherein the probes are bound to substrates are disclosed. The subject invention employs crosslinker-containing hybridization probes capable of forming covalent bonds between the probe and the target nucleic acid. Upon activation, the crosslinker will, if the probe has hybridized with its essentially complementary target, form covalent bonds with the complementary strand to covalently crosslink the probe to the target. Subsequently, stringent wash conditions may be employed to reduce background signals due to non-specific absorption or probes or targets, while retaining all crosslinked probe/target hybrids. Also disclosed are diagnostic kits for use in clinical and diagnostic laboratories.

Abstract: Processes are described for making a cryopreserved Composite Living Construct (CCLC) as well as a corresponding thawed and rinsed CCLC, comprised of separated layers of cultured fibroblasts and cultured keratinocytes, wherein the percent of cells that are viable, i.e., the cell viability, of such CCLC is at least about 70 %. The viable cell density in the CCLC is at least about 50% of that before cryopreservation. The storage stability of the CCLC is at least about 12 months. Additionally, the metabolic activity of thawed and rinsed CCLC is at least about 50% of the Composite Living Construct (CLC) before cryopreservation. The structural integrity of CCLC is substantially the same as the CLC before cryopreservation.

Abstract: A temporary and removable car bumper impact absorber protection device with adjustable straps for securing on or inside the trunk of an automobile has a cushioning material resting on and protecting the bumper of the automobile.

Abstract: This invention describes a collagen construct uniquely suited as a substrate for production of biologically active wound dressings, skin equivalents or skin substitutes. The collagen construct of the invention comprises a porous collagen sponge and a cell-impermeable transitional layer between the sponge and the boundary surface of the cell-impermeable transitional layer. Optionally, a further layer conducive to the attachment of cells, e.g. keratinocytes, may be coated as a third layer on the cell-impermeable layer. The sponge layer may be seeded with dermal cells, or other suitable cells and the boundary surface or the third layer may be seeded with epithelial cells, e.g. keratinocytes. The process used for the production of this construct also is described.

Abstract: Skin equivalents and processes for preparing them are described. The living skin equivalent comprises a layer of cultured keratinocyte cells, a layer of high purity, non-porous collagen and a dermal layer of cultured fibroblast cells in a porous, cross-linked collagen sponge. Processes are described for producing the skin equivalent with descriptions on how to obtain and treat skin precursor materials to yield suitable fibroblasts and keratinocytes.The collagen layers, the physical forms thereof, and treatments thereof are also described. Preferably, the non-porous, highly-purified collagen is selected from Type 1, Type 3, or mixtures of Type 1 and Type 3 collagen. The collagen is purified ideally by treatment with pepsin, to remove antigenic substances.The collagen sponge used can be any suitable form of collagen sponge which will support fibroblast growth.The keratinocytes used in the invention are preferably prepared by the "drop" method spotted evenly on culture media and incubated to coalescence.

Abstract: A three dimensional guidance system for locating the correct or optimal angles of implant insertion into a dental patient's jawbone is described. The optimum angles, depths, and positioning are obtained as follows: a surrogate of the patient's mouth is provided in the form of stone model of the intended implant region with the edentulous area being exposed, a diagnostic work-up, usually in wax, of the stone model, and perforce of the patient's mouth, is produced and fitted with a pontic tooth or teeth in the proper occlusal relationships, a three-dimensional guidance system in the form of a drill press containing a platform or table movable through all directions about a fixed point defined by the drill point. In practice, the radiographic guide is placed on the patient and a CT-scan taken.

Abstract: A drill instrument with calibrated depressions as markings on the shaft set at determinable distances apart, e.g. at 1 mm increments is disclosed. These calibrations are designed to give a visible depth gauge indication when the tip or point of the drill is at the full length of the depth of a drilled hole. A stop means is variably fixable to the drill at determinable locations. This stop defines a predetermined length available for drilling a hole into bone or a tooth canal up to the precise location of the stop on the drill corresponding to the depth desired to be drilled.An organizer block or kit accommodates the drills and stops of the invention and preferably provides an alignment device for preparing drills having the pre-determined lengths according to the invention via a drill-length determining device for applying the stop means to the drill at the desired pre-determined length.

Abstract: A skin piercing device which converts a longitudinal linear motion of a blade within the housing of the device into a vertical linear motion which, in consequence of the placement of biasing member, restraints and stops in the device, results in the ejection of the blade out of the housing and into the patient's skin and back again into the housing in a rapid "in-out" fashion. The dimensions of the restraints and stop s are individually controllable and, as a result, it is possible to achieve a length of cut which is independent of the depth of cut.

Abstract: There is described a skin piercing device which converts a longitudinal linear motion of a blade within the housing of the device into a vertical linear motion which, in consequence of the placement of a spring, restraints and stops in the device, results in the ejection of the blade out of the housing and into the patient's skin and back again into the housing in a rapid "in-out" fashion. The dimensions of the restraints and stops are individually controllable and, as a result, it is possible to achieve a length of cut which is independent of the depth of cut.

Abstract: A rotary fluid manipulator utilizable as a diagnostic device includes a porous body having fluid passages defined therein by fluid blocking means in the porosities of the body such as openings or slots in the body or compaction of areas of the porous body to define fluid passages therebetween. Various substances or binding partners such as receptors, immunoassay or other assay test materials and test specimens can be deposited on the porous body to permit various types of tests to be made by rotation of the manipulator to cause conjunctive centrifugal and wicking induced flow of fluids deposited thereupon.

Abstract: Disclosed is a device in the form of an adhesive tape stripping which in consequence of its configuration and presence of glue surfaces thereon facilitates the isolation of sawed particles of a cast material, for example, to the area of cutting as the material is being cut or sawed. Thus, for example, when a casting material is ready to be removed from a limb, the protective tape of the invention is applied to the cast in such a manner as to orient the cutting path preferably along the center of the tape. In a preferred case, a guide line is drawn on the tape for such purpose. The process of cutting generates the particles which instead of being dispersed into the atmosphere are accumulated on the adhesive surfaces of the trapping tape and are also embedded into the body of a thicker bottom adhesive layer of the tape thereby obviating the need for any vacuum equipment material and the associated personnel required therefor.

Abstract: Disclosed is a multi-layered test strip device for receiving whole blood on which a test for a suspected analyte is performed. The test confirms the presence, absence, or the amount of analyte, if present. The multi-layered device comprises two outside support layers between which are, in descending order relative to the horizontal plane, a) a spreading screen having defined characteristics, b) a separating layer which removes red blood cells at least partially via a red blood cell binding agent, and c) a membrane reagent layer; wherein the screen and each layer is in close and contiguous contact with the layer which follows it, and wherein at least one of layers a), b), and c) is conditioned by a pre-treatment.The screen can have openings of from 10-200 microns. The blood cell binding agents are antibodies to red blood cells, chemical agents, or lectins. The separating layer has screen opening of preferably 20-200 microns.

Abstract: A composite living skin equivalent is described comprising an epidermal layer of cultured keratinocyte cells, a layer of non-porous collagen, and a dermal layer of cultured fibroblast cells in a porous cross-linked collagen sponge matrix. Preferably the non-porous collagen is Type 1, Type 3 or mixtures of Types 1 and 3 bovine collagen, which has been pepsin treated. A process for preparing the skin equivalent is described, as well as a test kit for in vitro testing of the skin equivalent. The skin equivalent has use for skin grafting as well as in vitro testing of the effects of various substances on skin.

Abstract: A blood collection and separation system having multi-chamber collection assembly having a longitudinal axis. The assembly in a preferred embodiment is rotatable about its longitudinal axis and an alternate embodiment is rotatable about an axis parallel to its longitudinal axis. A porous separating body at one axial end of one chamber connects with a second chamber and allows flow of the lighter fraction of the blood from the one chamber to the other chamber during centrifugation, but blocks flow of the heavier fraction. Hydrostatic forces are created during centrifugation to cause flow of the lighter fraction through the body into the other chamber. Preferably the surface of the separating body which faces the first chamber slopes away the spinning axis so that centrifugal force tends to dislodge any particles of the heavier fraction which might be lodged on the surface. The assembly of the present invention affords handling of blood for testing or analysis without human exposure to the blood components.

Abstract: A dental implant is described which has greater stability in the jawbone and greatly reduces the potential for infection. The implant is made from an anatomically precise reproduction of the affected site of the jawbone, which reproduction is produced from computer generated data defining the affected site. The reproduction is used as the base for a cutting jig to fit on an exposed mandible or maxilla and the jig is used to route out a channel which will accommodate the implant. The technique allows the identification and location of sinuses, nerves, and compact bone and thus favors the placement of anchoring means in appropriate areas.

Abstract: Binding assay reagents for use in optical assay systems are disclosed. Assays, such as immunoassays, employing the reagent are also disclosed. The reagent is comprised of paired, associated polypeptides one of which has multiple optically active dye labels. The binding assay reagents exhibit enhanced binding activity over that of the dye labelled polypeptides alone and also enhance the sensitivity of the binding assay by providing increased amounts of optical label.

Abstract: Certain polyethyleneimines are used to coat solid carriers used in immunoassays to improve the sensitivity of the assay over what is obtained without the coating. Use of the invention in enzyme immunoassays yields sensitivities equal to that of radioimmunoassays. A post-coating is also used after the solid carrier has had a layer of capture molecule applied and before the assay is performed, to improve even further the sensitivity, reliability and dynamic range of the assay results.

Abstract: A composite living skin equivalent is described comprising an epidermal layer of cultured keratinocyte cells, a layer of non-porous collagen, and a dermal layer of cultured fibroblast cells in a porous cross-linked collagen sponge matrix. Preferably the non-porous collagen is Type 1, Type 3 or mixtures of Types 1 and 3 bovine collagen, which has been pepsin treated. A process for preparing the skin equivalent is described, as well as a test kit for in vitro testing of the skin equivalent. The skin equivalent has use for skin grafting as well as in vitro testing of the effects of various substances on skin.The questions raised in reexamination request No. 90/003,418, filed Apr. 25, 1994, have been considered and the results thereof are reflected in this reissue patent which constitutes the reexamination certificate required by 35 U.S.C. 307 as provided in 37 CFR 1.570(e).