7942 results about "In vivo" patented technology

An electrochemical analyte sensor having conductive traces on a substrate is used to determine a level of analyte in in vitro or in vivo analyte-containing fluids. The electrochemical analyte sensor includes a substrate and conductive material disposed on the substrate, the conductive material forming a working electrode. In some sensors, the conductive material is disposed in recessed channels formed in a surface of the sensor. An electron transfer agent and/or catalyst may be provided to facilitate the electrolysis of the analyte or of a second compound whose level depends on the level of the analyte. A potential is formed between the working electrode and a reference electrode or counter/reference electrode and the resulting current is a function of the concentration of the analyte in the fluid.

A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably three or four-layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer is overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited (third layer). An outer (fourth) layer is biocompatible.

Abstract of the Disclosure

An implantable analyte sensor including a sensing region for measuring the analyte and a non-sensing region for immobilizing the sensor body in the host. The sensor is implanted in a precisely dimensioned pocket to stabilize the analyte sensor in vivo and enable measurement of the concentration of the analyte in the host before and after formation of a foreign body capsule around the sensor. The sensor further provides a transmitter for RF transmission through the sensor body, electronic circuitry, and a power source optimized for long-term use in the miniaturized sensor body.

Self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric materials that may be implanted in vivo, and methods of making such materials are disclosed. The biopolymeric materials most preferably include reinforcing media, such as biocompatible fibrous or particulate materials. In use, the preformed, shaped biopolymeric materials may be applied to tissue in need of repair and then sealed around its edges with a liquid bioadhesive. In such a manner, repaired tissue which is capable of withstanding physiological pressures may be provided.

Abstract of the Disclosure

An implantable analyte sensor including a sensing region for measuring the analyte and a non-sensing region for immobilizing the sensor body in the host. The sensor is implanted in a precisely dimensioned pocket to stabilize the analyte sensor in vivo and enable measurement of the concentration of the analyte in the host before and after formation of a foreign body capsule around the sensor. The sensor further provides a transmitter for RF transmission through the sensor body, electronic circuitry, and a power source optimized for long-term use in the miniaturized sensor body.

Surgical accessories are presented in vivo and used by surgical tools in the surgical site to perform additional tasks without the need to remove the tools from the surgical site for tool change or instrument loading. Examples of in vivo accessories include fastening accessories such as surgical clips for use with a clip applier, single working member accessories such as a blade which can be grasped and manipulated by a grasping tool for cutting, sheath accessories that fit over working members of a tool, flow tubes for providing suction or introducing a fluid into the surgical site, and a retraction member resiliently biased to retract a tissue to expose an area in the surgical site for treatment. The accessories can be introduced into the surgical site by a dedicated accessory introducer, or can be supported on the body of a surgical tool inserted into the surgical site and be manipulated using another surgical tool in the surgical site. The accessory introducer can be resiliently biased to bias the accessories toward a predetermined position in the surgical site.

An implantable analyte-measuring device including a membrane adapted to promote vascularization and/or interfere with barrier cell layer formation. The membrane includes any combination of materials, architecture, and bioactive agents that facilitate analyte transport to provide long-term in vivo performance of the implantable analyte-measuring device.

An optical-based sensor for detecting the presence or amount of an analyte using both indicator and reference channels. The sensor has a sensor body with a source of radiation embedded therein. Radiation emitted by the source interacts with indicator membrane indicator molecules proximate the surface of the body. At least one optical characteristic of these indicator molecules varies with analyte concentration. For example, the level of fluorescence of fluorescent indicator molecules or the amount of light absorbed by light-absorbing indicator molecules can vary as a function of analyte concentration. In addition, radiation emitted by the source also interacts with reference membrane indicator molecules proximate the surface of the body. Radiation (e.g., light) emitted or reflected by these indicator molecules enters and is internally reflected in the sensor body. Photosensitive elements within the sensor body generate both indicator channel and reference channel signals to provide an accurate indication of the concentration of the analyte. Preferred embodiments are totally self-contained and are sized and shaped for use in vivo in a human being. Such embodiments preferably include a power source, e.g. an inductor, which powers the source of radiation using external means, as well as a transmitter, e.g. an inductor, to transmit to external pickup means the signal representing the level of analyte.

A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

A system for performing in vivo procedures is provided. The system may include a tool for performing an in vivo procedure. The tool may have an in vivo sensor for obtaining in vivo information; a functional element for performing an interventional or diagnostic in-vivo procedure; a processor in communication with the tool for receiving and optionally processing the in vivo information obtained by the tool and a monitor in communication with the processor for displaying the optionally processed in vivo information. The communication between the elements of the system may be wireless, or, optionally, wired.

Systems and methods for continuous measurement of a medicament in vivo are provided. In some embodiments, the system is configured to provide information associated with medicament titration and includes a continuous analyte sensor and a communication device. In some embodiments, the system is configured for continuous ambulatory drug testing, including an ambulatory host monitor having a continuous sensor, a location module, a processor module and a transmitter. In some embodiments, the system is configured for continuously monitoring a hormone level and includes a continuous hormone sensor and a communication device configured to output hormone information in real time. Yet another embodiment provides an analyte sensor for continuous monitoring of a host's nutritional status, and is configured for both continuous glucose detection and continuous albumin detection.

This disclosure provides several methods to generate nucleic acid mutations in vivo, for instance in such a way that no heterologous sequence is retained after the mutagenesis is complete. The methods employ integrative recombinant oligonucleotides (IROs). Specific examples of the described mutagenesis methods enable site-specific point mutations, deletions, and insertions. Also provided are methods that enable multiple rounds of mutation and random mutagenesis in a localized region. The described methods are applicable to any organism that has a homologous recombination system.

The present invention relates generally to systems and methods for measuring an analyte in a host. More particularly, the present invention relates to systems and methods for transcutaneous and subcutaneous measurement of glucose in a host.

A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

Disclosed are bioluminescent bioreporter integrated circuit devices that detect selected analytes in fluids when implanted in the body of an animal. The device comprises a bioreporter that has been genetically engineered to contain a nucleic acid segment that comprises a cis-activating response element that is responsive to the selected substance operably linked to a gene encoding a bioluminescent reporter polypeptide. In preferred embodiments, the target analyte is glucose, glucagons, or insulin. Exposure of the bioreporter to the target substance causes the response element to up-regulate the nucleic acid sequence encoding the reporter polypeptide to produce a luminescent response that is detected and quantitated. In illustrative embodiments, the bioreporter device is encapsulated on an integrated circuit that is capable of detecting the emitted light, processing the resultant signal, and then remotely reporting the results. Also disclosed are controlled drug delivery systems capable of being directly or indirectly controlled by the detection device that provide drugs such as insulin to the animal in reponse to the amount of target analyte present in the body fluids.

Abstract of the Disclosure

An implantable analyte sensor including a sensing region for measuring the analyte and a non-sensing region for immobilizing the sensor body in the host. The sensor is implanted in a precisely dimensioned pocket to stabilize the analyte sensor in vivo and enable measurement of the concentration of the analyte in the host before and after formation of a foreign body capsule around the sensor. The sensor further provides a transmitter for RF transmission through the sensor body, electronic circuitry, and a power source optimized for long-term use in the miniaturized sensor body.

A transcutaneous sensor device configured for continuously measuring analyte concentrations in a host is provided. In some embodiments, the transcutaneous sensor device 100 comprises an in vivo portion 160 configured for insertion under the skin 180 of the host and an ex vivo portion 170 configured to remain above the surface of the skin 180 of the host after sensor insertion of the in vivo portion. The in vivo portion may comprise a tissue piercing element 110 configured for piercing the skin 180 of the host and a sensor body 120 comprising a material or support member 130 that provides sufficient column strength to allow the sensor body to be pushable in a host tissue without substantial buckling. The ex vivo portion 170 may be configured to comprise (or operably connect to) a sensor electronics unit and may comprise a mounting unit 150. Also described here are various configurations of the sensor body and the tissue piercing element that may be used to protect the membrane of the sensor body.

Microneedle devices are provided for controlled sampling of biological fluids in a minimally-invasive, painless, and convenient manner. The microneedle devices permit in vivo sensing or withdrawal of biological fluids from the body, particularly from or through the skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The microneedle device includes one or more microneedles, preferably in a three-dimensional array, a substrate to which the microneedles are connected, and at least one collection chamber and/or sensor in communication with the microneedles. Preferred embodiments further include a means for inducing biological fluid to be drawn through the microneedles and into the collection chamber for analysis. In a preferred embodiment, this induction is accomplished by use of a pressure gradient, which can be created for example by selectively increasing the interior volume of the collection chamber, which includes an elastic or movable portion engaged to a rigid base. Preferred biological fluids for withdrawal and/or sensing include blood, lymph, interstitial fluid, and intracellular fluid. Examples of analytes in the biological fluid to be measured include glucose, cholesterol, bilirubin, creatine, metabolic enzymes, hemoglobin, heparin, clotting factors, uric acid, carcinoembryonic antigen or other tumor antigens, reproductive hormones, oxygen, pH, alcohol, tobacco metabolites, and illegal drugs.

A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

The invention provides novel methods by which adipose tissue, preadipocytes, and adipocytes can be generated for research purposes, and methods for identifying cell populations that can proliferate and differentiate into adipocytes in vivo. The invention further provides a means for the in vivo derivation of “designer” or “customized” adipose tissue, preadipocytes, and adipocytes. Also provided are methods for identifying agents that affect adipocytes and adipose tissue, as well as the agents themselves. In particular, the present invention allows for creation of tissues and cells that can be used to screen for agents useful for treating human disorders associated with adipose tissue, including obesity, metabolic syndrome, and diabetes.

Methods of monitoring and evaluating the status of a tumor undergoing treatment includes monitoring in vivo at least one physiological parameter associated with a tumor in a subject undergoing treatment, transmitting data from an in situ located sensor to a receiver external of the subject, analyzing the transmitted data, repeating the monitoring and transmitting steps at sequential points in time and evaluating a treatment strategy. The method provides dynamic tracking of the monitored parameters over time. The method can also include identifying in a substantially real time manner when conditions are favorable for treatment and when conditions are unfavorable for treatment and can verify or quantify how much of a known drug dose or radiation dose was actually received at the tumor. The method can include remote transmission from a non-clinical site to allow oversight of the tumor's condition even during non-active treatment periods (in between active treatments). The disclosure also includes monitoring systems with in situ in vivo biocompatible sensors and telemetry based operations and related computer program products.

In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful election of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

A dual sensor for the simultaneous amperometric monitoring of glucose and insulin, wherein the glucose probe is based on the biocatalytic action of glucose oxidase, and the insulin probe is based on the electrocatalytic activity of metal oxide. Further provided is an oxidase enzyme composite electrode with an internal oxygen-rich binder. The present invention also optionally includes metallizing components within the carbon paste to eliminate signals from interfering compounds. The present invention includes embodiments for both in vitro and in vivo uses.

The present invention provides a device for occluding an anatomical aperture, such as an atrial septal defect (ASD) or a patent foramen ovale (PFO). The occluder includes two sides connected by a central tube. The occluder is formed from a tube, which is cut to produce struts in each side. Upon the application of force, the struts deform into loops. The loops may be of various shapes, sizes, and configurations, and, in at least some embodiments, the loops have rounded peripheries. In some embodiments, at least one of the sides includes a tissue scaffold. The occluder further includes a catch system that maintains its deployed state in vivo. When the occluder is deployed in vivo, the two sides are disposed on opposite sides of the septal tissue surrounding the aperture and the catch system is deployed so that the occluder exerts a compressive force on the septal tissue and closes the aperture.

The present invention provides molecules, including IgGs, non-IgG immunoglobulin, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.

The present invention provides an implant capable of being cellularized in treatment of an injured organ or tissue in organisms. The present inventors found that a biocompatible implant comprising a biological molecule and a support is capable of being cellularized. The implant can be used instead of conventional implants which essentially comprise cells. The present invention provides a biocompatible implant comprising A) a biological molecule and B) a support. The present invention also provides A) a first layer having a rough surface, B) a rough surface; B) a second layer having a strength which allows the support to resist in vivo shock. The first layer is attached to the second layer via at least one point.

A stromal cell-based three-dimensional cell culture system is prepared which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue. For example, and not by way of limitation, the three-dimensional cultures can be used to form tubular tissue structures, like those of the gastrointestinal and genitourinary tracts, as well as blood vessels; tissues for hernia repair and/or tendons and ligaments; etc.

Molecular cross-linked gels comprise a variety of biologic and non-biologic polymers, such as proteins, polysaccharides, and synthetic polymers. Such molecular gels may be applied to target sites in a patient's body by extruding the gel through an orifice at the target site. Alternatively, the gels may be mechanically disrupted and used in implantable articles, such as breast implants. When used in vivo, the compositions are useful for inhibiting post-surgical spinal and other tissue adhesions, for filling tissue divots, tissue tracts, body cavities, surgical defects, and the like.

An in vivo biosensor disposed upon a subject comprising an electrochemical cell having a plurality of electrodes and a computer-controlled voltage source incorporating a potentiostat that is generative of a poise potential regime, which computer-controlled voltage source is operationally coupled to a computing device that: computes an output current whose magnitude is proportional to an amount of an analyte in a bodily fluid of the subject; and, adjusts the output current for drift due to biofouling at points in time greater than or equal to an induction period; and, outputs the amount of the analyte by transducing the adjusted output current. Methods and algorithms for adjusting the output current for drift due to biofouling are provided.

Disclosed herein are biointerface membranes including a macro-architecture and a micro-architecture co-continuous with and bonded to and/or located within at least a portion of the macro-architecture. The macro- and micro-architectures work together to manage and manipulate the high-level tissue organization and the low-level cellular organization of the foreign body response in vivo, thereby increasing neovascularization close to a device-tissue interface, interfering with barrier cell layer formation, and providing good tissue anchoring, while reducing the effects of motion artifact, and disrupting the organization and/or contracture of the FBC. The biointerface membranes of the preferred embodiments can be utilized with implantable devices such as devices for the detection of analyte concentrations in a biological sample (for example, from a body), cell transplantation devices, drug delivery devices, electrical signal delivering or measuring devices, and/or combinations thereof.