Abstract: Apparatuses and methods for pumping fluids such as fluid medications are disclosed. In illustrative embodiments of the invention, the architectural geometry of one or more fluid containing chambers within a fluid delivery device is constructed to incorporate design parameters that function to control movement of fluids within the device. Typical embodiments of the invention provide osmotic pumps that use such elements to control various fluid delivery parameters.

Abstract: According to one embodiment, a method of controlling a plurality of treatment dosages for Hepatitis C includes: setting a first dosage level to cause a viral load of a subject user to reduce at a rate over time; determining, after setting the first dosage level, if the rate of the viral load reduction changes over time by a first threshold; setting a second dosage level in response to determining that the rate of the viral load reduction changes by the first threshold; determining, after setting the second dosage level, if the rate of the viral load reduction changes over time by a second threshold; setting a third dosage level in response to determining that the rate of the viral load reduction changes by the second threshold; and maintaining the second dosage level in response to determining that the rate of the viral load reduction has not changed by the second threshold.

Abstract: A long term analyte sensor for measuring at least one analyte in the body of a user and which includes a housing, a plurality of analyte contacting sensor elements and at least one structure for relaying information away from the sensor. This plurality of analyte contacting sensor elements are typically disposed in an array. The analyte sensor further includes at least one sensor protection membrane that is controllable in a manner such that sensor elements may be activated (e.g. exposed to the external environment) at different times so as to extend the useful life of the sensor. In illustrative analyte sensors, the analyte is glucose.

Abstract: Embodiments of the invention include polypeptide formulations and methods for making, using and characterizing them. Embodiment of the invention include stabilized polypeptide formulations, for example stable glucose oxidase formulations that can be used with glucose sensors used in the management of diabetes. Another embodiment of the invention includes methods to characterize the concentration of nonionic surfactants in stabilized polypeptide formulation for example stable insulin formulations that can be used in the treatment of diabetes.

Abstract: Apparatuses and methods for pumping fluids such as fluid medications are disclosed. Embodiments of the invention provide an osmotic pump fluid delivery apparatus including elements designed to control the fluid delivery rate. Typical embodiments of the invention include an arrangement of elements such as solute reservoirs that can manipulate the solute concentrations within an inner osmotic compartment or compartments of an osmotic pump so as to control fluid delivery from the pump. Other embodiments include sealed electro-osmotic pumps that do not discharge ions into the surroundings or require water from an external source. These embodiments of the invention provide new ways to control fluid delivery in apparatuses that employ osmotic processes to function.

Abstract: Embodiments of the invention provide analyte sensors having elements designed to modulate their chemical reactions as well as methods for making and using such sensors. In certain embodiments of the invention, the sensor includes a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety.

Abstract: A pharmaceutical composition includes at least two of agents I)-iii), wherein agent i) is selected from the group consisting of an insulin, an insulin analog, a physiologically active fragment of said insulin and a physiologically active fragment of said insulin analog, agent ii) is selected from the group consisting of an insulin-related peptide, an insulin-related peptide analog, a physiologically active insulin-related peptide fragment and a physiologically active insulin-related peptide analog fragment, and agent iii) is an insulin sensitizer.

Abstract: A reusable analyte sensor site for use with a replaceable analyte sensor for determining a level of an analyte includes a site housing material and a resealable insertion site coupled to one end of the site housing material. Preferably, the site housing material is formed to have an interior cavity with an opening. The site housing material is selected to promote tissue ingrowth and vascularization, and yet be free of tissue ingress. Also, the site housing material permits the analyte to pass through the site housing material to the interior cavity to permit measurement by the replaceable analyte sensor. The resealable insertion site provides a for inserting the replaceable analyte sensor into the interior cavity of the site housing material.

Abstract: Embodiments of the invention include polypeptide formulations and methods for making, using and characterizing them. Embodiment of the invention include stabilized polypeptide formulations, for example stable glucose oxidase formulations that can be used with glucose sensors used in the management of diabetes. Another embodiment of the invention includes methods to characterize the concentration of nonionic surfactants in stabilized polypeptide formulation for example stable insulin formulations that can be used in the treatment of diabetes.

Abstract: A reusable analyte sensor site for use with a replaceable analyte sensor for determining a level of an analyte includes a site housing and a resealable insertion site coupled to one end of the site housing. Preferably, the site housing is formed to have an interior cavity, and includes an outer membrane made of a material selected to promote vascularization and having a first pore size, and an inner membrane made of a material selected to be free of tissue ingress. Also, the site housing permits the analyte to pass through the site housing to the interior cavity to permit measurement by the replaceable analyte sensor. The resealable insertion site is provided for inserting the replaceable analyte sensor into the interior cavity of the site housing.

Abstract: Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. These biosensor molecules address the problem of obtaining fluorescence emission at wavelengths greater than about 500 nm. Biosensor molecules generally include an (1) an acridine-based fluorophore, (2) a linker moiety and (3) a boronate substrate recognition/binding moiety, which binds polyhydroxylate analytes, such as glucose. These biosensor molecules further include a “switch” element that is drawn from the electronic interactions among these submolecular components. This fluorescent switch is generally “off” in the absence of bound polyhydroxylate analyte and is generally “on” in the presence of bound polyhydroxylate analyte. Thus, the reversible binding of a polyhydroxylate analyte essentially turns the fluorescent switch “on” and “off”.

Abstract: A sensor and method of making the same for implantation in a body that includes a substrate with notches cut in the substrate to form a necked down region in the substrate; and at least one sensor electrode formed from one or more conductive layers. Preferably, the thickness of the substrate ranges from approximately 25? to 350?, but the thickness of the substrate can range from 5? to 750?. The sensor may be incorporated in to a sensor assembly includes a slotted needle having a slot. The notches creating the necked down region allow the substrate to slide into the slotted needle, which that has the slot narrow enough to permit passage of the necked down region. However, a non-necked down region of the substrate is prevented from pulling out of the slotted needle through the slot. The slot of the slotted needle may also permit the necked down region of the substrate to slide down the slot.

Abstract: A circuit protection device for protection of sensitive components during high energy radiation sterilization that includes a support substrate and a protective housing. The substrate supports the sensitive components. The protective housing is hermetically coupled to the support substrate to seal the sensitive components within the protective housing. Preferably, the protective housing stops high energy used in the high energy sterilization from damaging the sensitive components from a predetermined exposure level of high energy sterilization. The circuit protection device may further include a protective conductor that is coupled to the support substrate on a side which is opposite the protective housing to prevent high energy from entering the opposite side of the support substrate.

Abstract: An improved pump, reservoir and reservoir piston are provided for controlled delivery of fluids. A motor is operably coupled to a drive member, such as a drive screw, which is adapted to advance a plunger slide in response to operation of the motor. The plunger slide is removably coupled to the piston. The piston comprises a first member and a second member. The first member has an external proximate side and an external distal side. The external proximate side is adapted to contact the fluid and is made of a material having a first stiffness. The second member has a first side and a second side and is at least partially disposed within the first member. The first side of the second member is adjacent to the external proximate side of the first member and is made of a material having a stiffness which is greater than the first stiffness.

Abstract: Embodiments of the invention provide polymer coated implantable medical devices having a bioactive material posited in or on at least a portion of the coating layer, wherein the coating layer provides for the controlled release of the bioactive material from the coating layer. Preferably, the medical device is an intravascular stent.

Abstract: A reusable analyte sensor site for use with a replaceable analyte sensor for determining a level of an analyte includes a site housing and a resealable insertion site coupled to one end of the site housing. Preferably, the site housing is formed to have an interior cavity, and includes an outer membrane made of a material selected to promote vascularization and having a first pore size, and an inner membrane made of a material selected to be free of tissue ingress. Also, the site housing permits the analyte to pass through the site housing to the interior cavity to permit measurement by the replaceable analyte sensor. The resealable insertion site is provided for inserting the replaceable analyte sensor into the interior cavity of the site housing.

Abstract: A method for optimizing the function of a sensor device, wherein a protein, such as an enzyme, is immobilized in a matrix, the matrix is adhered to the device and the protein comprises at least one reactive moiety. The immobilized protein is reacted with a redox agent, wherein the reacting increases the stability of the immobilized protein. The device can be sterilized after the reacting step. A typical device comprises a glucose sensor in which glucose oxidase is embedded in a polymer matrix adhered to the device, the reactive moiety comprises FADH2, and the redox agent is the reducing agent, sodium borohydride. Also provided is a method of measuring an analyte in a tissue of a subject comprising introducing a sensor device of the invention into the tissue of the subject and detecting the signal generated by the protein. The amount of signal corresponds to the amount of analyte.

Abstract: In a fluid delivery system for delivering a fluid into an individual's body, a leak detection system indicates that the fluid has leaked outside a normal fluid path of the fluid delivery system, such as near an infusion site or a fluid-filled reservoir. Preferably, the leak detection system includes a chemical positioned near the infusion site that reacts with preservatives in the leaking fluid to generate a highly visible, brightly colored, chemical complex. Alternatively, mechanical, electro-optical, electrochemical, electrical or other chemical systems may be used to detect the presence of fluid that is leaking near the infusion site. Further, the leak detection systems may be used to detect the presence of fluid that is leaking from or near other locations within the fluid delivery system, such as on or near a fluid-filled reservoir, or a flexible tube coupled between the reservoir and the infusion site.

Abstract: Embodiments of the invention are directed to a method of estimating the physical stability of a protein formulation. A particular embodiment of the invention places the protein formulation under an agitational stress that causes the protein to aggregate at an accelerated rate. In one embodiment, the change in protein aggregation is monitored spectroscopically using Thioflavin-T. Embodiments of the invention then utilize a survival curve analysis to ascertain the relative physical stability of the different protein formulations under study. This method was used to develop novel surfactant-stabilized insulin formulations in a rapid, cost efficient manner, thus illustrating the utility of the inventive method to the discovery and development of pharmaceutical protein formulations.

Abstract: A reusable analyte sensor site for use with a replaceable analyte sensor for determining a level of an analyte includes a site housing material and a resealable insertion site coupled to one end of the site housing material. Preferably, the site housing material is formed to have an interior cavity with an opening. The site housing material is selected to promote tissue ingrowth and vascularization, and yet be free of tissue ingress. Also, the site housing material permits the analyte to pass through the site housing material to the interior cavity to permit measurement by the replaceable analyte sensor. The resealable insertion site provides a for inserting the replaceable analyte sensor into the interior cavity of the site housing material.