A wearable, self-contained drug infusion device is disclosed that achieves the precise flow rate control needed for dose critical drugs. Valve or pump structures may be used with thermal flow sensors and closed-loop control circuits for providing the desired flow rate control. The device may have a two-part construction, where the electronic components are housed in a reusable portion and the fluid delivery components are housed in a separable disposable portion. This reduces the effective cost of the device to the user, assures sterility of the drug, and prevents fluid communication of the reusable portion by confining the fluid flow path to the disposable portion. The invention may include a wireless unit for controlling the operation of the drug infusion device. The wireless unit may communicate with the reusable portion using radio frequency (RF) methods, optical infrared (IR) methods, or other methods.

Wearable, self-contained drug infusion device

Mechanisms for inhibition of sulfate reduction and methane production in the zone of Fe(III) reduction in sediments were investigated. Addition of amorphic iron(III) oxyhydroxide to sediments in which sulfate reduction was the predominant terminal electron-accepting process inhibited sulfate reduction 86 to 100%. The decrease in electron flow to sulfate reduction was accompanied by a corresponding increase in electron flow to Fe(III) reduction. In a similar manner, Fe(III) additions also inhibited methane production in sulfate-depleted sediments. The inhibition of sulfate reduction and methane production was the result of substrate limitation, because the sediments retained the potential for sulfate reduction and methane production in the presence of excess hydrogen and acetate. Sediments in which Fe(III) reduction was the predominant terminal electron-accepting process had much lower concentrations of hydrogen and acetate than sediments in which sulfate reduction or methane production was the predominant terminal process. The low concentrations of hydrogen and acetate in the Fe(III)-reducing sediments were the result of metabolism by Fe(III)-reducing organisms of hydrogen and acetate at concentrations lower than sulfate reducers or methanogens could metabolize them. The results indicate that when Fe(III) is in a form that Fe(III)-reducing organisms can readily reduce, Fe(III)-reducing organisms can inhibit sulfate reduction and methane production by outcompeting sulfate reducers and methanogens for electron donors.

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Competitive mechanisms for inhibition of sulfate reduction and methane production in the zone of ferric iron reduction in sediments.

Fundamental Principles. L.W. Jelinsky, Experimental Methods. The Chemical Shift. Coupling of Nuclear Spins. Nuclear Relaxation and Chemical Rate Processes. P.A. Mirau and F.A. Bovey, Two-Dimensional Nuclear Magnetic Resonance Spectroscopy. Macromolecules. NMR of Solids. F.A. Bovey, L.W. Jelinsky, P.A. Mirau, Special Topics. Appendixes. Author Index. Subject Index.

Nuclear magnetic resonance spectroscopy.

Physical methods for gene transfer: Improving the kinetics of gene delivery into cells

Over the last 5 years, physical methods of plasmid delivery have revolutionized the efficiency of nonviral gene transfer, in some cases reaching the efficiencies of viral vectors. In vivo electroporation dramatically increases transfection efficiency for a variety of tissues. Other methods with clinical precedent, pressure-perfusion and ultrasound, also improve plasmid gene transfer. Alternatives such as focused laser, magnetic fields and ballistic (gene gun) approaches can also enhance delivery. As plasmid DNA appears to be a safe gene vector system, it seems likely that plasmid with physically enhanced delivery will be used increasingly in clinical trials.

Gene Therapy Progress and Prospects: Electroporation and other physical methods

Indirect photometric chromatography

Although particle-mediated gene transfer technology (gene gun) has been applied for gene transfer to external tissues, the application of this technology to other tissues has met with limited success. Here we report the development of a new design of a gene gun that uses helium discharge to propel DNA-coated gold beads that are suspended in liquid. Higher discharge pressures allow for the delivery of DNA to deeper tissues. Using the new gene gun to deliver a luciferase expression plasmid resulted in higher levels of gene expression in the skin than observed with conventional guns, as well as in subdermal tissues, including subcutaneous tumors. Even when using as little as 125 ng of DNA, gene expression in skin and muscle reached its peak level at 24 hr postbombardment and remained for at least 1 week. The use of a LacZ expression plasmid showed that gene expression was distributed throughout the skin with no observable pathology. The new gene gun was used to deliver a model tumor rejection antigen (a modified human papilloma virus [HPV] E7 gene) to mice. All of the treated animals developed protective immunity against HPV-positive tumors. These results demonstrate that our new design can be used in standard gene gun applications and extends the reach of gene gun technology to tissues that were previously unavailable.

Gene transfer to subdermal tissues via a new gene gun design.

Utilisation d'un seul chromatographe pour la separation et l'analyse des anions et cations par l'introduction de la chromatographie photometrique indirecte avec des colonnes echangeuses d'anions ou cations et un detecteur a deux longueurs d'ondes

Simultaneous independent analysis of anions and cations using indirect photometric chromatography

A novel method uses no orifices or moving parts but rather dual glass-encapsulated thermistor probes to impart a heat pulse into the flowing liquid and to detect its arrival down-stream. Detection triggers a subsequent upstream thermal pulse and the cycle repeats. The time of flight of the warmed zone is thus inversely related to liquid flow and the digital output is inherently computer compatible. A key to achieving dependable operation is electronic double time differentiation of sensor output to reject characteristically slower ambient thermal drift and to minimize response time in preparation for subsequent pulse detection. The meter is capable of measuring liquid flow rates between 0.1 and 10.0 cm/sup 3//min with a precision of at least 0.1% (sigma). The flow cell's glass and inert plastic composition makes it highly corrosion resistant. Besides its general utility in flow metering, this method is especially well suited to high performance liquid chromatography applications. 6 figures, 1 table.

Thermal pulse time-of-flight liquid flow meter

A liquid chromatographic method and apparatus is disclosed which employs an improved pump not requiring driven pistons or sliding seals. The pump comprises at least one length of tubing forming a chamber disposed between first and second check valves, controllable heating means to periodically heat liquid in said chamber effective to pump relatively low volumes of liquid from the chamber at relatively high pressures, means for measuring the pressure developed by the pump, and control means to increase and decrease the amount of heat imparted to the liquid to maintain the pump operation at a controlled pressure setpoint.

Theodore E. Miller

Papers

Indirect photometric chromatography

Gene transfer to subdermal tissues via a new gene gun design.

Simultaneous independent analysis of anions and cations using indirect photometric chromatography

Thermal pulse time-of-flight liquid flow meter

Liquid chromatographic pump