Maxim Integrated Products, Inc.

Pacific Diabetes Technologies Inc

Harris Corporation

Robert S Cargill

William Kenneth Ward

Gabriel Heinrich

Thomas Seidl

Sheila Benware

Mark Vreeke

Joseph D Kowalski

Gary E Mueller

A device for delivery of an insulin or insulin analog formulation and measurement of subcutaneous glucose concentration may comprise a hollow tube, and an amperometric glucose sensor located proximal to a distal end of the hollow tube. The amperometric glucose sensor may comprise a redox mediator and an enzyme comprising glucose oxidase or glucose dehydrogenase. An applied bias potential may allow an electrode layer of the amperometric glucose sensor to undergo substantially no electropolymerization of an excipient of the insulin or insulin analog formulation during continuous operation of amperometric glucose sensor. A sensitivity of the amperometric glucose sensor to the subcutaneous glucose concentration may be maintained in presence of the insulin or insulin analog formulation.

Measurement of glucose near an insulin delivery catheter by minimizing the adverse effects of insulin preservatives: alternative ligands and redox mediator metals

A method may comprise (a) inserting an insulin delivery device subcutaneously into a body of a subject, which comprises an amperometric glucose sensor comprising an electrode layer comprising an indicating electrode and underlying a redox-catalytic layer comprising a redox mediator; (b) using said insulin delivery device to deliver an insulin formulation (e.g., comprising a phenol or cresol excipient) subcutaneously to said subject; and (c) using said amperometric glucose sensor to measure a subcutaneous glucose concentration, which comprises using said redox-catalytic layer to allow electron transfer from subcutaneous glucose to said indicating electrode sufficient to cause a response of said amperometric glucose sensor at an applied bias potential of no more than +250 millivolts, wherein (b) and (c) are performed at the same time for at least one hour, while maintaining a sensor sensitivity of at least 50% of an initial sensor sensitivity for up to one hour.

Methods and systems for insulin delivery and glucose measurement

In an aspect, the present disclosure provides a method comprising: (a) positioning an insulin delivery device on a body of a subject via a single puncture site in said body of said subject; (b) using said insulin delivery device to deliver an insulin or insulin analog formulation to said subject via said single puncture site; and (c) using a sensor of said insulin delivery device to measure a glucose concentration in said body of said subject via said single puncture site, wherein (b) and (c) are performed at substantially the same time for a time period of at least 1 hour subsequent to said positioning in (a), while maintaining a sensitivity of said sensor of at least 50% of an initial sensitivity of said sensor.

This disclosure teaches the concept, and method of creating, a dual use device intended for persons who take insulin. In one embodiment, the novel device is an insulin delivery cannula, the outer wall of which contains electrodes, chemical compounds and electrical interconnects that allow continuous glucose sensing and delivery of data to a remote device. Heretofore, the main problem in attempting to sense glucose at the site of insulin delivery has been the high current resulting from oxidation by the sensor of the preservatives in the insulin formulations. One means of eliminating these interferences is to poise the indicating electrode(s) of the sensor at a bias sufficiently low to avoid the signal from oxidation of the preservatives. One way of obtaining a glucose signal at a low bias is to use an osmium-ligand-polymer complex instead of conventional hydrogen peroxide sensing. Another is to use a size exclusion filter located in line with the insulin delivery tubing in order to remove the smaller phenolic preservative molecules while allowing the larger insulin molecules to pass unimpeded. These filtration concepts can also be more broadly applied, that is, the general concept of removal of unwanted drug formulation excipients from a drug delivery system.

Measurement of glucose in an insulin delivery catheter by minimizing the adverse effects of insulin preservatives

High efficiency, low noise frequency tripler and method that generates an enhanced third harmonic of a frequency and suppresses the fundamental frequency component in the tripler output. The method comprises multiplying a constant plus a twice frequency component by a square wave at the fundamental frequency, such as by a modulator. The amplitude of the twice frequency component relative to the constant and the phase of the twice frequency component relative to the phase of the square wave are chosen to reduce the fundamental frequency component and enhance the third harmonic in the tripler output. An implementation using a differential Colpitts oscillator is disclosed.

High efficiency, low noise frequency tripler and method

Log-linear variable gain amplifiers and amplifier control apparatus and methods providing temperature compensated log-linear gain characteristics with a wide range of control for a current steered variable gain amplifier. The invention provides the sum of scaled linear and exponential terms, proportional to absolute temperature and responsive to an input control voltage. The sum of these terms is applied to a current steered variable gain amplifier to provide the desired log-linear variable gain control. Various embodiments are disclosed.

Log-linear variable gain amplifiers and amplifier control apparatus and

High efficiency base current helper to improve the accuracy of current mirrors particularly useful for current mirror utilizing relatively low beta bipolar junction transistors. The high efficiency base current helper utilizes two feedback loops, the first attempting to force the bias rail voltage to a mirror reference voltage and the second sensing excess current in the first loop and forcing it to match a reference level. This causes the first loop to be biased with no more excess current than desired for any process or temperature condition yielding dramatic reductions in wasted bias current. A specific exemplary embodiment is disclosed.

High efficiency base current helper

Hybrid differential pairs and methods of their hybridization by connecting and operating in parallel a degenerated differential pair with a multitanh. Proper matching of the degenerated differential pair and the multitanh results in higher linearity levels than can be attained with either approach individually. Also, the hybrid benefits from reduced process variation when compared with prior multitanh solutions. Increased gain, increased linearity, reduced noise and reduced supply current can all be achieved in a manufacturable fashion using the invention.

Hybrid differential pairs for flat transconductance

Low power, high linearity log-linear control method and apparatus wherein a master log-linear cell generates a control voltage that is buffered and applied to a slave log-linear cell. By breaking this function up into two pieces, the control loop characteristics are isolated from the signal path. Low impedance buffers can be used to drive the slave log-linear cell control ports, independent of the control loop, providing improved gain control range and linearity. This log-linear control is of particular value in applications that require low harmonic distortion and high gain control range in power or pin-constrained applications. Details of the method are disclosed.

Low power, high linearity log-linear control method and apparatus

A circuit and method for stabilizing a common mode voltage in a differential circuit provides a desired common mode voltage V.sub.cm to control terminals of two transistors which provide the variable resistance for setting the common mode voltage. V.sub.cm is sampled between load resistors R.sub.L connecting operating terminals of the two transistors and applied directly to their control terminals. A known common mode current I.sub.cm is accepted by each transistor, leaving a differential current I.sub.d to flow through load resistors R.sub.L. The circuit and method find application in a variety of uses, including transconductance and transresistance amplifiers and automatic gain control circuits.

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Portland, OR, United States of America

Robert S Cargill