PORTLAND, OR, United States

Pacific Diabetes Technologies

www.pacificdt.com
PORTLAND, OR, United States
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Ward W.K.,Pacific Diabetes Technologies | Ward W.K.,Oregon Health And Science University | Heinrich G.,Pacific Diabetes Technologies | Breen M.,Pacific Diabetes Technologies | And 11 more authors.
Diabetes Technology and Therapeutics | Year: 2017

Background: Labeling prohibits delivery of insulin at the site of subcutaneous continuous glucose monitoring (CGM). Integration of the sensing and insulin delivery functions into a single device would likely increase the usage of CGM in persons with type 1 diabetes. Methods: To understand the nature of such interference, we measured glucose at the site of bolus insulin delivery in swine using a flexible electrode strip that was laminated to the outer wall of an insulin delivery cannula. In terms of sensing design, we compared H2O2-measuring sensors biased at 600 mV with redox mediator-type sensors biased at 175 mV. Results: In H2O2-measuring sensors, but not in sensors with redox-mediated chemistry, a spurious rise in current was seen after insulin lis-pro boluses. This prolonged artifact was accompanied by electrode poisoning. In redox-mediated sensors, the patterns of sensor signals acquired during delivery of saline and without any liquid delivery were similar to those acquired during insulin delivery. Conclusion: Considering in vitro and in vivo findings together, it became clear that the mechanism of interference is the oxidation, at high bias potentials, of phenolic preservatives present in insulin formulations. This effect can be avoided by the use of redox mediator chemistry using a low bias potential. © 2017, Mary Ann Liebert, Inc.


Ward W.K.,Pacific Diabetes Technologies | Castle J.R.,Pacific Diabetes Technologies | Castle J.R.,Oregon Health And Science University | Jacobs P.G.,Pacific Diabetes Technologies | And 2 more authors.
Journal of Diabetes Science and Technology | Year: 2014

Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome. © 2014 Diabetes Technology Society.


Du X.,Oregon State University | Durgan C.J.,Oregon State University | Matthews D.J.,Oregon State University | Motley J.R.,Oregon State University | And 10 more authors.
ECS Journal of Solid State Science and Technology | Year: 2015

This study details the use of printing and other additive processes to fabricate a novel amperometric glucose sensor. The sensor was fabricated using a Au coated 12.7 μm thick polyimide substrate as a starting material, where micro-contact printing, electrochemical plating, chloridization, electrohydrodynamic jet (e-jet) printing, and spin coating were used to pattern, deposit, chloridize, print, and coat functional materials, respectively. We have found that e-jet printing was effective for the deposition and patterning of glucose oxidase inks with lateral feature sizes between ∼5 to 1000 μm in width, and that the glucose oxidase was still active after printing. The thickness of the permselective layer was optimized to obtain a linear response for glucose concentrations up to 32 mM and no response to acetaminophen, a common interfering compound, was observed. The use of such thin polyimide substrates allow wrapping of the sensors around catheters with high radius of curvature ∼250 μm, where additive and microfabrication methods may allow significant cost reductions. © 2015 The Electrochemical Society.


Patent
Pacific Diabetes Technologies and The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Orego | Date: 2014-06-13

A sensing assembly (10), including a body (12) and one or more first indicating electrodes disposed on the body (26). The first indicating electrodes include an electrochemically active layer (32) and a layer (38) of an active functioning enzyme of a first enzyme type on top of the electrochemically active layer. Also, one or more second indicating electrodes (24) are disposed on the body and include an electrochemically active layer (32) and a layer (36) of an inactivated enzyme of the first enzyme type on top of the electrochemically active layer. A reference electrode (22) is also disposed on the body. Finally, an electrical and data processing system (18) is adapted to bias the electrodes and measure electrical signals from the electrodes, and uses said signals to determine an analyte concentration and communicates the analyte concentration to a location apart from the first and second indicating electrodes.


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.


Patent
Pacific Diabetes Technologies | Date: 2015-03-24

A durable device is disclosed. This device allows concurrent measurement of an analyte such as glucose, and delivery of a glucose-active drug such as insulin. In order to carry out both functions, only one tubular structure is necessary. In one embodiment of the invention, wires or rings of platinum, gold, or carbon which serve as indicating electrodes are circumferentially disposed around a tubular reference electrode. In an embodiment, the reference electrode is made up of a hollow silver or silver-coated tube. The hollow characteristic is necessary in order to allow concurrent delivery of insulin or other drug through the lumen. In order to optimize sensor accuracy, there are multiple individually-addressable indicating electrodes circumferentially disposed around the shaft.


Patent
Pacific Diabetes Technologies | Date: 2015-12-31

This invention pertains to the concept of creating a strip that contains one or more amperometric biosensing electrodes and integrating this strip into the outer wall of a hollow catheter (cannula). The electrodes can be used for continuous sensing of an analyte such as glucose and the hollow lumen can be used concurrently for delivery of a drug such as insulin. There is a risk for electrode films to break apart during impact. However, if there is a metallic foil beneath (underlying) the thin film metal electrodes, durability and fatigue resistance are markedly improved. The term foil indicates a metal layer that is 2-15 m in thickness. Foils can be created by rolling, hammering, electroplating, printing, or vacuum-deposition. A foil-polymer laminate is suitable as a substrate because it permits low-cost patterning and assembly into a durable, fatigue-resistant sensor.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 222.74K | Year: 2013

DESCRIPTION (provided by applicant): Type 1 diabetes often leads to short-term and long-term complications which impair quality of life. Though many research groups are developing versions of an artificial endocrine pancreas (AP) system, current systems require at least one hormone delivery insertion site and at least one glucose sensor site. This complexity limits commercial viability and potential acceptance by patients. The risk of bacterial colonization and infection from the multiplicity of insertion sites merits reduction of the number of inserted devices. In this project, we propose to create a novel artificial pancreas technology that integrates into a single wearable device the following three elements: (1) an intelligent hormone delivery catheterwhose outer wall contains a multi-site amperometric continuous glucose monitor (CGM), the development of which is funded elsewhere; (2) a wireless sensor module with a transceiver, battery, and data acquisition unit; and (3) a quick connect/disconnect portthat attaches to the sensing catheter and to an insulin delivery tubing connector. This combination device is intended to allow more freedom of movement and increase patient comfort. We prefer the subcutaneous site over the intradermal site for sensing and hormone delivery because of a lower risk for catheter dislodgement. In order to avoid the need for perfusion- and waste fluid compartments, we prefer direct amperometry over microdialysis. In a separate project, we are using solid state design and microfabrication techniques to create the sensing catheter by placing a flat amperometric sensing array on a flexible polyimide substrate which will then be wrapped into a tube. In this application, we propose to develop the unified wearable device that will allow clinical use of the sensing catheter. This three-part device will connect to an insulin delivery line and will include an analog sensor electrical interface and a Bluetooth SMART transceiver. The combination will permit the commercial introduction of an intelligent infusion set that can connect to an insulin-only pump or an insulin/glucagon pump such as the one under development by Tandem Diabetes as funded by JDRF. This pump will likely incorporate a Bluetooth wireless interface capable of communication with our sensor module. We also propose to create an early prototype insertion device and carry out preliminary tests of the system in swine. In these tests, the three-part device with sensing catheter will be inserted subcutaneously into anesthetized pigs in order to allow (1) radiographic assessment of the catheter insertion angle and depth; (2) verification of telemetric data transmission to a remote smart phone receiver; and (3) leak-free delivery of insulin. Pig study costs will largely be covered elsewhere. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The potential for wide acceptance of artificial pancreas systems is currently limited due in part to the need for multiple device insertion sites for sensor and pump sets. Pacific Diabetes Technologies is developing a dual function catheter in which glucose sensing and hormone delivery capabilities are combined. In this application, we propose to design and create a multi- part structure that will attach to the sensing catheter, transmitsensor data to a remote receiver, and interface with an insulin delivery connector.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 224.15K | Year: 2016

DESCRIPTION provided by applicant People with Type diabetes T D are at high risk for acute and chronic complications that can be minimized by concurrent use of continuous insulin delivery and continuous glucose monitoring CGM However the use of two percutaneous devices is cumbersome and seldom used We are developing a single subcutaneous catheter that serves both as a CGM and as an insulin cannula The electrodes and chemicals necessary for CGM are disposed on the outer wall of the cannula Based on recent animal studies we now know that the electroactivity of insulin preservatives is incompatible with conventional amperometric sensing technology In order to minimize interference from these preservatives after bolus delivery we will work with an organic chemist to identify sensing chemistries that allow detection of glucose oxidation at low redox potentials where the preservatives have minimal to no electroactivity The chemistry will either be a a redox mediator coordinated within a pyridine or imidazole based ligand or b a horseradish peroxidase based system designed to measure reduction of H O at negative potentials Electrochemical screening will take place using solution phase cyclic voltammetry The chemistry will be optimized to immobilize sensing layers and create a durable sensor The most promising compounds will be immobilized on Au or Pt indicating electrodes followed by crosslinking to glucose oxidase The final choice of solid phase chemistry will be based in large part on maximizing the glucose cresol response ratio ensuring stable function for at least days and avoidance of leaching If a redox mediator is chosen the outer membrane will be selected to have very low permeability to oxygen due to the fact that oxygen competes with redox mediators An existing permeation cell will be used to measure oxygen and glucose membrane permeability In Yucatan pigs we will assess preservative interference during insulin delivery and days after sensor insertion The purpose of the second study at days is to determine if sensor sensitivity declines over this period which would suggest loss of reagents from the sensor In summary to minimize device burden in T D we will develop and test a sensing chemistry that avoids the large interference one sees from preservatives during insulin boluses thus allowing CGM and insulin delivery via a single catheter PUBLIC HEALTH RELEVANCE In this project a dual use catheter will be developed and tested in pigs The outer wall of this device will be used to continuously monitor glucose and the inner lumen will be a conduit through which insulin will be continuously infused The successful development of such a device would benefit Type diabetes T D patients who are at high risk for disease of the eyes kidneys nerves feet and cardiovascular system Despite the known efficacy of continuous subcutaneous insulin infusion CSII and continuous glucose monitoring CGM less than of people in the US with T D use both technologies concurrently This failure can be explained in large part by the inconvenience and body image threat from using two percutaneous andquot through the skinandquot devices Currently available glucose sensors are not able to measure glucose at the site of insulin delivery because the preservatives in insulin cause major interference in the glucose measurement In this project an alternative chemistry that avoids the preservative induced interference will be developed To the extent that the two functions can be combined into a single unified catheter it is likely that the concurrent usage of CGM and CSII would increase substantially This increased usage would be expected to reduce the incidence of acute and chronic diabetes complications


PubMed | Oregon State University and Pacific Diabetes Technologies
Type: Journal Article | Journal: ECS journal of solid state science and technology : JSS | Year: 2015

This study details the use of printing and other additive processes to fabricate a novel amperometric glucose sensor. The sensor was fabricated using a Au coated 12.7 m thick polyimide substrate as a starting material, where micro-contact printing, electrochemical plating, chloridization, electrohydrodynamic jet (e-jet) printing, and spin coating were used to pattern, deposit, chloridize, print, and coat functional materials, respectively. We have found that e-jet printing was effective for the deposition and patterning of glucose oxidase inks with lateral feature sizes between ~5 to 1000 m in width, and that the glucose oxidase was still active after printing. The thickness of the permselective layer was optimized to obtain a linear response for glucose concentrations up to 32 mM and no response to acetaminophen, a common interfering compound, was observed. The use of such thin polyimide substrates allow wrapping of the sensors around catheters with high radius of curvature ~250 m, where additive and microfabrication methods may allow significant cost reductions.

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