Entity

Time filter

Source Type

Storrs Mansfield, CT, United States

Vaddiraju S.,University of Connecticut | Vaddiraju S.,Biorasis Inc. | Wang Y.,University of Connecticut | Qiang L.,University of Connecticut | And 2 more authors.
Analytical Chemistry | Year: 2012

Biofouling and tissue inflammation present major challenges toward the realization of long-term implantable glucose sensors. Following sensor implantation, proteins and cells adsorb on sensor surfaces to not only inhibit glucose flux but also signal a cascade of inflammatory events that eventually lead to permeability-reducing fibrotic encapsulation. The use of drug-eluting hydrogels as outer sensor coatings has shown considerable promise to mitigate these problems via the localized delivery of tissue response modifiers to suppress inflammation and fibrosis, along with reducing protein and cell absorption. Biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres, encapsulated within a poly (vinyl alcohol) (PVA) hydrogel matrix, present a model coating where the localized delivery of the potent anti-inflammatory drug dexamethasone has been shown to suppress inflammation over a period of 1-3 months. Here, it is shown that the degradation of the PLGA microspheres provides an auxiliary venue to offset the negative effects of protein adsorption. This was realized by: (1) the creation of fresh porosity within the PVA hydrogel following microsphere degradation (which is sustained until the complete microsphere degradation) and (2) rigidification of the PVA hydrogel to prevent its complete collapse onto the newly created void space. Incubation of the coated sensors in phosphate buffered saline (PBS) led to a monotonic increase in glucose permeability (50%), with a corresponding enhancement in sensor sensitivity over a 1 month period. Incubation in serum resulted in biofouling and consequent clogging of the hydrogel microporosity. This, however, was partially offset by the generated macroscopic porosity following microsphere degradation. As a result of this, a 2-fold recovery in sensor sensitivity for devices with microsphere/hydrogel composite coatings was observed as opposed to similar devices with blank hydrogel coatings. These findings suggest that the use of macroscopic porosity can reduce sensitivity drifts resulting from biofouling, and this can be achieved synergistically with current efforts to mitigate negative tissue responses through localized and sustained drug delivery. © 2012 American Chemical Society. Source


Qiang L.,University of Connecticut | Vaddiraju S.,University of Connecticut | Vaddiraju S.,Biorasis Inc. | Patel D.,University of Connecticut | Papadimitrakopoulos F.,University of Connecticut
Biosensors and Bioelectronics | Year: 2011

The promise of implantable electrochemical sensors is often undermined by the critical requirement of device miniaturization that inadvertently degrades sensor performance in terms of sensitivity and selectivity. Herein, we report a novel miniaturized and flexible amperometric sensor grown at the 'edge plane' of a 25-μm gold wire. Such geometry affords extreme miniaturization along with ease of fabrication, minimal iR drop and 3-D diffusion for effective mass transfer. This together with electrochemical rebuilding of the Au working electrode and subsequent Pt nanoparticles deposition resulted in the highest H2O2 sensitivity (33mAmM-1cm-2), reported thus far. Concurrent electrodeposition of o-phenylenediamine with glucose oxidase afforded glucose detection at these edge-plane microsensors with a six fold improvement in sensitivity (1.2mAmM-1cm-2) over previous reports. In addition, these sensors exhibit low operation potential (0.3V), high selectivity (more than 95%) against in vivo interferences, and an apparent Michealis-Menten constant (Kmapp) of 17 and 75mM of glucose in the absence and presence of an outer polyurethane coating, respectively. These features render the edge-plane sensor architecture as a powerful platform for next-generation implantable biosensors. © 2011 Elsevier B.V. Source


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2011

This Small Business Innovation Research (SBIR) Phase I project aims to develop a wireless, needle implantable miniaturized (0.5 x 0.5 x 5 mm) sensor for continuous glucose monitoring, with provisions for internal self-calibration without the need for frequent, external fingerpricking. The proposed internal self-calibration is enabled through the use of novel pulse-mode sensor operation which quantifies sensitivity drifts internally. Pulsed-mode operation also results in improved power management as well as long sensor lifetime. Biocompatible coatings release various tissue response modifiers to control tissue inflammation. The device can be inserted under the skin and similarly removed via a needle, thus avoiding surgical implantation/removal. Phase-I seeks to develop the internal self-calibration routines and demonstrate proof-of-concept ex vivo. Phase II will focus on extensive in vivo studies thereby facilitating commercialization. The broader/commercial impacts of this research are enormous considering that there is an urgent need for continuous glucose monitoring devices in view of the growing number of diabetics. Implantable glucose sensors that afford minimal user intervention present a viable alternative, although their "user-independent" nature is often undermined by necessity for frequent external calibration by finger-pricking. The proposed project will result in a truly "user-independent" operation of implantable glucose sensors. In addition, the proposed internal calibration methodology is universal to all biosensors used for metabolic monitoring, rendering competitive market edge and job creation. The project will be performed in the Technology Incubation Program (TIP), at University of Connecticut. This industrial/academic collaboration provides training for the graduate and undergraduate students in the field ofbiosensors.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 150.00K | Year: 2011

This Small Business Innovation Research (SBIR) Phase I project aims to develop a wireless, needle implantable miniaturized (0.5 x 0.5 x 5 mm) sensor for continuous glucose monitoring, with provisions for internal self-calibration without the need for frequent, external fingerpricking. The proposed internal self-calibration is enabled through the use of novel pulse-mode sensor operation which quantifies sensitivity drifts internally. Pulsed-mode operation also results in improved power management as well as long sensor lifetime. Biocompatible coatings release various tissue response modifiers to control tissue inflammation. The device can be inserted under the skin and similarly removed via a needle, thus avoiding surgical implantation/removal. Phase-I seeks to develop the internal self-calibration routines and demonstrate proof-of-concept ex vivo. Phase II will focus on extensive in vivo studies thereby facilitating commercialization.

The broader/commercial impacts of this research are enormous considering that there is an urgent need for continuous glucose monitoring devices in view of the growing number of diabetics. Implantable glucose sensors that afford minimal user intervention present a viable alternative, although their user-independent nature is often undermined by necessity for frequent external calibration by finger-pricking. The proposed project will result in a truly user-independent operation of implantable glucose sensors. In addition, the proposed internal calibration methodology is universal to all biosensors used for metabolic monitoring, rendering competitive market edge and job creation. The project will be performed in the Technology Incubation Program (TIP), at University of Connecticut. This industrial/academic collaboration provides training for the graduate and undergraduate students in the field ofbiosensors.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 901.39K | Year: 2009

DESCRIPTION (provided by applicant): Background: Over the past five years, the University of Connecticut together with its start-up spin-off corporation (Biorasis Inc.) has been developing a totally implantable biosensor platform (0.5 mm x 0.5 mm x 5 mm) capable of continuously monitoring glucose. The underlying principle in developing this miniaturized sensor hinges on extreme miniaturization utilizing light, both as a powering source and a communication link. Such implant size reduction results in minimal tissue damage during implantation. The localized release of various tissue response modifiers has also afforded effective inflammation control and fibrosis suppression along with neo-angiogenesis. While significant progress has been achieved in the electrochemical determination of D-glucose using the highly-specific glucose oxidase enzyme, changes in user physiology (i.e. exercise, irregular homeostatis, anoxia/hypoxia, diet etc.) contribute to interferences that lower sensor accuracy. Objective/Hypothesis: By outfitting our implantable glucose sensing platform with two additional sensing elements capable of independently assessing oxygen and various interfering agent levels, the accuracy and reliability of glucose detection can be significantly improved, which will take us, a step closer to developing a closed-loop artificial pancreas. Study Design: We propose to develop a low-bias glucose+O2 sensing element (which is devoid of interference from endogenous redox-active species) and integrate it with two other (already-developed) sensing elements to accurately determine subcutaneous glucose concentrations irrespective of user physiology. This will be accomplished by outfitting the implantable platform with two additional potentiostats and an optically-coded, sensor-select circuit to sequentially interrogate each of the three sensing elements. All sensing elements and associated electrical and optical components will be integrated in a compact unit (0.75 x 0.75 x 9 mm) that is hermetically sealed against body fluids to enable long-term in vivo operation. This will be augmented by the respective optimization of the biocompatible sensor coatings to address the slightly enlarged sensor size, and develop in vitro release testing methods necessary for future FDA filing. Phase-II will focus on: (i) reducing the size of the multi-sensor unit, (ii) optimizing device assembly, and (iii) conducting extensive preclinical animal studies along with developing appropriate analytical methods necessary for FDA filing. Relevance: In view of the growing number of diabetics worldwide, there is a tremendous need for devices that provide accurate detection of glucose levels. In lieu of the difficulties associated with glucose monitoring using non-invasive methods, extreme miniaturization of a totally implantable device together with assured accuracy and long-term operation, present a viable alternative. The proposed multi-sensor platform addresses miniaturization and accurate glucose readings. In addition, the wireless communication and prolonged lifetime render it an effective device for diabetic care as well as a powerful tool for testing new drugs in small animals. PUBLIC HEALTH RELEVANCE: The increasing occurrence of diabetes (ca. 23.6 and 189 million diabetic patients in US and rest of the world, respectively) poses a serious health problem, especially when associated with obesity, renal failure and other serious conditions. Continuous glucose monitoring will provide the necessary warning to prevent hypo- and hyper-glycemic events as well as to minimize fluctuations in glucose levels that would otherwise lead to many debilitating complications associated with diabetes. Currently, there is no totally implantable device for continuous glucose monitoring available on the market. Therefore, diabetics must rely on either finger pricking (approximately five times per day) or microprobe, skin-penetrating devices that need to be replaced every 3-7 days due to their open-wound nature and associated negative tissue responses. A reliable, long-term, continuous monitoring is expected to provide the necessary corrective feedback to the patient so that together with appropriate insulin delivery, an effective sugar-level management can be attained to prevent hypo- and hyper-glycemic events. The proposed research intends to realize the first generation of a low-cost, miniaturized, implantable sensor that can continuously and accurately monitor blood glucose levels over a period of one month. This implantable sensor will establish a wireless link to a wrist-watch-like communicator capable of interacting with various digital accessories (such as, personal digital assistants, cell phones and personal computers). The implanted device can be inserted under the skin and similarly removed via a needle, thus avoiding the need for surgical implantation and removal. Another important feature of this sensor is its ability to delineate interferences and accurately obtain glucose levels, independent of user physiology (exercise, irregular homeostatis, anoxia/hypoxia, diet etc.). The miniaturized size of this sensory platform has immediate applicability not only in diabetes management, but also to diabetes research, where the ability of obtaining continuous glucose monitoring of the smallest research animals (i.e. mice, rats) will provide an invaluable tool in diabetes drug development.

Discover hidden collaborations