Analyte measuring device

Abstract

An implantable analyte-measuring device including a membrane adapted to promote vascularization and / or interfere with barrier cell layer formation. The membrane includes any combination of materials, architecture, and bioactive agents that facilitate analyte transport to provide long-term in vivo performance of the implantable analyte-measuring device.

Description

RELATED APPLICATIONS [0001] This application is a continuation-in-part of application Ser. No. 10 / 647,065, filed Aug. 22, 2003, which claims the benefit of priority under 35 U.S.C. § 119(e) to Provisional Application No. 60 / 472,673, filed May 21, 2003, and is a continuation-in-part of application Ser. No. 09 / 447,227, filed Nov. 22, 1999, which is a division of application Ser. No. 08 / 811,473, filed Mar. 4, 1997, now U.S. Pat. No. 6,001,067. This application claims the benefit of priority under 35 U.S.C. § 119(e) to Provisional Application No. 60 / 544722, filed Feb. 12, 2004. All above-referenced prior applications are incorporated by reference herein in their entirety.FIELD OF THE INVENTION [0002] The present invention relates generally to biointerface membranes that can be utilized with implantable devices, such as devices for the detection of analyte concentrations in a biological sample. The present invention further relates to methods for determining analyte levels using implanta...

AI Technical Summary

Benefits of technology

[0017] The biointerface membranes, devices including these membranes, and methods of use of these membranes according to the preferred embodiments allow for long term protection of implanted cells or drugs, as well as for obtaining continuous information regarding, for example, glucose levels of a host over extended periods of time. Because of these abilities, the biointerface membranes of the preferred embodiments can be extremely useful in implantable devices for the management of transplant patients, diabetic patients, and patients requiring frequent drug treatment.

[0110] The devices of the preferred embodiments allow continuous information regarding, for example, glucose levels. Such continuous information enables the determination of trends in glucose levels, which can be extremely desirable in the management of diabetic patients.

Problems solved by technology

Despite the increasing number of individuals diagnosed with diabetes and recent advances in the field of implantable glucose monitoring devices, currently used devices are unable to provide data safely and reliably for long periods of time (for example, months or years).

With reference to conventional devices that can be implanted in tissue, a disadvantage of these devices is that they tend to lose their function after the first few days to weeks following implantation.

While not wishing to be bound by any particular theory, it is believed that this loss of function is due to the lack of direct contact with circulating blood to deliver sample to the tip of the probe of the implanted device.

Because of these limitations, it has previously been difficult to obtain continuous and accurate glucose level measurements.

A disadvantage of cell-impermeable membranes is that they often stimulate a local inflammatory response, called the foreign body response (FBR) that has long been recognized as limiting the function of implanted devices that require solute transport.

Previous efforts to overcome this problem have been aimed at increasing local vascularization at the device-tissue interface, but have achieved only limited success.

This has led to widely supported speculation that poor transport of molecules across the device-tissue interface 26 is due to a lack of vascularization near the interface.

Previous efforts to overcome this problem have been aimed at increasing local vascularization at the device-tissue interface, but have achieved only limited success.

For example, when applied to an implantable glucose-measunng device, both glucose and its phosphorylated form do not readily transit the cell membrane.

However, it has been observed by the inventors that once the monolayer of cells (barrier cell layer) is established adjacent to a membrane, increasing angiogenesis is not sufficient to increase transport of molecules such as glucose and oxygen across the device-tissue interface 26.

Despite recent advances in the field of implantable glucose monitoring devices, presently used devices are unable to provide data safely and reliably for long periods of time (e.g., months or years).

Unfortunately, probes that are placed directly into the vasculature put the recipient at risk for thrombophlebosis, thromboembolism, and thrombophlebitis.

Similarly, in order to be effective, the probe consumes some oxygen and glucose, but not enough to perturb the available glucose which it is intended to measure; subcutaneously implanted probes often reside in a relatively stagnant environment in which oxygen or glucose depletion zones around the probe tip can result in erroneously low measured glucose levels.

Finally, the probe can be subject to “motion artifact” because the device is not adequately secured to the tissue, thus contributing to unreliable results.

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