Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving glucose or galactose
Reexamination Certificate
2000-07-24
2003-06-17
Gitomer, Ralph (Department: 1651)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving glucose or galactose
C435S004000, C435S817000
Reexamination Certificate
active
06579690
ABSTRACT:
The present invention is, in general, directed to devices and methods for the monitoring of the concentration of an analyte, such as glucose, using a subcutaneous sensor. More particularly, the present invention relates to devices and methods for the monitoring of an analyte using a subcutaneous electrochemical sensor to provide information to a patient about the level of the analyte in blood.
BACKGROUND OF THE INVENTION
The monitoring of the level of analytes, such as glucose, lactate or oxygen, in certain individuals is vitally important to their health. High or low levels of these analytes may have detrimental effects. For example, the monitoring of glucose is particularly important to individuals with diabetes, as they must determine when insulin is needed to reduce glucose levels in their bodies or when additional glucose is needed to raise the level of glucose.
A variety of methods have been used to measure analyte concentrations. For example, colorimetric, electrochemical, and optical methods have been developed for the determination of blood glucose concentration. Implanted electrochemical sensors may be used to periodically or continuously monitor glucose (or other analyte) concentration. Although sensors accurately measure the glucose concentration when inserted directly into the bloodstream, infection may occur at this implantation site.
A variety of sensors have been developed for implantation in subcutaneous tissue to measure the subcutaneous glucose concentration, which is thought to be well correlated with the blood glucose concentration at steady-state. Subcutaneously implanted glucose sensors, such as miniaturized electrodes “wired” to glucose oxidase, are one technology that hold promise for continuous monitoring of blood glucose levels by diabetic patients. These sensors measure subcutaneous glucose concentrations as glucose diffuses from the blood into the subcutaneous tissue and then to the enzyme electrode surface. At this surface, the glucose is oxidized and the reaction causes electrons to be transferred to the electrode surface. The resulting current is proportional to the concentration of glucose in the region of implantation.
In many cases, it is important to be able to convert a value from a subcutaneous concentration to a blood concentration. For example, a subcutaneous sensor may be calibrated using blood measurements or a diagnosis or method of treatment may depend on the knowledge of the blood analyte concentration that is obtained using a subcutaneous sensor. However, a lag typically results between the blood and subcutaneous glucose concentrations as the blood glucose level increases or decreases. In addition, the subcutaneous analyte concentrations obtained from sensor measurements may be different from the blood analyte concentration because of the existence of a mass transfer barrier. Thus, there is a need to develop devices and methods that can convert subcutaneous analyte measurements to blood analyte concentrations to ensure accuracy, compatibility, and comparability between measurements made by subcutaneous electrochemical sensors and those made using other conventional blood analysis techniques.
SUMMARY OF THE INVENTION
Generally, the present invention relates to methods and devices for determination of analyte concentration in one body fluid using analyte concentration measurements from a second body fluid. In particular, the present invention includes methods and devices for the determination of blood glucose concentration using glucose concentration measurements from subcutaneous fluids.
One embodiment of the invention is a method for obtaining an estimate of an analyte concentration in a first fluid. First, measurements of an analyte concentration in a second fluid are obtained using a sensing device. An analyte concentration estimate in the first body fluid is determined from these measurements by minimizing the relation:
f[b]=x
2
[b]+&lgr;&PSgr;[b],
where b is a vector representing analyte concentration in the first fluid, x
2
[b] is a function representing a fit between the estimates and the measurements, &lgr; is a weighting function, and &PSgr;[b] is a function indicating smoothness of the analyte concentration estimates in the first body fluid. Another embodiment includes a sensing device for obtaining the measurements of analyte concentration in the first fluid and a processor configured and arranged to determine the analyte concentration according to this method.
This method and device can be used, for example, to determine blood glucose concentration from measurements of the glucose concentration in subcutaneous tissue. These measurements may be made using in vitro or in vivo samples. In some instances, a subcutaneously implanted sensing device, such as an electrochemical sensor, is used to make the measurements.
Another embodiment is a method of determining blood analyte concentration including obtaining a subcutaneous analyte concentration from a subcutaneous region using a sensing device and determining a blood analyte concentration from the subcutaneous analyte concentration based on a) mass transfer of the analyte from blood to the subcutaneous region and b) uptake of the analyte by subcutaneous cells in the subcutaneous region. Examples of analytes include glucose, lactate, and oxygen. Yet another embodiment is an analyte measurement device including a processor configured and arranged to determine the analyte concentration according to this method and an optical sensing device, such as an electrochemical sensor, for obtaining the measurements of analyte concentration in the first fluid. In some instances, the electrochemical sensor may be subcutaneously implanted and the analyte measurement device may periodically or continuously monitor glucose.
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V
Bonnecaze Roger T.
Freeland Angela C.
Gitomer Ralph
Merchant & Gould P.C.
TheraSense Inc.
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