Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving glucose or galactose
Reexamination Certificate
2001-12-17
2003-08-05
Leary, Louise N. (Department: 1654)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving glucose or galactose
C435S004000, C435S283100, C435S025000
Reexamination Certificate
active
06602678
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to methods of continuous or rapid intermittent monitoring of body fluid for the presence and/or concentration of target analytes. More particularly, the invention relates to using diffusion of a target analyte from a body fluid such as interstitial fluid via a micro-pathway, and an interface contact element that is used to establish an equilibrium of analyte concentration between the body fluid and the interface contact element. The concentration of the target analyte can then be measured using a sensing material, thereby providing for continuous analyte monitoring such as continuous glucose monitoring by diabetic or hypoglycemic subjects.
BACKGROUND OF THE INVENTION
A number of tests are routinely performed on humans to evaluate the amount or existence of substances present in blood or other body fluids. These tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin. One particular test entails self-monitoring of blood glucose levels by diabetics.
Diabetes is a major health concern, and treatment of the more severe form of the condition, Type I (insulin-dependent) diabetes, requires one or more insulin injections per day. Insulin controls utilization of glucose or sugar in the blood and prevents hyperglycemia that, if left uncorrected, can lead to ketosis. On the other hand, improper administration of insulin therapy can result in hypoglycemic episodes, which can result in coma and death. Hyperglycemia in diabetics has been shown to have a number of adverse long-term effects, such as heart disease, peripheral neuropathies, atherosclerosis, blindness, stroke, hypertension and kidney failure.
The value of frequent monitoring of blood glucose as a means to avoid or at least minimize the complications of Type I diabetes is well established. According to the National Institutes of Health, glucose monitoring is recommended 4-6 times a day. Patients with Type II (non-insulin-dependent) diabetes can also benefit from blood glucose monitoring in the control of their condition by way of diet, exercise, and certain oral medications.
Conventional blood glucose monitoring methods generally require the drawing of a sample of whole blood (e.g., by finger prick) for each test, and a determination of the glucose level using an analytical instrument that reads glucose concentrations by electrochemical or colorimetric methods. Type I diabetics must obtain several finger prick blood glucose measurements each day in order to maintain precise glycemic control. However, the pain and inconvenience associated with this blood sampling, has lead to poor patient compliance, despite strong evidence that precise-maintained control dramatically reduces long-term diabetic complications. In fact, these considerations can often lead to an abatement of the monitoring process by the diabetic.
Alternatives to conventional blood glucose monitoring methods that require the drawing of capillary blood sample would include methods that assess glucose in interstitial fluid. As with whole blood sampling, interstitial fluid measurement also typically requires collecting a predetermined volume of fluid sample to perform each intermittent measurement. This can be accomplished by shallow skin-pricking with a micro-needle or lancet, by laser, electro-poration, skin ablation with heated elements or the like to avoid causing bleeding. Such techniques typically require application of pressure or vacuum to express an interstitial fluid sample. Interstitial fluid can be sampled through intact skin by means of electrophoretic techniques or by means of permeation enhancers. Due to the low volume of interstitial fluid in the tissue, expression of a sample through pierced skin can give inaccurate results depending upon the sample size required and the amount of trauma to the tissue from the collection procedure. Moreover, such methods cannot provide a continuous or even “real-time” monitoring of the glucose concentration in the interstitial fluid because of the time involved to access sufficient interstitial fluid to provide a measurable amount of glucose.
SUMMARY OF THE INVENTION
The present invention provides an apparatus and method for continuous or rapid intermittent monitoring of the concentration of a target analyte in a body fluid essentially without net mass fluid transport. This is achieved by diffusion of the target analyte between the body fluid and an interface contact element. The body fluid is exposed via micro-pathways that allow the body fluid to interface with the interface contact element. A portal generator, such as a particle injection device, is used to create such micro-pathways. A sensor (e.g., a hydrogel), comprising the interface contact element and a sensing material, can be incorporated into a patch that sits on the subject's skin. The patch can be configured to connect to a detector that provides quantitative results, such as by capturing an electrical signal. An instrument comprises the sensor and detector. Diffusion allows for an analytical measurement of concentration on a continuous or intermittent basis as the concentration gradient between the body fluid and interface contact element approaches continuous equilibrium. The access realized from this method allows much more frequent sampling and yields a more accurate result than existing interstitial fluid technology, and a painless measurement as opposed to the pain involved in whole blood sampling.
More particularly, the invention comprises an apparatus and method for continuous or intermittent monitoring of the concentration of a target analyte in a body fluid essentially without net mass fluid transport using diffusion of the target analyte and/or any byproducts of measurement from the body fluid to the interface contact element and vice versa. Such diffusion allows for analytical measurement of concentration on a continuous or intermittent basis as the concentration gradient between the body fluid and interface contact element approaches continuous equilibrium, and as the concentration shifts between different equilibria. The sensing material can comprise an enzyme, lectin, antibody or antibody fragment or, alternatively, a selectively reacting or binding bio-molecule or imprinted polymer to detect the presence and/or concentration of the target analyte by various analytical methods including electrochemical, (e.g., amperometric or coulometric), direct or reflective spectroscopic (e.g., absorbance, direct fluorescence, fluorescence quenching, chemiluminescence, and the like), as well as other methods.
A detector which receives the results of the analytical method can be incorporated into an instrument to detect the target analyte concentration intermittently on a cyclical basis or when triggered by the user. Such a cycle of intermittent measurement can be sufficiently short to approach continuous measurement of the target analyte concentration. The target analyte can comprise any substance significant for medical or forensic measurements including, but not limited to, nucleic acids; proteins; carbohydrates; lipids; electrolytes; drugs (e.g., anticonvulsant drugs, antipsychotic drugs, alcohol, cocaine, cannabinoids, opiates, stimulants, depressants, and/or their metabolites); gases; compounds; elements; ions; anabolic, catabolic or reproductive hormones; hormone analogs; conjugates or degradation products.
The interface contact element can be positioned on the exterior surface of the skin, the stratum corneum. The interface contact element provides a bridge between the sensing material of the sensor and the micro-pathways containing the body fluid. This interface can be facilitated by exposing the body fluid to the exterior surface of the stratum corneum by means of shallow incision, thermal ablation, tape stripping, puncturing, or lancing. In one embodiment, micro-pathways can be provided by accelerating inert, instantly dissolvable or longer-lived porous particles to a momentum sufficient to ballistically penetrate the str
Burkoth Terry L.
Kwon Sung Yun
Leary Louise N.
McCracken Thomas P.
PowderJect Research Limited
LandOfFree
Non- or minimally invasive monitoring methods does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Non- or minimally invasive monitoring methods, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Non- or minimally invasive monitoring methods will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3118512