Condensate Glucose Analyzer

Abstract

Systems and methods for analyzing glucose present in exhaled breath condensate (EBC). In certain embodiments, electrochemical- or coulometnc-based sensing technologies are used to analyze EBC for the presence and / or concentration of glucose. Based on the detected glucose m EBC, the subject invention provides systems and methods for non-invasive, accurate assessment of blood glucose levels.

Description

FIELD OF INVENTION[0001]The present invention relates to non-invasive monitoring of glucose concentrations in blood; and more particularly, to a system and method utilizing a breath condensate detection system for the frequent monitoring of glucose concentrations in subjects who are at risk for hypoglycemia, hyperglycemia, and / or glucose level fluctuations that put the subject at medical risk.BACKGROUND INFORMATION[0002]Abnormal levels of glucose in the blood of humans can have a number of consequences. For example, fluctuations of blood glucose levels outside of the physiological range can result in one of two states, hypoglycemia and hyperglycemia. Hypoglycemia is defined as plasma glucose levels below normal (70 mg / dL). Hypoglycemia can be symptomatic or asymptomatic. For example, subjects suffering from postprandial hypoglycemia generally have symptoms of adrenergic stimulation including diaphoresis, anxiety, irritability, palpitations, tremor, and hunger. Such symptoms typicall...

AI Technical Summary

Benefits of technology

[0026]Exhaled breath measurements can be used to monitor glucose levels and to correlate them with blood concentrations. By using breath to determine blood glucose concentrations, diabetics are freed from having to perform frequent blood sticks to determine their glucose concentrations or freed from the risk of developing tissue damage and infection from implantable monitoring devices. Further, continuous monitoring of breath glucose can be used in the operating room during surgery and / or the intensive care units since tight glucose control has been shown to improve wound healing and reduce the incidence of post-operative infection.

[0038]In a related embodiment, the subject glucose EBC test kit is provided in combination with other known methods for the diagnosis of hypoglycemia, hyperglycemia, diabetes, or insulin resistance. For example, in certain embodiments, the glucose EBC concentration test kit includes a means for detecting insulin resistance when blood glucose levels are still in the normal range and before 3-cell destruction leading to diabetes has occurred. To do so, the kits of the invention enable continuous monitoring of EBC insulin levels, where any change in levels of insulin in relation to blood / breath glucose or an delayed insulin response to a glucose load (such as a carbohydrate rich meal) would diagnose insulin resistance. Early diagnosis of diabetes could be achieved with the kits of the invention by the continuous monitoring of EBC insulin levels (e.g., through a ruthenium-oxide (RuOx)-type catalytic film sensor), where a measurement of inadequate insulin concentrations in response to a carbohydrate load would provide early diagnosis of diabetes.

[0039]In a related embodiment, the occasional or continuous measurement of glucose / insulin ratio is highly advantageous for use in early detection of insulin resistance, which will allow timely intervention to prevent the development of Type II diabetes and / or its complications. In addition, the present invention can be used to monitor the progress of any intervention therapies, including diet and exercise. In certain embodiments, the occasional or continuous measurement of glucagon / insulin ratio (where glucagon is a hormone that increases glucose concentration) may be used instead of the glucose / insulin ratio.

[0040]Advantages of the test kits of the invention include the following: they are practical, sensitive and specific; the validity of the test kits is not influenced by stress, exercise, hormone imbalances, or some drugs and medications; the test kits provide a non-invasive method for monitoring glucose levels; the test kits are simple to perform and can be readily used in physicians' offices, medical laboratories, or at any location by the subject; and the test kits are safe for use by children and women.

[0048]The condensate extracting system for extracting condensates present in end-tidal exhaled breath samples includes any one of many known devices for collecting condensates that are currently available to the skilled artisan. For example, one such device relies on gravity to form a condensate pool from which a sample for testing may be drawn. These types of devices require that condensate droplets become large enough to overcome water's naturally tendency to stick to the walls of a collection reservoir. Eventually, the amount of condensate in the collection area becomes large enough for analysis. In some cases, the collecting reservoir is inserted into an ice bucket or may even be separately cooled by refrigeration systems in order to increase the amount and speed of condensate formation. In a preferred embodiment, a Peltier device is placed in contact with one wall of the condensate collecting device and cooled so that EBC preferably condenses in the cooled area of the collecting device. In one related embodiment, samples of exhaled breath are cooled to temperatures at or around room temperature. In another related embodiment, samples of exhaled breath are cooled to temperatures at or below freezing. In some cases, a coating such as Teflon™ is applied to collecting reservoir to make the reservoir walls non-wetting and non-reactive with glucose and to enhance the speed and amount of condensate collected.

Problems solved by technology

In more severe cases, hypoglycemia can progress to confusion, blurring of vision, seizure, and ultimately loss of consciousness or seizure.

In diabetic subjects, glucose cannot enter the cells and subsequently, glucose builds up in the blood and the body's cells literally starve to death.

It has been observed that complications resulting from diabetes are the third leading cause of death in most developed countries.

The healthcare costs associated with the treatment of diabetes and diabetic complications are enormous and projected to increase with the number of American living to older ages and the increased incidence of obesity.

Present devices available for SMBG are complicated and difficult for many diabetics to use and often require them to obtain an adequate blood sample.

Most diabetics, even those aware of the complications of hypo- and hyperglycemia, do not test frequently enough (for Type I [insulin dependent] diabetics this may be 6-8 times / D and for Type II diabetics controlled with oral agent testing should ideally be performed at least 2 times / D) because they consider obtaining blood to be significantly more painful than the self-administration of insulin and SMBG is far more time consuming and complicated.

The FDA is fully aware of the many shortcomings of the devices used for SMBG, but newer technologies or matrices have not proven any more reliable.

Unfortunately, tears, saliva and sweat have failed as viable matrices for use as surrogates for blood in monitoring glucose levels.

It is less likely to be associated with the transfer of serious infections than other bodily fluids and collection of samples is straightforward and painless.

Such technology has not been effective because they have not been able to derive sufficient concentrations of target compounds (such as glucose) in the liquid EBC sample to afford accurate detection and quantification.

Further, such technology requires large sampling (roughly 75 breaths) to derive a sufficient amount of liquid EBC sample for testing.

Finally, such technology does not take into account variable humidity in exhaled breath and in the air when samples are taken as well as the random microparticle density of the sample, which can significantly effect the accuracy of measured target analyte in the sample as well as the correlation between the concentration of the target analyte in EBC versus blood concentration.

Thus, truly simple, non-invasive methods of measuring target analytes, specifically glucose, are not commercially available.

Further, no successful system or method has been developed that can accurately correlate glucose found in exhaled breath with the concentration found in blood.

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