Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2000-06-12
2002-04-09
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S316000, C600S322000
Reexamination Certificate
active
06370407
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to polarimetry, especially as applied to noninvasive measuring of blood glucose concentration in diabetics. It is known that this phenomenon offers the potential for developing a noninvasive blood glucose analyzer.
Diabetes is a disease which entails a large number of associated complications. Retinal deterioration leading to blindness and impaired circulation leading to limb amputation, kidney failure and heart disease are just some of the more serious complications. Many of these complications result from the large excursions in blood glucose concentrations common to diabetics due to dietary intake, inadequate exercise, genetic predisposition, and complicated by infrequent and inaccurate monitoring of the blood glucose levels. Current methods of in home monitoring of blood glucose involve the lancing or sticking of a finger and external measurement of the glucose content of the blood sample and or urine sampling by use of a litmus strip test comparing a color change relative to glucose concentrations.
Although many diabetes patients should use the “finger sticking” test to obtain blood for glucose concentration measurements four or more times per day, studies show that very few patients do this unless they absolutely have to, and many patients only do it a few times at the beginning of their treatment until they establish what they think is a pattern in their required medication schedule. They then stop the regular and frequent finger sticking tests and simply take their insulin injections or oral medications on the assumption that their body chemistry is thereafter constant. This leads to large changes in glucose concentration in the patient's blood, which in turn leads to a variety of serious medical consequences to the patient. For example, it is estimated that in 1996 there were over fifty thousand amputations of limbs due to complications of diabetes in the U.S.
Diabetics recover from cuts and bruises more slowly than do nondiabetics. This very real and basic discomfort also causes many diabetics to minimize the frequency of or altogether ignore blood glucose testing, resulting in a higher frequency of complications than otherwise would be the case. A small accurate device that could make blood glucose measurements on a non-invasive basis would be of great value to the diabetic in that it would greatly encourage frequent monitoring of blood glucose levels without pain.
It is well known that glucose in solution is an optically active material. That is, it will cause the plane of polarization of light traversing the solution to be rotated. The quantitative relationship between the amount of polarization rotation, the glucose concentration, and the optical path length of the solution has been clearly established. This is expressed mathematically as:
{
α
}
=
100
α
C
*
L
or
:
C
=
100
α
{
α
}
*
L
Where:
&agr; is the polarization rotation in degrees;
{&agr;}is the specific rotation constant of glucose; ({&agr;}=45.1 degrees per decimeter (dm) per gram per milliliter for glucose at a wavelength of 633 nanometers);
L is the path length in the solution in dm, (where 1 dm=10 centimeters (cm);
C is the glucose concentration in grams (g) per 100 milliliter of solution or g/dL. (From “Sugar Analysis”, 3rd Edition, Browne & Zerban, John Wiley & Sons, 1941, page 263.)
For the clinically meaningful glucose concentration range from 25 to 500 mg/dL (milligrams per deciliter) and a path length of 1 cm, the observed rotation ranges from about 0.00113 degrees to 0.02255 degrees at a wavelength of 633 nanometers.
It is known that human tissue has an absorption minima in the wavelength range from about 750 nanometers to 900 nanometers. Because there are no fundamental absorption processes in this region, human tissue has a reasonable optical transmission in this region of the spectrum. Light scattering by tissue remains a problem, which may limit the path length to less than 4 mm, dependent upon the type of tissue.
All of the prior art systems using crossed polarizers use only a single frequency, usually in conjunction with a null control system and a lock in amplifier that operates only at that single frequency. The prior art null compensation techniques all involve inserting a sample between the first and second polarizers and driving a Faraday modulator to reestablish the extinction condition. The problem with the prior techniques of establishing a null condition at extinction in a system using crossed polarizers is that the laser, optical modulator, and other components have parameters which drift from the time that the null condition or extinction is initially established and the time at which the sample to be measured is placed between the polarizers and an extinction condition is reestablished to determine the phase rotation caused by the sample.
According to the article “Non-Invasive Optical Glucose Sensing—An Overview” by Gerard L. Coté, PhD. Journal of Clinical Engineering, Vol. 22, No. 4, July/August 1997, a path length of 4 mm through human soft tissue (other than the eye) attenuates or scatters 95% of the signal. We conducted tests to confirm the general claims by Coté and found that both scattering and absorption are strongly wavelength dependent.
Because of the impracticality of using prior art devices and techniques to accurately measure such a small signal, the prior art use of polarimetry to measure glucose concentration levels in human tissue has been based primarily on passing light through the transparent tissue of the anterior chamber of the human eye.
The prior art fails to provide any practical, workable polarimeter system which can consistently provide accurate measurements of the glucose level in human tissue because of the inadequate sensitivity and the large degree of instability of the prior art devices. There is a strong but unmet need for a practical, reliable system which overcomes the problems of the prior art to provide a practical, reasonably priced, noninvasive system for measurement of human glucose levels.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the invention to provide a device capable of consistently and accurately measuring the concentration of an optically active ingredient in a sample.
It is another object of the invention to provide a practical, economical device for noninvasive measurement of glucose levels in diabetics.
It is another object of the invention to avoid instrument instability problems which have in part prevented success of prior attempts to provide a practical system using polarimetry to noninvasively measure blood glucose levels in diabetics.
It is another object of the invention to provide a device capable of measuring an optically sensitive ingredient in biological tissue in a noninvasive manner more accurately than has been achieved in the prior art.
It is another object of this invention to provide a new very sensitive and very stable polarization spectrometer which has applications in certain types of chemical analysis.
It is another object of the invention to provide a device capable of measuring optical rotation in the presence of large percentages of more than about 95% scattered light.
It is another object of the invention to provide an improved polarimeter which is more sensitive and more stable than prior art polarimeters.
Briefly described, and in accordance with one embodiment thereof, the invention provides a system for polarimetric measurement of the concentration of a substance, such as glucose, in a sample, including a laser beam passing through a first polarizer and an optical modulator and then split into (1) a measurement beam which is analyzed and directed to a first detector coupled to a first amplifier, and (2) a reference beam which is analyzed and directed to a second detector coupled to a second amplifier. Identical multiple filtering and summing operations are performed on outputs of the first and second amplifiers to produce a first &PSgr
Kroeger James K.
Leszinske Alan J.
Cahill Sutton & Thomas P.L.C.
Kremer Matthew
TecMed Incorporated
Winakur Eric F.
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