Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving glucose or galactose
Reexamination Certificate
2000-01-21
2002-05-07
Gitomer, Ralph (Department: 1623)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving glucose or galactose
C422S082060
Reexamination Certificate
active
06383767
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to a luminescent in vivo glucose measurement, and more particularly to a luminescent in vivo glucose measurement using quantum dots.
2. Description of the Background Art
Measurement of body chemistry components is an essential part of modern health care. By measuring individual body chemistry components of a subject animal or human, such as a subject's blood chemistry, specific health characteristics of the subject can be determined.
One such body chemistry component is glucose (blood sugar) level. The glucose level in a subject may be analyzed and tracked for a number of reasons, but especially for monitoring diseases such as diabetes. Control of glucose levels in diabetic subjects is know to minimize diabetes side effects and to prolong the life of the subject.
In the related art, glucose testing and monitoring may be performed in different ways. First, it may be done in vitro (in an artificial environment) by extracting and testing blood specimens. This is undesirable for a variety of reasons, including pain and discomfort, invasiveness, inconvenience, time required, and the provision of an unfortunate avenue for infection.
The second method is in vivo (i.e., in the body) method of glucose measurement. As the name implies, the measurement may be performed through the skin of the subject, and may be non-invasive in nature. This has been done in the related art by illuminating a blood vessel of the subject through the subject's skin and measuring the energy that is absorbed or scattered in the subject's bloodstream. This has advantages of non-invasiveness, quickness, and ease of use. However, it suffers from drawbacks in accuracy, as the results may depend on and be affected by other bloodstream components, blood vessel depth, skin characteristics, etc.
In another related art blood specimen testing and measurement method, the detection of glucose or blood sugar may be aided by the use of an organic luminescent dye. The related art organic luminescent dye, such as FITC (fluorescein), is capable of covalently bonding to a glucose containing molecule. After the related art luminescent dye has bonded to a glucose analogue which competes with glucose to bind to a substrate, it is illuminated with a light source, causing it to emit photons. The photon emission can be measured and correlated to an amount of glucose present in the sample. Detection and measurement of light emission may therefore yield an emitted light level substantially proportional to the blood sugar level of the subject's blood.
However, related art dyes are organic in nature, and suffer from several drawbacks. First, related art organic luminescent dyes suffer from decomposition, wherein the bond between the dye and the sugar weakens over time. This means that the test or measurement must be taken within a fairly restrictive time window in order to be acceptably accurate. As a result, the related art organic luminescent dye cannot be used for extended periods as is desired for in vivo measurements, and is suitable only for in vitro laboratory use.
Second, related art organic luminescent dyes suffer from photo-bleaching, wherein the illuminating light breaks bonds within the dye, resulting in a decrease in luminescence over time. Repeated illumination therefore weakens the luminescent effect.
A third drawback is that related art organic luminescent dyes have fairly broad emission spectra (i.e., they fluoresce across a relatively broad range of light wavelengths, often overlapping within the excitation wavelength). The emission spectra is a characteristic of the related art organic luminescent dye, and cannot be adjusted to have desired emission and absorption properties. In addition, skin is most transparent to light having a red or near infrared wavelength, but the related art organic luminescent dye produces a bright green luminescence (typically of a wavelength of about 520 nanometers).
There remains a need in the art, therefore, for an improved in vivo blood glucose measurement.
SUMMARY OF THE INVENTION
A luminescent in vivo glucose measurement method for measuring a glucose level in an interstitial fluid of a subject is provided according to a first aspect of the invention. The method comprises the steps of illuminating displaced luminescent molecules with illuminating light, the displaced luminescent molecules and associated captive glucose analogue molecules being contained within an implanted luminescent in vivo measurement apparatus implanted within the interstitial fluid of the subject, and measuring an emitted light, the emitted light being emitted in response to the illumination, wherein the emitted light is related to the glucose level in the interstitial fluid.
A luminescent in vivo glucose measurement apparatus for measuring a glucose level in an interstitial fluid of a subject is provided according to a second aspect of the invention. The apparatus comprises a container having an interior region and at least one surface region formed of a semi-permeable membrane that allows glucose to pass through, the container also having an illumination region wherein light may enter the container, an agglutinating layer on at least one interior surface region and apart from the illumination region, a plurality of captive glucose analogue molecules in the interior region, with a captive sugar of the plurality of captive glucose analogue molecules capable of reversibly attaching to the agglutinating layer, and a plurality of luminescent molecules in the interior region, with a luminescent molecule of the plurality of luminescent molecules being hydrophilic and being bonded to at least one associated captive glucose analogue molecule of the plurality of captive glucose analogue molecules, wherein when a glucose molecule of the subject passes through the at least one surface region formed of a semi-permeable membrane and attaches to the agglutinating layer, a displaced luminescent molecule and an associated captive glucose analogue molecule travels to the illumination region of the container, and wherein illumination of all displaced luminescent molecules and the associated captive glucose analogue molecules through the illumination region produces a luminescence that is related to the glucose level of the interstitial fluid.
A luminescent in vivo glucose measurement compound is provided according to a third aspect of the invention. The compound comprises a quantum dot having a core and a shell, the core selected from the group consisting of indium arsenide, indium nitride, indium phosphide, zinc tellurium, gallium arsenide, gallium antimony, indium antimony, and lead sulfide, and the shell selected from the group consisting of indium phosphide, indium nitride, cadmium sulfide, zinc selenide, zinc sulfide, and lead selenide, at least one captive glucose analogue molecule, and at least one binding molecule that is hydrophilic and is capable of bonding to the at least one captive glucose analogue molecule and to the quantum dot, wherein the quantum dot is capable of absorbing light and emitting light as a result of the absorbing.
The above and other features and advantages of the present invention will be further understood from the following description of the preferred embodiments thereof, taken in conjunction with the accompanying drawings.
REFERENCES:
patent: 5342789 (1994-08-01), Chick et al.
patent: 5990479 (1999-11-01), Weiss et al.
patent: 6040194 (2000-03-01), Chick et al.
patent: 6081736 (2000-06-01), Colvin et al.
patent: 6134461 (2000-10-01), Say et al.
patent: 6163714 (2000-12-01), Stanley et al.
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