Electrochemical |
Enzymatic |
First generation |
1. Highly specific to glucose |
1. Interferences from co-substrate (i.e., oxygen) and endogenous species |
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2. High sensor sensitivity |
2. High operating potential required |
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3. Must use outer membranes, which increase sensor response times |
Second generation |
1. Highly specific to glucose and free of changes in levels of co-substrate |
1. Mediators used may be toxic |
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2. Low overpotential renders the sensor free of interferences |
2. Competition between mediators and oxygen still exists |
Third generation |
1. Highly specific to glucose and free of changes in the level of co-substrate |
1. Toxicity and biocompatibility of required nanomaterials is untested |
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2. Low overpotential renders the sensor free from interferences |
2. The issue of repeatability is still untested |
Non-GOx based |
1. Does not use oxygen as co-substrate and so no interferences from oxygen |
1. Shown to oxidize other sugars as well as common alcohols |
Nonenzymatic |
1. No enzymes used and so no question of degradation |
1. Not specific to glucose |
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2. Substantial electrode fouling by the products of glucose oxidation |
Optical |
Fluorophore-based |
Fluorescence or FRET intensity |
1. Highly specific to glucose because of the use of fluorophore with binding specificity to glucose |
1. Photobleaching of the fluorophore and scattering in tissue |
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2. Dependent on skin pigmentation, redness, epidermal thickness |
FRET lifetime |
1. Independent of scattering in tissue |
1. Miniaturization of photodetectors and time resolved spectrometers is not trivial |
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2. Independent of fluorophore concentration and so no issue of photobleaching or fluorophore loss through leaching |
2. Fool-proof demonstration in animals and humans is yet to be demonstrated |
Ocular spectroscopy |
1. Truly noninvasive since it measures glucose concentration in tears |
1. Leaching of boronic acid derivative |
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2. No handheld instruments |
2. Effected by pH and ionic strength |
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3. Glucose levels can be assessed visually |
3. When used in tears, a lag between the blood and tear glucose is observed |
Nonfluorophore based |
Optical coherence tomography |
1. Unlike other optical techniques, it is not affected by urea, ionic strength, temperature, heart rate, and hematocrit |
1. Shown to be affected by motion and tissue heterogeneity |
Polarimetry |
1. Can utilize visible light, easily available |
1. Effected by scattering in the tissue, pH, and temperature |
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2. All the components can be easily miniaturized |
2. Lack of specificity as molecules such as albumin and ascorbic acid are known to polarize light |
Thermal infrared spectroscopy |
1. Same as polarimetry |
1. Effected by scattering in the tissue, pH, probe position, fever, and temperature |
Photoacoustic spectroscopy |
1. Unlike other optical techniques, it is not affected by ionic strength or albumins |
1. Effected by scattering in the tissue |
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2. Miniaturization of instrument is not trivial |
Raman spectroscopy |
1. Unlike NIR, it shows sharper peaks and less overlap |
1. Longer stabilization times |
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2. No interference from luminescence and fluorescence |
2. Effected by tissue density, thickness, hematocrit |
Combinatorial |
Impedance spectroscopy |
1. Can measure glucose levels in the vascular compartment, so no lag time in sensor response |
1. Temperature and disease state of the body may affect measurements |
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2. Changes in blood dielectric properties are not specific to glucose |
Electromagnetic spectroscopy |
1. Same as impedance spectroscopy |
1. Body temperature, sweating, and motion affect glucose measurements |