Misc. Forms of current glucose testing with minimal or non-invaisve means

Non-invasive Glucose TestingEric MurrayTim FicarraBarbara DeschampOutlineEricSpectroscopyTimReverse IontophoresisBarbaraFluorescenceSpectroscopyStudy of the interaction of matter and lightLight is focused on some area of the bodyLight is absorbed and reflected in different ways by different substances.Subcategories include near-infrared, mid-infrared, and photoacoustic spectroscopy.

Goal is to understand glucose's spectroscopic properties, in order to identify its presence in a sample3Near-Infrared SpectroscopyFunctions in .7 2.5 micrometer rangeExplores tissue depths of 1 to 100 millimetersDiffuse Reflection:Using NIR light to illuminate a spot on the bodyLight is partially absorbed, scattered, and reflected back to a detectorReflectance spectrum of skin is compared to reflectance spectrum of the glucose.4Near-Infrared SpectroscopyA graph of the absorbance spectrum of skin contains different spectral signatures for different components that are present.Glucose bands located at 1613, 1689, 1732, 2105, 2273, and 2326 nm.5Near-Infrared SpectroscopyWork by Malin et al. Used custom-built scanning near-infrared spectrometers.Detectors were composed of indium-gallium-arsenideHuman forearm was the targetInstrument observed the intensity spectra for diffuse reflectance for the wavelength range 1050-2450 nmSampling interval was 1 ns.

6Near-Infrared SpectroscopyData from Malin's experiments

Prediction error of 9.1%Prediction error of 3.6%Image Source: Malin, Stephen F, et al. Noninvasive Prediction of Glucose by Near Infrared Diffuse Reflectance Spectroscopy. Clinical Chemistry, Vol. 45, No. 9. 19997NIR Spectroscopy: Future DeviceSensys GTS by Sensys Medical, Inc.Been in development for 16 yearsDesign changes have been a result of the dynamic nature of skinTextureColorTemperatureFurther design changes to address positioning of the skin.

8Mid-Infrared SpectroscopyGlucose is very effective at absorbing mid-infrared lightUnfortunately, so is waterThe body's emission spectrum can be used to measure glucose.If the glucose to be measured is at the same temperature as the tissue it's present in, no glucose spectrum will be observed in the emission spectrum.

9This can be solved by introducing a temperature gradient (i.e. cooling the surface) Then you can measure the signal to background noise ration S/B for the absorption of glucose in blood. h : Planck's constantk : Blotzman's constantDelta T : Temperature gradient between body temperature (T) and surroundingsG : Optical extinction coefficients of glucoseB : Optical extinction coefficients of bloodd : length of thermal gradient in skinMid-Infrared Spectroscopy

10Sample Product: OptiScannerDeveloped by OptiScan Biomedical Corporation.Uses mid-infrared spectroscopyUnfortunately, their current implementation is invasive, drawing blood every 15 minutes.Used for patients in critical condition.

Image source: http://optiscancorp.com/optiscanner.html11Photoacoustic SpectroscopyA beam of light is used to heat a target.Optical energy from the light is converted into acoustic energy.This acoustic wave can be measured with a microphone.The optimum wavelength for glucose detection is 9.676 micrometers.12Photoacoustic SpectoscopyOne study (MacKenzie et al.) used near-infrared pulse laser sources, and piezoelectric transducers.The following relationship was found:y = 0.21x 0.02where y is the change in the photoacoustic response and x is the glucose concentrationCorrelation coefficient was 0.99

13Photoacoustic SpectroscopyVery accurate and promisingEquipment is expensiveTesting equipment is extremely sensitive and requires a controlled environment.14Reverse IontophoresisTechnique for extracting subdermal moleculesApply DC current to the skinCurrent attracts charged moleculesForce of the flow also draws neutral moleculesGlucose and lactate are among the molecules which can be extracted

GlucoWatchFirst commercially available non-invasive glucose measurement techniqueContinuous monitoringRequires blood test for calibrationSuffers inaccuracy in detecting hypoglycemiaDiscontinued by Animas Corporation in 2007

Lactate MeasurementThere is a metabolic relationship between lactate and glucose levelsLactate can be extracted using reverse iontophoresisLactate measurement could be used to improve accuracy of GlucoWatch or similar technologiesLactate measurement is still being investigated

EZ ScanTool for blood sugar testingTwo minute testUtilizes five sensorsIn regions rich with sweat glands2 hands, 2 feet, 1 foreheadRequires no calibrationStill in developmental stages

Narrow topics Metabolic heat conformationCarbon nantoubes (reverse iontophoreris)Fluorescence

Focus is on Fluorescence by means of a contact lens, most diabetics need corrective lenses due to vision problems caused by the disease Ultimately it was most continuous and non invasive formMeasurement of body heat and oxygen supply. Monitor through sensing device of finger optically and thermally. Not enough information on this method.19FluorescenceEmission of light by a substance that has absorbed light of a different wavelength

Wavelength A is absorbedWavelength B is then emittedFluorescenceUsing a boronic acid doped contact lens, glucose levels are monitored through tears binding with the boronic acidThe sensor responds to the different concentrations through the diffraction of light7 therefore changing fluorescence and wavelength Measurements are taken by a handheld device that correspond to blood glucose levels

Why boronic acid?It is a electron deficient acidWith the presence of glucose becomes electron richThe changes of the boron atom can be noticed by fluorescence spectral changes in the probe

Fluorescence-contact lens designsDoped lenses which react to tear glucose level and measured by handheld device Sensors on the lens that change color according to the glucose concentration in tears ExperimentsElevated tear glucose levels were first demonstrated by Michail, as early as 1937 7Does not suffer from fluctuations of ambient lightHas a 30 min lag time with blood glucose levelsCorrelation coefficient of 0.998 9

ObstaclesResponse to various pH (in the range of 6.5-8.5)Polarity response Sensitivity enough to detect low concentrations of healthy person the high levels of a diabetic Comfort (daily disposable contact lens)6

Problems and future workBiocompatibilitySensitivityLow pH and polarity Toxicity (one study uses off the shelf lenses)7

References1. Current development in non-invasive glucose monitoring, Amaral et al., Science Direct, Medical Engineering & Physics 30(2008)541-5492. A glucose-sensing contact lens: from bench top to patient, Lakowics, Current Opinion Biotechnology 2005;16,100-1073. Fluorescent measurement in the non-invasive contact lens glucose sensor. Diabetes Technology Therapeutics 2006;8, 312-3174. Fluorescence glucose detection: advances toward the ideal in vivo biosensor, Moschou et al Journal of Fluorescence, 14,5: September 20045. Current Problems and Potential Techniques in In Vivo Glucose Monitoring, Wickramasinghe et al, Journal of Fluorescence, Vol 14, : September 2004 6. Clinical trial of noninvasive contact lens glucose sensor, March et al Diabetes Technology Therapeutics. Volume 6; 782-789Dec 20047. A Glucose sensing contact lens: A new approach to non-invasive continuous physiological glucose monitoring, Badugu et al, Journal of Fluorescence vol. 13, No.5 September 20038. The Pursuit of Noninvasive Glucose: Hunting the deceitful Turkey, John L. Smith9. Contact-lens Type Glucose Sensor Fabricated using Bionic-Mems Techniques for monitoring of Tear Sugar, Chu, TokyoReferences10.. "Diabetes Statistics - American Diabetes Association." 26 Jan. 2011. Web. 28 Feb. 2011. .9. Mathur, Ruchi. "Hemoglobin A1c Test Information on MedicineNet.com." MedicineNet. Ed. William C. Shiel. 15 Jan. 2009. Web. 01 Mar. 2011. .10 "Diabetes - What Should My Blood Sugar Levels Be? - Diabetes Mellitus, Type 2 Diabetes, Type 1, and Metabolic Disorders Treatment and Medications on MedicineNet.com." MedicineNet. Ed. William C. Shiel. 29 Mar. 2002. Web. 01 Mar. 2011. .

11. "Product Information." Medtronic Minimed, Inc. Web. 01 Mar. 2011. .12. Mendosa, David. "GlucoWatch." David Mendosa: A Writer About Diabetes. 31 Oct. 2007. Web. 01 Mar. 2011. .13. C.T.S. Ching, P. Conolly, Asian Journal of Health and Information Sciences, Vol. 1, No. 4, pp. 393-410, 2007.14. A. Ramachandran, et al., A New Non-Invasive Technology to Screen for Dysglycaemia Including Diabetes, Diab. Res. Clin. Pract., 2010.

15. Tak S Ching, Patricia Connolly, Simultaneous Transdermal Extraction of Glucose and Lactate from Human Subjects by Reverse Iontophoresis, International Journal of Nanomedicine, 2008References16 Kiel. Near Infrared Spectroscopy. Introduction into the method. 2004. Web. 04 Apr. 2011.

17. Malin, Stephen F., et al. Noninvasive Prediction of Glucose by Near-Infrared Diffuse ReflectanceSpectroscopy. Clinical Chemistry, Vol. 45, No. 9. 1999. 18. "Sensys Medial, Inc Near-Infreared Spectroscopy." Diabetes Mall. 2010. Web. 03 Apr. 2011. .

19. Klonoff, David C., et al. Mid-Infrared Spectroscopy for Noninvasive Glucose Monitoring. IEEE - The World's Largest Professional Association for the Advancement of Technology. Apr. 1998. Web. 02 Apr. 2011. .

20. "Optiscan, Mid-Range Infrared Technology for the Measurement of Blood Glucose." Diabetes Mall. 2010. Web. 03 Apr. 2011..

21. "OptiScanner | Glucose Monitoring." OptiScan Corp. Web. 04 Apr. 2011. .

22. Christison GB, MacKenzie HA. Laser photoacoustic determination of physiological glucose concentrations in human whole blood. Med Biol Eng Comput 1993;31:284 90.

23. MacKenzie, Hugh A. et al. Advances in Photoacoustic Noninvasive Glucose Testing. Clinical Chemistry, Vol. 45, No 9. 1999.

24. Waynant, R. W., and V. M. Chenault. "Overview of Non-Invasive Optical Glucose Monitoring Techniques." IEEE - The World's Largest Professional Association for the Advancement of Technology. Apr. 1998. Web. 01 Mar. 2011.