Faculty/Staff Websites & Bios | Web Services | How We Can ...



Noninvasive Glucose Measurement

Barbara Deschamp, Timothy Ficarra, Eric Murray

Abstract:

Diabetes mellitus is a metabolic disease that affects over 25 million people in the United States. Those with the disease need to be have constant awareness of their blood glucose levels, or can suffer severe consequences. In this paper, we discuss the current methods used by diabetics for blood glucose measurement, and explore the current implementations of noninvasive glucometry strategies in order to make a prediction as to which measurement techniques may eventually replace today's blood sampling methods.

1. Introduction

People with diabetes are tasked with monitoring their blood glucose levels throughout the day to ensure that these levels remain in a healthy range. Because this measurement is so crucial to their health, it is important that people can take it safely and easily. The most popular method for measuring the glucose content of blood is to obtain a blood sample and apply it to a glucometer. As a result, millions of people are forced to prick the skin in their fingers many times a day in order to draw blood. However, scientists and engineers have been working on many different approaches to eliminate this inconvenience by way of noninvasive glucose monitors: sensors that can obtain an accurate reading of blood glucose levels without the need for a blood sample.

The rest of the paper is outlines as follows. Section 2 provides an overview of what diabetes is and how it affects people. Section 3 discusses the invasive glucose measurement strategies currently in use today. In Section 4, the traditional strategies for noninvasive glucose measurement are discussed, as well as the products currently in development. Section 5 addresses new approaches to noninvasive glucometry that have recently come to fruition. Finally, Section 6 gives the main conclusions regarding the feasibility of the methods described in Section 4 and 5.

2. Overview of Diabetes

Diabetes is an autoimmune disease that results from the pancreas losing its ability to provide the quantity or quality of insulin needed to break down glucose. When carbohydrates enter the digestive system, they are broken down into glucose that is normally utilized by the cells for energy. However, insulin is needed for the cells to actually use that glucose. If the pancreas cannot produce the necessary amount of insulin, excess glucose will build up in the blood stream, causing major consequences.

Two types of diabetes exist. Type I, Insulin Dependent Diabetes Mellitus, accounts for 5-10% of cases. It usually occurs in childhood as a result of a genetic predisposition and an environmental trigger (although that trigger is not yet known). The pancreas loses its ability to produce insulin, so diabetics need to directly inject insulin into their bloodstream. Type II, Non-Insulin Dependent, generally occurs later in life, as a result of obesity and other factors. In this case, the pancreas is still functioning, but it cannot meet the body's demands for insulin. Therefore, insulin is taken orally. In some cases, Type II diabetes is curable with weight loss, diet, and exercise.

If a person's blood sugar is left unregulated, it can lead to a multitude of complications over time. The combination of the inability to utilize the glucose in the body and the extra work required to remove the excess glucose can damage many organ. Among these are the eyes, the kidneys, and the heart. Furthermore, peripheral neuropathy, or nerve damage, can occur all over the body which can result in amputation. Also, a diabetic has a greater risk of stroke [1].

Diabetes has a profound presence. There are current 25.8 million people in the United States with diabetes, which accounts for 8.3% of the country's population [1]. An estimated 7 million people have diabetes but are undiagnosed. In 2010 alone, 1.9 million new cases of diabetes were diagnosed in people over the age of 20. Furthermore, childhood Type II diabetes is at an all time high, as it is directly linked to childhood obesity.

Along with the large number of people affected by diabetes are the large health care costs. In 2007, $174 billion was spent treating diagnosed diabetes [1]. $116 billion of that was for direct medical costs, while another $58 billion was for disability and work loss costs. Minimizing the costs of diabetes-related health care requires the prevention of major complications through by controlling blood sugar levels. If a diabetic can maintain his or her blood glucose levels with accurate measurement and treatment then the risks of complications goes down significantly. Therefore, reliable glucose measurement methods are needed to keep people healthy and keep health care costs low.

3. Invasive Glucose Measurement

Currently there are two main methods of measuring blood glucose levels. The first is called the A1C test. A1C is a simple lab test where a small amount of blood is drawn for analysis. The objective is to determine the average glucose level in a patient over the last three months. These results are an indication of a person's risk for the medical complications described in Section 2, and are presently the best way of monitoring a diabetic's health over a long term basis. For diabetics, an A1C test is recommended at least twice a year. Table 1 shows the relationship between the A1C level and average glucose level. Although the A1C test is an important indicator of long-term health, diabetics also need to conduct frequent self tests.

Table 1. A1C Testing Relationship [2].

|A1C Level |Average Glucose Level |

|12 |345 |

|11 |310 |

|10 |275 |

|9 |240 |

|8 |205 |

|7 |170 |

|6 |135 |

Diabetics perform self tests for blood glucose levels on a daily or even hourly basis. These tests reveal the current amount of glucose present in the blood, so that immediate action can be taken if necessary. First, the person pricks his or her finger with a lancet to extract a drop of blood. Next, that blood is placed onto a strip containing glucose sensitive chemicals. An optical meter then analyzes this sample to provide a numerical reading of the blood glucose level. Depending on the sensor in use, either the plasma or the whole blood content is used for the sample. For a plasma sensor, a value of 90-130 mg/dL is healthy before meals, with a value of less than 180 mg/dL 1 to 2 hours after meals. Comparatively, for a whole blood value glucometer, 80-120 mg/dL and 170 mg/dL are expected before and after a meal, respectively [3].

Other self test methods that exist include meters that use alternative site tests, such as upper arms and forearm, although these are not a replacement for finger pricks. Another method involves using a Laser to draw blood which was approved by the FDA in 1998. There is also an invasive continuous monitoring system that exists: The MiniMed monitoring system [4]. This device involves works by inserting a small plastic catheter under the skin to continually take readings and even inject insulin automatically.

The concern with these testing methods is that they cause discomfort to those who have to administer them on a regular basis. The blood sampling methods are an even greater challenge for people prone to having vasovagal episodes and fainting at the sight of blood. For this reason, many scientists are looking for a noninvasive alternative, measuring blood glucose levels without direct contact with blood.

4. Noninvasive Glucose Measurement Strategies

Ideally, diabetics want a noninvasive measurement technique which produces no pain or discomfort, involves no blood or other bodily fluid obtained by piercing the skin, and does not cause tissue damage, injury, or deterioration. Despite many attempts by several universities and manufacturers, no such product has yet to exist. However, many different strategies are being tested now, including reverse iontophoresis and spectroscopy.

4.1 Reverse Iontophoresis

Reverse iontophoresis is a technique in which electrical current is applied to the skin in order to extract molecules. The flow of molecules due to the electrical charge is a dominant force which allows for the movement of neutral molecules in addition to charged ones. This allows for the extraction and detection of sub-dermal chemicals, such as glucose. As a result of this fact, reverse iontophoresis is a technique being researched to address the need for a non-invasive glucose measurement solution.

The first commercially available solution for non-invasive glucose measurement was the GlucoWatch developed my Animas Corporation [5]. The GlucoWatch was a continuous blood glucose monitor which utilized reverse iontophoresis. Unfortunately, the product was discontinued due to several problems. First, continuous electrical charge of the watch could cause skin irritation and burns. Second, the watch was significantly inaccurate in detecting hypoglycemia - 25% of the time the readings would be as much as 30% inaccurate. Third, the watch still required a blood sample for calibration and required two hours to become calibrated and ready for use. Animas Corporation discontinued manufacture and support for the GlucoWatch in 2008.

It has been observed that glucose and lactate levels are metabolically linked [ 6]. This implies that monitoring lactate levels can help to ascertain the 'healthy functioning' of a patient. The GlucoWatch was a revolutionary idea which suffered from inaccuracies when glucose measurements were low. By redesigning the GlucoWatch to also measure lactate levels in addition to glucose levels, reverse iontophoresis may prove to be the key to non-invasive glucose measurement. This approach is still in the research stages.

Following the GlucoWatch is the EZ Scan which is built upon the same technology. There are three major differences between the GlucoWatch and the EZ Scan: 1) the EZ Scan does not conduct continuous monitoring, 2) the EZ scan does not require a blood test for calibration, and 3) the EZ Scan is much more accurate. The EZ scan apparatus uses five sensors applied to regions rich in sweat glands - feet, hands, and forehead. The patient stands on two sensor pads, grips two sensors, and wears a headband. Over the course of two minutes fifteen tests are conducted - various combinations of DC voltages and polarities - to determine the current state of the blood glucose level of the patient [7]. The system requires no calibration or supervision. It is still in developmental stages.

Since the discontinuation of the GlucoWatch there has been no commercially available non-invasive glucose monitoring solution available for diabetics. Presently undergoing clinical trials is a new transdermal continuous glucose monitor (tCGM) designed by Echo Therapeutics called the Symphony tCGM [28]. The product has been undergoing clinical trials since 2004 and uses a proprietary skin preparation system to improve the accuracy of the reverse iontophoresis technique. The skin preparation system, Prelude, is a tool which uses electricity and feedback algorithms to painlessly remove the top layer of skin. This layer is mainly comprised of dead skin cells and has been observed to greatly reduce the accuracy of results in transdermal measurement. Once the skin has been prepped by the Prelude system, the Symphony sensor is applied to the skin. It is capable of functioning as a continuous, real-time glucose monitor, and is equipped with a wireless transmitter for sending data to a monitoring station for analysis.

The FDA acceptance of the GlucoWatch was an important step towards the goal of a non-invasive technique; consequently the inadequacies of the produce were a setback. Fortunately, the GlucoWatch showed that a solution is possible, and upcoming technologies such as the EZ Scan and the Symphony tCGM are building upon the failures of the GlucoWatch. With the creation of the Prelude skin-prep system we have a solution to the inadequacies which killed the GlucoWatch. Considering the products being developed and the research being conducted, it seems that reverse iontophoresis is one of the most viable solutions for non-invasive glucose monitoring.

4.2 Spectroscopy

Spectroscopy is the study of the interaction of matter in light. Usually a beam of light is focused on some area of the body. Depending on what substances are present, the light will react in different ways. The change in light characteristics are then measured and interpreted. In glucometry, the goal of spectroscopy is to use light to measure the presence of glucose in a sample or blood or tissue. This method can be broken down into different subcategories: mid infrared, near infrared spectroscopy, photo acoustic spectroscopy, and scatter changes. Each of these strategies have different challenges and obstacles that must be overcome in order to accurately measure the presence of glucose and avoid interference from water and other materials present in samples.

4.2.1 Near-Infrared Spectroscopy

Near-infrared spectroscopy functions in the .7 – 2.5 micrometer range of the light spectrum. It explores tissue depths of 1 to 100 millimeters. Near-infrared spectra show less intensity and broader bands than the mid-infrared region where sharp absorption peaks are typical [9]. Also, reflection intensity in the near-infrared region is higher than that of mid-infrared.

One method of detecting glucose is near-infrared diffuse reflectance spectroscopy. This method involves the using a low-energy near-infrared light to illuminate a spot on the body. This light is partially absorbed and scattered as a result of the chemical characteristics of the skin, before being reflected back to a detector. The reflectance spectrum of the skin compared to the reflectance of the instrument calibrator is used to make a prediction as to what amount of glucose is present in the body. Typically, a graph of the absorbance spectrum of skin contains different spectral signatures for the different components that are present, including water, fat, protein, and glucose. For example, peaks in the absorbance will occur for 1448, 1787, 1948, and 2600 nm wavelengths as a result of the absorbance properties of water. According to Malin et al., the absorbance attributable to glucose is four to five orders of magnitude less than the absorbance of water, with bands located at 1613, 1689, 1732, 2105, 2273, and 2326 nm [10].

In the experiments done by Malin et al., custom-built scanning near-infrared spectrometers were used. Using the forearm as the target, the instrument observed the intensity spectra in diffuse reflectance for the wavelength range 1050-2450 nm, with a spectral sampling interval of 1 nm and a signal-to-noise ratio at about 90 decibels. These detectors were composed of indium-gallium-arsenide. In order to obtain consistent results, temperature and forearm position were monitored for each test. Then, blood samples were taken from each subject as a baseline to compare the spectroscopic results to.

One of the companies currently working on a commercial glucometer using near-infrared spectroscopy is Sensys Medical, Inc. However, their upcoming device, the Sensys GTS, has been redesigned many times to account for various complications in the spectroscopy process [11]. First, there is the challenge of getting consistent results from a subject's skin. A person's skin is dynamic, as it experiences changes in texture, color, and temperature. These changes can affect the way the skin absorbs and reflects light, which in turn will affect the accuracy of the glucose measurement. In order to overcome these obstacles, Sensys is developing a position system to reduce spectral variation, as well as coming up with a way of controlling several skin properties. At this point in time their website is not functional, so no information about the product's release is available.

4.2.2 Mid Infrared Spectroscopy

At first glance, mid-infrared spectroscopy seems like a practical approach to glucose measurement. Glucose is very effective at absorbing mid-infrared light, and this type of spectroscopic measurement gets minimal interference from other particles that are present [12]. The human body is an effective blackbody emitter of mid-IR light at the right spectral region, so the necessary radiation is therefore already present inside the body near enough to the surface (within 10’s of microns) that its emission spectrum may be used to measure glucose. The major setback however, is that water has similar absorption characteristics to glucose in the mid-infrared region, and a sample of blood or other bodily fluid will contain water. Therefore, instead of just looking at the absorption spectrum for the glucose, researchers have chosen to use an emission spectroscopy approach for glucose measurement.

The human body acts as a blackbody emitter of mid-infrared light, which means that within the skin's surface is the radiation necessary to observe the body's emission spectrum. The emission/absorption characteristics of glucose changes with temperature, so by cooling the outside of the skin sample where the glucose lies, the glucose absorption spectrum can be observed. This spectrum can then be superimposed on the normal blackbody emission spectrum of the body to make a determination about the amount of glucose present.

One company that is developing these mid-infrared glucose sensors is OptiScan Biomedical Corporation [14]. What OptiScan has developed is an automated, bedside glucose monitoring system to provide serial blood glucose measurements at 15-minute intervals, called the OptiScanner. Although the company's original intention was to develop a mid-infrared noninvasive glucometer, this device requires a 120 mL blood sample to generate a result, while the traditional glucose measuring strips use between .3 and 1.2 uL [13]. Therefore, this product is actually more invasive than the methods described in Section 3, and is not marketed towards diabetics, but for critically ill patients who need constant blood glucose measurement. At this point in time, the company has not announced any plans to utilize their technology in a non-invasive fashion for diabetics.

4.2.3 Photoacoustic Spectroscopy

Photoacoustic spectroscopy is when a beam of light rapidly heats a target. The optical energy from the light is converted into acoustic energy, where the beam generates an acoustic pressure wave. This wave can then be measured with a microphone.

In the work done by MacKenzie et al., a wavelength of 9.676 micrometers was determined to be the optimum light source for photo acoustic tests [15]. Using this light source, a linear response correlating to the concentration of glucose in a solution was observed. Specifically, the equation found was

y = 0.21x – 0.02

where y is the change in the photoacoustic response and x is the glucose concentration. The test data showed a correlation coefficient of 0.99, indicating that their observations accurately reflected the equations to model the data.

In later work, MacKenzie et al. developed a special mount containing a piezoelectric transducer was created for holding a subject's right index finger while a laser pulse was incident on the side of the finger through an optical fiber [16]. The transducer was able to detect the photoacoustic pulses, which were administered for 5-second periods at 5-minute intervals. Researchers found that there was a strong correlation between the photoacoustic measurement and the actual blood glucose concentration, however, a unique gradient and offset existed for each person being tested. Therefore, a commodity device using this method would have to be calibrated with the patient in order for it to be safe and effective.

While accurate glucose readings are possible with this method, the equipment is expensive and sensitive to environmental changes [17]. Therefore, current research is focused on improving the repeatability and sensitivity of photoacoustic measurement, as well as the investigation of ideal detection sites on the human body.

4.2.3 Upcoming Spectroscopy Products

One product that is expected to be released within the next two years is the Scout DS from VeraLight, Inc. [33]. This product consists of a light source, an optical detector, and a spectrometer, built into an arm rest with an indicated display. The spectrometer is tuned to measure advanced glycation end products (AGE). Glycation is the process a cell uses to bind a protein or lipid to glucose, and is a way for the body to dispose of glucose when insulin is not available. The presence of AGE's indicates a history of hyperglycemia in the body, which can be used to predict the development of diabetes. While effective at determining a risk of diabetes and a history of high blood glucose levels, the Scout DS does not provide the current information about the body's blood glucose levels. It may, however, replace the blood test used in type 2 diabetes screening.

Another product that shows promising results for the future is the LighTouch Glucose Monitor from LighTouch Medical, Inc [34]. Currently, LighTouch has 12 patents issued and more pending. Their sensor projects a specific wavelength of light onto a person's fingertip and detects the wavelength of the reflected light. Unlike the Scout DS, this device has been designed to replace the finger-pricking method used by diabetics today, offering the same accuracy in a non-invasive manner. Clinical trials for the LighTouch sensor began in 1999 with Joslin Diabetes Center of Syracuse, New York. Over the last decade, the monitor has been continually redesigned in order to improve its speed and accuracy, while reducing the cost and form-factor. LighTouch is currently in the process of getting FDA approval. The company plans on releasing their monitor for home use six to nine months after approval. Furthermore, LighTouch anticipates on releasing modified versions of their sensor for the detection of other blood analytes.

One last glucose monitor that shows promise is the NBM-200G from OrSense Ltd [35]. This product is a modified version of an existing product of theirs, the NBM-200MP. The 200MP is a multipurpose monitor that wraps around the finger, in order to measure hemoglobin, oximetry, and pulse rate. OrSense's products are based on their proprietary Occlusion Spectroscopy technology. In this process, a sensor wraps around a person's finger to constrict blood flow. The change in blood dynamics is used to allow a strong optical response for integrated spectrometer. OrSense currently has 51 patents worldwide, with more than 20 patents pending. The NFM-200G is currently undergoing clinical trial to test the device's accuracy. As of 2011, this product has been tested on over 450 subjects, taking measurements over a 24-hour period. Unfortunately, according to OrSense Ltd., “at this stage the NBM-200G glucose monitor is utilized for investigation and market awareness purpose only” [35]. This statement reveals that the company has made no commitment to getting the product onto the market as an alternative to the finger-pricking method, despite its feasibility.

4.3 Scatter Changes

Scatter changes involves the refractive index of a sample. Specifically, the increase in the presence of glucose in a sample will increase the sample's refractive index. Measuring light refraction against the abdomen has been found to be a very accurate indicator of blood glucose levels. The problem with scatter change methods is that calibrating a baseline, which is the normal refraction index of the sample, is very difficult. The process also needs to account for signal shift due to environmental factors [17]. At the time of this writing, no specific scatter change research publications have been found.

5. Other Methods

Some recent glucometry methods that deviate from the traditional methods described in the previous section include: metabolic heat conformation, carbon nanotubes which uses the method of reverse iontophoresis and fluorescence. The topics were narrowed by focusing on the fluorescence method. This method was applied by means of a contact lens. The opinion to focus on this topic was mainly the thought that is the most feasible of the three. The reason is because it was most continuous and non invasive form.

Metabolic heat conformation is a method of measuring body heat and oxygen supply. This is achieved by monitoring glucose levels through a sensing device of finger optically and thermally [19]. There is not enough information on this method and it seems that big bulky devices are necessary for readouts which are not optimal. Carbon nanotubes utilized reverse iontophoresis which we previously discussed. There come several problems with this method which we have already mentioned.

5.1 Fluorescence

Fluorescence is the emission of light by a substance that has absorbed a different wavelength of light. It usually has one wavelength absorbed and another longer wavelength emitted which has less energy. George Gabriel Stokes named this phenomena in which are named after the mineral fluorite. The most popular reference to these phenomena is usually when an invisible is absorbed and a visible light is emitted. Examples of this include underwater or aquatic life such as minerals or fish that appear to glow.

Glucose monitoring can be utilized by fluorescence through means of a boronic acid doped contact lens [18]. The glucose levels are monitored through the tears. Elevated tear glucose levels were first demonstrated by Michail et al as early as 1937[24]. It has been found that the glucose in the tears binds with the boronic acid. The sensor responds to the different concentrations through the diffraction of light therefore changing fluorescence and wavelength.

The lenses are boron acid doped because it is electron deficient acid and with the presence of glucose becomes electron rich. These changes of the boron atom can then be noticed by fluorescence spectral changes in the probe [20]. The spectral changes are measured by a handheld device that corresponds to blood glucose levels. Experiments have found that results are favorable. This includes a 30 min lag time with the blood glucose levels. This method does not suffer from fluctuations of ambient light. One sensor that was tested had a glucose testing correlation coefficient of 0.998[19]. It was also found that most diabetics need corrective lenses due to vision problems caused by the disease. An experiments have used off the shelf lenses which would require no adjustment in daily life. One study showed that the lenses were found comfortable even by those who had never worn contact lenses [23].

Some of the concerns with the design include: pH response, polarity response, leaching, sensitivity and comfort [21]. The sensitivity has to have a high range which can detect low concentrations of healthy person the high levels of a diabetic. The comfort of the lens has been addressed by using off the shelf daily disposable lenses. The pH was addressed and found to be successful [22]. Also long term research needs to be addressed in the area of biocompatibility and toxicity [21].

Another concern from the interaction with sugars is leaching which could reduce the intensity [19]. Leaching is the extraction of certain materials from a carrier into a liquid.  One study showed about an 8% change in the fluorescent intensity due to leaching [19]. Although it is possible to attach probes to the contact lens polymer which would eliminate any leaching there are other considerations. It is ideal not to change the lens design so that the optical parameters and physiological characteristics do not change.

5.2 Most Likely Products for Commercial Use

Two products that are likely be on the market in the near future are the GlucoScope and Glucoview. The GlucoScope monitor is produced by Visual Pathways Inc. This company is a vision care diagnostic company based out of Prescott, Arizona. In 2003, they received a federal grant under the U.S. Department of the Army Medical Research Acquisition Activity and developed a prototype in 2003 [29]. They received a patent in December 2004 for the GlucoScope monitor.

The monitor works by measuring the glucose levels in the fluid of the anterior chamber of the eye.  It is a handheld device that looks like a small pair of binoculars. It uses infrared light to rapidly measure glucose levels in the aqueous humor of the eye. The glucose concentration in the bloodstream is directly correlated to the concentration in the aqueous humor. Therefore any variation in the glucose concentration will cause variations in the index of refraction. Then using interferometry the refractive index can be measured.

Interferometry is a technique which uses the addition of waves propagating in order to extract some information.  In this device two beams are directed into the eye and caused to interfere.  The interference produces a fringe pattern which is then analyzed.  The index of refraction can then be determined by this analysis. From the index of refraction we can then determine the glucose concentration which will give us the correlated glucose level that is given by a digital output on the monitor.

Some of the benefits of the GlucoScope Monitor is that is handheld, portable, non-invasive and easy to use. The drawback is that it is still in the research and development phase and not commercially available.

The second product is the Glucoview that is produced by the Sentek Group and licensed from the University of Pittsburg [27].  The Glucoview is a disposable contact lens which changes color according to the glucose levels in the tears. The technology is similar to the previous contact fluorescence method but requires no extra instrumentation. This is achieved by the ground state binding of glucose to the boronic acid doping agent. The Glucoview uses a Crystalline Colloidal Array Technology (CCA) in its lens. When the CCA is polymerized within a hydrogel, polymerized CCA optically reports volume changes experienced by the hydrogel [31]. For instance a red shift indicates hyperglycemia and a purple shift indicates hypoglycemia. This is due to the fact that the observed diffraction wavelength is directly related to the spacing between the lattices.

The CCAs are brightly colored because they diffract visible light due to Bragg’s diffraction:

nλ = 2dsinθ where, n is the refractive index of the system, λ is the wavelength of the incident wave and d is the spacing of the lattice and θ is the glancing angle between the diffracting planes and the incident light. Bragg diffraction depends on the refractive index of the system and spacing between the diffracting planes [36].

Benefits of the Glucoview lenses include continuous monitoring of glucose levels. Another benefit of the lens is that you are able to get easily measurable, quantitative results. It also requires no instrumentation to collect fluids and doesn’t require any instrumentation to analyze results. It is non-invasive and would be extremely helpful for caretakers of children and elderly. Most diabetics have vision impairments due to the diabetes which patients may already be used to wearing contacts. A drawback is that it does not collect data for future analysis.  There still needs to be future studies on calibration, environmental effects and eye irritation.

6. Conclusion

While research into noninvasive glucose measurement has been going on for decades, there is still no alternative to the finger-pricking method that diabetics depend on. However, there are promising designs scheduled to make it to market within the next two years.

The product that we feel has the best chance of replacing the traditional finger-pricking method is the Symphony tCGM and its accompanying skin preparation device, Prelude. It is a variation and improvement upon a preexisting and established technology, utilizing the only glucose measurement strategy to ever be commercially accepted, reverse iontophoresis. Echo Therapeutics, the company developing these two products, has already developed numerous prototypes, and has continued to perform clinical testing in order to improve the effectiveness of their designs. Therefore, we look forward to seeing this product on the market at some point in the future, and hopefully it can do the job it was designed for: replace the invasive finger-pricking method that diabetics must deal with on a daily basis.

7. References

[1] "Diabetes Statistics - American Diabetes Association." 26 Jan. 2011. Web. 28 Feb. 2011. .

[2] Mathur, Ruchi. "Hemoglobin A1c Test Information on ." MedicineNet. Ed. William C. Shiel. 15 Jan. 2009. Web. 01 Mar. 2011. .

[3] "Diabetes - What Should My Blood Sugar Levels Be? - Diabetes Mellitus, Type 2 Diabetes, Type 1, and Metabolic Disorders Treatment and Medications on ." MedicineNet. Ed. William C. Shiel. 29 Mar. 2002. Web. 01 Mar. 2011. .

[4] "Product Information." Medtronic Minimed, Inc. Web. 01 Mar. 2011. .

[5] Mendosa, David. "GlucoWatch." David Mendosa: A Writer About Diabetes. 31 Oct. 2007. Web.

01 Mar. 2011. .

[6] C.T.S. Ching, P. Conolly, Asian Journal of Health and Information Sciences, Vol. 1, No. 4,

pp. 393-410, 2007.

[7] A. Ramachandran, et al., A New Non-Invasive Technology to Screen for Dysglycaemia Including Diabetes, Diab. Res. Clin. Pract., 2010.

[8] Tak S Ching, Patricia Connolly, Simultaneous Transdermal Extraction of Glucose and Lactate from Human Subjects by Reverse Iontophoresis, International Journal of Nanomedicine, 2008

[9] Kiel. “Near Infrared Spectroscopy. Introduction into the method.” 2004. Web. 04 Apr. 2011.

[10] Malin, Stephen F., et al. “Noninvasive Prediction of Glucose by Near-Infrared Diffuse Reflectance

Spectroscopy.” Clinical Chemistry, Vol. 45, No. 9. 1999.

[11] "Sensys Medial, Inc – Near-Infrared Spectroscopy." Diabetes Mall. 2010. Web. 03 Apr. 2011. .

[12] 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. .

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

[14] "OptiScanner | Glucose Monitoring." OptiScan Corp. Web. 04 Apr. 2011. .

[15] Christison GB, MacKenzie HA. “Laser photoacoustic determination of physiological glucose concentrations in human whole blood.” Med Biol Eng Comput1993; 31: 284 –90.

[16] MacKenzie, Hugh A. et al. “Advances in Photoacoustic Noninvasive Glucose Testing.” Clinical Chemistry, Vol. 45, No 9. 1999.

[17] 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. .

[18] Current development in non-invasive glucose monitoring, Amaral et al., Science Direct, Medical

Engineering & Physics 30(2008)541-549

[19] A glucose-sensing contact lens: from bench top to patient, Lakowics, Current Opinion

Biotechnology 2005;16,100-107

[20] Fluorescent measurement in the non-invasive contact lens glucose sensor. Diabetes Technology

Therapeutics 2006;8, 312-317

[21] Fluorescence glucose detection: advances toward the ideal in vivo biosensor, Moschou et al

Journal of Fluorescence, 14,5: September 2004

[22] Current Problems and Potential Techniques in In Vivo Glucose Monitoring, Wickramasinghe et al,

Journal of Fluorescence, Vol 14, September 2004

[23] Clinical trial of noninvasive contact lens glucose sensor, March et al Diabetes Technology

Therapeutics. Volume 6; 782-789Dec 2004

[24] 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 2003

[25] The Pursuit of Noninvasive Glucose: “Hunting the deceitful Turkey”, John L. Smith, 2006

[26] Contact-lens Type Glucose Sensor Fabricated using Bionic-Mems Techniques for monitoring of

Tear Sugar, Chu, Tokyo, 2009

[27] "Sentek Group Inc. - Gluvociew ocular Insert." Diabetes Mall. 2010. Web. 28 Apr. 2011.

.

[28] “Symphony tCGM System.” Echo Therapeutics. Web. 28 Apr 2011. .

[29] “Visual Pathways receives federal funding to revolutionize glucose testing for people with diabetes.” Visual Pathways. 25 Feb. 2003. Web. 28 Apr. 2011.

[30] Muscatello et al. Polymerized Crystalline Colloidal Array Sensing of High Glucose Concentrations, Analytical Chemistry, Vol. 81 No. 12, June 15, 2009.

[31] United States Patent 6836337. Dec. 2004.

[32] United States Patent 6187599. Feb 2011.

[33] “The VeraLight SCOUT DS.” VeraLight, Inc. Web. 28 Apr. 2011. .

[34] “The Glucose Monitor.” LighTouch Medical, Inc. Web. 28 Apr. 2011.

.

[35] “Glucose Monitoring.” Orsense Ltd. Web. 28 Apr. 2011.

.

[36] Non-invasive Photonic-Crystal Material for Sensing Glucose in Tears, Khalil, Clinical Chemistry

Vol.50;12:Nov.12,2004

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download