Seeking the Key to Non-Invasive Diabetes Diagnosis and Monitoring

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Diabetes is a chronic disease that affects more than 420 million people worldwide, roughly 8.5% of the population. Rates of diabetes have nearly doubled in the last three decades as more developing countries face increased urbanization and adopt Western eating habits.

Treating diabetes requires constant monitoring and maintenance, which poses a significant burden for the afflicted, their families, and their communities. Additionally, increases in the rates of diabetes are taxing healthcare systems and national economies.

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Current diagnostic standards and therapies for diabetes are invasive and burdensome, but recent advances in medical sensing technology have put non-invasive diabetes testing and blood glucose monitoring within the reach of medical researchers. Avantes is proud to be at the forefront of the exciting breakthroughs emerging in the field of biomedical sensing.

Current Standards for the Diagnosis and Treatment of Diabetes

The diagnosis and ongoing management of diabetes currently require direct measurement of blood glucose or glycated hemoglobin levels. There are a few methods used by medical professionals, including glucose tolerance tests and random or fasting blood sugar tests. These methods are primarily known as amperometric detection tests because the reaction of blood sugar to a reagent generates a small electrical charge proportional to the levels of sugar in the sample. This method can be very accurate when performed in a laboratory setting and is also standardized and well understood.

Current testing methods, while well established, still pose numerous problems for patients and medical professionals around the world. In some cultures, there may be taboos or societal strictures regarding the drawing of blood that makes it difficult to secure patient compliance. Blood samples are also unstable and require refrigeration. This can be a significant issue in developing nations, especially in rural areas where electricity and refrigeration might not be readily available.

The chronic nature of managing diabetes requires those afflicted to monitor their glucose levels frequently on a daily basis. This involves collecting a tiny sample of blood, usually with a lancet prick to a finger. This procedure can be painful and can create additional complications if a diabetic has suppressed healing abilities, and they must be performed repeatedly on a daily basis.

While handheld blood glucose monitors are becoming more readily available around the world (accounting for roughly 85% of all biomedical sensors sold to consumers today), the monitoring of glucose is still a manual process requiring test strips. Combined with environmental factors that could affect the test such as temperature and humidity, these blood-testing meters might not provide accurate measurements under all conditions.

The Search for Non-Invasive Glucose Monitoring

Because of the invasive and repetitive nature of glucose testing, and the difficulties associated with blood testing around the world, researchers are eagerly seeking non-invasive alternatives to standard amperometric detection tests. Researchers have investigated many alternatives including electrochemical testing and carbon nanotube-based methods. Recently, the focus has shifted to optical methods of detection using NIR absorbance and Raman spectroscopy.

Even among researchers working with NIR spectroscopy, there are several avenues of investigation. Beyond blood glucose, it is possible to detect glycated proteins (proteins that have bonded to glucose) in hair and fingernails, in the aqueous humours of the eye, and in urine.

Two of the most promising methods under investigation include the use of near-infrared light to measure blood glucose directly through the skin, with much the same functional design as a pulse oximeter. Another method under investigation involves the use of fingernails as a testing sample.

The largest hurdle researchers face when developing a new non-invasive testing protocol for diabetes is the creation of standardized models for interpreting results. Measurement parameters must account for absorption patterns, linear uptake rates, and countless other factors that doctors and scientists must understand to develop a repeatable and standardized model for interpreting and predicting spectra response. There are also variations across human characteristics and these variations must also be neutralized to allow for the standardization of a new protocol.

Near-Infrared and the Diagnostic Window

Much of the optical sensing technology for biomedical applications centers around the near-infrared due to a peculiar phenomenon researchers refer to as the diagnostic window or the optical window.

Light absorption by human tissues is wavelength-specific. Proteins and DNA absorb the ultraviolet (UV) spectrum, visible light is absorbed by hemoglobin in the blood, and the infrared range is highly absorbed by water. At the very end of the visible spectrum, however, and into the near-infrared (NIR) range between 650 nm and 1100 nm, there is little absorption by water or hemoglobin and less scattering than in the UV and visible ranges. And, most importantly, it is possible to use light in this range on living subjects without causing tissue damage.

Try this:

In a darkened room, shine a strong flashlight through the palm of your hand. Looking at the back of your hand, you will see a red spot of light on the back of the hand. What you see is the tail end of the spectrum of visible light, the red light between 650-750 nm, which falls within the optical diagnostic window of rn650-1100 nm

This optical diagnostic window allows doctors and researchers a view into the body. Dr Frans F. Jöbsis at Duke University demonstrated in his landmark 1977 study that oxygenated and deoxygenated tissues show distinct absorption properties in the NIR. Since then, NIR spectroscopy has been used in the study of metabolic diseases like diabetes, cancers, cardiovascular diseases, neurological disorders, and many other conditions afflicting our societies.

NIR Raman Spectroscopy

Recent experiments in the development of optical biosensors couple the optical window available in the Vis/NIR range with the molecular fingerprinting specificity of Raman spectroscopy. The potential of this technique is very promising, but the added complexity of Raman analysis increases the barriers to developing standardized diagnostic models.

Visible Spectrum — Visible Light Spectrum

Glycated Nail Protein Suitability for Diabetes Testing

Because glucose testing is of vital importance to a growing diabetic population, and because the demand for glucose sensors represents 85% of the biosensors market, Biomedical device developers are in a race to present the next wave of advancement in blood monitoring technology.

One line of investigation involves the assay of glycated keratin proteins. Keratin, the protein that makes up our fingernails and hair, can bond with glucose. This glycation has a linear relationship to blood glucose levels over time. Researchers seeking a spectral model for diagnosing diabetes choose fingernails due to observable differences in nail characteristics of diabetics. For the purposes of developing a standardized model, fingernails are also preferable because there is less growth-rate variation than for hair.

The use of fingernail clippings in this method has the potential to improve testing for the initial diagnosis of diabetes, especially in developing nations. Fingernail clippings can be collected without pain and without requiring special training. Additionally, psychological and cultural attitudes regarding fingernail clippings are relaxed compared to bodily fluids like blood; and since they are stable, fingernails can be stored without refrigeration for several weeks without loss of sample viability.

For testing, fingernail samples are ground and mixed with a reactive agent. Because nails are not very permeable to these reactive agents, the samples require preparation time and possibly further processing. This method, while minimally invasive, does still require expert sample preparation that should be done in a lab by trained personnel and, unfortunately, will not be suitable for home glucose monitoring.

Transmittance via Earlobe for Home Use

The transmittance measurement technique is another one that researchers are developing, and one that would be suitable for home monitoring applications. Lobe transmittance measurements actually require a combination of wavelengths applied to the ear lobe simultaneously. The attenuated light is caught by sensors on either side of the earlobe. First, the reflectance of green visible light is used to determine skin parameters such as tissue thickness. Next, red light transmittance/absorption is used to determine blood volume, and finally, the NIR wavelength is used to determine glucose concentrations.

This method shows a great deal of promise, as it is a simple design involving a clip for the earlobe which connects to a spectrometer with fiber cables making it relatively easy for anyone without special training. Additionally, the lack of sample preparation and easy design means that it will not require laboratory oversight and can be performed by anyone.

Overcoming Barriers to Optical Glucose Monitoring

For many diagnostic methods being investigated today, the main barrier to full testing validation is researchers’ ability to reconcile individual variation to create a standardized model for analysis of the results. The work of these scientists and experts brings us closer every day to the reality of non-invasive, inexpensive, and accurate blood glucose monitoring alternatives.

While it is impossible to predict when a new method or technology will win the approval of the Federal Drug Administration (FDA) or relevant medical certifying bodies, it is becoming increasingly likely. In the near future, diabetes patients will no longer need to suffer through painful blood testing and it will be thanks to the work of dedicated scientists, doctors, and researchers working today on these exciting optical testing methods.

Avantes at the Forefront of Medical Research

Avantes is proud to be at the forefront of this research. Avantes equipment is found in labs all over the world, supporting the doctors and scientists working on diabetes research.

Dr. Angelika M. Domschke, previously with the University of Hamburg, is researching ophthalmic glucose monitoring using the Avantes AvaSpec-ULS2048 to test and monitor the development of a contact lens that sits in the eye and provides continuous monitoring. The ULS2048 provided Dr. Domschke and her team with exceptional response speed and a signal-to-noise ratio of 200:1. This is the reliable workhorse of the Avantes StarLine spectrometers.

Researchers at Groningen University in the Netherlands are studying skin fluorescence to monitor vascular damage. Diabetes patients are susceptible to vascular damage, poor circulation, and slow healing in their extremities, this team aims to make treating diabetic foot complications easier. These researchers used an older model from Avantes, but our AvaSpec-Hero offers the highest sensitivity due to the 0.22 numerical aperture of the optical bench and thermo-electrically cooled back-thinned detector. This instrument is ideally suited for the demands of high-sensitivity measurements in the NIR.

Dr Ishan Barman, in his doctoral thesis in the MIT Department of Mechanical Engineering, studied the challenge of developing accurate diagnostic models with NIR Raman spectroscopy. In his work ‘Unraveling the puzzles of spectroscopy-based non-invasive blood glucose detection,’ his system recommendations for a spectrometer describe an instrument that matches the system specs of the AvaSpec-Hero. This instrument offers optimal sensitivity with a 0.22 numerical aperture which collects the full light carried by a fiber optic. The Hero offers the optimal balance between high sensitivity and high resolution, with a TE Cooled back-thinned detector. It is capable of facilitating longer integration times in low-light applications, making this your optimal choice in Raman systems.

Researchers around the world trust Avantes instruments for biomedical research. The Avantes SensLine of spectrometers offers several models tailored for applications with low light levels with standard or thermoelectrically cooled options.

Another great solution is the Avantes CompactLine of miniature spectrometers. The AvaSpec-Mini packs a lot of power into a compact size. At about the size of a deck of cards, this unit performs on par with many of our larger form factor instruments.

Contact an Avantes Sales Engineer today to find out which Avantes system is right for your biomedical research application.