More than 420 million people globally, roughly 8.5% of the population, are affected by diabetes, a chronic medical condition. Rates of diabetes have almost doubled over the past three decades as more developing countries experience increased urbanization and adopt western eating habits.
Non invasive testing
Treating diabetes needs constant monitoring and maintenance which poses a major burden for the afflicted, their communities and their families. Moreover, increasing rates of diabetes is taxing on national economies and healthcare systems.
Present diagnostic standards and therapies for diabetes are burdensome and invasive, but latest advances in medical sensing technology has put non-invasive diabetes testing and blood glucose monitoring in reach of Medical Researchers. Avantes is proud to be on the forefront of the exciting advances evolving in the area of biomedical sensing.
Current Standards for the Diagnosis and Treatment of Diabetes
The diagnosis and ongoing management of diabetes presently needs direct measurement of blood glucose or glycated hemoglobin levels. There are a few methods used by medical professionals, including the random or fasting blood sugar tests and glucose tolerance tests. These methods are mainly referred to as amperometric detection tests because the reaction of blood sugar to a reagent produces a small electrical charge in proportion to the levels of sugar in the sample. This method can be extremely accurate when carried out in a laboratory setting and is also well understood and standardized.
Even though the current testing methods are well-established, they still pose many problems for medical professionals and patients all over the world. In some cultures, there may be societal strictures or taboos concerning the drawing of blood that makes it difficult to secure patient compliance. Blood samples are also unstable and need refrigeration. This can be a major issue in developing nations, particularly rural areas where refrigeration and electricity might not be readily available.
The chronic nature of managing diabetes needs those afflicted to frequently monitor their glucose levels on a daily basis. This includes collecting a small sample of blood, usually with a lancet prick to a finger. This can be a painful procedure and can lead to additional complications if a diabetic has suppressed healing abilities, and they must be carried out repeatedly on a daily basis.
Although handheld blood glucose monitors are becoming more readily available all over the world (accounting for about 85% of all biomedical sensors currently sold for consumers), the monitoring of glucose is still considered to be a manual process needing test strips. Together with environmental factors capable of affecting the tests, such as temperature and humidity, these blood testing meters may fail to provide accurate measurements under all conditions.
The Search for Non-Invasive Glucose
Researchers are eagerly looking out for non-invasive alternatives to standard amperometric detection tests because of the repetitive and invasive nature of glucose testing, and the difficulties related to blood testing worldwide. Researchers have analyzed many alternatives including carbon nanotube-based methods and electrochemical testing. The focus has recently shifted to optical methods of detection using Raman spectroscopy and NIR absorbance.
Even among Researchers working with NIR spectroscopy, there are a number of avenues of investigation. Beyond blood glucose, glycated proteins (proteins that have bonded to glucose) can be detected in fingernails and hair, in urine and in the aqueous humors of the eye.
Two of the most promising methods under study include the use of near infrared light in order to measure blood glucose directly via the skin, with much the same functional design as a pulse oximeter. The use of fingernails as a testing sample is another method under investigation.
The biggest hurdle Researchers face when developing a new non-invasive testing protocol for diabetes is the development of standardized models for understanding results. Measurement parameters must account for linear uptake rates, absorption patterns and countless other factors that Scientists and Doctors must understand in order to develop a standardized and repeatable model for interpreting and predicting spectra response. There are also differences across human characteristics and these differences must also be neutralized to allow for standardization of a new protocol.
Near Infrared and the Diagnostic Window
Much of the optical sensing technology for biomedical applications revolves around the near infrared because of a peculiar phenomenon researchers refer to as the optical window, or the diagnostic window.
Light absorption by human tissues is specific to wavelength. DNA and proteins absorb the ultraviolet (UV) spectrum, the infrared range is highly absorbed by water, and the visible light is absorbed by hemoglobin in the blood. However, at the very end of the visible spectrum, and into the near infrared (NIR) range between 650 nm and 1100 nm, there is little absorption by hemoglobin or water and less scattering than in the UV and visible ranges. Most importantly, it is possible to use light in this range on living subjects without causing any damage to the tissue.
Try this: In a darkened room, individuals can shine a powerful flashlight via their palm. Looking at the back of their hand, they will observe a red spot of light on the back of the hand. What they 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 650-1100 nm.
Through this optical diagnostic window, Researchers and Doctors can look inside the body. In his landmark 1977 study, Dr. Frans Jobsis at Duke University demonstrated that deoxygenated and oxygenated tissues show distinct absorption properties in the NIR. Since then, NIR spectroscopy has been employed in the study of metabolic diseases like cancers, cardiovascular diseases, diabetes, neurological disorders and several other conditions afflicting the societies.
NIR Raman Spectroscopy
In the latest experiments dealing with the development of optical biosensors, the optical window available in the Vis/NIR range is coupled with the molecular fingerprinting specificity of Raman spectroscopy. While the potential of this technique is extremely promising, the added complexity of Raman analysis increases the barriers to developing standardized diagnostic models.
Glycated Nail Protein Suitability for Diabetes Testing
Biomedical Device Developers are competing to present the next wave advancement in blood monitoring technology since glucose testing is of vital importance to a growing diabetic population, and also because the demand for glucose sensors accounts for 85% of the biosensors market.
One line of investigation deals with the assay of glycated keratin proteins. Keratin, the protein that makes up the hair and fingernails, can bond with glucose. This glycation has a linear relationship to blood glucose levels over time. Researchers in search of a spectral model for diagnosing diabetes select fingernails because of observable differences in nail characteristics of diabetics. Fingernails are also preferable for the purposes of developing a standardized model as there is less growth rate variation than for hair.
The use of fingernail clippings in this method has the potential to enhance testing for initial diagnosis of diabetes, particularly in developing nations. It is possible to collect fingernail clippings without pain and without the need for special training. Additionally, cultural and psychological attitudes regarding fingernail clippings are relaxed when compared to bodily fluids such as blood; and since fingernails are stable, they can be stored without refrigeration for a number of weeks without loss of sample viability.
Fingernail samples are ground and mixed with a reactive agent for testing. Since nails are not extremely permeable to these reactive agents, the samples need preparation time and possibly further processing. This method, while minimally invasive, still needs expert sample preparation that should be performed in a lab by trained personnel and, unfortunately, will not be appropriate for home glucose monitoring.
Transmittance via Earlobe for Home Use
Researchers are also developing the transmittance measurement technique, which would be perfect for home monitoring applications. Lobe transmittance measurements actually need a combination of wavelengths applied to the ear lobe at the same time. The attenuated light is caught by sensors on either side of the ear lobe. First, the reflectance of green visible light is used for determining skin parameters such as tissue thickness. This is followed by using red light transmittance/absorption to determine blood volume, and finally the NIR wavelength is used to determine glucose concentrations.
This method shows a good deal of promise as it is a simple design involving a clip for the ear lobe which is connected to a spectrometer with fiber cables making it relatively easy for anyone without special training. Additionally, easy design and the lack of sample preparation mean that it can be performed by anyone and will not require laboratory oversight.
Overcoming Barriers to Optical Glucose Monitoring
For many diagnostic methods that are currently being investigated, the main barrier to full testing validation is the ability of the Researchers to settle individual variation in order to create a standardized model for analysis of the results. The work of these experts and Scientists brings us closer every day to the reality of inexpensive, non-invasive and accurate blood glucose monitoring alternatives.
While it is not possible to predict when a new technology or method will win approval of the Federal Drug Administration (FDA) or relevant medical certifying bodies, the possibility is becoming more realistic. Thanks to the work of dedicated Doctors, Scientists and Researchers working today on these exciting optical testing methods, diabetes patients will no longer need to suffer through painful blood testing in the near future.
Avantes on the Forefront of Medical Research
Avantes is proud to be on the forefront of this research. Avantes equipment is used in laboratories throughout the world, supporting the Scientists and Doctors working on diabetes research.
Dr. Angelika M. Domschke, previously with the University of Hamburg, is researching ophthalmic glucose monitoring with the help of the Avantes AvaSpec-ULS2048 in order to test and monitor the development of a contact lens that sits in the eye and provides constant monitoring. The ULS2048 provided Dr. Domschke and her team with excellent response speed and a signal to noise ratio of 200:1. This is considered to be the reliable workhorse of the Avantes StarLine spectrometers.
Researchers at Groningen University in the Netherlands are currently studying skin fluorescence in order to monitor vascular damage. Diabetes patients are vulnerable to poor circulation, vascular damage and slow healing in their extremities, and this team focuses on making the treatment of diabetic foot complications easier.
The Researchers used an older model from Avantes, but the AvaSpec-HS1024x58/122TEC provides the highest sensitivity because of the thermo-electrically cooled, back-thinned detector and the 0.22 numerical aperture of the optical bench. This instrument is preferably suited for the demands of high sensitivity measurements in the NIR.
Dr. Ishan Barman, in his doctoral thesis at MIT Department of Mechanical Engineering, studied the challenge of producing 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 talk about an instrument that matches the system specifications of the AvaSpec-HS1024x58TEC (AvaSpec-HERO).
This instrument provides optimal sensitivity with a 0.22 numerical aperture which is capable of collecting the full light carried by a fiber optic. The AvaSpec-Hero provides the optimal balance between high resolution and high sensitivity, with a TE Cooled back-thinned detector. It has the potential to facilitate longer integration times in low light applications making this the optimal choice in Raman systems.
Researchers from all over the world trust Avantes instruments for biomedical research. The Avantes SensLine of spectrometers offer a number of models customized for applications with low light levels with standard or thermoelectrically cooled options.
The Avantes CompactLine of miniature spectrometers is another great solution. The AvaSpec-Mini is capable of packing a lot of power into a compact size. At about the size of a deck of cards, this unit operates on par with many of Avantes’ larger form factor instruments.
This information has been sourced, reviewed and adapted from materials provided by Avantes BV.
For more information on this source, please visit Avantes BV.