Editorial Feature

Non-Invasive Method To Monitor Blood Glucose Level With Raman Spectroscopy

Article Updated on 9th December 2020

The number of diabetics in the world is increasing drastically – it is predicted that 1 in 11 adults have diabetes (425 million people). On average, 1 in 2 adults with diabetes are undiagnosed (212 million people). According to the International Diabetes Federation (IDF), over 1 million children and adolescents also have type 1 diabetes.

Treatment costs of diabetes and the complications resulting from it are estimated to be between 10% and 18% of national health care budgets; especially in developed countries.

Continuous monitoring is required for patients with diabetes mellitus to establish the quantity of glucose in the blood. Measurements to do this include pricking the finger with a blood glucose meter, but these can cause serious health concerns and hassle in patient’s daily lives. These problems include the weakening of skin, which leads to trouble with fast healing, and also the risk of infections, pain, etc.

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Therefore, scientists and researchers have looked to develop new methods, which would permit the monitoring of blood glucose levels using Raman spectroscopy. Simplified Raman spectrometer consists of a fiber-optical probe and a computing device which calculates the glucose concentration. One of the benefits would be the miniaturization of the monitoring devices.

This is a short article on a non-invasive method to monitor blood glucose level, with focus on Raman spectroscopy. A broad range of techniques have been applied to the problem of non-invasive blood glucose monitoring, and we will explore them here.


Fluorescence is a highly sensitive technique used to analyze protein-protein, protein-nucleic acid, ligand-receptor, and ligand-lipid interactions. However, there are several drawbacks with its application, including the scattering of tissues.

Numerous approaches have been made for blood glucose monitoring, including excitation through UV light and discovery of fluorescence from the skin, detection of glucose in tears, or alteration in autofluorescence of enzymes, such as NAD(P)H.

Optical Coherence Tomography

Optical coherence tomography detects the backscattered light from the samples. Although this method operates mainly in near-infrared biological windows, allowing for light penetration of about 1 mm into the tissues, it lacks chemical specificity.

The scattering changes induced by a change of refractive index of the medium due to glucose interfere with other tissue components, thus reducing this method's usefulness.

Near-Infrared Spectroscopy

Near-infrared spectroscopy (NIRS) relies on the measurements of transmitted or reflected light at a wavelength range of 750 nm-2500 nm. It allows for deep penetration into the skin, which is used in measurements of the absorption of light by specific molecules, as well as in laser therapy applications.

Near-infrared spectroscopy is an accepted method for the measurements of oxygenation-deoxygenation of hemoglobin and blood volume pulses known as photoplethysmography (PPG).

The complexity of background spectra arising from the presence of other tissue components is a major obstruction in the progress of a noninvasive Raman spectroscopy based blood glucose sensor. Moreover, changes in skin absorption and scattering properties, as well as ecological factors, play significant roles.

Mid-Infrared Spectroscopy

In mid-infrared spectroscopy difficulty in measurements is observed due to the intrusion of hemoglobin and blood.

Raman Spectroscopy

Dingari N C et al., 2015 in their research showed use of NIRS blood glucose sensing, which shows potential due to its chemical steadiness, good breach depth with near-infrared sources, as well as the number of developed methods of quantitative data analysis.

Raman spectra show information about the influence of laser light irradiation which causes a change in molecular energy levels. Random noise, interference of signals from other substances in the tissues, strong fluorescence background are some limiting factors for application of this method.

Simplified Raman Spectrometer Setup

The basic setup consists of components: a laser light source, an optical probe, a spectrometer and a PC or other data-processing device.

Setup Simplification

The majority of Raman studies are performed using benchtop laboratory systems. Such devices are often massive, immobile, and expensive. However, simplified Raman spectrometer is nonmassive, mobile and less expensive. With the use of modern techniques, it is possible to allow for further simplification of such devices, without the loss in their performance.

A simplified detection setup requires the use of a set of photodetectors and optical filters in the place of a spectrograph, diffraction grating, and a CCD camera. A miniature IR diode laser modules can be used to reduce space requirements. Chemometric data processing will be required to detect Raman band intensity with change in glucose quantity.

It is possible to detect the bands which bear the informational content related to the investigated analyte, which can be seen in the specific components. Then, only Raman signal in those selected bands should be detected by a set of photodetectors; the received data is transferred to a device where the data processing can be performed and the data projected to the end-user; possible devices include a laptop, microcontroller, or a smartphone.

Therefore, miniaturization, the permutation of advanced techniques and harmonized detection scheme will solve the inter-patient unevenness and allow for commercial purposes. So far such use of a synchronous detection for non-invasive Raman spectroscopy has not been investigated in-depth.

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