2. Literature Review
Conventional invasive finger-prick methods, though widely used, are associated with significant drawbacks, including pain, discomfort, risk of infection, and reduced patient compliance. These limitations have motivated researchers to explore non-invasive alternatives. Recent literature highlights infrared-based glucose sensing techniques as promising due to their ability to estimate glucose concentrations without the need for blood samples. However, despite encouraging results, challenges remain in terms of accuracy, calibration, and clinical validation. This gap underscores the need for further research, and it provides the rationale for selecting infrared radiation as the focus of the present study.
Diabetes, typically seen as a condition requiring constant care, is a dangerous and often poorly managed illness. It happens when the body cannot keeps blood sugar levels in a normal range [
11]. If blood glucose levels are not controlled, it can lead to serious diabetes complications. These complications include heart disease, renal failure, blindness, amputations, and an increased risk of early death. To prevent the complications of diabetes, it is crucial to manage the condition effectively. Therefore, monitoring and measuring blood glucose levels is a difficult part of managing diabetes, especially for people who are diagnosed with Type I diabetes. Diabetes is a medical illness that happens when the body produces too much insulin or when the cells do not use it properly [
12,
13].
Traditional glucose monitoring systems use the electrochemical method, which means that a small blood sample must be taken by either pricking a finger or inserting a microneedle under the skin in a way that is not too intrusive [
14]. The difference is that the first approach just gives a temporary reading of the glucose level at a certain time and does not need a specialist to accomplish it [
15].
Many individuals with diabetes do not like to check their blood sugar levels all the time. A little blood sample must be collected by pricking the finger or implanting a tiny lancet under the skin for traditional glucose monitors to work [
16]. Self-monitoring blood glucose (SMBG) is the first method. It may be done without help from a doctor and shows the glucose level at one point in time [
9]. On the other hand, the second method employs Continuous Glucose Monitoring (CGM) to keep track of blood glucose levels all the time [
17].
The new study differentiates itself from existing glucose monitoring techniques and the prevalent usage of glucose test strips by eliminating the need to obtain a blood sample for the measurement of blood glucose concentration or analytes [
18]. In contrast, the study endeavors to develop a non-invasive technique using mid-infrared light absorption spectroscopy to quantify a blood analyte by examining the absorption spectra across several wavelengths.
Various methods have been discussed in the literature related to the non-penetrating method in the measurement of the concentration of blood glucose, such as transdermal ISF sampling by reversed iontophoresis, crystalline colloidal array, optical rotation of polarized light, radio-wave impedance, photo-acoustic spectroscopy, scatter changes and fluorescence measurement techniques, and infrared spectroscopy [
19].
Even though there are now various ways to detect blood sugar levels that do not need cutting into the skin, no method has been created that is both specific and highly selective for blood glucose [
20]. Such a method would also need to account for the physiological factors that affect the signal. These factors include tissue structure, local blood flow, and individual differences like age, sex, skin texture, skin color, and the specific location of the measurement [
21].
After extensive laborious experimentation, the present inventor has meritoriously developed a non-invasive method to provide a convenient, inexpensive, portable, accurate and easily operational technique for measuring blood glucose concentration. The method primarily employs the usage of mid-wavelength infrared radiation absorption spectroscopy for measuring blood glucose concentration or any blood analyte [
22].
3. Research Methodology
The primary objective of the present work is the development of a non-invasive and needle-free approach for glucose level detection using infrared-based sensing methodology. This objective was explicitly defined to address the limitations of conventional invasive techniques and to explore the potential of infrared radiation as a reliable alternative.
To ensure clarity and continuity, the methodology has been reorganized into a systematic format. The process begins with the selection of appropriate infrared wavelengths sensitive to glucose absorption, followed by calibration using reference samples. Subsequent steps involve signal acquisition, preprocessing to reduce noise, and application of analytical models for glucose estimation. Each stage is connected logically to the next, thereby improving readability and ensuring that the workflow can be replicated or validated in future studies.
The research work is based on mid-infrared radiation absorption spectroscopy to measure blood glucose concentration by irradiating an area of measurement with a beam of infrared radiation [
23]. The research work uses infrared radiation having wavelengths in a region between 2.5 µm and 25 µm that is absorbed through the area of measurement, for example, a fingertip composed of blood analytes. The present inventor meritoriously investigated and experimentally identified that there are certain wavelengths in the region between 2.5 µm and 25 µm where the glucose molecules are absorbed to the maximum extent as compared to other blood analytes, showing minimum or no interference from other blood analytes. These specific wavelengths add to the quantification of blood glucose concentration with better accuracy compared to known prior art techniques.
The present research work provides a non-invasive method for measuring blood glucose concentration in a warm-blooded subject by irradiating an area of measurement using a beam of infrared radiation and then analyzing the mid-infrared region absorption spectrum at multiple wavelengths. These wavelengths absorb glucose molecules to the maximum extent as compared to other blood analytes, showing minimum or no interference from other blood analytes.
The blood glucose concentration is measured and detected by its unique spectral signature in the mid-infrared radiation region obtained by processing a signal corresponding to blood glucose through a sufficiently high signal-to-noise ratio (SNR) signal processing system. The distinctive spectral signature of glucose is used to determine how much glucose is in a sample using an empirical formula. Along with assessing the amount of glucose in the blood, the technology utilized in this study may also be used to find and analyze any blood analyte that has a distinctive spectral signature [
24].
One embodiment of the present research work relates to a method for measuring an analyte concentration in a subject which comprises the step of irradiating an area of measurement with a beam of infrared radiation, analyzing mid-infrared radiation absorption spectroscopy at multiple wavelengths, and measuring the analyte concentration by detecting and correlating the analyte’s unique spectral signature to the analyte concentration.
In another embodiment, the present research work relates to a method for measuring an analyte in a subject which comprises the step of irradiating an area of measurement by infrared radiation, analyzing mi-infrared radiation absorption spectroscopy at multiple wavelengths, processing a signal corresponding to the analyte through sufficiently high signal-to-noise ratio (SNR) signal processing system to determine analyte’s unique spectral signature, and measuring the analyte concentration by correlating the analyte’s unique spectral signature to the analyte concentration. The accompanying explanation will explain the characteristics, benefits, and new elements of this study. These will also be clear to experts in the field when they review the information provided, or they may be discovered via practical use of the suggested methods. Therefore, this suggested work also includes any alterations and adjustments that fit within the original goals and limits of the project, since these changes would be clear to someone with the right expertise after reading this extensive description.
Figure 2 represents a block diagram for absorption spectroscopy. The selected wavelengths in the desired region of spectroscopy are made incident on the sample. The sample is placed in a container called a cuvette in the form of a solution. The cuvettes are held in place by a detachable holder. In the case of a solid sample, palettes are prepared and placed in the holder. The exact shape and design parameters of the sample chamber and sample holder are based on the type of spectroscopy and the characteristics of the sample. The transmitted radiation is found with the help of a detector, and then the signal is processed based on the initial intensity using a reagent blank.
Infrared light absorption has been the most promising approach for developing non-invasive glucose monitoring. This is because the presence of fingerprint areas for the substances being measured limits interference from physical and chemical factors. Moreover, there is the prospect of universal calibration, which might expand the technology’s use to include substances other than blood glucose [
25]. A major benefit is that this method does not need any chemicals or disposable sensors for measurement, and it may employ fiber optic components. Furthermore, a spectrometer may be built without moving components, which leads to a more robust design.
To test blood glucose, a harmless infrared light is projected on a specific location or a part of the blood vessels in a warm-blooded animal. The blood glucose level in a living organism is determined by examining the spectral data from the radiation that comes out of the region. In addition, other chemical compounds, including water, alanine, albumin, hemoglobin, urea, and lactate, also show high absorption at various infrared wavelengths. Some of these components are found in the bloodstream in a particular amount similar to or greater than that of glucose. Therefore, in this method to proceed, the spectral signature of glucose should be different from the signatures of all other chemical components present in the human body. Again, the precise information must be gathered with a high enough signal-to-noise ratio to reliably distinguish glucose-dependent signals from those produced by other blood components [
26].
The Beer-Lambert Law describes how radiation is absorbed in a material that does not scatter light. According to this rule, the absorbance (A) of a substance that absorbs light, when dissolved in a medium that does not absorb light, is directly related to the concentration of the substance in the solution (c) and the distance the light travels through the solution (b) [
27]:
A is the measurement of absorbance in optical densities, Io is the intensity of radiation that hits the medium, I is the amount of radiation that goes through the medium, a. is the specific extinction coefficient of the absorbing compound measured in micromolar/cm, c is the amount of the absorbing compound in the solution measured in micromolar, and b is the distance between the points where the light enters and leaves the medium. The term I/Io is also called transmittance [
28]. The absorption coefficient of the medium µa is the product of ac. The total extinction coefficient for a medium with many absorbing compounds is the sum of the contributions from each compound:
A chromophore is a material that absorbs photons in the spectrum-relevant part.
Every chromophore has a unique absorption spectrum, which shows how much light it absorbs at each wavelength.
3.1. The Modified Beer-Lambert Law
The Beer-Lambert law is altered when applied to a substance that exhibits a significant amount of scattering. In order to take into account the longer optical path that scattering creates, this modification includes the addition of a multiplicative factor as well as a new term that accounts for scattering losses. Comparatively, the scaling factor is referred to as the differential path length factor (DPF), while the real optical distance is referred to as the differential path length (DP).
where b is the distance in space. The revised Beer-Lambert law, including these two species of knowledge, is presented as follows:
The term G, which stands for compensating for the scattering losses, is unknown and is contingent upon the scattering coefficient of the tissue under investigation and the measurement geometry. The geometrical distance b and the differential path length factor, which is the initial optical route length that the dispersed radiation has, are two pieces of information that are required in order to determine the degree to which the concentration has become different. The distance between the sites where the radiation enters and exits the medium is represented by the letter “b.” However, figuring out DPF is harder. DPF can be quantified in tissue using a variety of techniques. Factors influencing the total optical path length include tissue type, Absorption coefficient, wavelength and geometry of source/detector [
29].
3.2. Optical Signature of Glucose in MIR
The Mid-infrared region, as stated above, encompasses wavelengths ranging from 2.5 µm to 25 µm. Significant absorptions are caused by the excitation of vibrations within the different molecular substructures, corresponding to fundamental and combination bands and providing a unique molecular identification and quantification. Hence, this region is the most common for organic chemists as it gives a “fingerprint “ of the characteristics of molecular species.
This area contains a wide range of absorptions that match the basic vibrations of the species being studied.
Figure 3 shows the infrared source of 2.5 µm to 25 µm, which emits radiation that is incident on the sample. Glucose molecules in the sample absorb radiation, and the difference can be visualized in the transmitted radiation.
3.3. The Glucose Molecule
Glucose is a naturally occurring substance and the main source of energy supply in human beings. As a chemical molecule, glucose can bind covalently with a variety of biological molecules and decompose to CO2 and H2O under certain conditions. Moreover, the RI of the glucose solution is related to the glucose concentration. These attributes can serve as the principle of measurement of glucose concentration. In terms of optics, some optical properties of glucose, like optical rotatory power, infrared absorption, Raman, etc., can also be used for glucose concentration measurement.
3.4. Considerations for Whole Blood and In Vivo Optical Signature
Determination of the optical signature of blood glucose in vivo is of prime importance as it is the first step towards non-invasive measurement [
30]. The absorbance spectrum carried in vivo contains a mixture of spectral signatures of many tissue components, blood constituents and others like water, fat, proteins, etc., along with blood glucose. Water is a very important part of the spectrum of aqueous materials found in the body. The high-water content and the fact that OH groups are very good at absorbing water cause huge water absorption bands to form.
The concept of using multiple wavelengths in collaborative matter reduces the interference from the other components of this complex matrix [
31]. This is because the detection and quantification of glucose based on a single wavelength is susceptible to interference from the other components of the matrix. Theoretically, the optical signature identification should be carried out with as many wavelengths as possible to rule out the possibility of any interference.
Nevertheless, for practical applications, it is typically sufficient to employ spectral data at a limited number of specific wavelengths, rather than the entire spectral spectrum [
32]. We have shown that the glucose concentration in whole blood from a patient can be estimated in vivo using a few selected wavelengths of the optical signature as shown in
Figure 4. In this regard, other sharp peaks for unique quantification come from the second derivative spectra.
The practical issues in working with mid-infrared are path length, blackbody radiation and the signal strength. The impact of these factors can be reduced by a substantial amount by using tuned sources and detectors, and adaptive signal processing of background noise. SNR improvement is achieved by an instrumentation amplifier. Monochromatic radiation with the initial power in the range of 10–20 mW is currently being employed to partly overcome the issue of path length and lower penetration depth [
15].
Calibration procedures include the influence of the various factors like skin color, texture, thickness, age and sex. Compensation for these factors is taken into consideration during data processing.
3.5. Concentration Estimation
Transmittances T at four discrete wavelengths λ1, λ2, λ3 and λ4 are measured one at a time. For a selected wavelength, the final transmittance T (λ) is obtained by averaging at least 10 transmittance readings.
The corresponding absorbance is calculated as:
To get the concentration at these wavelengths, you plug the numbers into Equation (1) of Beer-Lambert’s law. The next step was to get the weighted average of the concentrations, which were calculated by:
The weights W
1, W
2 … W
n are determined by feeding the values determined by standard methods into a neural network during the training process.
Figure 5 shows process of concentration estimation. Significant numbers of the data set are employed in training the network. The procedure is repeated for a different set of wavelengths with a varying number from 1 to 15. Losses due to the scattering effect were compensated in the absorbance calculation as per Equation (4) [
33].
3.6. Research Methodology (Spectral Considerations)
In the present work, infrared radiation within the wavelength range of 2.5–25 µm was selected, corresponding to the mid- to far-infrared region. This spectral window is particularly significant because various biochemical constituents, including glucose, exhibit characteristic vibrational absorption bands in this region. By directing infrared radiation onto biological tissues such as the fingertip, the interaction of glucose-related analytes can be studied in a non-invasive manner.
It is acknowledged, however, that tissue absorption—especially due to the high water content of biological samples—may influence penetration depth and signal acquisition in certain infrared regions. To address this, the manuscript has been revised to provide a more scientifically supported explanation of the chosen wavelength range, highlighting its relevance to glucose sensing while recognizing potential limitations. Appropriate references have been incorporated to substantiate the spectral principles and sensing methodology discussed.
Although the proposed infrared-based sensing technique is entirely non-invasive and does not require blood extraction or needle insertion, conventional glucometer readings obtained through standard finger-prick methods were used as reference values. These invasive measurements served solely for calibration and validation purposes during experimental analysis, ensuring that the non-invasive results could be compared against established clinical standards. This distinction clarifies that the developed methodology itself is needle-free, while reference blood samples were incorporated only to verify accuracy and reliability.
5. Results
5.1. Absorption Peaks for GLUCOSE in Mid Infrared Region
Figure 7 shows the absorption peaks for pure glucose in the mid-infrared range, from 2.2 µm to around 16 µm, as well as their sizes. The results are obtained from the sample analysis at the Department of Pharmacy, Shri G.S. Institute of Technology and Science, Indore, by the FTIR method.
Figure 7 shows the relative absorbance of the various absorption peaks recorded for the pure glucose in the mid-infrared range by an FTIR instrument.
All 75 peaks were recorded in the above range with different peak absorption values.
Figure 8 shows the relative absorbance of the various absorption peaks recorded. The wavelength peaks at which absorbance is greater than 1.2767 are given in
Table 1.
In addition to the above wavelengths, a few more wavelengths are investigated after performing a detailed study on the correlation charts for a sufficiently large number of components of body fluids and drugs. Based on the above study, a few more wavelengths suitable for taking measurements are determined at which the interference from the other components of the matrix is negligible. These are indicated in
Table 2.
The result of this method is used for the measurement of the concentration of glucose in aqueous solution, which is shown in
Figure 9. On the same graph, corresponding results obtained by the standard laboratory methods are also plotted to present the comparison.
The results of the method applied to measure the glucose concentration in the human subject, which was measured by the available glucometer of Control D, are shown in
Figure 10. Measurements for the selected wavelengths were taken multiple times. Also, the patient was allowed to do the glucose testing by the invasive method simultaneously.
Figure 10 also shows the results of the method applied to measure the glucose concentration in a human subject and that measured by the available standard method. The reference was determined by the radiation intensity at known levels of blood glucose for the same patients at times apart from measurements. Our research method demonstrates a notable improvement in accuracy, achieving a rate of 74% compared to the invasive method. This significant enhancement underscores the efficacy of our approach, highlighting its potential as a reliable alternative to traditional invasive techniques.
In comparison to the 62% accuracy found for glucose detection using tear analysis, the MIR method yields a 68% accuracy rate. One significant disadvantage was identified: the detection of the glucose tear analysis method is time-consuming.
5.2. Discussion
To contextualize the contribution of the present work, a comparative analysis was conducted against conventional invasive glucometers and state-of-the-art non-invasive techniques such as NIR-based spectroscopy, MIR-based sensing, and optical antenna-based glucose monitoring. While invasive glucometers remain the clinical gold standard, they are limited by patient discomfort and risk of infection. In contrast, NIR and MIR systems offer non-invasive alternatives but often suffer from signal instability and high instrumentation costs. The proposed approach demonstrates competitive accuracy while maintaining a simplified sensing framework, thereby offering a more patient-friendly solution.
The findings of this study highlight the clinical importance of non-invasive glucose monitoring in the management of diabetes.
Figure 11 shows comparative analysis with different wavelengths. Unlike traditional finger-prick methods, non-invasive approaches significantly reduce patient discomfort and eliminate the risk of infection associated with repeated skin punctures. This improvement in patient experience directly enhances adherence to regular monitoring, which is critical for maintaining glycemic control and preventing long-term complications such as retinopathy, nephropathy, and cardiovascular disease.
Moreover, the ability of non-invasive devices to provide continuous glucose data offers a more comprehensive picture of glycemic trends compared to single-point invasive readings. This continuous monitoring enables early detection of hypo- and hyperglycemic episodes, thereby reducing emergency interventions and improving overall patient safety. Integration of these technologies with digital health platforms further strengthens their clinical utility, allowing remote monitoring and timely intervention by healthcare providers.
While challenges remain in terms of accuracy, cost, and accessibility, the clinical implications of non-invasive glucose monitoring are profound. By improving patient comfort, adherence, and real-time data availability, these technologies represent a transformative step toward more effective and patient-centered diabetes care.
5.3. Comparison with Existing Methods
To position the present work within the existing body of research, a comparative discussion has been included to highlight the differences between the proposed infrared-based non-invasive sensing approach and previously reported techniques. Conventional invasive methods rely on blood sampling through finger-prick tests, which are associated with pain, discomfort, and reduced patient compliance. In contrast, the proposed methodology is entirely non-invasive, eliminating the need for blood extraction and thereby improving patient comfort and usability.
Compared to other non-invasive approaches such as Raman spectroscopy, optical coherence techniques, or sweat-based biosensors, the infrared-based sensing method offers distinct advantages in terms of portability, ease of use, and potential for continuous monitoring. Furthermore, the cost-effectiveness and practical applicability of infrared sensing make it a promising candidate for integration into wearable devices and point-of-care systems.
By incorporating recent literature, this comparison underscores the novelty of the present work and its contribution to advancing non-invasive glucose monitoring technologies.
5.4. Limitations
While the present study demonstrates the potential of infrared-based non-invasive glucose sensing, several limitations must be acknowledged. First, blood viscosity may indirectly influence optical measurements by altering scattering and absorption behavior within biological tissues. Although this effect was relatively limited under controlled conditions, it may contribute to signal variability in real-world applications.
Second, tissue water content represents a major source of absorption in the mid- to far-infrared region, which can reduce penetration depth and complicate signal acquisition. This factor highlights the need for careful wavelength selection and calibration strategies to minimize interference.
Third, inter-individual variability in tissue composition and physiological parameters may affect measurement accuracy, requiring robust models and larger-scale validation studies. Finally, the current methodology was tested under controlled laboratory conditions; translation to clinical practice will demand further optimization, including portable device design, real-time calibration, and long-term stability testing.
5.5. Future Work
Building on the limitations identified, future research should focus on refining infrared-based non-invasive glucose sensing to improve accuracy and clinical applicability. One important direction is the development of advanced signal processing algorithms and correction models to account for physiological factors such as blood viscosity, tissue water content, and inter-individual variability. Incorporating these parameters into predictive models may enhance measurement robustness across diverse patient populations.
Additionally, expanding the study to larger cohorts under real-world conditions will be essential to validate the technique beyond controlled laboratory environments. The integration of portable, wearable devices capable of continuous monitoring represents another promising avenue, enabling real-time glucose tracking and remote healthcare support. Future work should also explore hybrid sensing approaches that combine infrared spectroscopy with complementary modalities, such as Raman spectroscopy or optical coherence techniques, to further strengthen accuracy and reliability.
Finally, collaboration with clinical practitioners and biomedical engineers will be crucial to translate these findings into practical, patient-friendly devices. Such interdisciplinary efforts can accelerate the pathway from experimental validation to widespread adoption in diabetes management.
6. Conclusions
The contribution of this work lies in demonstrating the feasibility of a non-invasive infrared-based glucose measurement framework, supported by spectral response analysis. Interference considerations are acknowledged as part of the broader sensing environment, but the primary focus remains on glucose estimation methodology and patient-friendly implementation.
Observations were made to compare the proposed research method with the existing method. Firstly, the concept was applied to measure the glucose concentration in an aqueous matrix. The concentration of glucose in an aqueous solution was found with the help of a standard laboratory method as well as by the multiple wavelength method. Readings were obtained by using different combinations of the infrared radiation at discrete wavelengths as mentioned. The data thus obtained were analyzed, and weights were determined. Later on, the system was tested with a set of aqueous solutions. The second observation was made on a human using a crude fingertip probe fitted with fiber to incident the radiation on the finger. The transmitted radiation was measured to obtain the transmittance offered at that particular wavelength.
This method is especially useful for diabetic people, as it allows them to track their glucose levels anytime and anywhere, without disturbing their daily routine. In demanding environments where regular medical check-ups are not always possible, this technique provides a quick and authentic way to stay informed about their health. By having continuous access to glucose information, army personnel can manage their energy levels better, prevent sudden health issues, and remain physically and mentally fit while carrying out their responsibilities in challenging and unpredictable conditions.