Noninvasive Glucose Monitoring Using Spectroscopic Methods

Abstract

Noninvasive glucose monitoring has long been considered the “holy grail” of diabetes management, offering the promise of accurate, painless, and convenient measurement without the need for blood sampling. Invasive self-monitoring approaches remain the clinical standard but impose significant physical and psychological burdens on patients. Over the past three decades, extensive research has been devoted to developing noninvasive or minimally invasive methods for measuring blood glucose, ranging from optical spectroscopy (near-infrared, mid-infrared, Raman, autofluorescence) to biophysical and biochemical approaches such as radiofrequency impedance, nuclear magnetic resonance, and interstitial fluid extraction. Despite substantial technological innovation and billions of dollars invested, none of these approaches has achieved reliable, regulatory-approved performance for continuous glucose monitoring. This set of articles reports recent research work on noninvasive glucose measurement. In general, these articles are overly optimistic, reporting success for small datasets and mostly feasibility-type work. It is important to note that although interesting, these studies fall far short of clinical-level studies and U.S. FDA approval. In reviewing these studies, it is important to highlight the persistent barriers that must be overcome to translate research into practical, approved medical devices for home or clinical diabetes care.

Fingerstick bead of blood for traditional invasive glucose testing © ddukang-chronicles-stock.adobe.com

Introduction

Diabetes mellitus represents one of the most significant global health challenges of the modern era. Effective management depends critically on the ability to measure and control blood glucose concentrations (1). Conventional self-monitoring relies on invasive finger-prick sampling and enzymatic glucose assays, which—despite their accuracy—introduce pain, inconvenience, and psychosocial barriers that limit patient compliance. The need for accurate, painless, and user-friendly glucose monitoring technologies has therefore driven intense interest in noninvasive measurement methods (2).

The appeal of noninvasive glucose monitoring lies in its potential to provide real-time, continuous assessment of glucose metabolism without the trauma of blood extraction. Technologies investigated include optical spectroscopy in the near- and mid-infrared, Raman scattering, autofluorescence, and white light scattering, all of which attempt to correlate spectral features with glucose concentration. Other approaches have examined radiofrequency impedance, microvascular retinal analysis, acoustic impedance, nuclear magnetic resonance spectroscopy, and even glucose-responsive hydrogels in tear fluid. Parallel developments in nearly noninvasive and minimally invasive methods—such as reverse iontophoresis, interstitial fluid extraction, and implantable optical or enzymatic sensors—have demonstrated feasibility but continue to struggle with calibration drift, biological interference, inflammation, and limited accuracy (2).

Despite decades of effort and massive financial investment, no fully noninvasive glucose monitor has yet gained FDA approval for clinical use. The challenges are both technical and biological: glucose is a weak optical absorber compared to dominant endogenous molecules such as water, lipids, proteins, and hemoglobin, making selective detection extremely difficult. Furthermore, local tissue responses, interstitial-blood glucose lag times, and device calibration needs complicate accurate measurement. Yet the goal remains compelling: a simple, portable, and reliable noninvasive glucose monitor that not only reports absolute glucose levels but also tracks trends and rates of change in real-time, thereby transforming the landscape of diabetes care (2).

Here are recent news articles posted in Spectroscopy for noninvasive glucose monitoring research.

Near-Infrared Spectrophotometric Analysis of Human Blood Glucose: Influence of Repeating Errors on Prediction Accuracy

The authors examine the influence of repeating errors on the results of human blood glucose measurements using NIR. Near-infrared (NIR) spectrophotometric analysis is the most promising approach for noninvasive blood glucose measurement, and usually obtains a diffuse-reflectance spectrum. To decrease the specular reflection, the diffuse reflection spectrum is typically acquired by touch measurement, such that the optical probe directly touches the tested part. In the case of constant temperature, when repeatedly measuring by moving the tested finger from the optical probe then turning it back quickly, the acquired plurality of spectra result in a discrepancy. Specifically, there are many repeating errors among the tested spectrum data. Blood glucose concentrations change somewhat in a very short time span; therefore, slight changes in the pressure and temperature are the main reasons for repeating errors, which are the main factors influencing the accuracy of NIR noninvasive blood glucose measurement (3).

New Mini-NIR Device Shows Promise for Non-Invasive Blood Glucose Monitoring

Researchers have developed a small near-infrared (NIR) spectrometer dedicated to achieve painless, accurate glucose measurements. A team of scientists from the SRM Institute of Science and Technology in India has made significant strides in developing a non-invasive method for blood glucose monitoring. Their pilot study, published in IRBM, explores the potential of near-infrared (NIR) optical techniques as an alternative to traditional invasive glucose testing methods (4).

Glucose Monitoring for Diabetes Using Non-Invasive Raman Spectroscopy

Researchers at the Institute of Photonics and Photon-Technology, Northwest University, China, have described a non-invasive method for monitoring blood glucose using Raman spectroscopy. Their study, published in Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, explores the technique’s effectiveness in both animal models and human subjects, showing promise for future clinical applications (5).

Molar Absorptivity Model Powers Near-Infrared Glucose Testing

Researchers from Sharif University of Technology, Tehran, present an approach using near-infrared absorbance and molar absorptivity to estimate blood glucose with a drawn blood sample—showing comparable performance to methods that apply principal components regression (PCR) (6).

New Infrared Device Measures Blood Sugar Without a Prick

Researchers have developed a miniature non-invasive blood glucose monitoring system using near-infrared (NIR) technology. The compact, low-cost device uses infrared light to measure sugar levels through the fingertip, offering a painless alternative to traditional finger-prick tests (7).

Precision Signal Boost for Non-Invasive Blood-Glucose Tests with Advanced FT-IR and Machine Learning

A new study demonstrates that combining multi-pass FT-IR with a quantum cascade laser, two-dimensional correlation spectroscopy, and machine learning reportedly boosts the accuracy of non-invasive blood-glucose testing. The approach reports a 98.8% classification accuracy, suggesting potential for clinically viable, needle-free diabetes monitoring (8).

Mid-Infrared Emission Study Proposes New Principle for Noninvasive Blood Sugar Measurement

A research team in Japan has proposed a new principle, called the emission integral effect, to explain how mid-infrared passive spectroscopic imaging can detect blood glucose levels without invasive methods. Their findings suggest that dilute components like glucose may be more identifiable than concentrated ones when using this technique (9).

References

(1) World Health Organization. Diabetes. https://www.who.int/news-room/fact-sheets/detail/diabetes (accessed 2025-09-17).

(2) Workman, J. J.; Lambert, C. R.; Coleman, R. L. Non-Invasive Measurement of Analytes. U.S. Patent 8,509,867, August 13, 2013. https://patents.google.com/patent/US8509867B2/en (accessed 2025-09-17).

(3) Spectroscopy Editors. Near-Infrared Spectrophotometric Analysis of Human Blood Glucose: Influence of Repeating Errors on Prediction Accuracy. Spectroscopy 2010, June 1. https://www.spectroscopyonline.com/view/near-infrared-spectrophotometric-analysis-human-blood-glucose-influence-repeating-errors-prediction (accessed 2025-09-17).

(4) Sameera, F. M.; Kumar, J. S.; Jeya, P. A.; Selvaraj, J.; Angeline, K. S. Potential of Near-Infrared Optical Techniques for Non-Invasive Blood Glucose Measurement: A Pilot Study. IRBM 2025, 46 (1), 100870. DOI: 10.1016/j.irbm.2024.100870

(5) Liu, J.; Chu, J.; Xu, J.; Zhang, Z.; Wang, S. In Vivo Raman Spectroscopy for Non-Invasive Transcutaneous Glucose Monitoring in Animal Models and Human Subjects. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2025, 329, 125584. DOI: 10.1016/j.saa.2024.125584

(6) Barati, H.; Mousavi Madani, A.; Shadzinavaz, S.; Fardmanesh, M. Principal Component Analysis and Near-Infrared Spectroscopy as Noninvasive Blood Glucose Assay Methods. Appl. Spectrosc. 2025, 79 (7), 1047–1055. DOI: 10.1177/00037028241300535

(7) Al-Jammas, M. H.; Iobaid, A. S.; Al-Deen, M. M.; Aziz, Y. W. A Non-Invasive Blood Glucose Monitoring System. Comput. Biol. Med. 2025, 191, 110133. DOI: 10.1016/j.compbiomed.2025.110133

(8) Song, L.; Han, Z.; Shum, P. W.; Lau, W. M. Enhancing the Accuracy of Blood-Glucose Tests by Upgrading FT-IR with Multiple-Reflections, Quantum Cascade Laser, Two-Dimensional Correlation Spectroscopy and Machine Learning. Spectrochim. Acta, Part A 2025, 327, 125400. DOI: 10.1016/j.saa.2024.125400

(9) Anabuki, D.; Tahara, S.; Yano, H.; Nishiyama, A.; Wada, K.; Nishimura, A.; Ishimaru, I. Emission Integral Effect on Non-Invasive Blood Glucose Measurements Made Using Mid-Infrared Passive Spectroscopic Imaging. Sensors 2025, 25 (6), 1674. DOI: 10.3390/s25061674