The use of microwave technology is currently under investigation for non-invasive estimation of glycemia in patients with diabetes. Due to their construction, metamaterial (MTM)-based sensors have the potential to provide higher sensitivity of the phase shift of the S21 parameter (∠S21) to changes in glucose concentration compared to standard microstrip transmission line (MSTL)-based sensors. In this study, a MSTL sensor and three MTM sensors with 5, 7, and 9 MTM unit cells are exposed to liquid phantoms with different dielectric properties mimicking a change in blood glucose concentration from 0 to 14 mmol/L. Numerical models were created for the individual experiments, and the calculated S-parameters show good agreement with experimental results, expressed by the maximum relative error of 8.89% and 0.96% at a frequency of 1.99 GHz for MSTL and MTM sensor with nine unit cells, respectively. MTM sensors with an increasing number of cells show higher sensitivity of 0.62° per mmol/L and unit cell to blood glucose concentration as measured by changes in ∠S21. In accordance with the numerical simulations, the MTM sensor with nine unit cells showed the highest sensitivity of the sensors proposed by us, with an average of 3.66° per mmol/L at a frequency of 1.99 GHz, compared to only 0.48° per mmol/L for the MSTL sensor. The multi-cell MTM sensor has the potential to proceed with evaluation of human blood samples.

Department of Radiation Oncology Thomas Jefferson University Philadelphia PA 19107 USA

Faculty of Biomedical Engineering Czech Technical University Prague 160 00 Prague Czech Republic

See more in PubMed

Wilkinson I.B., Raine T., Wiles K., Goodhart A., Hall C., O’Neill H. Oxford Handbook of Clinical Medicine. 10th ed. OUP Oxford; Oxford, UK: 2017.

Siddiqui S.A., Zhang Y., Lloret J., Song H., Obradovic Z. Pain-Free Blood Glucose Monitoring Using Wearable Sensors: Recent Advancements and Future Prospects. IEEE Rev. Biomed. Eng. 2018;11:21–35. doi: 10.1109/RBME.2018.2822301. PubMed DOI

Lin X., Xu Y., Pan X., Xu J., Ding Y., Sun X., Song X., Ren Y., Shan P.-F. Global, Regional, and National Burden and Trend of Diabetes in 195 Countries and Territories: An Analysis from 1990 to 2025. Sci. Rep. 2020;10:14790. doi: 10.1038/s41598-020-71908-9. PubMed DOI PMC

Tasker R.C., Acerini C.L., Holloway E., Shah A., Lillitos P. Oxford Handbook of Paediatrics. 3rd ed. Oxford University Press; Oxford, UK: 2021.

Bruen D., Delaney C., Florea L., Diamond D. Glucose Sensing for Diabetes Monitoring: Recent Developments. Sensors. 2017;17:1866. doi: 10.3390/s17081866. PubMed DOI PMC

Tang L., Chang S.J., Chen C.-J., Liu J.-T. Non-Invasive Blood Glucose Monitoring Technology: A Review. Sensors. 2020;20:6925. doi: 10.3390/s20236925. PubMed DOI PMC

Jang C., Lee H.-J., Yook J.-G. Radio-Frequency Biosensors for Real-Time and Continuous Glucose Detection. Sensors. 2021;21:1843. doi: 10.3390/s21051843. PubMed DOI PMC

Yilmaz T., Foster R., Hao Y. Radio-Frequency and Microwave Techniques for Non-Invasive Measurement of Blood Glucose Levels. Diagnostics. 2019;9:6. doi: 10.3390/diagnostics9010006. PubMed DOI PMC

GlucoTrack®, Your Track to Health! Integrity Applications; Ashdod, Israel: 2021. DF-F.

CoG—Hybrid Glucometer|Cnoga Digital Care. [(accessed on 15 August 2021)]. Available online: https://www.cnogacare.co/cog-hybrid-glucometer.

Pleus S., Schauer S., Jendrike N., Zschornack E., Link M., Hepp K.D., Haug C., Freckmann G. Proof of Concept for a New Raman-Based Prototype for Noninvasive Glucose Monitoring. J. Diabetes Sci. Technol. 2021;15:11–18. doi: 10.1177/1932296820947112. PubMed DOI PMC

Lundsgaard-Nielsen S.M., Pors A., Banke S.O., Henriksen J.E., Hepp D.K., Weber A. Critical-Depth Raman Spectroscopy Enables Home-Use Non-Invasive Glucose Monitoring. PLoS ONE. 2018;13:e0197134. doi: 10.1371/journal.pone.0197134. PubMed DOI PMC

Gabriel C., Gabriel S., Corthout E. The Dielectric Properties of Biological Tissues: I. Literature Survey. Phys. Med. Biol. 1996;41:2231–2249. doi: 10.1088/0031-9155/41/11/001. PubMed DOI

Beam K., Venkataraman J. Phantom Models for In-Vitro Measurements of Blood Glucose; Proceedings of the 2011 IEEE International Symposium on Antennas and Propagation (APSURSI); Spokane, WA, USA. 3–8 July 2011; Piscataway, NJ, USA: Institute of Electrical and Electronics Engineers; 2011. pp. 1860–1862.

Karacolak T., Moreland E.C., Topsakal E. Cole-Cole Model for Glucose-Dependent Dielectric Properties of Blood Plasma for Continuous Glucose Monitoring. Microw. Opt. Technol. Lett. 2013;55:1160–1164. doi: 10.1002/mop.27515. DOI

So C.-F., Choi K.-S., Wong T.K., Chung J.W. Recent Advances in Noninvasive Glucose Monitoring. Med. Devices Auckl. NZ. 2012;5:45–52. doi: 10.2147/MDER.S28134. PubMed DOI PMC

Hofmann M., Fischer G., Weigel R., Kissinger D. Microwave-Based Noninvasive Concentration Measurements for Biomedical Applications. IEEE Trans. Microw. Theory Tech. 2013;61:2195–2204. doi: 10.1109/TMTT.2013.2250516. DOI

Hayashi Y., Livshits L., Caduff A., Feldman Y. Dielectric Spectroscopy Study of Specific Glucose Influence on Human Erythrocyte Membranes. J. Phys. Appl. Phys. 2003;36:369. doi: 10.1088/0022-3727/36/4/307. DOI

Freer B., Venkataraman J. Feasibility Study for Non-Invasive Blood Glucose Monitoring; Proceedings of the 2010 IEEE Antennas and Propagation Society International Symposium (APSURSI); Toronto, ON, Canada. 11–17 July 2010; Piscataway, NJ, USA: Institute of Electrical and Electronics Engineers; pp. 1–4.

Huang S., Omkar, Yoshida Y., Inda A., Chia X.X., Mu W.C., Meng Y., Yu W. Microstrip Line-Based Glucose Sensor for Noninvasive Continuous Monitoring Using the Main Field for Sensing and Multivariable Crosschecking. IEEE Sens. J. 2019;19:535–547. doi: 10.1109/JSEN.2018.2877691. DOI

Yilmaz T., Ozturk T., Joof S. A Comparative Study for Development of Microwave Glucose Sensors; Proceedings of the 32nd URSI General Assembly and Scientific Symposium (URSI GASS 2017); Montreal, QC, Canada. 19–26 August 2017; Ghent, Belgium: International Union of Radio Science (URSI); 2017.

Saleh G., Ateeq I.S., Al-Naib I. Glucose Level Sensing Using Single Asymmetric Split Ring Resonator. Sensors. 2021;21:2945. doi: 10.3390/s21092945. PubMed DOI PMC

Odabashyan L., Babajanyan A., Baghdasaryan Z., Kim S., Kim J., Friedman B., Lee J.-H., Lee K. Real-Time Noninvasive Measurement of Glucose Concentration Using a Modified Hilbert Shaped Microwave Sensor. Sensors. 2019;19:5525. doi: 10.3390/s19245525. PubMed DOI PMC

Kumar A., Wang C., Meng F.-Y., Zhou Z.-L., Zhao M., Yan G.-F., Kim E.-S., Kim N.-Y. High-Sensitivity, Quantified, Linear and Mediator-Free Resonator-Based Microwave Biosensor for Glucose Detection. Sensors. 2020;20:4024. doi: 10.3390/s20144024. PubMed DOI PMC

Camli B., Kusakci E., Lafçi B., Salman S., Torun H., Yalcinkaya A. Cost-Effective, Microstrip Antenna Driven Ring Resonator Microwave Biosensor for Biospecific Detection of Glucose. IEEE J. Sel. Top. Quantum Electron. 2017;23:404–409. doi: 10.1109/JSTQE.2017.2659226. DOI

Sidley M. Ph.D. Thesis. Rochester Institute of Technology; Rochester, NY, USA: 2013. Calibration for Real-Time Non-Invasive Blood Glucose Monitoring.

Omkar, Yu W., Huang S.Y. T-Shaped Patterned Microstrip Line for Noninvasive Continuous Glucose Sensing. IEEE Microw. Wirel. Compon. Lett. 2018;28:942–944. doi: 10.1109/LMWC.2018.2861565. DOI

Zeising S., Kirchner J., Khalili H.F., Ahmed D., Lübke M., Thalmayer A., Fischer G. Towards Realisation of a Non-Invasive Blood Glucose Sensor Using Microstripline. TechRxiv. 2021 doi: 10.36227/techrxiv.13553528.v1. preprint. DOI

Vrba J., Vrba D. A Microwave Metamaterial Inspired Sensor for Non-Invasive Blood Glucose Monitoring. Radioengineering. 2015;24:877–884. doi: 10.13164/re.2015.0877. DOI

Pozar D.M. Microwave Engineering. 2nd ed. John Wiley and Sons; New York, NY, USA: 1998.

Damm C., Schussler M., Puentes M., Maune H., Maasch M., Jakoby R. Artificial Transmission Lines for High Sensitive Microwave Sensors; Proceedings of the 2009 IEEE Sensors; Christchurch, New Zealand. 25–28 October 2009; Piscataway, NJ, USA: Institute of Electrical and Electronics Engineers; 2009. pp. 755–758.

Vrba J., Vrba D., Díaz L., Fišer O. Metamaterial Sensor for Microwave Non-invasive Blood Glucose Monitoring. [(accessed on 25 June 2021)]. Available online: https://www.springerprofessional.de/metamaterial-sensor-for-microwave-non-invasive-blood-glucose-mon/15802180.

Yilmaz T., Foster R., Hao Y. Broadband Tissue Mimicking Phantoms and a Patch Resonator for Evaluating Noninvasive Monitoring of Blood Glucose Levels. IEEE Trans. Antennas Propag. 2014;62:3064–3075. doi: 10.1109/TAP.2014.2313139. DOI

Adhyapak A., Sidley M., Venkataraman J. Analytical Model for Real Time, Noninvasive Estimation of Blood Glucose Level; Proceedings of the 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBC 2014; Chicago, IL, USA. 26–30 August 2014; Piscataway, NJ, USA: Institute of Electrical and Electronics Engineers; 2014. pp. 5020–5023. PubMed

DAK » SPEAG, Schmid & Partner Engineering AG. [(accessed on 15 August 2021)]. Available online: https://speag.swiss/products/dak/dak-probes/

R&S®ZNB Vector Network Analyzer. [(accessed on 15 August 2021)]. Available online: https://www.rohde-schwarz.com/pl/products/test-and-measurement/network-analyzers/rs-znb-vector-network-analyzer_63493-11648.html.

Tyrrell J.A. Lectures on curves on an algebraic surface: A book review. J. Lond. Math. Soc. 1968;s1-43:570–571. doi: 10.1112/jlms/s1-43.1.570b. DOI

Ro4000-Laminates-Ro4003c-and-Ro4350b-Data-Sheet. Rogers Corporation; Shanghai, China: 2018.

I-Tera Mt40 Data Sheet. Isola Group; Chandler, AZ, USA: 2017.

PLA—Prusa Research. [(accessed on 15 August 2021)]. Available online: https://shop.prusa3d.com/en/21-pla.

COMSOL . Multiphysics Reference Manual 2019. COMSOL Inc.; Burlington, MA, USA: 2019.

Pham H. A New Criterion for Model Selection. Mathematics. 2019;7:1215. doi: 10.3390/math7121215. DOI

Hasgall P.A., di Gennaro F., Baumgartner C., Neufeld E., Lloyd B., Gosselin M.C., Payne D., Klingenboeck A., Kuster N. Tissue Properties Database V4.0 2018. IT’IS Foundation; Zurich, Switzerland: 2018.