High-Sensitivity, Quantified, Linear and Mediator-Free Resonator-Based Microwave Biosensor for Glucose Detection

This article presents a high-sensitivity, quantified, linear, and mediator-free resonator-based microwave biosensor for glucose sensing application. The proposed biosensor comprises an air-bridge-type asymmetrical differential inductor (L) and a center-loaded circular finger-based inter-digital capacitor (C) fabricated on Gallium Arsenide (GaAs) substrate using advanced micro-fabrication technology. The intertwined asymmetrical differential inductor is used to achieve a high inductance value with a suitable Q-factor, and the centralized inter-digital capacitor is introduced to generate an intensified electric field. The designed microwave sensor is optimized to operate at a low resonating frequency that increases the electric field penetration depth and interaction area in the glucose sample. The microwave biosensor is tested with different glucose concentrations (0.3–5 mg/ml), under different ambient temperatures (10–50 °C). The involvement of advanced micro-fabrication technology effectively miniaturized the microwave biosensor (0.006λ0 × 0.005λ0) and enhanced its filling factor. The proposed microwave biosensor demonstrates a high sensitivity of 117.5 MHz/mgmL-1 with a linear response (r2 = 0.9987), good amplitude variation of 0.49 dB/mgmL-1 with a linear response (r2 = 0.9954), and maximum reproducibility of 0.78% at 2 mg/mL. Additionally, mathematical modelling was performed to estimate the dielectric value of the frequency-dependent glucose sample. The measured and analyzed results indicate that the proposed biosensor is suitable for real-time blood glucose detection measurements.

[1]  Ji Chen.  On-chip Spiral Inductor/transformer Design And Modeling For Rf Applications , 2006 .

[2]  Kiejin Lee,et al.  Microwave dielectric resonator biosensor for aqueous glucose solution. , 2008, The Review of scientific instruments.

[3]  C. Radhakumary,et al.  Naked eye detection of glucose in urine using glucose oxidase immobilized gold nanoparticles. , 2011, Analytical chemistry.

[4]  Kishor Kumar Adhikari,et al.  Ultrahigh-Sensitivity Mediator-Free Biosensor Based on a Microfabricated Microwave Resonator for the Detection of Micromolar Glucose Concentrations , 2016, IEEE Transactions on Microwave Theory and Techniques.

[5]  Zhaopeng Chen,et al.  Highly sensitive on-site detection of glucose in human urine with naked eye based on enzymatic-like reaction mediated etching of gold nanorods. , 2017, Biosensors & bioelectronics.

[6]  P. Patel,et al.  An ENG resonator-based microwave sensor for the characterization of aqueous glucose , 2018 .

[7]  J. Osma,et al.  Low cost wireless passive microsensors for the detection of hazardous compounds in water systems for control and monitoring , 2013 .

[8]  Lei Wang,et al.  High-sensitivity radio frequency noncontact sensing and accurate quantification of uric acid in temperature-variant aqueous solutions , 2018, Applied Physics Express.

[9]  Mauro Ferrari,et al.  Mesoporous silica as a membrane for ultra-thin implantable direct glucose fuel cells. , 2011, Lab on a chip.

[10]  A. Takshi,et al.  An Electrospun Nanofibrous Membrane Based Electrochemical Glucose Sensor , 2020, IEEE Sensors Letters.

[11]  Rehab S. Hassan,et al.  A Minimally Invasive Implantable Sensor for Continuous Wireless Glucose Monitoring Based on a Passive Resonator , 2020, IEEE Antennas and Wireless Propagation Letters.

[12]  Alexander Naylon.  Microwave resonant sensors , 2011 .

[13]  A. Giacca,et al.  In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats. , 2012, Lab on a chip.

[14]  Qun Wu,et al.  Real-time accurate quantification of nanoliter ethanol using performance-optimized micro-fabricated microwave resonant sensor , 2019, Journal of Physics D: Applied Physics.

[15]  A. Sanati‐Nezhad,et al.  Sensitive, Real-time and Non-Intrusive Detection of Concentration and Growth of Pathogenic Bacteria using Microfluidic-Microwave Ring Resonator Biosensor , 2018, Scientific Reports.

[16]  T. Kawada.  Depression and type 2 diabetes. , 2017, Primary Care Diabetes.

[17]  Hee-Jo Lee,et al.  Microwave transmission properties of D-(+)-glucose solution with concentration variations , 2019, Journal of Physics D: Applied Physics.

[18]  K. Ghorbani,et al.  Microwave reflective biosensor for glucose level detection in aqueous solutions , 2020 .

[19]  Pingshan Wang,et al.  The Design and Operation of Ultra-Sensitive and Tunable Radio-Frequency Interferometers , 2014, IEEE Transactions on Microwave Theory and Techniques.

[20]  S. M. Hossain,et al.  Multi-Parametric Optical Glucose Sensor Based on Surface Functionalized Nano-Porous Silicon , 2018, IEEE Sensors Journal.

[21]  Izzet Kale,et al.  Permittivity extraction of glucose solutions through artificial neural networks and non-invasive microwave glucose sensing , 2018, Sensors and Actuators A: Physical.

[22]  Derek Abbott,et al.  High-Sensitivity Metamaterial-Inspired Sensor for Microfluidic Dielectric Characterization , 2014, IEEE Sensors Journal.

[23]  Kiejin Lee,et al.  Real-Time Noninvasive Measurement of Glucose Concentration Using a Modified Hilbert Shaped Microwave Sensor , 2019, Sensors.

[24]  K. K. Adhikari,et al.  A reusable robust radio frequency biosensor using microwave resonator by integrated passive device technology for quantitative detection of glucose level. , 2015, Biosensors & bioelectronics.

[25]  Margaret McCann,et al.  Fundamentals of Medical-Surgical Nursing: A Systems Approach , 2014 .

[26]  Soon Chong Johnson Lim,et al.  MICROSTRIP DEFECTED GROUND STRUCTURE FOR DETERMINATION OF BLOOD GLUCOSE CONCENTRATION , 2020 .

[27]  R. Tripathy,et al.  A Simulation Approach to Study the Effect of Ultrasonic MEMS Based Receiver for Blood Glucose Sensing Applications , 2017, IEEE Sensors Letters.

[28]  Nam-Young Kim,et al.  Flexible screen printed biosensor with high-Q microwave resonator for rapid and sensitive detection of glucose , 2014, IEEE MTT-S International Microwave Workshop Series on RF and Wireless Technologies for Biomedical and Healthcare Applications.

[29]  A. A. Salema,et al.  Dielectric properties and microwave heating of oil palm biomass and biochar , 2013 .

[30]  Yi Lu,et al.  Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets. , 2011, Nature chemistry.

[31]  Yang Li,et al.  Reusable, Non-Invasive, and Ultrafast Radio Frequency Biosensor Based on Optimized Integrated Passive Device Fabrication Process for Quantitative Detection of Glucose Levels , 2020, Sensors.

[32]  Fang Zhang,et al.  A novel method for the fabrication of integrated passive devices on SI-GaAs substrate , 2011 .

[33]  J. Fuchs,et al.  Detection of free radicals in skin: a review of the literature and new developments. , 2001, Current problems in dermatology.

[34]  Benjamin Potelon,et al.  Concentration Measurement of Microliter-Volume Water–Glucose Solutions Using $Q$ Factor of Microwave Sensors , 2019, IEEE Transactions on Instrumentation and Measurement.

[35]  Mojgan Daneshmand,et al.  Noncontact and Nonintrusive Microwave-Microfluidic Flow Sensor for Energy and Biomedical Engineering , 2018, Scientific Reports.

[36]  E. Sanjaya,et al.  Glucose Sensing Using Capacitive Biosensor Based on Polyvinylidene Fluoride Thin Film , 2018, Biosensors.

[37]  Yongle Wu,et al.  GaAs-Based IPD-Fabricated Center-Frequency-Controllable Bandpass Filter With Asymmetrical Differential Inductor and Air-Bridge Enhanced Capacitor , 2019, IEEE Access.

[38]  F Valgimigli,et al.  Novel planar glucose biosensors for continuous monitoring use. , 2005, Biosensors & bioelectronics.

[39]  Jonathan Lees,et al.  Dual Mode Microwave Microfluidic Sensor for Temperature Variant Liquid Characterization , 2017, IEEE Transactions on Microwave Theory and Techniques.

[40]  Jingzhen Li,et al.  Highly Sensitive Closed Loop Enclosed Split Ring Biosensor With High Field Confinement for Aqueous and Blood-Glucose Measurements , 2020, Scientific Reports.

[41]  Cong Wang,et al.  Design Analysis of Integrated Passive Device-Based Balun Devices With High Selectivity for Mobile Application , 2019, IEEE Access.

[42]  Yuanjin Zheng,et al.  Noninvasive Electromagnetic Wave Sensing of Glucose , 2018, Sensors.

[43]  M. Zarifi,et al.  Passive Split Ring Resonator Tag Configuration for RFID-Based Wireless Permittivity Sensing , 2020, IEEE Sensors Journal.

[44]  Son T. Nguyen,et al.  In-Vivo and Ex-Vivo Measurements of Blood Glucose Using Whispering Gallery Modes , 2020, Sensors.

[46]  Gi-Ho Yun,et al.  Temperature-Corrected Fluidic Glucose Sensor Based on Microwave Resonator , 2018, Sensors.

[47]  Jong-Gwan Yook,et al.  A planar split-ring resonator-based microwave biosensor for label-free detection of biomolecules , 2012 .

[48]  David L Kaplan,et al.  Functional, RF‐Trilayer Sensors for Tooth‐Mounted, Wireless Monitoring of the Oral Cavity and Food Consumption , 2018, Advanced materials.

[49]  Kiejin Lee,et al.  Sensing of Glucose Concentration by Using a Surface Plasmon Polariton , 2008 .