Highly Sensitive and Linear Resonator-Based Biosensor for White Blood Cell Counting: Feasible Measurement Method and Intrinsic Mechanism Exploration

• Published in: Biosensors (Basel) Vol. 14; no. 4; p. 180
• Main Authors: Wang, Yi-Ke, Shi, Bo-Wen, Zhao, Jun-Ming, Wang, Yan-Xiong, Jiang, Yan-Feng, Yang, Gang-Long, Gao, Xiao-Dong, Qiang, Tian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Automation; Bacterial infections; Biological properties; Biological samples; Biosensing Techniques; Biosensors; Blood; Blood cell count; Blood tests; Cardiovascular disease; Cells; Diabetes; Dielectric constant; Dielectric properties; Disease prevention; Electrical properties; Electromagnetic fields; Evaluation; Evaporation; Fabrication; Frequency shift; Hematology; highly sensitive; Humans; Inductors; Infections; Laboratories; Leukocyte Count; Leukocytes; Leukocytes - cytology; linear response; Mathematical models; Measurement methods; Medical examination; microwave biosensor; Microwave sensors; Microwaves; Osmosis; Osmotic pressure; Permittivity; permittivity-inspired; Resonators; Sensors; Substrates; WBC counting; China; linear response; highly sensitive; microwave biosensor; permittivity-inspired; WBC counting
• ISSN: 2079-6374; 2079-6374
• DOI: 10.3390/bios14040180

Since different quantities of white blood cells (WBCs) in solution possess an adaptive osmotic pressure of cells, the WBCs themselves and in solution have similar concentrations, resulting in them having similar dielectric properties. Therefore, a microwave sensor could have difficulty in sensing the quantity variation when WBCs are in solution. This paper presents a highly sensitive, linear permittivity-inspired microwave biosensor for WBCs, counting through the evaporation method. Such a measurement method is proposed to record measurements after the cell solution is dripped onto the chip and is completely evaporated naturally. The proposed biosensor consists of an air-bridged asymmetric differential inductor and a centrally located circular fork-finger capacitor fabricated on a GaAs substrate using integrated passive fabrication technology. It is optimized to feature a larger sensitive area and improved Q-factor, which increases the effective area of interaction between cells and the electromagnetic field and facilitates the detection of their changes in number. The sensing relies on the dielectric properties of the cells and the change in the dielectric constant for different concentrations, and the change in resonance properties, which mainly represents the frequency shift, corresponds to the macroscopic change in the concentration of the cells. The microwave biosensors are used to measure biological samples with concentrations ranging from 0.25 × 10 to 8 × 10 cells per mL in a temperature (26.00 ± 0.40 °C) and humidity (54.40 ± 3.90 RH%) environment. The measurement results show a high sensitivity of 25.06 Hz/cells·mL with a highly linear response of = 0.99748. In addition, a mathematical modeling of individual cells in suspension is performed to estimate the dielectric constant of individual cells and further explain the working mechanism of the proposed microwave biosensor.