Microwave biosensors utilizing metamaterial enhancement: Design and application

In recent years, microwave biosensors have attracted significant attention due to their exceptional sensitivity and rapid response in detecting biomolecules.¹ Microwave biosensors typically offer noninvasive or nondestructive capabilities, thereby preserving sample integrity without the need for sample processing or disruption. Consequently, they enable real-time monitoring of changes in biological samples, facilitating continuous monitoring and tracking of biological processes. The robustness of microwave biosensors, along with their higher signal-to-noise ratio, excellent integration capability with backend circuits, and potential for wireless transmission, have forged a new path for the development of biosensing technology.^1–6 However, enhancing and controlling biosensing signals to improve integration and frequency matching poses a challenge. The integration of metamaterial enhancement represents a cutting-edge approach to further enhance the performance of microwave biosensors, enabling improved detection limits and specificity.^7–10 This paper aims to comprehensively explore metamaterial-enhanced microwave biosensors, starting by elucidating the basic principles of microwave biosensors and focusing on the interaction between electromagnetic waves and biomolecules. This foundational understanding serves as the basis for discussing the potential of metamaterial enhancement to enhance sensor sensitivity and specificity. The paper then delves deeper into the design strategies employed in developing microwave biosensors with metamaterial enhancement, including optimization of sensor geometry and material selection. Comprehensive studies of the application of microwave biosensors in various fields such as biomedical diagnostics, environmental monitoring, and food safety are conducted. Lastly, the importance of addressing current challenges and planning future research directions in this field is discussed. By confronting issues such as sample preparation complexities and sensor miniaturization, it is possible to pave the way for further advances in microwave biosensors with metamaterial enhancement.

In the wake of burgeoning economic development, scientific understanding has undergone profound advances. Amidst the expansive landscape of physical sciences, the realm of biochemistry has unveiled a plethora of previously unexplored avenues. Notably, microwave technology has pervaded various sectors, spanning from industry,^11–14 to food evaluation analysis,^15–18 to biomedical applications,^19–24 thereby assuming an indispensable role. Consequently, research into microwave sensing has witnessed an unprecedented surge of interest and expansion. Microwaves predominantly inhabit the frequency band between 300 MHz and 300 GHz²⁵ and are distinguished by their high-frequency attributes but exhibit minimal effects at lower frequencies. Within the electromagnetic spectrum, microwaves find themselves sandwiched between ultrashort waves and infrared radiation. It is their longer wavelengths that endow them with unparalleled penetration capabilities, facilitating their utility across diverse applications. Microwaves are typically categorized into decimeter, centimeter, millimeter, and submillimeter bands, and have many applications in these different bands (Table I).²⁶ The L band belongs to the decimeter one, the C, X, Ku and K belong to the centimeter, and the V, W, and mm wave bands belong to the millimeter. Unaffected by temperature fluctuations, airflow, or ambient light, microwave sensors boast robust anti-interference properties, rendering them highly stable and accurate, with rapid response times and directional capabilities.^27–29 It is these attributes of microwave sensing technology that render it amenable to contactless and lossless detection across a broad spectrum of fields and industries. Therefore, despite the commercial mainstream dominance of electrochemical biosensors, the low-cost, contactless, nondestructive, and marker-free detection characteristics of microwave biosensors have attracted great attention.^30,31

Microwave sensing has emerged as a valuable technology for biometrics, encompassing a wide range of applications in both in vitro and in vivo settings. In vitro biometric substance detection involves the analysis of samples outside of living organisms, such as food products,^32,33 environmental samples,^34,35 or laboratory cultures.^36,37 In contrast, in vivo biometric substance analysis focuses on detecting and monitoring biological substances within living organisms, including humans and animals.^19,38–40

In the realm of in vitro biological substance detection, microwave sensors offer numerous advantages. They can accurately measure various properties of samples, such as moisture content,^41,42 sugar levels,^43,44 or chemical composition,^45,46 with high sensitivity and specificity. This capability has significant implications for industries such as agriculture, food production, environmental monitoring, and materials science, where precise measurement of biological substances is essential for quality control, safety assurance, and research purposes. For example, microwave sensors can detect contaminants or adulterants in food products,^8,47 monitor the quality and freshness of agricultural produce,^48,49 or analyze the composition of environmental samples.^50,51 These applications rely on the ability of microwave sensors to interact with and differentiate between different substances based on their dielectric properties, such as permittivity and conductivity.

In the realm of in vivo biological substance analysis, microwave sensors offer unique capabilities for noninvasive and real-time monitoring of biological samples. By measuring changes in dielectric properties or electromagnetic responses of tissues or bodily fluids, microwave sensors can provide valuable information about physiological processes, disease states, or drug interactions. For instance, microwave sensors can monitor glucose levels in diabetic patients,^52,53 detect cancerous tissues in breast or prostate examinations, or analyze the composition of spinal fluid for diagnostic purposes.^54–56 These applications utilize the ability of microwave sensors to penetrate biological tissues, interact with biomolecules, and even enable noninvasive quantitative measurements of biological substances.

Overall, microwave biosensing represents a powerful and versatile approach for analyzing biological substances in a wide range of applications. By combining the principles of microwave sensing with advanced measurement techniques and signal processing algorithms, researchers and practitioners can develop innovative solutions for biomedical research, clinical diagnostics, environmental monitoring, and industrial quality control.

The exploration of metamaterials, substances engineered to have properties not found in naturally occurring materials, has emerged as a transformative approach compensating for the limitations of traditional sensor designs. Metamaterials, with their periodic resonant structures, boast extraordinary resonant properties that are not inherently present in conventional materials. These properties include negative permittivity, permeability, and refractive index, alongside strong electromagnetic coupling capabilities. Such characteristics enable the design of high-sensitivity sensors capable of detecting minute biological changes. The genesis of metamaterials can be traced back to the groundbreaking 1968 work of Vesselago,⁵⁷ who first theorized their potential. Since then, the field has seen exponential growth, with ongoing research aimed at leveraging metamaterials to achieve unprecedented levels of sensitivity and resolution in sensor technology. Owing to their subwavelength structures, metamaterials are widely applied in the sensing of GHz and THz wavebands,⁵⁸ where different designs can be utilized for electromagnetic interactions at various frequencies.⁵⁹ In the microwave sensing domain of interest in this paper, metamaterials exhibit unique characteristics compared with those used in other frequency ranges. The primary distinction lies in the geometric structures of the materials, which are specifically designed to manipulate electromagnetic waves in the microwave frequency band, with dimensions comparable to the wavelength of microwaves.⁶⁰ In relative terms, metamaterials designed for optical or THz frequencies employ different micro/nanostructures or plasmonic resonators to achieve similar negative refractive index properties,⁶¹ with the dimensions and compositions of these structures being tailored to interact with electromagnetic waves of shorter wavelengths.

Among the myriad of metamaterial topologies, the split-ring resonator (SRR) and its counterpart, the complementary split-ring resonator (CSRR), have garnered significant attention. The SRR and CSRR are two commonly used structures in microwave metamaterials, playing crucial roles in achieving negative refractive indices and left-handed materials. An SRR consists of two concentric metallic rings, each with a small gap, with the opening angles of the two rings offset by 180°. This configuration resembles a miniature LC circuit, where the inductances of the rings and the capacitance between them interact to produce resonance [Fig. 1(a)]. When the resonant frequency of the SRR structure matches the frequency of the incident electromagnetic wave, the SRR can generate a negative permeability, causing the material to exhibit left-handed characteristics, where the electric field, magnetic field, and direction of propagation form a left-hand rule. SRRs are primarily used to achieve negative permeability and are often combined with other structures, such as metallic wires, to achieve negative refraction. The CSRR is the complementary structure of the SRR, consisting of two concentric ring-shaped gaps etched in a metallic plane, where the roles of metal and gap in the original SRR design are interchanged [Fig. 1(b)]. Unlike SRRs, CSRRs are primarily used to achieve negative permittivity. When electromagnetic waves impinge upon the CSRR structure, the gap areas produce localized electric field concentrations due to electromagnetic induction, leading to resonance. This resonance can cause the material to exhibit negative permittivity within a specific frequency range. Both SRRs and CSRRs play important roles in the design of microwave sensors based on metamaterials, with their dimensions, shapes, and arrangements precisely engineered to achieve specific electromagnetic responses.⁶² These topologies are favored for their versatility, finding application in a diverse range of devices, including absorbers, filters, radio-frequency (RF) antennas, and sensors. SRR and CSRR devices, which can adopt various shapes such as circular, square, triangular, and hexagonal, represent complementary structures that significantly influence the resonance performance of sensors.⁶² 

The sensitivity of different shapes of CSRRs has been explored, and it has been found that their inductances remain almost constant under variations in dielectric material, while circular CSRRs exhibit higher resonant frequency changes than rectangular CSRRs under load conditions. Additionally, resonant ring arrays, excitable by microstrip lines, broaden the spectrum of metamaterial forms, including disk-shaped, helical, V-shaped, and Jerusalem junction structures, among others. Cao et al.⁶³ proposed an asymmetric electric split-ring resonator (AESRR) metamaterial structure [Figs. 2(a) and 2(b)], which has many advantages, such as low cost, high sensitivity, high robustness, and extensive detection range. It has great potential for future implementation in a lab-on-a-chip sensor system. Abdulkarim et al.⁶⁴ described metamaterial-based sensors for detecting the presence of compounds and liquids. Abdulkarim et al.⁶⁵ proposed a metamaterial-based sensor loaded with corona-shaped microwave resonators for COVID-19 detection [Figs. 2(c) and 2(d)]. Metamaterial-based sensors herald a new era in biosensing systems, advancing biosensor detection sensitivity toward single-molecule detection.

On the other hand, a diverse array of nanomaterials and nanostructures based on various metamaterials lays the foundation for high-performance sensing devices, such as those based on nanoparticles (NPs), nanotubes (NTs), or nanowires (NWs). A defining characteristic of these nanostructured materials is their high surface-to-volume ratio, with one or more physical dimensions smaller than or equivalent to the charge shielding length, known as the Debye length. The Debye length is a physical quantity that characterizes the screening effect of charge carriers in semiconductors or electrolytes, typically related to the carrier concentration and temperature of the material.⁶⁶ When the dimensions of nanomaterials based on metamaterials are smaller than the Debye length, the performance of microwave sensors loaded with these nanomaterials can be significantly impacted.⁶⁷ Consequently, these materials often exhibit superior sensitivity in chemical surface treatments. Enhanced electromagnetic wave-induced resonance, achieved through metal surface roughening, significantly amplifies the electric field strength. Nanowires, as nanomaterials fabricated via conductive polymer imprinting, have shown promise in improving antenna sensitivity. Xue et al.²³ introduced nanocrystalline metamaterial-enhanced sensing based on sub-100-nm ordered conductive polymer poly(3,4-ethylenedioxythiophene) poly(styrene sulfonate) (PEDOT:PSS) nanowire arrays, exhibiting improved biomedical detection applications (Fig. 3). Silicon nanowires (SiNWs), renowned for their sensitivity, find widespread use in biological and chemical detection.

Microwave sensors operate on the fundamental principle of utilizing electromagnetic waves in the microwave frequency range to interact with and analyze materials of interest. These sensors emit microwave signals generated by transmitters, which are then directed toward the target object or sample. Upon interaction with the sample, the microwave signal undergoes various processes, including absorption, reflection, and scattering, depending on the material’s properties.

The interaction between the microwave signal and the sample results in alterations to the electromagnetic parameters of the signal, such as its amplitude, phase, and frequency. These changes encode valuable information about the sample’s composition, structure, and properties. For instance, materials with high water content may exhibit different absorption characteristics compared with materials with low water content, leading to distinct alterations in the microwave signal. After interacting with the sample, the modified microwave signal is received and processed using specialized circuits or instruments. These processing techniques aim to extract relevant information from the received signal and translate it into meaningful data about the sample. This may involve analyzing changes in signal amplitude, phase shifts, or frequency shifts to infer properties such as dielectric constant, conductivity, or molecular composition. The principles of microwave sensing are rooted in the understanding of electromagnetic wave behavior and the interactions between electromagnetic fields and matter. The nature of these resonant frequency shifts is due to changes in sensor capacitance induced by dielectric perturbations induced by biomolecular loading. Therefore, metamaterial-based biosensors can be directly used for label-free biomolecular detection. By leveraging these principles, researchers and engineers can design and optimize microwave sensors for a wide range of applications, including biological detection.

In the context of biological detection, microwave sensors offer several advantages. Their ability to penetrate nonmetallic materials and interact with water molecules makes them well-suited for analyzing biological samples, which often contain water as a major component. Additionally, microwave sensors can operate in noncontact mode, allowing for nondestructive and minimally invasive measurements, which is particularly beneficial for sensitive biological samples. Furthermore, microwave sensors can provide real-time measurements with high sensitivity and specificity, enabling rapid and accurate detection of biological substances. This capability has significant implications for various fields, including medical diagnostics, food safety, environmental monitoring, and pharmaceutical research.

Overall, the principle of microwave sensing for biological detection is grounded in the interaction between electromagnetic waves and matter. By harnessing this interaction, microwave sensors offer a powerful and versatile tool for analyzing biological samples and detecting biological substances with high sensitivity, specificity, and efficiency.

The advent of metamaterials represents a pivotal shift in the landscape of microwave sensor technology, introducing unprecedented opportunities for enhancing sensitivity and specificity in biochemical sensing applications. Microwave sensors, which are integral to a wide array of applications, range from microwave resonant cavity designs, to planar circuit microwave sensors employing the cancellation principle, to resonant microwave sensors. Each of these types has its inherent advantages and limitations, with microwave resonant cavities being notably bulky, and planar circuits, despite their innovative cancellation principle, suffering from a lack of portability. In contrast, resonant planar sensors, while offering a more practical solution, have historically been hampered by their low quality factor Q, a measure of the resonator’s bandwidth relative to its central frequency, which is crucial for the sensor’s sensitivity and selectivity. The average size of metamaterials is generally less than a quarter wavelength λ/4,⁵⁹ and the nature of the sensor’s response is based on this synthetic structure, in addition to its properties such as dielectric constant and permeability. Such a sensor also has the advantages of small size and low cost. The subwavelength structure of metamaterials results in high resonance in a narrow frequency range, and it is easier to obtain high Q values than with traditional microwave resonant sensors. The basic principle of metamaterial-based microwave biosensors also depends on the dielectric perturbation phenomenon, and this high Q value has also meant higher resolution and sensitivity. Therefore, the performance of microwave biosensors based on metamaterials is also better when loaded with biological materials, and the high resonance phenomenon in the small size range is also more conducive to analyzing the composition and change of biological molecules and other information. It is precisely because of the strong electromagnetic properties of metamaterials that dielectric perturbations caused by molecular binding events can be represented through changes in electromagnetic signals, thus enabling marker-free biological detection, which improves the specificity of microwave biosensors and gives them screening power.⁶⁸ 

Microwave resonance methods, particularly those employing planar resonators like the SRR and its complementary counterpart CSRR, are lauded for their compactness, straightforward geometry, ease of fabrication, and cost-effectiveness.⁶⁹ The SRR noted for its dual concentric rings with symmetrical gaps, typically fashioned from metallic materials. This configuration allows for the manipulation of resonance characteristics, crucial for optimizing sensor performance. The resonance frequency of an SRR, determined by the interplay between its inductance L_s and capacitance C_s, highlights the intricate balance required to achieve optimal resonance, a balance further complicated and enriched by the electromagnetic properties of metamaterials. An SRR exhibits a cross-polarization phenomenon, achieving optimal resonance when excited simultaneously by the magnetic field perpendicular to the torus and the electric field parallel to it. However, magnetic field excitation perpendicular to the torus is the predominant method, widely employed in coplanar waveguides and rectangular waveguides. Conversely, a CSRR, a hollow etching of SRR on metal, strictly couples with an SRR. As per Babinet’s theorem, the equivalent inductance L_s in the original SRR circuit is replaced by C_c in the CSRR. Electric field excitation perpendicular to the torus is the primary excitation mode for CSRR, typically amplifying the capacitive effect and thus enhancing sensitivity compared with an SRR.⁷⁰ 

These structures, when integrated with microstrip transmission lines, form resonant sensors that leverage interdigital capacitance for improved performance. The adoption of CSRR structures into the ground plane of planar transmission lines, manifesting in single or double loops, creates what is known as a defect ground structure (DGS).⁷¹ An important characteristic of a DGS is a slow-wave characteristic and a slow-pass characteristic.⁷² DGSs have been widely used in various microwave filter designs, such as low-pass filters, band-stop filters, and band-pass filters,⁷³ DGS geometries reported in the literature include rectangular dumbbells, circular dumbbells, U-shaped, V-shaped, H-shaped, cruciform, spiral, concentric rings, CSRR, and fractal.⁷⁰ This technique has found widespread application in enhancing the design of microwave filters, amplifiers, and antennas, contributing to device miniaturization, reduced cross-polarization, diminished mutual coupling in antenna arrays, and the facilitation of multiband operation and higher-harmonic suppression. Al-Gburi et al.⁷⁴ achieved a high Q-factor amplitude by integrating a CSRR curve-feed sensor with a DGS [Fig. 4(a)]. The proposed sensor exhibited excellent performance with high precision and a minimum average error detection rate of 0.23%. It had a Q factor of 520 at 2.5 GHz, and an acceptable sensitivity of ∼1.072 MHz/ɛ_r. Buragohain et al.⁷⁵ designed and manufactured a highly size-optimized triple-CSRR microwave sensor [Fig. 4(b)], which uses the dielectric constant of the sensor liquid sample to achieve high precision determination. The transmission coefficient (S₂₁) signal response of the sensor was measured using a vector network analyzer (VNA) and was found to achieve a high sensitivity of 0.87%, significantly surpassing most reported sensors. Additionally, fitting equations were developed for the real and imaginary parts of the dielectric constant, enabling the determination of the complex dielectric constant of unknown samples with an error of less than 4%.

In the biosensing domain, the demand for microstrip antennas that combine high sensitivity with compactness is met by innovative designs such as multiresonant loops, which augment sensitivity while conserving space [Fig. 4(c)].⁷⁶ Pandit et al.⁷⁷ proposed a multiband planar microwave sensor based on highly sensitive plasma metamaterials, which has been successfully used for labeling free detection of water-borne biological samples. This sensor comprises a spoof surface whispering gallery mode (SS-WGM) resonator connected to a spoof surface plasmon polariton (SSPP) transmission line in a special arrangement [Fig. 5(a)]. The sensor’s SS-WGM resonator has a slow-wave property and is therefore able to locate the electromagnetic field to within a specific area. The interaction time between the sample under test (SUT) and the electromagnetic wave has been extended to achieve higher sensitivity. In terms of glucose concentration detection, the proposed sensor exhibited a linear dynamic working range of 0–200 mg/ml, with a maximum measurement sensitivity of 77.3 × 10⁻² MHz/(mg/ml). Compared with state-of-the-art technologies, the sensitivity has been significantly enhanced, making it a potential candidate for aqueous biotic sensing applications. Wang et al.⁷⁸ proposed a novel double-SRR (DSRR) microwave humidity sensor in which the interdigital coupling extends the electric-field region from the split gaps to the DSRR for a higher sensitivity [Figs. 5(b) and 5(d)]. Within the humidity range of 30%–90% RH, the microwave humidity sensor exhibited sensitivities as high as 880.0 kHz/%RH and 0.322 dB/%RH, respectively. This approach exemplifies the integration of novel structures to refine the functional attributes of microstrip antennas.

On the one hand, the detection of biomolecules by microwave biosensors based on metamaterials is mostly due to the change in resonant frequency caused by the combination with the metamaterial resonator. Biomolecules are fixed on the surface of the sensor as ligands, and the biomolecules to be analyzed cross the surface of the sensor and selectively interact with the fixed biomolecules, resulting in dielectric perturbation. The powerful electromagnetic characteristics of the metamaterial sensor make the sensor signal change obviously. On the other hand, when biological substances such as glucose interact with sensors, based on the interaction between samples such as glucose and time-varying electromagnetic fields, the amplitude and frequency of sensor signals change to achieve detection purposes. In either case, a high-Q metamaterial microwave sensor can achieve higher sensitivity.

This advantage is exemplified in Fig. 6(a), which illustrates how Lee et al.⁷⁹ demonstrated the practical application of biosensing techniques using an SRR equipped with dual rings. The compact DSRR was excited by a microstrip transmission line, and the DNA hybridization in which single-stranded DNA (ss-DNA) was coupled with a complementary DNA (c-DNA) was recognized by a change in S₂₁ resonant frequency. When ss-DNA was immobilized onto a gold surface and then coupled with c-DNA, the resonant frequency was altered by Δf_ss-DNA = 20 MHz and Δf_{hybridization} = 60 MHz for the two cases. It was evident that the DSRR could be utilized as a DNA sensing element in the microwave regime, and this microwave biosensor exhibited sensitivity to biochemical changes. Ebrahimi et al.⁴³ prepared a noninvasive microwave microfluidic sensor containing an open microstrip transmission line fitted with a CSRR. The CSRR exhibited a very strong electric field strength when resonating, was highly sensitive to glucose level, and predicted glucose concentration through resonant frequency and amplitude changes [Fig. 6(b)]. The sensitivity of the resonant frequency and the magnitude of the reflection coefficient S₁₁ reached 0.5 × 10⁻³ mg/ml and 0.5 dB/(mg/ml), respectively, within the concentration range of 0–5 mg/ml glucose solution. The sensor measured glucose concentrations as low as physiological levels, making it feasible to monitor blood sugar levels and rendering it a highly competitive option among microwave glucose biosensors. Nejad et al.⁸⁰ proposed a kind of metamaterial microwave sensor with SRR, which was composed of a microstrip transmission line and a shunt transmission line. It was easy to use and operate, and could detect cancerous tissue to give early warning of tumors. The minimum resolution of the sample to be tested in this biosensor was 10 MHz.

Microwave biosensors incorporating metamaterials have demonstrated remarkable potential in enhancing sensor performance, particularly in terms of sensitivity and specificity. In this section, we delve into the design strategies employed in the development of metamaterial-based microwave biosensors, aiming to optimize their capabilities for bioanalytical applications.

Size and shape optimization of metamaterials are critical aspects of designing high-performance microwave biosensors. Tailoring the geometrical parameters of metamaterials enables precise control over their electromagnetic properties and enhances sensor sensitivity and selectivity. Several key considerations regarding size and shape optimization of metamaterials such as unit cell dimensions, aspect ratio and geometrical arrangements, resonance frequency control, and miniaturization and integration are essential.^81–84 

The dimensions of the unit cell, including the size and shape of subwavelength structures, significantly influence the resonance frequencies and electromagnetic responses of metamaterials. Optimizing unit cell dimensions allows designers to tune the sensor’s response to specific frequencies relevant to the target analytes and operating conditions. For example, reducing the size of the unit cell can shift the resonance frequency to higher values, enabling detection of smaller analytes or higher-frequency biomolecular interactions. By reducing the diameter of the inner ring of the CSRR, increasing the operating frequency of the sensor, realizing the testing of eight different liquids, and predicting the dielectric constants (real and imaginary parts) of ethanol and 1-butanol used as unknown samples with high accuracy, Buragohain et al.⁷⁵ [Fig. 7(a)] proved that it could be used to predict the dielectric constants of any unknown liquid samples. In the process of design and experiment, it was also proved that the size of the substrate had no significant effect on the performance of the sensor, and so the overall size of the sensor was optimized. Aiswarya et al.⁸⁵ introduced a compact dielectric sensor for detecting adulteration in solid and liquid samples, utilizing a planar resonator. Six filter prototypes operating at 2.4 GHz were proposed, optimized, evaluated, fabricated, and experimentally verified [Fig. 7(b)]. The sensor demonstrated remarkable sensitivity in detecting adulteration in various food samples, exhibiting excellent performance when dopants were added to the original samples.

The aspect ratio and geometrical arrangements of subwavelength structures within the unit cell play a crucial role in shaping the electromagnetic properties of metamaterials. Varying the aspect ratio, such as by changing the width-to-height ratio of SRRs or adjusting the spacing between unit cells in periodic arrays, allows designers to engineer desired resonance modes and dispersion characteristics. Different geometrical arrangements, such as square, circular, or triangular unit cells, offer unique electromagnetic responses and enable tailored sensor designs for specific applications.⁸⁶ Islam et al.⁹ proposed and analyzed a novel metamaterial sensor based on adjacent three-circle SRRs. Figures 8(a) and 8(b) show the sensor structure and equivalent circuit. The reflection coefficient parameter was utilized to analyze and identify the dielectric constant of the sample placed on the sensor. The width of the resonator, the gap of the crack, the radius of the single circle, and the substrate size of metamaterials sensor were optimized. The sensor structure with the best performance among the five hypothetical resonator structural designs was selected [structure 1 in Fig. 8(c)]. The parameters of the metamaterial sensor were finalized as follows: split gap 0.5 mm, circle radius 2.3 mm, and resonator width 0.6 mm. Reversing the proposed circular split ring pattern reduced the mutual coupling effect of the capacitor and increased the resonant frequency to meet the design requirements. Ultimately, the sensor demonstrated the ability to identify multiple types of oil (olive oil, corn oil, sunflower oil, and palm oil) and oil adulteration concentrations [Fig. 8(d)], with high sensitivity, excellent accuracy, and high Q values, which were additional features of the sensor. Its sensing performance exceeded that of other reported metamaterial sensors, with a mass factor, sensitivity, and quality factor of 135, 0.56, and 76, respectively.

By optimizing the size and shape of metamaterials, designers can precisely control the resonance frequencies and bandwidths of sensors. Fine-tuning these parameters enables alignment of a sensor’s resonance frequencies with characteristic frequencies of target analytes or specific molecular interactions, enhancing sensor sensitivity and selectivity. Techniques such as numerical simulations and parametric studies facilitate the exploration of size and shape optimization parameters and guide the design process toward achieving desired sensor performance. Among the most notable advances are the diverse iterations of SRRs, including but not limited to circular SRRs, square SRRs, band bridge SRRs, open SRRs, and CSRRs, as well as asymmetric coplanar waveguide (CPW)-type SRRs. These variations have been meticulously proposed and implemented by researchers aiming to refine the quality factor, sensitivity, and detection accuracy of SRRs, thereby enhancing the overall efficacy of microwave sensors in biochemical applications.^{30,31,87–94}

In addition, there are some new metamaterial structures and shapes that have been applied in the field of metamaterial-based microwave biosensing. As shown in Figs. 9(a)–9(d), Abdulkarim et al.⁹⁵ successfully designed and manufactured a resonator that produced a frequency shift of the sensor signal with different objects to be measured. The dielectric constants of corn and olive oil are 3.2 and 3.08, respectively, which can be used for real-time, fast, low-cost, durable and accurate sample detection. This sensor has potential applications in medicine and liquid reagent detection. Khalil et al.⁹⁶ proposed a chiral four-component metamaterial sensor consisting of four square SRRs of different sizes, as shown in Figs. 9(e)–9(h), with a width and length both 20 mm, which was very suitable for microwave band sensing. The relationship between the size of the cell and the resonant frequency was studied, and a negative correlation was found. In addition, as the capacitance decreased, the resonant frequency increased, and so the shunt width was adjusted to change the coupling capacitance to achieve adjustment of the resonant frequency. The sensor had high sensitivity and high Q values, and it could be used in the future for detection of liquid adulteration.

Miniaturization and integration are fundamental aspects of designing metamaterial-based microwave biosensors, enabling compact, portable, and multifunctional sensor platforms for various bioanalytical applications. Achieving miniaturization and seamless integration with sensing elements and readout systems are essential for enhancing sensor performance, functionality, and practical usability. By minimizing the physical dimensions of metamaterials and associated components, such as microfluidic channels, antennas, and signal processing circuits, it is possible to develop compact biosensors suitable for point-of-care diagnostics, wearable devices, and field-deployable applications. Integrating metamaterial-based biosensors with microfluidic systems enables on-chip sample handling, processing, and analysis, leading to enhanced sensitivity, throughput, and automation. Furthermore, microfluidic integration enables multiplexed sensing of multiple analytes in parallel and real-time monitoring of dynamic biochemical processes. By addressing miniaturization and integration challenges, it is possible to develop advanced metamaterial-based microwave biosensors with compact form factors, enhanced functionality, and improved practical usability. Through seamless integration with microfluidic systems, on-chip signal processing, wireless communication interfaces, and multifunctional sensor platforms, metamaterial-based biosensors offer unprecedented capabilities for real-time, portable, and autonomous bioanalytical sensing in various healthcare, environmental, and biomedical applications.^97,98

As illustrated in Figs. 10(a)–10(d), Mondal et al.⁹⁹ proposed a microstrip-coupled CSRR integrated with a microfluidic channel for noninvasive detection of glucose concentration, offering higher sensitivity and a smaller size. The microfluidic channels, constructed from polydimethylsiloxane (PDMS), were biocompatible, cost-effective, and customizable, ensuring the protection of samples from external contamination. These channels enabled testing of very small volumes of biological samples (microliters) using microfluidic sensing methods. A solution containing varying proportions of water–glucose solution was passed through the sensitive area, making it suitable for biomedical applications. By employing an integrated microwave sensor system, a minimum glucose concentration of 20 mg/ml (100 μl) was successfully detected. Additionally, a relationship between detection frequency and glucose concentration was established to determine any concentration of glucose in an aqueous solution. Qiu et al.¹⁰⁰ proposed a novel microwave sensor comprising two metallic spiral resonators excited by a spoof surface plasmon polariton (SSPP) transmission line (TL) and two microfluidic chips with channels designed for detecting the permittivity of liquids [Fig. 10(e)]. These microfluidic chips featured spiral channels engraved in PDMS, facilitating the transportation of liquid samples while enhancing the interaction between the electromagnetic (EM) fields and the liquid sample at the resonance frequency. Experimental results demonstrated that this innovative sensor could detect the permittivity of unknown liquids with low fabrication cost, minimal liquid consumption, high sensitivity, and operation at a high frequency. Pandit et al.⁷⁷ utilized glucose plasma with varying glucose concentration levels as biological samples. They adopted a metamaterial-inspired microwave biosensor combined with microfluidic channels to achieve label-free, high-sensitivity detection of water-based biological samples. This approach is beneficial for the layout of modern microwave-based lab-on-a-chip systems.

Through careful size and shape optimization of metamaterials, it is possible to develop microwave biosensors with enhanced sensitivity, selectivity, and miniaturization capabilities. By leveraging advanced design tools and simulation techniques, designers can explore a wide range of parameter variations and optimize metamaterials’ geometrical properties to meet the specific requirements of bioanalytical applications. This systematic approach facilitates the development of next-generation biosensors capable of addressing diverse challenges in healthcare, environmental monitoring, and food safety.

The selection of appropriate metamaterials is crucial in determining the performance of microwave biosensors. Various factors, including the desired operating frequency range, dielectric properties of the target analytes, and fabrication constraints, must be considered. Commonly used metamaterials for biosensing applications include SRRs, CSRRs,⁶⁸ periodic arrays,¹⁰¹ and others.

Different metamaterials exhibit unique electromagnetic responses, including negative refractive index, dispersion, and resonance phenomena, within specific frequency bands. For instance, SRRs and CSRRs are commonly used in the microwave frequency range owing to their resonance behavior.

The selection of metamaterials for microwave biosensors is critical, with the operating frequency range being a key consideration. This range determines the frequency band within which the sensor will effectively operate. The choice of metamaterials hinges on their electromagnetic response characteristics, which should align with the desired operating frequency range for biosensing applications. Practical factors such as the availability of measurement equipment and compatibility with existing microwave systems also influence metamaterial selection. Designers must ensure that the chosen metamaterials can be effectively characterized and integrated into the biosensor platform using available measurement techniques. Buragohain et al.⁷⁵ designed a sensor to operate at 2.4 GHz, within the industrial, scientific, and medical (ISM) band, enabling easy integration with RF modules like Wi-Fi and Bluetooth without requiring a license. Therefore, future sensors could potentially be seamlessly integrated with these modules. Özkaner et al.¹⁰² presented a sensor structure based on a transmission line and SRR with high sensitivity. The dielectric layer height and copper thickness were set at 1.6 mm and 0.035 mm, respectively, with overall dimensions of 16 × 16 mm². The operating frequency was chosen within the ISM bands, particularly around 2.45 GHz. The innovation of this design lies in its ability to precisely detect the ratio of methanol in water with a simple layout [Figs. 11(a) and 11(b)]. The sensor’s sensitivity was evaluated at 1 MHz, making it applicable for methanol detection in medical, military, and chemical research. Kakani et al.⁴⁷ introduced a nondestructive method for detecting adulteration in edible oils using an open complementary split-ring resonator (OCSRR) structure. The OCSRR-based RF sensor, designed on a 1.6 mm-thick FR4 substrate (ɛ_r = 4.4) to operate at 3.6 GHz, was tested with mustard, coconut, olive, and sunflower oils [Figs. 11(c) and 11(d)]. By measuring the shift in the OCSRR’s resonant frequency, the sensor estimated the percentage of adulterant in an oil sample, detecting about 50% adulteration. The numerical sensitivity (NS) of the sensor ranged from 11.67% to 18.33% for different oil samples.

By carefully considering these factors, it is possible to select metamaterials that offer optimal electromagnetic properties within a desired operating frequency range, thereby maximizing the sensitivity and specificity of metamaterial-based microwave biosensors for bioanalytical applications.

The dielectric properties of analytes play a crucial role in the design and performance optimization of metamaterial-based microwave biosensors. Understanding and exploiting these properties such as permittivity and permeability, frequency dependence, dielectric contrast, and temperature and environmental effects enables selective detection and characterization of target analytes. Several key considerations regarding the dielectric properties of analytes are essential.

The complex permittivity and permeability of analytes dictate their interaction with electromagnetic fields and influence a sensor’s sensitivity and selectivity. These properties vary depending on the composition, structure, and concentration of analytes. For instance, biomolecules such as proteins, nucleic acids, and carbohydrates exhibit specific dielectric properties that can be exploited for biosensing applications.¹⁰³ Govind et al.⁹⁸ proposed a high-sensitivity microwave microfluidic sensor with an SRR integrated with an interdigital capacitor (IDC) in the resonator gap to detect glucose concentration in aqueous solution. The novel design of this sensor enhanced the electric field density of the surface, thus providing higher sensitivity for the testing of biological samples [Figs. 12(a)–12(e)]. Kayal et al.¹⁰⁴ designed and demonstrated a compact planar metamaterial sensor with mu negative (MNG) for highly sensitive liquid characterization. They also developed and validated two novel nonlinear equations that can correlate the dielectric properties of liquid analytes with the parameters of the sensor [Fig. 12(f)]. These equations are valuable for determining the complex permittivity of unknown liquids. The high sensitivity and compact design of the sensor enhance its integrity and usability for industrial and medical applications.

The dielectric properties of analytes may vary with frequency, particularly in the microwave frequency range. Analyzing the frequency-dependent dielectric response of analytes enables the design of sensors capable of detecting specific biomolecular interactions at different frequencies.¹⁰⁵ This frequency dependence can be leveraged to enhance sensor sensitivity and selectivity by tuning the operating frequency to match the characteristic response of the analytes.^81, Figures 13(a)–13(d) depict a biosensing scheme for a graphene-based RFID sensor system proposed by Mannoor et al.¹⁰⁵ to detect bacteria on tooth enamel. The biofunctionalization of graphene involved treating it with bifocal peptides to effectively identify pathogenic bacteria such as Odorrana grahami, Helicobacter pylori, Escherichia coli, and Staphylococcus aureus.¹⁰⁶ Specific peptides self-assembled on graphene to identify these bacteria. In this biosensing scheme, graphene was patterned on an aqueous solution filament and used to identify remote pathogens by utilizing an inductor (L)–capacitor (C) circuit, a resonant circuit used to select a specific frequency. Additionally, this study demonstrated the use of wireless circuits integrated into teeth to detect specific bacteria in saliva. Lee et al.¹⁰⁷ used SRR arrays to detect biotin and streptavidin. The capacitance of SRR changed when biotin and streptavidin were combined with the system, affecting the resonant frequency change and proving the ability of metamaterials to detect specific biomolecules. The analyte reacted with antibodies fixed to the sensitive region of the SRR through a protein-G-mediated biocoupling process, resulting in a frequency shift of the sample analyte at different concentrations. Antigens such as prostate-specific antigen (PSA) and cortisol were also tested in a label-free manner by RF biosensors based on planar SRRs [Figs. 13(e)–13(g)].^108,109 Ordered nanowires prepared by Xue et al.²³ using a low-cost nanoscale printing method not only greatly enhanced the microwave signal, but also directly doped the GOx enzyme into the nanostrips via biotin–streptavidin coupling, enabling specific glucose sensing.

The dielectric contrast between analytes and surrounding media, such as buffer solutions or biological matrices, is crucial for achieving high sensitivity in biosensing applications. Metamaterials can be engineered to enhance the electromagnetic interaction with analytes by exploiting the dielectric contrast. By tailoring the electromagnetic properties of metamaterials to match or amplify the dielectric contrast, it is possible to achieve enhanced sensor performance and detection limits. Environmental factors such as temperature, humidity, and pH can influence the dielectric properties of analytes and affect sensor performance. Designing metamaterial-based biosensors capable of operating under varying environmental conditions requires careful consideration of these factors. Temperature compensation techniques and environmental shielding measures can be employed to mitigate the effects of environmental variability on sensor performance.¹¹⁰ 

In summary, the dielectric properties of analytes have a direct impact on the design and performance of microwave biosensors. The dielectric properties of the analytes should remain stable during the detection process to avoid introducing errors or interference.¹¹¹ This is crucial for ensuring the repeatability and accuracy of a sensor. The dielectric properties of the analytes should match the microwave frequency at which the sensor operates. Within the operating frequency band of the sensor, the dielectric properties of the analytes should exhibit a clear response for easy detection and analysis. In biosensing applications, maintaining the integrity and viability of biological samples is essential for accurately reflecting their dielectric properties.¹¹² By considering the dielectric properties of analytes in the design of metamaterial-based microwave biosensors, it is possible to tailor sensor performance to specific bioanalytical applications. By exploiting the frequency-dependent and temperature-sensitive nature of dielectric properties, metamaterial-based biosensors offer a versatile platform for label-free, real-time detection of biomolecular interactions with high sensitivity and selectivity. By precisely controlling and optimizing sensor design to accommodate the dielectric properties of the corresponding analytes, sensor sensitivity, specificity, and accuracy can be significantly enhanced.

Manufacturing considerations have also played a key role in the development of metamaterial-based microwave biosensors, affecting their performance, scalability and repeatability. Factors such as manufacturing technology, material selection, scalability and repeatability, integration with biosensing platforms, and cost-effectiveness must be carefully considered during the manufacturing process to ensure the successful implementation of metamaterials in biosensing applications.

Various fabrication techniques are employed to produce metamaterials with subwavelength features necessary for their unique electromagnetic properties. Electron beam lithography (EBL), photolithography, nanoimprint lithography (NIL), and self-assembly processes are commonly used methods for fabricating metamaterials. Each technique offers distinct advantages and limitations in terms of resolution, throughput, and material compatibility. The choice of materials for metamaterial fabrication is critical for achieving the desired electromagnetic responses and ensuring compatibility with biosensing environments. Dielectric materials such as silicon, silicon dioxide, and polymers are often used for fabricating metamaterials owing to their low-loss properties and ease of processing.¹¹³ Metallic materials such as gold, silver, and copper are employed for structures requiring conductivity and plasmonic effects. Fabrication techniques must be scalable to enable the production of metamaterials over large areas with uniform properties.¹¹⁴ 

Additionally, ensuring reproducibility is essential for manufacturing metamaterial-based biosensors with consistent performance across multiple devices and batches. Optimizing fabrication parameters, such as exposure dose and substrate preparation, helps achieve reproducible results. Fabrication processes should be compatible with the integration of metamaterials into biosensing platforms, such as microfluidic devices or functionalized surfaces. Designing metamaterials that can be seamlessly integrated with sensing elements, such as microfluidic channels or biomolecular coatings, enhances biosensor performance and functionality. In the process of developing microfluid-based microwave integrated biosensors, Shahri et al. optimized microwave components, designed the structure and manufacturing process, measured the dielectric properties of biological substances (such as glucose and cell suspension), realized the determination of glucose concentration change and cell quantization, and improved the performance of metamaterial-based microwave biosensors in terms of sensitivity and repeatability.^115,116 Cost-effective fabrication methods are crucial for the widespread adoption of metamaterial-based biosensors. By optimizing fabrication processes and materials usage, it is possible to reduce manufacturing costs without compromising sensor performance. Additionally, leveraging scalable fabrication techniques and batch processing enables high-throughput production of metamaterials at reduced costs.

Overall, addressing fabrication considerations is essential for realizing metamaterial-based microwave biosensors with optimal performance, scalability, reproducibility, and cost-effectiveness. By carefully selecting fabrication techniques, materials, and integration strategies, it is possible to overcome fabrication challenges and advance the development of metamaterial-based biosensors for various bioanalytical applications.

Microwave biosensors, enhanced with metamaterials, have emerged as versatile tools across various bioanalytical applications. This section delves into the extensive array of applications where metamaterial-based microwave biosensors exhibit remarkable capabilities, particularly in biomedical diagnostics, environmental monitoring, food safety, and beyond. Through a meticulous review and analysis of recent advancements and case studies, this section elucidates the pivotal role of metamaterial-based microwave biosensors in addressing critical challenges and driving innovation in bioanalytical research.

The field of metamaterial-based microwave sensing boasts considerable biological advantages that set it markedly apart from the conventional chemical and optical sensing methodologies traditionally employed. Its unique noncontact and nondestructive nature not only preserves the original state of the test subjects, but also minimizes the risk of contaminating the samples. This contrast is stark when compared with traditional methods, which often rely on the introduction of biomarkers and may inadvertently induce chemical changes within the substances under examination. Thus, microwave sensing emerges as a pioneering approach in the realm of noninvasive medical diagnostics and testing.

Diabetes, a condition characterized by elevated blood sugar levels, represents a rapidly growing global health crisis, with its prevalence and the associated societal costs soaring to unprecedented levels. According to statistics from the International Diabetes Federation (IDF), the number of individuals living with diabetes worldwide has surpassed 450 million and is on an upward trajectory at an alarmingly unpredictable rate.¹¹⁷ This scenario underscores an urgent requirement for consistent diabetes monitoring, which is increasingly being acknowledged as a critical component of preventive healthcare strategies. Although invasive devices have made it possible to conduct blood glucose measurements at home, their inherent limitations, including the risk of infection, the necessity for puncturing the skin at fixed locations, and the accompanying discomfort and financial burden, highlight a significant demand for noninvasive techniques for monitoring blood glucose levels. Noninvasive glucose monitoring technologies, encompassing optical,^118,119 electrochemical,¹²⁰ impedance-based,¹²¹ and microwave-based^122–124 methods, have emerged as innovative alternatives. Metamaterial-based microwave sensing, in particular, has demonstrated its potential in facilitating noninvasive, real-time, continuous monitoring of blood glucose levels within controlled laboratory environments.²⁰ 

For noninvasive in situ blood glucose measurement, Omer et al.⁵³ developed an improved portable metamaterial microwave sensor. This sensor consists of four hexagonal CSRR units arranged in a honeycomb structure on an FR4 dielectric substrate. The CSRR sensing elements were coupled to a planar microstrip line connected to a radar board operating in the 2.4–2.5 GHz ISM band [Fig. 14(a)]. The design and geometric parameters of the planar transmission lines and the CSRR units were optimized to maximize resonance strength and confine the resonant electromagnetic field within the sensor’s dielectric constant sensing region [Figs. 14(b)–14(e)].

Two preliminary prototypes were numerically simulated, fabricated, and tested for monitoring changes in glucose levels ranging from 70 to120 mg/dl in simulated blood aqueous solutions. The proposed CSRR sensor exhibited impressive sensitivity in detecting changes in blood sugar levels, with a distinguishable frequency shift resolution of ∼0.94 MHz/(mg/dl). This sensitivity surpasses that of conventional SRR/CSRR structures. A preliminary in vivo experiment demonstrated the efficacy of the integrated sensor in tracking blood glucose level patterns from the fingertips. With proper artificial intelligence (AI) signal processing and personalized invasive calibration, the device has potential for personalized, rapid, accurate, and noninvasive monitoring of blood sugar levels to control and prevent diabetes. Additionally, the sensor’s miniature scale provides a significant advantage for wearable technology integration, such as in a smartwatch, enabling continuous glucose sensing similar to monitoring breathing and heart rate. These results represent a paradigm shift for microwave sensors in personalized biomedical applications, particularly in diabetes monitoring, and pave the way for their commercialization.

Furthermore, Omer et al.²⁰ proposed coupling three circular CSRRs with planar microstrip lines to achieve a compact, portable microwave biomedical sensor operating in the 1–6 GHz centimeter band for real-time monitoring of blood glucose concentration in type 2 diabetes [Fig. 14(f)]. The sensor demonstrated high sensitivity to glucose level changes, with a sensitivity performance of about 6.2 dB/(mg/ml) in |S₂₁|, superior to other existing sensors in terms of resonance amplitude resolution [Fig. 14(g)]. The proposed microwave sensor can be easily fabricated at low cost and miniaturized, offering great potential for integration with other microwave components in embedded sensors and systems-on-chip to realize a preliminary wearable or portable noninvasive device for real-time glycemia level monitoring. These achievements underscore the profound capability of metamaterial-based microwave sensors in the domain of noninvasive blood glucose monitoring.

The outbreak of COVID-19, caused by the novel coronavirus SARS-CoV-2, has spurred an urgent demand for innovative diagnostic technologies capable of rapid and accurate detection. Conventional diagnostic methods, while effective, often suffer from limitations such as lengthy turnaround times and complex sample processing requirements. In response to these challenges, researchers have increasingly turned to advanced biosensing technologies, particularly those leveraging the unique properties of metamaterials, to develop next-generation diagnostic platforms. Metamaterial-based microwave biosensors represent a promising avenue for COVID-19 detection. By integrating metamaterial structures with microfluidic systems and functionalized surfaces, these biosensors offer enhanced sensitivity, selectivity, and real-time monitoring capabilities. Furthermore, the tunability of metamaterial properties enables the design of multifunctional biosensing platforms capable of detecting multiple biomarkers associated with SARS-CoV-2 infection. Abdulkarim et al.⁶⁵ designed a compact metamaterial-based microwave sensor (17.5 × 17.5 mm²) featuring a symmetrical structure with a corona-shaped resonator connected to a transmission line [Fig. 15(a)]. The sensor showed resonant peaks at 4.78, 6.5, and 7.88 GHz [Fig. 15(b)]. Their study also investigated the relationship between lymphocyte count and the dielectric constant of blood components.^125,126 Ermolina et al.¹²⁵ demonstrated that the static dielectric constant of blood is nearly linear with cell volume proportion, up to 20%. Most COVID-19 cases exhibit a lymphocyte percentage (LYM%) of less than 5%,¹²⁷ which correlates with a decrease in blood capacitance and permittivity due to the immune response.¹²⁸ The response frequency of blood samples from infected people changed by 740 MHz compared with blood samples from normal people. The sensor’s unique response to COVID-19-infected blood, with dielectric properties 5% lower than normal blood, indicates its potential for COVID-19 detection.

The density and detection of bacteria are also important topics. as early as 2007, Godin et al.¹²⁹ used a suspended microchannel resonator to measure the density of Escherichia coli. Narang et al.²¹ later explored a microfluidic-integrated metamaterial-based microwave biosensor for real-time detection of E. coli concentration and proliferation. Cultured bacteria were diluted to the desired concentration and introduced into the microwave–microfluidic platform. The resonator’s electrical signal was analyzed using a VNA to gather resonant profiles for bacteria in varying concentrations and environmental pH, enabling long-term screening of their growth [Fig. 15(c)]. This sensing platform offers several advantages, including minimal sample and reagent volumes (∼400 nl), heightened detection sensitivity (capable of detecting OD₆₀₀ values as low as 0.003, although the precise limit of detection has not been established), rapid detection kinetics (almost instantaneous), and enhanced combinatorial capabilities compared with various alternative electrical sensing modalities.

Furthermore, the methodology allows for direct visualization and enumeration of bacterial populations. Microscopic examination of bacteria suspended within the microchannel revealed a uniform distribution along its length, without any adhesion to the PDMS substrate. This study provides insights into the dielectric properties of E. coli K12 MG1655 and their correlation with the resonant amplitude and frequency of the resonating sensor [Fig. 15(d)]. The sensor showed a near-instant response to changes in bacterial concentration, with a maximum sensitivity of 3.4 MHz. The linear relationship between the electrical signal and bacterial concentration suggests the potential for further experimentation using metamaterial-based microwave–microfluidic platforms to develop diagnostic techniques and antibiotic susceptibility testing (AST). Implementing these advances could significantly streamline workflows in clinical microbiology laboratories and enhance infection diagnosis and management capabilities.

In the contemporary era, marked by rapid industrial and economic development, environmental issues have risen to the forefront of societal concerns, particularly regarding air quality. The significance of air quality extends beyond mere environmental considerations, directly impacting human health and overall quality of life. For instance, pollution from inhalable particulate matter has been conclusively linked to detrimental effects on respiratory health.^130,131 Moreover, while nontoxic gases such as carbon dioxide are generally harmless at normal levels, their concentrations can reach fatal thresholds under certain conditions. Additionally, the presence of toxic gases like formaldehyde, ozone, carbon monoxide, and ammonia beyond their permissible exposure limits can lead to a spectrum of health risks, underscoring the necessity for vigilant air quality monitoring.

Industries operating in various sectors require rigorous control over the quality of gases within their operational and experimental environments to ensure safety and compliance with environmental standards. Similarly, medical facilities are subject to even more stringent gas quality requirements to safeguard patient health. The cornerstone of gas quality assessment lies in the deployment of gas sensors, which are broadly classified into categories such as semiconductor, electrochemical, photochemical, polymer, surface acoustic wave, and additional types, each with its specific application and sensitivity profiles.

Gas sensing technology involves a two-step process:¹³² the initial sensitive interaction where the gas molecules physically or chemically engage with the sensor’s sensitive materials, followed by signal transduction. This latter phase involves the conversion of these molecular interactions into quantifiable signals through various mechanisms, including conductance,¹³³ light conduction,¹³⁴ mass transfer,¹³⁵ and electrochemical conversion.¹³⁶ The critical area of concern is the detection of methanol and ammonia gas, hazardous volatile organic and inorganic compounds emanating from diverse sources such as chemical industries, fossil fuel processing, agricultural activities, and biological decay. Methanol and ammonia exposure can result in severe health complications, including bronchoconstriction, narrowing of airways, and metabolic disruption.^137,138

Traditional methods for detecting these gases often require high operational temperatures, leading to increased costs and limited practicality for widespread application.¹³⁹ There is therefore a pronounced need for the development of gas sensors that combine rapid response and recovery times with high sensitivity at ambient temperature.⁴² Recent innovations in metamaterial-based microwave sensors have emerged as promising solutions for room-temperature gas detection. Nonetheless, the quest to achieve optimal sensitivity, ensure commercial viability, and minimize costs presents ongoing challenges within the field.

Pioneering efforts by researchers such as Khuhro¹⁴⁰ and Omer⁵³ have introduced promising strategies to overcome these hurdles. These include the development of portable integrated circuits aimed at reducing the financial burden associated with gas detection systems and the exploration of new sensing materials designed to enhance the efficacy of microwave sensors. Such advances are paving the way toward the realization of efficient, cost-effective gas sensors capable of meeting the stringent demands of contemporary environmental and health standards. A notable contribution by Kumar et al.¹⁴¹ involved the integration of a polyindole (PIn) circuit within a microwave sensor, specifically designed for the detection of methanol. This sensor capitalized on the slow hydrolytic degradation of PIn to significantly improve both response and recovery times, a feature that is vividly depicted in Fig. 16(a). The methanol detection results of the sensor showed high sensitivity in terms of frequency shift (3.33 kHz/ppm), amplitude shift (0.005 dB/ppm), bandwidth spread (3.66 kHz/ppm), and load Q factor (10.60 Q value/ppm). Additionally, the detection of ammonia gas, a critical requirement in various industrial and environmental monitoring applications, has seen considerable advances. In a related study, Bailly et al.¹⁴² explored the effects of metal oxide exposure to an ammonia atmosphere, revealing notable changes in both the S₁₁ and the S₂₁ of the microstrip antenna [Fig. 16(b)]. At 500 ppm, the S₁₁ response amplitude of the sensor to ammonia was −0.17 dB, and the S₂₁ response amplitude was 0.1 dB, which decreased linearly with the concentration. These alterations established a direct correlation between ammonia concentration levels and the microwave signal’s characteristics. Wang et al.¹⁴³ introduced an innovative SnO₂/bionic porous (BP) carbon microwave gas sensor. Compared with previously reported ammonia microwave sensors, it exhibited a higher sensitivity to lower concentrations of ammonia, with a lower detection limit (10 ppm) and shorter response/recovery times (60 s/120 s). It boasted a broad detection range, exceptional reversibility, stability, and selectivity, marking a significant milestone in ammonia gas microwave sensing technology, as illustrated in Figs. 16(c)–16(e).

Ensuring food safety is of utmost importance, given the significant public health risks posed by food adulteration. Despite the advent of technological advances and the development of diverse detection methods, the persistence of fraudulent practices underscores the critical need for effective food quality assessment strategies. Food adulteration, especially prevalent in developing countries, presents a significant challenge to ensuring food safety. Unethical practices, which involve the addition of inferior substitutes to food products to increase profitability, remain widespread.

Dairy products, for example, are highly valued for their nutritional benefits, including their role in bone development and as a dietary supplement. As such, the integrity of dairy product quality is of critical concern. To address the issue of dairy product adulteration, a variety of detection techniques have been explored, ranging from electrical impedance¹⁴⁴ and infrared diffuse reflection¹⁴⁵ to optical jet microviscometry,¹⁴⁶ microwave absorption-based sensing,¹⁴⁷ near-infrared spectroscopy,¹⁴⁸ resonant cavity sensors,¹⁴⁹ and metamaterial-based microwave biosensors. Among these, metamaterial-based microwave biosensors have shown particular promise in determining the protein and fat content of dairy products. To combat the risks associated with the adulteration of liquid substances in daily consumption, Bhushan et al.¹⁵⁰ developed a microwave sensor based on SRRs. This sensor was designed to be user-friendly, providing rapid and accurate results, with changes in resonant frequency used as the detection parameter. Operating at a resonant frequency of 9.24 GHz, the sensor incorporated a defected ground structure to achieve a sharp resonant frequency response. Experimental testing demonstrated the sensor’s ability to detect adulterated water (containing sugar, salt, and soap) as well as adulterated milk, with the resonant frequency shifting from 9.24 to 8.4 GHz in the case of milk detection [Fig. 17(a)]. Similarly, Carpio-Concha et al.¹⁵¹ introduced a dual-band sensor employing SRRs for detecting water adulteration in milk. Operating at frequencies of 2.5 and 3.5 GHz within the ISM band, this sensor was fabricated on a Rogers substrate and utilized a single port. Detection of milk adulteration, specifically with water, involved immersing the sensor in various samples. By observing the displacement in resonance frequency, a numerical model was developed to correlate the physical properties of milk (mass density and viscosity) with its dielectric characteristics. The proposed sensor offers a low-cost, easy-to-implement, and user-friendly solution for detecting milk adulteration. [Fig. 17(b)].

Contamination in cooking oil can arise from deliberate adulteration or from factors such as aging or improper packaging. The proliferation of cheap, adulterated vegetable oils poses a growing threat to consumer health worldwide, leading to various ailments, including cardiovascular and throat diseases. Addressing this issue, Bhatti et al.⁸ proposed a highly sensitive and cost-effective CSRR-based microwave sensor for detecting and characterizing adulteration in edible oils [Fig. 17(c)]. The sensor could detect 10%– 30% adulteration in olive oil with maximum sensitivity, frequency shift, and mass factor of 4.6, 530 MHz and 39, respectively. Additionally, Chuma et al.¹⁵² developed a metamaterial-based sensor for simultaneous microwave dielectric and near-infrared (NIR) spectroscopy. The sensor used a planar circular split-ring resonator for dielectric measurement and NIR spectroscopy within the same structure. It achieved 100% accuracy in identifying olive oil adulteration with just 14 training samples, compared with over 50 samples required by other methods. This sensor reduced the training samples needed for accurate detection by 72%, thereby cutting computing requirements and time [Fig. 17(d)]. These innovative approaches signify significant strides in combating food adulteration and safeguarding public health.

Moreover, innovative applications of metamaterial-based microwave sensors have also been explored in the monitoring of fermentation processes. Hosseini and Baghelani¹⁶ have utilized metamaterial-based microwave sensing technology for real-time noncontact monitoring of key parameters such as ethanol, water, and sugar levels throughout the fermentation cycle. When analyzing the fermentation process at different stages, the average error was as low as 0.0878. This capability facilitates a multivariate approach to fermentation control, enhancing the efficiency and quality of production processes [Fig. 18(a)]. Additionally, metamaterial-based microwave sensors have been adeptly applied to the food industry, enabling the detection of variations in sugar content in soft drinks due to temperature changes and handling.¹⁷ This application ensures the maintenance of consistent taste and quality in consumer products. Further extending the versatility of microwave sensing, Kazemi et al.¹⁵³ have developed a wearable sensor capable of identifying hazardous droplets on hydrophobic fabric surfaces. The resonant frequency sensitivity of the sensor under the superhydrophobic treated fabric was 370 kHz/μl, and that under the untreated fabric was 1 MHz/μl. Thus, this microwave sensor is a good candidate for wearable detection of harmful droplets on fabrics, which can improve human safety in the case of exposure to environments containing hazardous substances [Fig. 18(b)].

Microwave biosensors with metamaterial enhancement are instrumental in ensuring food safety and quality control throughout the food supply chain. Through their enhanced sensitivity, specificity, and speed, metamaterial-enhanced biosensors contribute to preventing foodborne illnesses, ensuring compliance with food safety regulations, and maintaining consumer confidence in the food supply chain. Continued research and innovation in this field are essential for addressing emerging food safety challenges and advancing the development of next-generation biosensing technologies for food safety applications.

Standardization and validation protocols are fundamental aspects of ensuring the reliability, reproducibility, and comparability of microwave biosensor data. In this section, we delve deeper into the challenges associated with standardization and validation in the context of metamaterial-enhanced microwave biosensors, and propose strategic approaches to address these challenges.

One of the primary challenges in standardization is the diversity of methodologies employed in biosensor fabrication, calibration, and validation. Common calibration methods include standard solutions, temperature control, pH control, and more. Metamaterial-based microwave sensors are calibrated with standard solutions of known concentrations to establish the relationship between sensor response and analyte concentration. Since the response of biosensors may be influenced by temperature, calibration at a constant temperature is important. For certain biosensors, such as enzyme-based sensors, the pH may affect the activity of the sensor, necessitating calibration at a specific pH value. Validation methods include repeatability tests, specificity tests, sensitivity, and detection limit tests, among others. Similarly, Mahmudunnabi et al.²² also argued that changes in manufacturing techniques, material properties, and experimental settings can lead to inconsistent sensor performance and data interpretation. The absence of consensus-driven standardization protocols further exacerbates the challenge. Without universally accepted guidelines, researchers may employ disparate approaches, making it difficult to compare results across studies and establish benchmarks for performance evaluation. Validating the performance of metamaterial-enhanced microwave biosensors presents unique challenges due to the complex interplay between sensor design, material properties, and electromagnetic interactions. Traditional validation methods may be inadequate to capture the intricacies of biosensor functionality and performance.

Collaborative efforts between academia, industry, and regulatory bodies are essential for developing comprehensive guidelines and standard operating procedures (SOPs) for biosensor standardization and validation. These guidelines should encompass all stages of biosensor development, from design and fabrication to calibration and performance evaluation. Conducting interlaboratory studies can facilitate the identification of sources of variability and harmonization of methodologies. By participating in collaborative validation exercises, it is possible to benchmark their biosensor performance against established standards and enhance confidence in the reliability of their results. Implementing robust quality assurance practices, such as regular calibration checks, instrument validation, and adherence to Good Laboratory Practices (GLP), can enhance the reproducibility and reliability of biosensor data. Standardized reporting formats and data-sharing platforms can further promote transparency and facilitate cross-study comparisons.

Information and System Management (ISM) is paramount for ensuring the credibility and trustworthiness of metamaterial-enhanced microwave biosensors. By addressing challenges through collaborative initiatives, establishing guidelines, and embracing quality assurance practices, it is possible to overcome barriers to standardization and facilitate the translation of research findings into real-world applications. Through concerted efforts, it is possible to foster confidence in biosensor technologies and unlock their full potential for transformative impact in healthcare, environmental monitoring, and beyond.

Cost-effectiveness and scalability are crucial considerations in the development and deployment of metamaterial-enhanced microwave biosensors. This subsection delves into the multifaceted challenges and strategic approaches associated with achieving cost-effectiveness and scalability in metamaterial-enhanced biosensors, emphasizing the importance of innovative solutions and collaborative efforts.

Traditional fabrication techniques for metamaterial-enhanced biosensors often involve high material and equipment costs, rendering them economically prohibitive for large-scale production. The complexity of fabrication processes and the use of specialized materials contribute to elevated production expenses. The scalability of metamaterial-enhanced biosensors is constrained by factors such as fabrication throughput, material availability, and manufacturing infrastructure. Scaling up production to meet market demand while maintaining consistent quality and performance presents significant challenges. Biosensor development requires substantial resources in terms of time, labor, and capital investment. The iterative nature of research and development, coupled with the need for specialized expertize and equipment, contributes to resource intensiveness and adds to the overall cost of biosensor production.¹⁵⁴ 

Exploring alternative materials with similar electromagnetic properties but lower costs can mitigate production expenses. Conductive polymers, carbon-based nanomaterials, and other emerging materials offer potential cost-effective alternatives to conventional metamaterials, enabling more affordable biosensor fabrication. Transitioning to scalable manufacturing processes such as printing, roll-to-roll fabrication, and self-assembly techniques can significantly reduce production costs and increase throughput. These methods offer higher efficiency, lower material wastage, and enhanced scalability compared to traditional fabrication techniques. Camli et al.⁴ fabricated an SRR on a flame-retardant (FR) 4 substrate using a simple printed circuit board fabrication technique and fixed glucose oxidase to the sensor surface using PEDOT:PSS. The sensor showed a significant response to glucose in the detection of fructose, sucrose, glucose, and NaCl samples, thus demonstrating its glucose biospecificity [Figs. 19(a)–19(c)]. Therefore, this sensor not only provides biological specificity, it is also very simple and cost-effective. Teymoori and Yalçınkaya¹⁵⁵ developed an innovative transduction method inspired by metamaterials, utilizing microwave paper for dielectric sensing. This approach, using paper as both a microfluidic channel and resonator substrate, offers significant cost, complexity, and environmental advantages for sensing devices. The study demonstrated dielectric detection of various analytes with different dielectric constants as a proof of concept [Figs. 19(d) and 19(e)]. Results indicated a sensitivity of 2.14 MHz/RPU for analytes with dielectric constants below 30. The design showcases the integration of a porous-medium microfluidic channel with a paper-based microwave resonator, highlighting its potential application in biosensing due to its linear sensing performance.

Addressing cost-effectiveness and scalability challenges is essential for realizing the full potential of metamaterial-enhanced microwave biosensors. By adopting innovative materials, scalable manufacturing processes, and strategic partnerships, it is possible to overcome barriers to cost-effective production and scalability. Collaborative efforts between academia, industry, and government agencies are essential for driving innovation, fostering technology transfer, and accelerating the adoption of cost-effective and scalable biosensor solutions to address pressing societal challenges. Through concerted action and continuous innovation, it is possible to unlock the transformative potential of metamaterial-enhanced biosensors for diverse applications in healthcare, environmental monitoring, and beyond.

The exploration of emerging applications represents a pivotal avenue for advancing the field of metamaterial-enhanced microwave biosensors. This subsection delves into the diverse array of potential applications beyond traditional biomedical diagnostics and environmental monitoring, highlighting the transformative impact of metamaterial-enhanced biosensors in emerging domains.

Metamaterial-enhanced biosensors hold promise for enabling real-time health monitoring through wearable devices. Integrating biosensors into wearable platforms, such as smartwatches, wristbands, and clothing,¹⁵⁶ can provide continuous physiological monitoring for early detection of health abnormalities and personalized healthcare interventions. These wearable biosensors offer unprecedented convenience, comfort, and mobility, empowering individuals to monitor their health status seamlessly in everyday life. Implantable biosensors augmented by metamaterials offer revolutionary opportunities for remote health monitoring and disease management. By implanting biosensors directly into the body, clinicians can continuously monitor biomarkers, vital signs, and disease progression in real time. These implantable devices have the potential to revolutionize healthcare delivery by enabling early detection of diseases, optimizing treatment regimens, and facilitating timely interventions, thereby improving patient outcomes and quality of life.¹⁵⁴ Integrating metamaterial-enhanced biosensors into the Internet of Things (IoT) ecosystem enables seamless connectivity and data exchange across diverse applications.¹⁵⁷ By embedding biosensors into IoT-enabled devices and infrastructure, such as smart home systems, environmental monitoring networks, and industrial automation systems, metamaterial-enhanced biosensors can facilitate data-driven decision-making, predictive analytics, and autonomous control. This convergence of biosensing technology with IoT platforms unlocks new opportunities for real-time monitoring, predictive maintenance, and resource optimization across various sectors.

For instance, Hanna et al.⁵² investigated an innovative approach involving body-matched, vasculature-inspired, quasi-antenna arrays designed as metamaterial-based microwave biosensors for real-time, continuous, and wireless monitoring of glucose fluctuations in the bloodstream [Fig. 20(a)]. These personalized sensors utilized electromagnetic waves and were seamlessly integrated with a custom machine-learning-based signal-processing module. Designed to be flexible and incorporated into wearable garments, such as socks, they ensured conformity to curved skin surfaces and resilience to movement [Figs. 20(b) and 20(c)]. The entire wearable system underwent rigorous calibration against factors like temperature, humidity, and movement, resulting in highly precise tracking of glucose variations [Fig. 20(d)]. In vivo experiments conducted on diabetic rats and pigs showcased a diagnostic accuracy rate of 100% across a broad spectrum of glucose fluctuations. Human trials involving patients with diabetes and healthy individuals further demonstrated a clinical accuracy of continuous glucose monitoring at 99.01% in 28 subjects who underwent oral glucose tolerance tests. Consequently, this innovative approach ensures continuous and reliable tracking of glucose variations from hypoglycemic to hyperglycemic levels.

The exploration of emerging applications represents a paradigm shift in the field of metamaterial-enhanced microwave biosensors, unlocking new opportunities for transformative impact in diverse domains. By embracing wearable health monitoring, implantable biosensors, IoT integration, and precision agriculture, metamaterial-enhanced biosensors can revolutionize healthcare delivery, environmental monitoring, and agricultural practices. Interdisciplinary collaboration, regulatory compliance, and technology transfer are key enablers for realizing the full potential of metamaterial-enhanced biosensors in emerging applications. Through concerted efforts and innovative approaches, it is possible to harness the power of metamaterial-enhanced biosensors to address pressing societal challenges and pave the way for a more sustainable and connected future.

In conclusion, this exhaustive review has meticulously scrutinized the intricate landscape of metamaterial-enhanced microwave biosensors, accentuating their pivotal role in contemporary bioanalytical endeavors. Through a comprehensive exploration of foundational principles, design methodologies, application ranges, and prospective trajectories, this discourse has illuminated the profound significance of metamaterials in reshaping the contours of biosensing technologies.

Throughout this discourse, we have meticulously dissected the underpinnings of metamaterial-enhanced biosensors, underscored by their innate capacity to orchestrate electromagnetic phenomena at subwavelength scales. This orchestration empowers biosensors with unprecedented sensitivity, specificity, and discernment, thereby transcending conventional limits and fostering a new beginning for ultra-sensitive bioanalytical instrumentation. Furthermore, our discourse has traversed the labyrinth of design paradigms governing metamaterial-enhanced biosensors, delving into the nuances of sensor geometry optimization and selection considerations. These design intricacies, meticulously woven into the fabric of biosensor development, are indispensable for achieving pinnacle performance benchmarks while navigating the labyrinth of size constraints, cost considerations, and scalability imperatives. Moreover, a wide range of applications has been revealed, wherein metamaterial-enhanced biosensors emerge as veritable stalwarts across biomedical diagnostics, environmental surveillance, and food safety domains. From the swift diagnosis of ailments to the vigilant monitoring of environmental contaminants, the transformative potential of metamaterial-enhanced biosensors reverberates across diverse societal strata, promising a tangible metamorphosis in public health and environmental stewardship paradigms. Looking forward, an assemblage of challenges and vistas await, delineating an intellectual horizon ripe with possibilities and imperatives. Standardization protocols beckon for concerted endeavors, foreshadowing the convergence of disparate methodologies into a harmonious standard lexicon. Moreover, the clarion call for cost-effectiveness and scalability resonates, heralding an era of resource optimization and manufacturing innovation. The exploration of emerging applications raises the need for expanded disciplinary collaboration. By fostering partnerships between academia, industry, and government agencies, it is possible to catalyze innovation and address pressing societal challenges in healthcare, environmental sustainability, and agriculture.

In summary, the fusion of metamaterials with microwave biosensors heralds a new dawn in bioanalytical prowess, embarking on an odyssey of discovery and innovation that promises to redefine the contours of biosensing methodologies. Fueled by scientific exploration and technological advances, the trajectory of metamaterial-enhanced biosensors is poized to chart an impressive course across the landscape of scientific achievement, ushering in a future brimming with transformative possibilities.

The authors gratefully acknowledge financial support from the National Key R&D Program of China (2021YFC3002204) and the National Natural Science Foundation of China (NSFC No. U2233206). Special thanks are due Quanning Li, Xuejiao Chen, Wenlan Guo, and Chen Sun for their invaluable assistance in gathering materials.

The authors have no conflits to disclose.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Jiaxu Wang received a B.E. degree from Tianjin University, China in 2021, majoring in Measurement and Control Technology and Instruments. She is currently pursuing an M.E. degree at Tianjin University. Her research interests focus on biosensors for toxin detection and screening based on microwave technology.

Rongheng Wang received a B.E. degree from Liaoning University, China in 2022, majoring in Measurement and Control Technology and Instruments. He is currently pursuing an M.E. degree at Tianjin University, China. His research interests focus on on-chip wearable microsensor systems based on radio-frequency identification (RFID) technology for detecting human biological indicators.

Shen Zhou received a B.E. degree from Tianjin University, China in 2023, majoring in Measurement and Control Technology and Instruments. She is currently pursuing a master’s degree at Tianjin University. Her main research interests focus on microwave sensors and microwave detection.

Bohua Liu received a B.E. degree from Hebei University of Technology, Tianjin, China. Currently, he is an engineer in the School of Precision and Opto-electronics Engineering, Tianjin University. His research focuses on the area of MEMS processes.

Chongling Sun received a B.E. degree from Tianjin University, Tianjin, China. Currently, she is an engineer in the School of Precision Instrument and Opto-electronics Engineering, Tianjin University. Her research focuses on the area of MEMS processes.

Qiannan Xue is currently working as an Associate Professor in the School of Precision Instruments and Optoelectronics Engineering, Tianjin University, China. She is familiar with the characteristics of high-frequency sensing technology and microwave sensor devices, and is involved in research on microsensor systems and micro–nano devices.