Micro-Nanotechnology Sensors for Biomedical and Environmental Challenges: Comparison
Please note this is a comparison between Version 1 by Francisco J Tovar-Lopez and Version 4 by Rita Xu.

Micro- and nanotechnology-enabled sensors have made remarkable advancements in the fields of biomedicine and the environment, enabling the sensitive and selective detection and quantification of diverse analytes. In biomedicine, these sensors have facilitated disease diagnosis, drug discovery, and point-of-care devices. In environmental monitoring, they have played a crucial role in assessing air, water, and soil quality, as well as ensured food safety. Despite notable progress, numerous challenges persist. This review article addresses recent developments in micro- and nanotechnology-enabled sensors for biomedical and environmental challenges, focusing on enhancing basic sensing techniques through micro/nanotechnology. Additionally, it explores the applications of these sensors in addressing current challenges in both biomedical and environmental domains. The article concludes by emphasizing the need for further research to expand the detection capabilities of sensors/devices, enhance sensitivity and selectivity, integrate wireless communication and energy-harvesting technologies, and optimize sample preparation, material selection, and automated components for sensor design, fabrication, and characterization.

  • microtechnology
  • nanotechnology
  • sensors
  • biomedical
  • enviromental
  • non communicative
  • diabetes
  • cardiovascular
  • cancer
  • mental health
  • plastic pollution
  • eutrophication
  • deforestation
  • air pollution
  • climate change
  • fatberg

1. Introduction

The development of micro- and nanotechnology-enabled sensors has been a significant technological advancement that has led to several new applications in the biomedical and environmental fields [1][2][3][4][5][6][7][8][1,2,3,4,5,6,7,8]. These devices have enabled the detection and quantification of various analytes with high sensitivity and selectivity, making them ideal for applications such as vital sign monitoring [3][9][10][3,9,10], disease diagnosis [11][12][13][11,12,13], environmental monitoring [5][6][14][15][16][5,6,14,15,16], and food safety [17][18][19][20][17,18,19,20]. In recent years, there has been significant progress in the development of sensors, driven by the need to address critical challenges in these fields.
In the biomedical field, these devices have enabled the detection and quantification of biological molecules such as proteins and nucleic acids with high accuracy and in real time [21][22][23][24][25][26][27][28][29][30][21,22,23,24,25,26,27,28,29,30]. They have also enabled the development of point-of-care devices that can rapidly diagnose diseases and monitor treatment outcomes [31][32][33][34][35][31,32,33,34,35]. The use of micro- and nanotechnology-enabled sensors in the field of drug discovery and antibiotic resistance has also been significant. These devices have enabled the high-throughput screening of drug candidates and the characterization of their biological activities [4][36][37][38][39][40][41][4,36,37,38,39,40,41]. Additionally, the integration of sensors with emerging technologies such as artificial intelligence and machine learning has further expanded their potential applications in the biomedical field [10][42][10,42].
In the environmental field, sensors have been used to monitor the quality of air, water, and soil [6][43][44][6,43,44]. These devices can detect pollutants with high accuracy and in real time, enabling timely interventions to mitigate environmental pollution [16][45][46][16,45,46]. The use of sensors in the agricultural industry has also been significant [7][47][48][49][7,47,48,49]. These devices can monitor the quality of food and agricultural products, ensuring their safety and quality [7][48][49][7,48,49]. The development of biosensors that use biological components to detect environmental pollutants has further expanded their applications in this field [14][50][14,50].
Despite the significant progress made in sensors, several challenges remain to be addressed. For instance, there is a need to develop sensors that can detect a wider range of analytes with higher sensitivity and selectivity. Additionally, the integration of these sensors with other devices with easier sample preparation and technologies such as wireless communication enabling the Internet of Things (IoT), automation, and energy harvesting remains a challenge. These technological challenges, compounded by the global challenges faced in the biomedical and environmental fields (as depicted in Figure 1), render this area an intriguing subject for further investigation.
Figure 1. Schematic illustrating various sensing techniques and micro/nanotechnology approaches that enhance their performance in terms of specificity and sensitivity, enabling the development of new technologies to address upcoming biomedical and environmental challenges. The innermost circle shows fundamental sensing techniques, such as resistive sensing, capacitive sensing, piezoelectric sensing, optical sensing, acoustic sensing, and electrochemical sensing. The middle circle represents reported micro- and nanotechnology advances, including nanoparticles, nanomaterials, microfluidics, and MEMS. These technologies, together with the Internet of Things (IoT), are currently being applied to the fundamental techniques to enhance their performance. The outermost circle shows biomedical (blue) and environmental (green) challenges where these technologies are being applied.

2. Innovations Enabled by Nanotechnology in Sensing Techniques

2.1. Resistive Sensing

Resistive sensing is a method of measuring physical parameters, such as pressure, force, or temperature, by detecting changes in electrical resistance. This technique is based on the principle that the electrical resistance of a material changes when it is subjected to an external stimulus. This technique is simple and low-cost. However, resistive sensing can be affected by factors such as temperature changes and mechanical wear and tear, which can affect the accuracy of the measurements over time.
Nanotechnology has brought many different advances to the field of resistive sensing through the development of different techniques, such as the resistive measurement of nanostructured materials for gas-sensing applications [51], nanocomposites for resistive strain sensors using multiwalled carbon nanotubes (MWNTs, diameters 8–15 nm) [52] (Figure 2A), or the development of resistive pulse sensors (Coulter counter principle), which have been used to characterize everything from whole cells to small molecules [21][22][21,22]. In the work of Feng et al. [52], a method to transform conductive nanocomposites into dielectrics using tensile strain was developed. The main application of this phenomenon is integrated resistive–capacitive strain sensors, which show potential in e-skin applications. Additionally, resistive sensing can be used in aqueous solutions to investigate the fluid composition. There is a recent study on a resistive pulse sensing device with nanochannels embedded using nanotechnology to enable label-free biomolecule and bionanoparticle analysis, showing a promising sensing strategy that is not only capable of label-free analysis for nanoscale biomolecules and bionanoparticles but also cost-effective for large-scale manufacturing [53]. Recently, using solid-state nanopores, the dynamics of knots in double-stranded DNA under unique regimes of nanometer-scale confinement, large forces, and short time scales were studied in order to investigate the static and dynamic properties of biopolymers [54]. In terms of environmental applications, a tunable 3D-printed microfluidic resistive pulse sensor was developed for the characterization of algae and microplastics [55], showing promising results. See Figure 2C. On the other hand, a study on high-performance resistive humidity sensors based on Ag nanoparticles (AgNPs) decorated with graphene quantum dots (GQDs) showed that a 1:1 ratio of the GQD/AgNP nanocomposite exhibited the best humidity response of 98.14%, with an exponential relation in the humidity range of 25–95% relative humidity at room temperature, as well as faster response/recovery times than a commercial one in the same conditions [56].

2.2. Capacitive Sensing

Capacitive sensing is a technique that has the ability to detect and gauge the presence or absence of virtually any type of object, irrespective of its material composition. This technology operates as a non-contact method by utilizing the unique properties of an electric capacitor and its electrical field. Capacitive sensors are able to create a highly sensitive system that can detect even the slightest changes in the electric field.
Capacitive pressure sensor arrays have been applied to electronic skin, medical prosthetics, wearable devices, biometrics, touch pads, and touch screens [57]. Recent progress in capacitive sensing includes the development of flexible wearable devices with high sensitivity and wide ranges [58][59][58,59]. There has also been progress in pressure sensors for wearable electronics, including porous pyramidal PDMS dielectric layers [60].
Finally, Cao et al. presented a review of conductive polymer composites with different micro/nano-conductive network structures based on the fundamental tunneling percolation theory and their potentialities and drawbacks for tactile sensor applications. They highlighted how model simulations can be used to clearly elucidate the structure-and-property relationship and guide the modulation of the network structure of conductive composites, discussing how emerging machine learning paradigms may create newly conductive polymer composites in the future [61].

2.3. Piezoelectricity Sensing

In a piezoelectric material, the material generates an electric potential in response to a deformation. This property can be used for sensing and actuation. Recent advances in nanotechnology for piezoelectric sensing include the development of biosensors for detecting heavy metals [62]. Piezoelectric thin films such as zinc oxide and aluminum nitride have found applications in acoustic biosensors [63].
Piezoelectric-based biosensors utilize bioreceptors attached to materials such as ceramics and quartz. These materials generate a measurable signal in response to mass-induced oscillations on the surface of the piezoelectric crystal, enabling the detection of low concentrations of lead ions [62].
In an emerging application, piezoelectric, photoexcitation, and semiconductor properties can be coupled in two-way or multiway interactions, leading to the emergence of new research fields, such as piezotronics and piezo-phototronics. These areas of research have garnered significant attention due to their potential applications in utilizing basic mechanical stimuli and designing new strain sensors based on the alteration of semiconductor properties caused by strain [64].
On the other hand, Du et al. [65] comprehensively discussed the latest advancements in hydrogel-based piezoelectric devices for biomedical applications. The article particularly emphasizes the potential of such devices in wearable sensing technology, including biosignal sensing, energy harvesting, wound healing, and ultrasonic stimulation. The authors provide a comprehensive overview of the current state-of-the-art research in this field, highlighting the key challenges and opportunities for future development. On a similar topic, a composite hydrogel with piezoresistive and piezoelectric sensing for flexible strain sensors with enhanced sensitivity and a wide frequency band response for smart wearable strain sensors was reported by [66].
These advances in nanotechnology have enabled the development of piezoelectric sensors with improved sensitivity, stability, efficiency, and affordability. The use of nanotechnology has allowed for the creation of piezoelectric sensors that can be used for a wide range of applications, including structural health monitoring, force sensing, and energy harvesting.
Figure 2. Resistive, capacitive, and resistive pulsing sensors. (A) The device can be transformed from conductive to non conductive Electrical and dielectric results of nanocomposites of MWNTs and PDMS with various weight fractions. When W(MWNT) = 8.03%, transformation occurs due to tensile strain. (B) Schematic showing the integrated R-C strain sensor and characterization method and the performance of the R-C sensor. (C) Capacitive pressure sensor based on porous Ecoflex-multiwalled carbon nanotube composite (PEMC) structures, with a sensitivity (6.42 and 1.72 kPa ×101 in a range of 0–2 and 2–10 kPa, respectively) due to the synergetic effect of the porous elastomer and the percolation of carbon nanotube fillers. The figure shows a 3D model of a constructed prosthetic arm with an integrated robot finger for grasping movements; an LED is attached to the index finger to gauge the pressure sensed by the PEMC-based pressure sensor embedded into the thumb. Demonstration of the grasping abilities of the robot finger for a soft material (top 4 insets), and a hard material (plastic ball; bottom 4 insets), for both cases i-iv: Demonstrate progressive and reversible increase of capacitance as a function of robot finger force. Reprinted (adapted) with permission from [67]. Copyright 2020 American Chemical Society. (D) A low-cost and high-throughput multi-use resistive pulse sensor (RPS) produced through additive manufacturing demonstrated the ability to selectively detect and characterize both microplastics (shed from tea bags) and two algae species. Reprinted (adapted) with permission from [55]. Copyright 2020 American Chemical Society.

2.4. Thermoelectricity Sensing

The thermoelectric effect, which converts heat energy into electrical energy, can be achieved through any of the three fundamental phenomena: the Seebeck effect, the Peltier effect, and the Thomson effect. These phenomena are essential for the development of thermoelectric materials and can be used as sensing techniques [68].
The Seebeck effect refers to the phenomenon in which a temperature gradient (Δ Δ T) across a thermoelectric material can produce the direct conversion of heat energy into electrical energy. The Peltier effect is characterized by the absorption or release of heat at the interface of two different materials as a result of the passage of an electric current. The Thomson effect is observed when a uniform conductor is subjected to a constant current, and the application of a temperature gradient causes the absorption or release of additional heat.
Recent progress in thermoelectric sensing includes advances in materials and device designs for wearable technology [69], computational methods for discovering new thermoelectric materials [70], and the use of two-dimensional heterostructures for thermoelectric applications [71]. Flexible thermoelectric devices have also been developed to convert body heat into useful energy [72].
Thermoelectric sensing has a wide range of applications, including biomedical, thermal-cycling, optical, and sensor applications in the telecom, automotive, consumer, and even power generation industries [9]. Thermoelectric generators are also used in sensors that monitor the vital signs, movements, and physiological conditions of the body in a noninvasive way [9]. Thermoelectric generators (TEGs) are attractive candidates for power sources or self-powered heat sensors for portable devices [73].
Wearable thermoelectric generators (TEGs) are attracting interest due to their ability to self-power these electronic devices or sensors by harvesting human body heat. Wang et al. developed a numerical model to investigate the performance of wearable TEGs on the curved human wrist [74]. See Figure 3A.
The use of nanotechnology has enabled the creation of thermoelectric devices with improved sensitivity, stability, and efficiency, which can be used to measure temperature with improved accuracy and precision.
Figure 3. Thermoelectric sensing and electrochemical sensing. (A) Wearable thermoelectric generators (TEGs) are attracting interest due to their ability to self-power these electronic devices or sensors by harvesting human body heat. Wang et al. developed a numerical model to investigate the performance of wearable TEGs on the curved human wrist. (B) Combining microfluidics and laser-engraved fabrication methods, Yang et al. developed a wearable sensor for sensitive detection of uric acid and tyrosine in sweat.

2.5. Acoustic Sensing

Acoustic sensing refers to the use of technology to detect, analyze, and measure sound waves or acoustic signals in various environments and is used to detect a wide range of sounds, from human speech and music to machinery noise and environmental sounds. Acoustic sensing technology typically consists of a sensor that can detect sound waves and can convert them into an electrical signal, which is then processed and analyzed using specialized software or hardware. The sensor may be a microphone or a more complex device, such as an acoustic resonator or a piezoelectric sensor.
Recent advances in nanomaterial-enabled acoustic devices have greatly improved the sensitivity, tunability, and other limitations of conventional acoustic sensors; however, further exploration of flexible acoustic devices is a key priority and will have a great impact on the advancement of intelligent robot–human interaction and flexible electronics [75]. Wei et al. presented a review of nanomechanical resonators, which are able to detect very small changes in acoustic waves [76]. The coupling of micro- or nanomechanical resonators via a shared substrate is intensively exploited to build systems for fundamental studies. This can be exploited to realize high-quality phonon cavities, an alternative to acoustic radiation shielding, acoustic superlenses, waveguides, vibration attenuation, mass sensing, and phononic graphene [77].
Other applications use nanowire-based acoustic sensors, which are a type of sensor that incorporates nanowires. A soft resistive acoustic sensor based on suspended nanowires has also been developed for future wearable voice recognition devices, cochlear implants, and human–machine interfaces [78]. A flexible, localized acoustic sensor with a mass block-beam using silver nanowires coated on polydimethylsiloxane (PDMS) has also been designed to test the sound source orientation [79]. Nanowire-based sensors have been studied in the context of 1D nanostructures, nanowire synthesis for sensing, and composite nanowire materials to determine the freshness status of mackerel fish (Scomber scombrus) in a quick and noninvasive way [80]. In terms of fabrication, nanocrystalline diamonds are ideal materials for manufacturing various microelectromechanical devices and mass sensors due to their high-frequency working range and excellent material properties. Recently, a low-cost method to fabricate diamond-based micro-resonators using a modified home/office desktop inkjet printer was used to locally deposit nanodiamond ink as ϕ 50–60 μ μ m spots [81].

2.6. Electrochemical Sensing

Electrochemical sensing is a technique that uses electrochemical principles to detect and measure the concentration of a specific chemical species in a sample. Electrochemical sensors typically consist of a three-electrode cell: an interrogating electrode, a reference electrode, and a counter electrode. A signal is generated within the electrochemical cell and then measured and analyzed by a potentiostat [82]. Nanotechnology has brought significant progress to the field of electrochemical sensing by enabling the development of highly sensitive and selective sensors with improved performance characteristics.
One of the main advantages of nanotechnology in electrochemical sensing is the ability to increase the surface area of the electrode, which enhances the sensitivity and selectivity of the sensor. This can be achieved by using nanomaterials such as carbon nanotubes, graphene, and metal nanoparticles to modify the electrode surface [82].
Nanotechnology has also enabled the development of new sensing mechanisms, such as surface-enhanced Raman spectroscopy (SERS) and electrochemiluminescence (ECL), which offer high sensitivity and selectivity for certain analytes [18].
Recent advancements in electrochemical sensors include the development of microfluidic-based electrochemical sensors for sensing foodborne pathogens [18], advances in electrochemical sensing platforms enabling the detection of biomolecules and whole cells [23], and the integration of a flexible electrochemical sensor into a microfluidic chip for simulating and monitoring vascular mechanotransduction [83].
For other applications, various nanomaterials, such as carbon nanotubes, graphene, and metal nanoparticles, have been integrated into electrochemical sensors to enhance their performance, such as sensitivity, selectivity, and stability [24][84][85][24,84,85].
For wearable applications, electrochemical sensors have been developed using microfluidics and nanotechnology to monitor various physiological parameters, such as glucose, lactate, and pH in real time and even lead and cadmium from a sample sweat [86]. These sensors are noninvasive and comfortable to wear, and some can transmit data wirelessly to a smartphone or a cloud server, as discussed by [87][88][87,88].
On the other hand, paper-based electrochemical sensors have been developed using microfluidics and nanotechnology for point-of-care diagnosis in resource-limited settings. These sensors are low-cost and portable and can detect various analytes, such as glucose, cholesterol, and DNA. Recent advancement are ePADs (electrochemical paper-based analytical devices), including several preparation methods [31] and printed paper-based electrochemical sensors for low-cost point-of-care disease and environmental diagnostics [32]. The development of electrochemical and optical detection methods based on microfluidic paper-based analytical devices ( μ Pads) for point-of-care testing applications is discussed by Hou et al. [33]. Combining microfluidics and laser-engraved fabrication methods, Yang et al. developed a wearable sensor for the sensitive detection of uric acid and tyrosine in sweat [34]. See Figure 3B.
Lastly, multiplexed electrochemical sensors have been developed using microfluidics to detect multiple analytes simultaneously. These sensors can be used for the high-throughput screening of samples and can reduce the cost and time required for analysis [88]. Multiplexing sensing refers to the simultaneous detection of multiple analytes using a single sensor platform. This approach offers several advantages, such as reduced analysis time, increased throughput, and cost-effectiveness compared to traditional single-analyte detection methods [34]. Multi-analyte electrochemical detection can enhance the efficiency of analyzing multiple food safety hazards. However, interference and cross-reactions among analytes can impede simultaneous detection by electrochemical sensors. This interference can arise from similar analytes, interferences between channels, and low detection sensitivity. To address these challenges, different nanostructuring options can be employed. These include incorporating nanoparticles to enhance electrocatalytic properties, utilizing nanostructured electrodes to improve sensitivity and selectivity, depositing nanostructured films or coatings to enhance selectivity and stability, incorporating nanopores or nanochannels for controlled analyte diffusion, and employing nanostructured catalysts to enhance electrochemical reactions. These nanostructuring approaches mitigate interference and improve the performance of electrochemical sensors in the simultaneous detection of analytes [89][90][91][92][89,90,91,92]. Some recent advancements in multiplexing sensing include the development of an antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids [93].
Overall, these advancements in electrochemical sensors hold promise for a wide range of applications in healthcare, environmental monitoring, food safety, and many other areas.

2.7. Optical Sensing

Optical sensing refers to the process of detecting and measuring light or other forms of electromagnetic radiation using specialized sensors or devices. Optical sensing works by detecting changes in the intensity, wavelength, polarization, phase, or direction of light or other forms of electromagnetic radiation. Common types of optical sensors include photodiodes, phototransistors, photovoltaic cells, and charge-coupled devices (CCDs).

2.7.1. Photodetection Sensing

A photodetector (PD) is an optoelectronic device that converts incident light or other electromagnetic radiation in the UV, visible, and infrared spectral regions into electrical signals [94]. Nanotechnology has brought recent progress to photodetection sensing by enabling the development of low-dimensional photodetectors [95] and nanostructured photodetector technology for UV sensing and pollution detection [96]. There are also recent developments in lead-free double perovskites for X-ray and UV-vis photodetection [97].
Graphene and semiconductor nanocrystals have been used in the development of photodetectors due to their unique optical and electronic properties, such as high absorption coefficients and high charge carrier mobility. In this context, nanostructured materials have been developed, such as perovskites, which have a long carrier lifetime, high carrier mobility, and facile synthesis [98]. Low-dimensional semiconductor/Si hybrid heterostructures provide a great platform for fabricating high-performance photodetectors [99]. Various absorber materials, such as quantum dots (QDs), plasmonic metal nanoparticles, perovskites, and organic materials, have been investigated to improve broadband absorption [100].

2.7.2. Plasmonic Nanosensors

Microdevices and nanotechnology have had a significant impact on the field of optical sensing by enabling the development of more sensitive and selective sensors with higher resolution and faster response times. The use of nanoscale materials, advanced fabrication methods, and surface plasmon resonance (SPR) in plasmonic nanosensors has enabled the development of highly sensitive and selective sensing technologies for a wide range of applications, including biomedical diagnostics, environmental monitoring, and food safety [101][102][101,102].
SPR is a phenomenon that occurs when light interacts with a thin metal film or nanoparticle at a specific angle, causing the conduction electrons in the metal to oscillate and generate an electromagnetic field known as a surface plasmon. This electromagnetic field is highly sensitive to changes in the refractive index of the surrounding environment, making SPR a popular technique for sensing applications [103].
Plasmonic biosensors use evanescent waves to detect analytes such as proteins, nucleic acids, pathogens, and drugs without the need for labeling. This label-free detection provides exceptional sensitivity in a real-time one-step format [104].
Plasmonic nanosensors take advantage of the SPR phenomenon to detect changes in the environment. By functionalizing metal nanoparticles with specific biomolecules or chemical groups, plasmonic nanosensors can detect the presence of specific analytes or molecules in a sample. The interaction between the analyte and the functionalized nanoparticles causes a shift in the SPR signal, which can be measured to determine the concentration or presence of the analyte [25].
Recent advancements in surface plasmon resonance (SPR) include the development of highly sensitive pathogen biosensing techniques [105]. There have been significant developments in SPR sensing devices for the detection of various chemical and biological molecules [26]. A review by Huo et al. describes the principle of SPR imaging and discusses recent developments in prism-coupled and non-prism-coupled SPRI techniques in detail [106].
Knoezer et al. demonstrated how an optical frequency comb can be used to enhance the functionality of an integrated photonic biosensor platform by sampling the spectral response of a Mach–Zehnder interferometer and arranging the sample response to periodic intervals to combine them into a single measurement of the interferometer phase, resulting in a lower limit of detection of 3.7 × 10 7 RIU [107].
In another application, a dual-functional nanoprobe based on dopant-driven plasmonic oxides was recently developed, demonstrating a maximum accuracy above 90% in distinguishing single THP-1 cells (related to leukemia) from peripheral blood mononuclear cells (PBMCs) and human embryonic kidney (HEK) 293 cells from the human macrophage cell line U937 based on their surface-enhanced Raman spectroscopy (SERS) patterns [108]. See Figure 4A.
Lastly, in terms of the tunability of materials, nanoscale materials are commonly used in plasmonic nanosensors to tune the plasmonic properties of the material and increase sensitivity. Researchers can control the size, shape, and composition of nanoparticles to optimize sensor performance, and the high surface-area-to-volume ratio of nanoscale materials allows for their functionalization. Two-dimensional nanomaterials such as graphene and transition metal dichalcogenides have been studied for their potential to improve SPR sensor performance with increased sensitivity and narrower full-width half-maxima [26]. Similarly, metal–organic frameworks provide many attractive features, including tailorable porosity, high surface areas, good chemical/thermal stability, and various host–guest interactions, making them appealing candidates for volatile organic compound capture and sensing [109].
Figure 4. Optical sensing and electromagnetic wave technology. (AC) Single-cell analysis using a dual-functional nanoprobe based on dopant-driven plasmonic oxides, which enables the identification of a single THP-1 (related to leukemia) cells from peripheral blood mononuclear cells (PBMCs) and human embryonic kidney cells from human macrophage cells based on their surface-enhanced Raman spectroscopy (SERS) patterns. (B,C) (I) Cells are coated with PO (plasmonic oxide) via incubation. (II) Illustration (left) and optical image (right) of the PO-coated cells infused into a microfluidic chip and settled separately in the small grooves (highlighted in red). (D) Millimeter-wave technology. Schematic of the developed ultra-wideband millimeter-wave imaging system for real-time in vivo skin cancer imaging, achieving an overall synthetic bandwidth of 98 GHz. At each scanning step, two sub-band antennas are placed in front of the target, transmit their signals in their respective sub-band frequency ranges, and record the backscattered signals. (E) Metamaterial-inspired biosensors using THz detection and a label-free biosensing approach for molecular classification of glioma cells. A metamaterial biosensor consisting of cut wires and split-ring resonators is used to realize polarization-independent electromagnetically induced transparency (EIT) at THz frequencies. The theoretical sensitivity of the biosensor was evaluated up to 496.01 GHz/RIU. The measured results indicated that mutant and wild-type glioma cells can be distinguished directly by observing variations in both the EIT resonance frequency and magnitude at any cell concentration without antibody introduction.

2.7.3. Photonic Crystals

Photonic crystals are periodic structures with a periodicity on the order of the wavelength of light. By controlling the periodicity and composition of photonic crystals, it is possible to create sensors that are highly sensitive to changes in the refractive index of a sample. For example, photonic crystal sensors have been used to detect small changes in the concentration of glucose in blood samples [110][112]. The sensor is able to perform at an ultrahigh sensitivity of 4200 nm/RIU, is a low-cost, tunable design, enables real-accurate detection, and has a simple structure, which is supportive of an industrial design using low-cost product nanofabrication techniques. On the other hand, Boes et al. presented an excellent review of lithium niobate, showing its capabilities to open a new-generation field in sensor development due to its virtues, such as a large dynamic range [111][113]. Additionally, integrated photonics on thin-film lithium niobate holds great promise for realizing low-cost and scaled optical solutions for communication, sensing, and computation [111][113].
Overall, nanotechnology has allowed for the development of optical sensors with higher sensitivity, selectivity, and resolution, making them valuable tools for a wide range of applications, from biomedical diagnostics to environmental monitoring.
 
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