Flexible sensors have been extensively employed in wearable technologies for physiological monitoring given the technological advancement in recent years. Conventional sensors made of silicon or glass substrates may be limited by their rigid structures, bulkiness, and incapability for continuous monitoring of vital signs, such as blood pressure (BP). Two-dimensional (2D) nanomaterials have received considerable attention in fabrication of flexible sensors due to their large surface area-to-volume ratio, high electrical conductivity, cost-effectiveness, flexibility, and lightweight.
The capacitive effect of an Si-based sensor was first studied by Michael Faraday in 1831 [45]. The capacitive transduction mechanism differs from piezoelectric and piezoresistive mechanisms in that no pressure is applied to introduce deformation, but it instead involves the contact between two plates. The parallel-plate capacitor is a typical arrangement of a capacitive sensor, wherein two plates are separated from each other by a dielectric layer. A Si-based organic polymer known as polydimethylsilixone (PDMS) has been widely investigated as a dielectric layer in capacitive sensors due to its great flexibility, biocompatibility, and low toxicity [46][47]. A reduction in separation distance between plates leads to a change in capacitance [48].
Capacitive sensor has a number of advantages over piezoelectric-based sensor in terms of lower power consumption, wider detection range, and higher sensitivity for detection of low pressure. However, this sensor has slow response time, expensive fabrication procedure, and power source dependency.
The piezoresistive effect has been widely investigated and used in a broad range of fields, such as microelectromechanical systems. Various piezoresistive flexible sensors have been proposed to monitor the physiology of an individual owing to its ease of fabrication, simplicity in structure, cost-effectiveness, capability for detection of static and dynamic signals, low power consumption, biocompatibility, and wide pressure-sensing range. However, this type of sensor suffers from low sensitivity for detection of low pressure and power source dependency.
Triboelectric sensor exhibits excellent properties for wearable applications, particularly physiological monitoring, due to its ability to self-power and detect dynamic signals, lightweight, and low fabrication cost. However, when this sensor is employed to monitor the vital signs of individuals, several issues, such as biocompatibility, biodegradability, and short service lifetime, occur.
Therefore, identifying the type of vital signs being monitored is crucial prior to the fabrication of flexible sensors. For instance, sensors developed in the form of patches are more suitable for continuous BP monitoring because they exhibit greater flexibility on the skin and comfortable for long wear. Piezoresistive sensor has attracted much research attention in the field of health monitoring system through wearable flexible sensors due to advantages including dynamic sensing, low cost and power consumption, and biocompatibility.
Due et al. [72] successfully fabricated a wearable piezoresistive sensor by facile preparation methods. Gr was grown on a non-woven fabric (GNWF) substrate to produce a wearable sensor that is compatible with cloth. The sensor had excellent sensitivity of around 0.057 kPa-1 and GF of -7.1 at the applied strain of 1% for 10,000 cycles. Ai et al. [73] demonstrated a piezoresistive sensor based on reduced-graphene-oxide (rGO) sandwiched in between PDMS films. This sensor was tested on a healthy subject and successfully detected pulse waveform, including the diastolic tail in which tonometry method failed to sense. The results showed that this flexible sensor can be further extended into health wearables to monitor BP continuous with 50.9 kPa-1 sensitivity, 3 Pa LOD, ~1 µW power consumption, 50 ms response time, and high durability. Luo et al. [74] presented a piezocapacitive sensor that was micro-fabricated with graphene nanowalls (GNW), PDMS, and zinc oxide (ZnO) to monitor pulse for wearable applications. The proposed technique exhibited improved sensing performance with 22.3 kPa-1 sensitivity, 25 ms response time, and 22 kPa sensing range. Wu et al. [75] developed a Gr-based piezoresistive sensor by using laser scribing method for monitoring BP. The sensor showed an average sensitivity of 12.3 kPa-1 and enabled different BP measurement locations, which is advantageous for non-invasive monitoring,
Gr has the disadvantages of high fabrication cost and lack of well-established synthesis methodologies, contributing to the challenging preparation of monolayer with excellent quality, controllable thickness, and mass-produced Gr [76]. Albeit the continuous switching behavior of Gr, making it difficult for energy-storage devices, this problem can be addressed by opening the bandgap with regard to the favorable on–off switching properties.For instance, Qiu et al. [82] proposed a piezoelectric MoS2 sensor by forming conductive networks between MoS2 nanosheets and Ag nanofibers in an elastic conductive film. The developed sensor possessed significant potential as health wearables due to its ability to detect systolic and diastolic peaks, sensitivity of 3, 3000, 0–13% strain range, and relatively fast response of ∼850 ms for stretching and relaxation time. Furthermore, Tannarana et al. [83] reported a wearable multimodal sensor developed from SnSe2 nanosheets grown on paper substrate through liquid-phase exfoliation. The sensor exhibited excellent sensing performance with 868% responsivity, 1.79 kPa-1, 100 ms response time, 2–100 kPa detection range, and 5, 000 cycles of loading pressure. Moreover, Pataniya et al. [84] manufactured a flexible piezoresistive sensor based on MoS2 nanosheets by using a cellulose paper as substrate. The sensor had high sensitivity of 18.42 kPa-1 for low-pressure range, sensing range of 0.001–0.5 kPa, and fast response time. The time difference between systolic and diastolic peaks measured was 260 ms, which is in agreement with previous studies.
TMDs have shown potential for flexible sensors to monitor vital signs; however, the current synthesis techniques are yet scalable and reliable for producing monolayers that are defect free and have controllable thickness and excellent quality [85][86][87][85,86,87].
A novel flexible piezoresistive sensor based on Ti3C2Tx/PDMS developed by Cheng et al. [98] using simple abrasive paper stencil printing to detect the pulse wave of an individual. The sensor detected three important peaks of pulse waveform and achieved sensitivity of 151.4 kPa-1, response time of <130 ms, and LOD of 4.4 Pa. The sensor’s response showed high competency in continuous health monitoring. Li et al. [99] developed Ti3C2Tx flexible piezoresistive sensor on poly (vinylidene fluoride) trifluoroethylene (P(VDF-TrFE)) substrate by spin coating. The prepared sensor successfully detected the pulse wave peaks and exhibited excellent properties, with 817.4 kPa-1 sensitivity, 16 ms response time, and 0.072–0.74 Pa detection range. Su et al. [100] fabricated a flexible piezoresistive sensor based on Ti3C2Tx by using honeycomb approach on PDMS conductive film. The sensor had sensitivity of 0.61 kPa-1, response time of 160 ms, and detection range of 0–50 kPa. Not only that, radial pulse waveforms were detected in real-time using this sensor.
Although Mxene can be regarded as an ideal candidate for flexible sensing application, it has several disadvantages that can affect its long-term stability. MXene films have greater tendency to experience fracture due to poor mechanical properties caused by the weak van der Waals interaction in MXene nanosheets [101][102][101,102]. Moreover, the exfoliation of the Al layer from the MAX phase by using HF etchant may introduce nanosheet restacking, leading to easy oxidation in the ambient environment and reduced biocompatibility [103].
In summary, 2D nanomaterials exhibit potential as functional materials in flexible sensors due to their large surface area-to-volume ratio, which leads to high sensitivity, fast response time, and wide detection range. Although a number of studies have reported on flexible sensors utilizing these nanomaterials, well-grounded conceptual and methodological approaches for continuous BP monitoring are lacking. Majority of these studies on wearable applications have focused only on human activity detection. Few studies have attempted to validate the BP readings obtained from the proposed sensors with those from a commercial cuff sphygmomanometer.
Dagdeviren et al. [108][109] fabricated a piezoelectric pressure sensor by using PZT and Si substrate for long-term BP monitoring. Here, the design of the sensor played a significant role as the PZT is more susceptible to the deformation than the Si substrate, allowing the sensor to be skin-mounted. The average SBP and DBP readings of three volunteers recorded using this device are in agreement with the cuff BP values, with averages of 110 and 65 mmHg for SBP and DBP, respectively. The sensor can stretch up to 30% of its size and has 0.1 ms response time, 25 µm thickness, and 0.005 Pa LOD. The developed sensor can be beneficial for continuous monitoring of human health. Luo et al. [109][110] documented a skin patch that can monitor continuous BP non-invasively. The sensing mechanism is based on the piezoresistive properties of carbon-made textile and epidermal ECG sensors. Compared with the cuff BP monitor, the fabricated sensor had small deviations of 6.5 ± 4.9 and -0.4 ± 3.9 mmHg for SBP and DBP, respectively, as well as low power consumption of 3 nW. Hence, the sensor has potential to be integrated in health wearables.
Wang et al. [110][111] reported an ultrasonic wearable sensor for continuous monitoring BP. Piezoelectric composites and thin Si layer were used as the sensing element and elastomer, respectively. Ultrasonic waves were employed to provide deeper penetration for BP detection. The proposed sensor had remarkable results and exhibited superior properties over tonometry modality for long-term monitoring of BP with up to 60% stretchability, 23.6 mW power consumption, and ~5 Pa loading pressure on the skin. Sempionatto et al. [111][112] extended the work by Wang et al. by developing ultrasonic electrochemical sensors based on PZT and printed polymer composites for monitoring BP and other physiological parameters, such as heart rate (HR), glucose, and lactate. Participants were given different stimuli, including food and drink, as well as physical activities, before and after measurement of the parameters. The developed epidermal sensor exhibited satisfactory performance when validated with cuff BP readings, thus demonstrating its suitability as a multimodal sensing device for wearable BP application.
Laurila et al. [112][15] proposed inkjet and blade coating fabrication methods for developing an e-tattoo sensor with piezoelectric properties. The fabricated device is the thinnest fully printed piezoelectric sensor with 4.2 µm thickness. The sensor showed improved sensitivity of ~50 times than the reference BP monitor that exploits the arterial tonometry principle. The biomedical company Vivalink introduced the first commercial multi-sensing patch to monitor BP continuously and remotely [113][130]. The sensor detected various vital signs such as SBP, DBP, and HR with the universal regulatory clearance. This technology features small design, wireless connection, real-time monitoring, and water resistance.
Long-term remote BP monitoring is feasible and relatively accurate with the emergence of advanced technologies and 2D nanomaterials. The ground-breaking research efforts are significant for the early diagnosis and prognosis of health complications such as cardiovascular diseases (CVD). The detection of CVD continues to be a challenge for physicians, and late-stage diagnosis often leads to stroke incidence and mortality. Continuous BP monitoring using wearables, such as epidermal patches and e-tattoos, enables timely treatment for high-risk patients, particularly those with hypertension as it is an underlying risk factor of CVD. This monitoring system is expected to facilitate real-time BP monitoring through automated notification of abnormal BP readings, triaging perioperative patients, and mitigating motion artifacts in other cuffless BP monitors.Despite the successful development of laboratory-based cuffless sensors for continuous BP monitoring, further improvements are required to address their limitations prior to reaching market readiness and clinical acceptability. Thus far, the synthesis of 2D nanomaterials remains a major challenge in wearable sensing implementation. Current techniques suffer from weaknesses that hinder their abilities to fabricate a high quality and zero-defect sensing layer. To address this issue, scholars should develop new surface modification techniques with the benefits of low fabrication cost and mass production of 2D nanomaterials.
Another key challenge for the implementation of wearable is biodegradability, which is a growing health concern worldwide. For instance, the use of toxic chemicals, such as HF acid, to produce 2D nanomaterials can cause adverse effects on the environment and humans through release of chemical wastes and emission of poisonous gases. Therefore, continuous research efforts are needed to fabricate wearable sensors based on 2D nanomaterials that contain non-harmful by-products and are safe for humans.
Monitoring of BP is technically challenging because it involves manual handling task. In the future, the potential use of artificial intelligence (AI) should be explored because it is at the forefront of smart wearables for continuous physiological monitoring. Aspects that should be investigated are the integration of machine learning, as a subset of AI, to enhance the performance of wearable sensors through the prediction of vital signs, generation of precise outputs, real-time monitoring and seamless transmission of signals.
Despite the potential of 2D nanomaterials in flexible sensors, their commercial applications to wearable BP devices are still far from being achieved. One of the challenges is the stability of 2D nanomaterials when integrated into wearable technologies, leading to difficulty in large-scale production. This problem has inspired researchers to work on wearables with improved sensor performance through available and emerging techniques.