Recent advances in sustainable nature-based functional materials for biomedical sensor technologies

Abstract

The lightweight, low-density, and low-cost natural polymers like cellulose, chitosan, and silk have good chemical and biodegradable properties due to their individually unique structural and functional elements. However, the mechanical properties of these polymers differ from each other. In this scenario, chitosan lacks good mechanical properties than cellulose and silk. The synthesis of nano natural polymer and reinforcement with suitable chemical compounds as the development of nanocomposite gives them promising multidisciplinary applications. Many kinds of research are already published with innovative bio-derived polymeric functional materials (Bd-PFM) applications. Most research interest is carried out on health concerns. Lots of attention has been paid to biomedical applications of Bd-PFM as biosensors. This review aims to provide a glimpse of the nanostructures Bd-PFM biosensors.

Introduction

Electronic devices have been more important in biomedical applications during the last few decades (Wang et al. 2017a, b). The market for flexible and wearable sensors has grown in response to the growing demand for real-time monitoring of human activity and physiological parameters (Khan et al. 2016). In general, electronic devices were attached to various body parts, such as the hand or chest, to instantly monitor some essential physiological parameters without needing an expensive wired-based medical apparatus. This device gives information, alerts users about their diseases, and offers precautions to shield their health from danger (Rogers et al. 2019). The development of wearable devices has reached a new high due to the continuous use of smart wearable sensors in our daily lifestyle. The global income from wearable gadgets is expected to reach $97.8 billion in 5 years (Yao et al. 2018).

While there is an increasing need for wearable sensors in medical uses, numerous sensors for practical uses have little potential for improving biocompatibility. A significant barrier in practical applications is the inability of the sensors without biocompatibility to provide secure and safe biological contact. These restrictions may not hinder the easy usage of wearable sensors from tracking pulses and heartbeat fluctuations daily for nonstandard health monitoring (Ray et al. 2019). The standard wearable sensor could provide adequate heartbeat monitoring for entertaining purposes. Unfortunately, due to the absence of specialized bioactivity in wearable sensors, even accurate wearable technologies cannot give safe and dependable clinical information.

As a result of continuous research in the development of electronic devices and manufacturing technologies, the demand for bio-derived functional wearable sensor material has grown. Sensors that are biodegradable, bioabsorbable, self-repairing, and biocompatible with the human body are needed to satisfy this growing consumer demand (Xu et al. 2019; Li et al. 2018).

A biosensor is a device that detects changes in physical quantity and converts them into a signal which is observed by an instrument. The application of biosensors in medical treatment, pharmaceutical, and healthcare industries has sparked much research interest. Disease diagnosis (Akhavan et al. 2014a), prevention, patient rehabilitation, and health management (Demolder et al. 2021) have all been effective with biosensors. Bacteria (Akhavan and Ghaderi 2011), pathogens (Singh et al. 2016), and the virus (Shinoda et al. 2021) can also be detected with biosensors. Numerous sensors have been developed to track walking patterns, body oxygen levels, blood pressure, and heart rate, among other things. Fitbit has set wrist activity trackers, and other companies have launched smartwatches, smart bands, and various mobile phone apps to track physical activity and steps, allowing people to acquire and enhance healthy habits. These tools open doors for individuals working in clinical science as well. People can use this device to get information about the chemicals in our bodies. They used chemicals to track our various body functions, and this information can be accessed at the touch of fingertips using a smartphone app and shared with a physician, family member, or anybody else (Choi 2020; Zadran et al. 2012).

Due to the rapid spread of the COVID-19 pandemic, there has been an increasing demand for home-based portable medical devices. CRISPR-Cas9 paper strip, nucleic acid and antigen-Au/Ag nanoparticle-based biosensor, and surface plasmon resonance are among the recently designed biosensors employed to detect RNA viruses (Haleem et al. 2021). The growing public awareness of smart medical devices and the development of health monitoring sensors and other biomarkers capable of real-time patient health monitoring are driving smart medical devices. Molecular markers are handy for measuring different health parameters like temperature, cardiac activity, dehydration, and body sugar levels. The laboratory is developing a portable sensing device for protein biomarkers (Pollard et al. 2021; Yu et al. 2021).

Biosensors have a number of benefits over conventional sensors. Biosensors can typically detect analytes without the need for previous separation. The ability to monitor manufacturing and biological processes in real time is also made possible by their quick response times. Other advantages include the fact that they are straightforward to use, that measurement may be carried out in the field or at the point of care, that they are adaptable and simple to prepare, and that they have the potential to be miniaturized and automated (Cristea et al. 2014). Although many specimens are only available in small quantities, miniaturization is crucial because in vivo monitoring requires minimizing tissue damage. Modern medical equipment’s mobility, functionality, and dependability for point-of-care analysis and real-time diagnosis have all increased because of biosensors (Morrison et al. 2008). Compared to other analytical approaches, biosensors continue to have a few limitations. Electrochemical interferences, low response reproducibility, and the reduced stability of the bioreceptor element are the three challenges pertaining to biosensors that are the most difficult to address and resolve. When removed from their natural environment, most biocomponents tend to lose their activity at an increasingly rapid rate. Because of this, the sensor has a shorter lifespan. For instance, the enzymes employed for detecting a variety of analytes are not stable in solutions over the long term and need to be immobilized before they can be utilized again (Cristea et al. 2014).

Furthermore, the rapid advancement of technology in recent years and research and development in nanotechnology are the key factors for the growing biomedical sensors market. This is expected to reach $36.7 billion by 2026, with a market value of $25.5 billion in 2021. Over the past few decades, natural biopolymers have become the main bioactive materials utilized in medical materials. These are lengthy chains, such as covalently bound repeats of amino acids, nucleotides, or monosaccharides. Such polymers often contain biofunctional chemicals that guarantee bioactivity, biomimetic nature, and natural restructuring. The most significant characteristics of natural polymers include bioactivity, biocompatibility, 3D geometry, antigenicity, non-toxic byproducts of biodegradation, and intrinsic structural similarity (Ogueri et al. 2019). Wearable sensing devices are frequently considered suitable options when bio-based polymers with inherent biocompatibility and biodegradability are used in their construction. Biopolymers like cellulose, chitosan, and silk fibroin are selected as potential components for biosensor construction (Cui et al. 2020). Details on the benefits and drawbacks of using biopolymer are provided in Table 1. This review covers the recent development in bio-derived functional material as a biomedical application sensor.

Table 1.

Pros and cons of biopolymers

Biopolymer	Properties/benefit	Drawback	References
Cellulose	Hydrophilicity, biocompatibility, cytocompatibility, bioactivity, high mechanical strength	In the human organism it behaves as a nondegradable or very slowly degradable	Müller et al.2006, Novotna et al.2013, Salmoria et al.2009
Silk	Light weight having exceptional strength and elasticity, osteoconductivity biocompatible, thermally stable, moderately degradable	Prolonged presence of silk may induce degradation, which releases certain residues or degraded products that may prompt the immune response	Tandon et al.2020, Liu et al. 2015, Santi et al.2021
Chitosan	Bioactivity. Anti-inflammatory, osteoconductivity, hemostatic potential	Stability. High viscosity and low solubility at neutral pH, Rapid in-vivo degradation rate	Gnavi et al.2013, Ahmed and Ikram 2016, Pita-López et al. 2021, Sivashankari and Prabaharan 2016

Bioderived functional material

Biopolymer, also known as bio-derived polymer, is a naturally occurring polymer derived from bio-based materials through various chemical and biological processes (Kamita et al. 2016). Biopolymers have several unique features that make them a good choice for use as a sensing material. Biopolymers have a number of benefits over nanomaterials, including natural abundance, mechanical robustness, hydrophilicity, tunable properties, low molecular weight, mechanically flexible, biocompatible, biodegradable, non-toxic, environment friendly, and inexpensive.

Biopolymers are emerging materials for developing environmentally sustainable flexible sensors (Kamita et al. 2016; Li et al. 2020). Biopolymer-based sensors have some special qualities, such as self-cleaning and repairing properties, which prevent interference from environmental effects, i.e., moisture, heat, and dust and increase result accuracy. Furthermore, the cost-effectiveness, low molecular weight, and benign and biological properties allow for large-scale manufacturing of sensors and reduce the irritation of long-period attachment to the skin’s surface. Sensors of this type have shown tremendous potential in monitoring human health. Last but not least, the fact that biopolymers include a plethora of functional groups, such as -OH, -COOH, and -NH₂ groups (Li et al. 2020), makes it feasible to modify biopolymers and provide them with new capabilities through the use of functional groups. The three most prevalent biopolymers, silk, cellulose, and chitosan (Fig. 1), are briefly discussed, along with their chemical structures and properties.

Fig. 1.

Three biopolymers and their unique properties for sensor

Silk

Structure and properties

Various creatures create natural silk, such as spiders, silkworms, and others. Noncovalent interactions build these unusual fibrous proteins, which contain many repeating amino acid sequences (Ling et al. 2018). The most adequately investigated silk materials are spider and silkworm silks, which are recognized for their exceptional mechanical characteristics and outstanding toughness, flexibility, and robustness, surpassing most biomaterials and engineering materials (Omenetto and Kaplan 2010).

Moreover, due to the large-scale production, outstanding mechanical strength, and biocompatible and biodegradable nature, silkworm silks generated by cultured Bombyx mori have fascinated researchers’ interest in investigating their structure, properties, and uses.

The main component of silk is fibroin fibers, which act as an inner core and provide mechanical strength, while sericin acts as an outside glue-like protein. Sericin coats two silk fibroin (SF) filaments in each silk fiber (Koh et al. 2015). SF comprises multiple amino groups joined by peptide bonds, including serine, alanine, and glycine (Fig. 2). Polypeptide chains, which are made up of large H-type chains and small L-type chains, are created (Nguyen et al. 2014).

Fig. 2.

Amino acid sequence in silk fibroin

Because of interactions between molecules and interactions within molecules, the hydrophobic repeating parts of the H-chain can form nanoscale crystallites. These nanoscale crystallites are necessary for the intriguing mechanical characteristics of the H-chain (Jian et al. 2020). The particular hierarchical structure of SF, formed from the material’s ordered and linked pattern, can help increase the material’s mechanical characteristics (Wang et al. 2019a, b). SF contains amino acids responsible for water solubility, biocompatibility, and biodegradability.

These unique properties make silk an excellent choice for creating intelligent and biomedical devices (Niu et al. 2020; Yang et al. 2020). Silk-based hydrogel, fiber, nanowire, and film were also employed to construct smart electronic devices through chemical modification, which will be explored in detail inside the application part.

Cellulose

Structure and properties

Cellulose is one of the most versatile biopolymers on the planet. It is a linear polysaccharide composed of D-glucose units linked by β (1 → 4) bonds. The hydroxyl (–OH) groups in D-glucose can interact by inter and intramolecular hydrogen bonding forming a powerful and vast hydrogen-bonding network within polymeric chains. This gives cellulose material a high degree of crystallinity and rigidity (Zhao et al. 2020), and these amorphous regions connect these bonds to form cellulose chains. Nanofibers of < 35 nm are created from these chains that are then aligned and bonded to form fibrils of < 1 μm and fibers of 10–50 μm, exhibiting a hierarchical structure (Zhu et al. 2013).

Cellulose possesses many properties, such as the ability to undergo extensive chemical modifications, biocompatibility (Rahighi et al. 2021), biodegradability (Kalka et al. 2014), hydrophilicity, and chirality, and it can also undergo extensive chemical modifications. These properties allow cellulose to give rise to various cellulose derivatives. Because of these characteristics, cellulose has garnered a lot of attention and generated a lot of research activity on cellulose-functionalized materials. This is because cellulose can be used to make things like paper and plastic. The solubility, crystallinity, and reactivity of the -OH groups on cellulose can be affected by intramolecular bonding patterns and intermolecular bonding patterns (Fig. 3) (Yang and Cranston 2014; Koschella et al. 2006; Desmet et al. 2011; Hu et al. 2014).

Fig. 3.

Hydrogen bonding patterns in cellulose (Jarvis 2003).

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Cellulose is an environmentally friendly material with superior mechanical properties, thermal stability, ease of modification, good biocompatibility, and biodegradability. Furthermore, to meet the demands of various uses, cellulose functionalized material can be used in various forms, including fibers, films, papers, aerogels, and hydrogels (Kaushik and Moores 2016; Nogi et al. 2009; Yang and Wyman 2004; Jiang et al. 2018; Kontturi et al. 2018; Wang et al. 2016).

The cellulose functionalized material can be created by combining cellulose with metal and metal oxide nanoparticles (Nechyporchuk et al. 2017), carbon nanomaterials (Zheng et al. 2015), and conducting polymers (Wang et al. 2015). The methodologies outlined above provide unique composite functions and allow the production of intelligent sensors and electronic devices (Zhu et al. 2016a, b; Dutta et al. 2017; Zhang et al. 2018). Thus, cellulose is receiving a lot of interest for being used in sensing electronic devices because of its unique structures and good qualities.

Chitosan

Structure and properties

Chitosan (CS) is a deacetylated derivative of chitin, a linear biopolymer. Chitin is the second most prevalent biopolymer on the planet behind cellulose, and it is found in the exoskeletons of crabs and the cell walls of some fungi (Zargar et al. 2015). It is a renewable natural polymer with an unusual combination of abundance, excellent biocompatibility, and outstanding biodegradability, and it is environmentally friendly.

However, its extremely crystalline structure is insoluble in commonly used solvents (Pillai et al. 2009), which may limit the manufacturing of useful materials and their uses. As a derivative of chitin, chitosan possesses enhanced solubility, ease of processing, pH sensitivity, and technologically advanced activity, allowing for a wide range of innovative uses in environmental, biomedical, and electronic devices (Azuma et al. 2015; Shukla et al. 2013).

The N-deacetylated method can be used to make chitosan from chitin. As illustrated in Fig. 4, it is a linear polysaccharide consisting of copolymers of D-glucosamine and N-acetyl-D-glucosamine joined by β- (1,4) glycosidic linkages. CS has various properties and molecular weights based on the degree of deacetylation. CS can be divided into three groups depending on the degree of deacetylation: high, having a molecular weight > 500 kDa; medium, having a molecular weight of 50–500 kDa; and low, having a molecular weight of 50 kDa (Zeng et al. 2012). CS has several unique physical features, including viscosity, mucoadhesive, and potential solubility in various mediums.

Fig. 4.

Structure of chitin and chitosan

Chitosan has unique chemical and physical properties by regulating the chain length in chitin and the degree of chemical processing, such as deacetylation (Suginta et al. 2013). Chitosan’s structure comprises certain -NH₂ and -OH groups that are commonly accessible for cross-linking (Fig. 3) (Mohammadi et al. 2020).

Chitosan has unusual qualities due to its reactive groups, which can be used as a platform for complex modification to afford unique properties (Saeedi et al. 2022). In particular, grafting and physical alteration of CS allows for the creation of chitosan polymers with special functions (Shukla et al. 2013). Various CS-functionalized materials, such as nanomaterial, composites, membranes, hydrogels, and aerogels, were developed recently to lay the foundation for the desired uses (Xu et al. 2016). Chitosan-based materials are becoming a vital natural polymer for producing smart sensing and electronic devices due to their availability, low cost, superior biocompatibility, biodegradability, controlled mechanical properties, and varied biological features (Ivanova and Philipchenko 2012; Bonardd et al. 2020; Tong et al. 2019).

Bioderived functional material as a sensor for biomedical application

Biosensors have found their most useful uses in various industries, the most prominent of which are medical, healthcare, and clinical services. The possibilities of biosensors that fall within the category of healthcare and linked services are explored in Fig. 5. Diagnosis of disease (Salek-Maghsoudi et al. 2018), retinal prostheses (Zhou and Greenberg 2013), magnetic resonance imaging (MRI) (Moradi et al. 2015), cardiac diagnostics (Ouyang et al. 2021), medical mycology (Teles 2013), health monitoring (Kim et al. 2019) DNA sequencing (Akhavan et al. 2012), etc. are the important applications of the biosensor. These broad capacities of biosensors raise healthcare to a new level (Tan et al. 2017; Kudr et al. 2021). Table 2 outlines the use of biosensors in the field of biomedical.

Fig. 5.

Typical capabilities of biosensors in healthcare services

Table 2.

Application of biosensors in the biomedical field

Biosensor	Analyte	Detection range	Limit of detection	Sensitivity	Reference
GOx immobilized on cellulose paper	Glucose	1 to 5 mM	0.18 mM	–	Lawrence et al.2014
Polypyrrole-cellulose nanocrystal-based composites with GOx	Glucose	1.0 to 20 mM	(50 $\pm$ 10) µM	–	Esmaeili et al. 2015
Fc–COOH/GOx/cellulose/SPCEs	Glucose	1.0–5.0 mM	0.18 mM	–	Lawrence et al. 2014
Et Fc/Chi/GOx/GCEs	Glucose	1.0–6.0 mM	–	8.6 (nA/mM mm2)	Yang et al. 2007
CHI-CdS QDs	Cholesterol		0.64–12.9 mM	0.384 µA/mM/cm2	Dhyani et al.2015
Cu2O NPs@CSs/CSF		0.001–2 mM	0.29 µM	462.6 µA/cm2/mM	Lu et al. 2019
SF-rGO	Glucose	–	1 µM	150.8 µA mM/cm2	Li et al.2019

COVID-19 is a highly contagious pandemic spread by a recently found coronavirus that has spread around the globe. In recent years, numerous viral diseases such as avian flu, SARS, Hendra (HeV), Nipah (NiV), and others have sparked significant attention. As a result, biosensors offer enormous potential and capability for detecting such diseases (Rabiee et al. 2022). Another essential feature of the biosensor is its capacity to diagnose heart problems (Haleem et al. 2021).

Electronic devices made of inorganic materials are widely used today and have greatly improved our lives. However, the widespread use of electronics has produced electronic trash and dangerous, non-biodegradable compounds.

Furthermore, the novel devices’ flexible, biocompatible, and robust nature allows them to correspond to interfaces with soft tissues/organs, making them useful for human activity monitoring, human-device interfaces, detection of diseases, and treatment (Wang et al. 2019a, b; Jian et al. 2017; Zhu et al. 2016a, b).

Due to their cost-effectiveness, biodegradability, less toxicity, biocompatibility, and low molecular weight, natural biopolymers were progressively becoming an appealing fundamental unit for the manufacture of next-generation smart portable, flexible, wearable, and biocompatible sensing and electronic devices (Wang et al. 2017a, b; Tan et al. 2016; Wang et al. 2018; Irimia-Vladu 2014; Wu et al. 2018; Sampaio et al.2023; Ugrinic et al. 2023).

This review paper discussed the present significant advancement in applying bio-derived material as a sensor for various medical applications based on the above great features of biopolymers (Fig. 5).

Silk based sensor

Silk is a natural biomaterial that has been used in human society for a long time, because of its biocompatibility, biodegradability, great mechanical qualities, and low cost. Silk has recently been mostly used as a matrix for electronics (Wang et al. 2019a, b). For example, SF is gaining popularity as a functional material for the development of flexible sensors, such as humidity sensors (Liu et al. 2019; Diao et al. 2013), temperature sensors (Wen et al. 2020), pressure sensors (Yang et al. 2019), and electrochemical sensors (Khalid et al. 2020; Chakravarty et al. 2018).

It was found that cross-linking RSF with horseradish peroxidase (HRP) and adding CaCl₂ in more significant amounts to retain water resulted in the formation of conductive silk-based hydrogel (Fig. 6). The Ca²⁺ ions in the RSF/CaCl₂/HRP hydrogel make it flexible and transparent, preventing the formation of silk fibroin β-sheet crystals in the hydrogel. It also has strain- and temperature-sensing capabilities. As a result, it may be used as a dual-sensing device and is an excellent choice for ionotronic skin. The results demonstrate that this hydrogel is good at tracking body motions and can detect spoken information based on neck movements (Fig. 7) (Zhao et al. 2021a, b).

Fig. 6.

Preparation of the RSF/CaCl₂/HRP hydrogel (Zhao et al. 2021a, b).

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Fig. 7.

Various roles of RSF-based hydrogel on skin (Zhao et al. 2021a, b).

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Kadumudi and colleagues have developed a multifunctional composite material combining silk fibroin with reduced graphene oxide. This substance, known as “Care Gum,” utilizes phenolic glue to facilitate sacrificial and hierarchical H-bonding. Compared with its new counterpart, the hierarchal bonding scheme produces high mechanical toughness, a record-breaking elongation capacity of approximately 25 000%, outstanding conformability, 3D printability, and electrical conductivityincreases tenfold, and Young’s modulus increases4-fold. Using these unique properties, a robust and self-healing E-glove for hand motion sensing has been developed (Kadumudi et al. 2021). Zhao’s group used one-pot thermal polymerization to create a ternary system hydrogel composed of SF, acrylamide, and acrylic acid. Silk fibroin-doped hydrogels (SFH) can be used as a pressure sensor to track various movements of a human (Zhao et al. 2021a, b).

He and his coworker created a flexible conducting hydrogel by proportionately combining SF, polyacrylamide (PA), graphene oxide (GO), and Poly(3,4-ethylene dioxythiophene)-poly (styrene sulfonate) (Fig. 8). The PSGP hydrogel has high flexibility and compressibility and is used to create dual sensor strain as well as pressure with a broad range and consistent stability. The corresponding sensor could then monitor a range of physiological signals from the body, such as joint motion, facial expression, heart rate, and respiration (Fig. 9). This sensor, in particular, is compatible with no irritation on the skin (He et al. 2020).

Fig. 8.

PSG P hydrogel fabrication and structure (He et al. 2020).

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Fig. 9.

Uses of PSGP sensor to detect different body signals. Variation in relative resistance of several face expression a smile, b angry, c sadness, d laugh, e eating, and e blinking g real-time resistance signals of fisting h wrist pulse rate monitoring i single-pulse in the waveform (He et al. 2020).

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Liu and his coworker create a micro-structured, SFprotein-based adhesive (MSFA) for skin adhesion that is extremely conformal, relaxing, tunable, and sustainable (Fig. 10). Even in a humid or moist environment, the MSFA shows a consistent and stable binding force on the skin, and it may be easily removed apart without causing substantial pain. Because of its conformal and adjustable adherence to the skin, MSFA can considerably increase the sensitivity and recyclability of epidermal strain sensors. In the era of customized healthcare, the MFSA has the potential as an efficient adhesive for numerous skin sensing devices (Fig. 11) (Liu et al. 2020).

Fig. 10.

a Fabrication of MSFA (Liu et al. 2020).

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Fig. 11.

Signal from MSFA strain sensors attached to wrist radial artery a MSFA sensorattached to wrist. Artery pulse signals of MSFA sensor (b, c), with a flat fibroin adhesive layer (d, e) (Liu et al. 2020).

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Zhang et al. prepared the SF/graphene composite film by casting (Fig. 12). This film possesses excellent electrical and mechanical properties. This material is used as wearable, implantable internal sensors in the biomedical field (Zhang et al. 2019).

Fig. 12.

Flow chart for preparation of SF/graphene film (Zhang et al. 2019).

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Cellulose-based sensor

Nanocellulose (NC) is among the most appealing cellulose functionalized nanomaterials in sensing and biomedical applications due to its exceptional properties (Portaccio et al. 2007; Tavares et al. 2016; Incani et al. 2013; Morales-Narvaez et al. 2015). Neubauerova and his coworker created an NC-based biosensor for detecting glucose in diabetic patients’ urine samples.

This research includes the TEMPO-oxidation using microcrystalline cellulose (MCC) to create carboxyl-NC (Fig. 13). Its use in the production of glucose colorimetric test strips (Fig. 14). MCC oxidation and also the incorporation of the glucose oxidase (GOx) into the cellulose/-NC-based substrate and the capacity to develop color in the presence of H₂O₂ have all been optimized. In general, the work presented here is the first to report combining NC with an enzyme biosensor to detect glucose in diabetic individuals (Neubauerova et al. 2020).

Fig. 13.

Preparation of the carboxyl-NC using TEMPO oxidation (Neubauerova et al. 2020).

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Fig. 14.

Formation of glucosecolorimetric test-strip by casting on NC and binding GOx by A adsorption or B covalent bonding (Neubauerova et al. 2020).

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Wang et al. announced the development of a reinforced cellulose nanofiber ionic conductor with potential sensing applications. For the ionic conductor, scientists employed natural bacterial cellulose (BC) and polymerizable deep eutectic solvents (PDES) (Fig. 15). BC-PDES is extremely sturdy because of its dense network of nanofibers in three dimensions (3D) and the high quality of the interface contact between the various materials. The composites outperformed deliquescent PDES composites in terms of mechanical stability, retaining incredible mechanical strength even after being subjected to high humidity for 120 days. These materials showing various sensitivities to external stimuli, including strain, bending, and temperature, were established in these materials. As a result, they may readily be used as hyper sensors to detect human physical fitness such as leg movement, throat motion, and writing [Fig. 16] (Wang et al. 2020).

Fig. 15.

The interactions of NC fibres with acrylic acid (AA) and choline chloride result in the formation of the BC-PDES ionic conductor (Wang et al. 2020).

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Fig. 16.

Application of BC-PDES sensors. a Changes in relative resistance over time as a function of the time taken to bend and release the index wrist, elbow, and knee, respectively. b A diagram of the vocal sensing system. c Changes in resistance over time when a sensor is applied to the neck to detect tiny movements like coughing and drinking (Wang et al. 2020).

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Chen’s research group has created compressed and elastic carbon aerogels (CECA), which show significant potential for use in wearable devices and electronic devices for the skin. MXenes are attractive materials for piezoresistive sensors since they are novel two-dimensional materials with exceptional characteristics. However, CECA fabrication is problematic due to the absence of sufficient contact between MXene nanosheets. After that, Chen et al. used BC as a nano binder to connect MXene (Ti₃C₂) nanosheets into a lamellar macrostructure, producing a lightweight CECA with exceptional mechanical and sensing capabilities (Fig. 17). Because of its wide aspect ratio and pliability, BC may be used to entangle and connect MXene nanosheets. Continuous, directed, and wave-shaped lamellas are formed when the connection strength between Ti₃C₂ nanosheets is sufficient, resulting in high flexibility, elasticity, and fatigue resistance. Furthermore, the prepared aerogels are a susceptible material that can reliably record output data across a broad range of pressure and strain and catch minute pressure changes. Because of these advantages, the CECA could be used in flexible wearable devices to monitor bio-signals (Fig. 18) (Chen et al. 2019).

Fig. 17.

Formation of carbon aerogel C-MX/BC-x (Chen et al. 2019).

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Fig. 18.

C-MX/BC-2 usage in bio-signal monitoring. a Sensor construction. b Current signals are emitted by the words carbon and super. c Signals are derived from facial appearance. d Human jugular vein pulse monitoring. e Monitoring the pulse of a human arm. Signals from bending the f finger, g elbow, and h wrist. (i) Time to respond and recover (Chen et al. 2019).

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Chitosan based sensor

CS is a biopolymer with a wide range of applications. Because of its multifunctional qualities, CS has found its way into a variety of sensing applications. It is biocompatible, biodegradable, low toxic, and has excellent mechanical strength.

Wang and his coworker make flexible bi-modal e-skins from a bionic CS/MXene (CS/MX) hybrid film. CS is employed as a bridging agent to create a continual laminated macrostructure (Fig. 19). This hybrid film-based e-skins can detect pressure rapidly and monitor humidity regularly and consistently. Biomimetic hybrid films performed well in a cytotoxicity test, indicating that they pose less of a threat to human health. In addition, CS/MX film-based e-skins (Fig. 23) can be used to build robust systems of the future thanks to its multipurpose sensing devices' ability to reliably differentiate between the body’s many physiological activities such as heart rate, noise signals, and respiration (Wang et al. 2021).

Fig. 19.

Bionic CTS/MX hybrid film formation. a Demonstration of a sensing device used to detect fitness. b The structure of the bimodal sensor and c humidity and pressure sensor. d SEM image and 3D structure of the CTS/MX hybrid film. e Demonstration of the pressure sensing mechanism of the sensor. f Stress Vs. strain curves of the hybrid film (Wang et al. 2021).

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Fig. 23.

Synthesis route and cross-linking mechanism of hydrogel OPPC (O-CMCS, PCD-CHO, PVA, and CNTs) (Ren et al. 2021).

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To improve electron transfer capacity and limit insulating capacity, Buaki-Sogó et al. created flexible and biocompatible conducting bioelectrodes using CS and carbon black (CB) (Fig. 20). It is used as a bioelectrode in the fabrication of biofuel cells (BFC) and biosensors, namely for the anode and working electrodes, respectively. As a result, glucose detection has been evaluated to see if it is suitable for future wearable device design (Fig. 21) (Buaki-Sogó et al. 2021).

Fig. 20.

Flexible CS-CB membrane with 100% CB by weight. A Fabrication strategy and B visual inspection of mechanical strain resistance (i) stretching, (ii) bending, and (iii) twisting (Buaki-Sogó et al. 2021).

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Fig. 21.

Performance of enzyme-modified CS-CB membranes in sensing A amperometry for glucose detection in the presence of O₂ using GOxmodified CS-CB electrode, linear range calibration plot (100–600 _M). B Glucose BFC power density in PBS 0.1 M with varying glucose concentration (Buaki-Sogó et al. 2021).

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Ren and his coworker created a hydrogel sensor for measuring human and organ motions using O-carboxymethyl chitosan (O-CMCS) and poly (vinyl alcohol) (PVA) (Fig. 22). Based on the host-guest complex combination between poly(β-cyclodextrin) (PCD) with diamantane cross-linker comprising several -CHO groups were developed for cross-linking to O-CMCS via Schiff base. Borax was employed as a second cross-linker to cross-link PVA using reactive borate ester linkages (Fig. 23). To increase the electrical and mechanical properties of the hydrogels, carbon nanotubes (CNTs) were introduced. The breathing action of pig lungs and the pumping of the heart in the rat may be monitored with this hydrogel sensor (Fig. 24) (Ren et al. 2021).

Fig. 22.

Synthesis route of PCD-CHO (Ren et al. 2021).

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Fig. 24.

Schematic diagram of respiration monitoring using a sphygmomanometer balloon (a) and a pump (b) are used to charge and deflate the air. Electrical impulses of pig lung respiration through the pump (c) and sphygmomanometer balloon (d). The beating of a rat’s heart, as recorded by a hydrogel OPPC sensor, is seen schematically in this diagram (e). A mouse heart is linked to a hydrogel called OPPC in this diagram (f). The electrical impulses are produced by beating a rat’s heart (g) (Ren et al. 2021).

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Hosseini et al. developed a flexible pressure sensor based on self-standing biodegradable glycine-chitosan piezoelectric sheets. The piezoelectric films are made from a stable glycine spherulite framework (size varied from a few millimeters to 1 cm) encapsulated in an amorphous CS and are made by self-assembled biomolecules of glycine inside a water-based solution of CS. This biobased film can be a biodegradable sensor for biomedical applications (Hosseini et al. 2020).

Sarcosine, also known as N-methylglycine (a by-product of glycine synthesis and breakdown), was detected usingTi₃C₂TX (where T = terminal groups i.e. = O, -OH, and -F) biosensor (Fig. 25). For the first time, it is being evaluated in urine as a possible glandular prostate cancer biomarker (Hroncekova et al. 2020).

Fig. 25.

A glassy carbon electrode (GCE) containing an MX/CS nanocomposite as a substrate for immobilization of sarcosine oxidase (SOx) and detection of sarcosine in urine indirectly using hydrogen peroxide electrochemical reduction is shown schematically. The SOx structure was taken from the Protein Data Bank (code 1EL5) (Wagner et al. 2000).

Copyright 2000 American Chemical Society

Jang and his coworkers proposed a tunable color filter made up of a metal-insulator-metal (MIM) multilayer with chitosan hydrogel as the insulator. When paired with a photovoltaic (PV) cell, this color filter can be used as a humidity sensor. CH film is placed between two extremely thin silver (Ag) layers manufactured on a glass substrate in this structure (Jang et al. 2020).

Conclusion, outlook, and future perspective

The design and development of biosensors have developed enormously during the last few years. Biosensors are predicted to play a crucial part in detecting viruses and microbes in the future, such as HIV, COVID-19, Omicron, and SARS-CoV2.

It will allow researchers to reliably monitor the effects of potential treatments on the body in the future, allowing them to determine if a medicine can continue to evolve medically. Furthermore, biosensor chip technology could be implanted into the body to discover complicated blood DNA alterations before the beginning of disease symptoms (Akhavan et al. 2014b). With the Internet of Things (IoT), intelligent systems, and 5G, biosensors have made this industry more confident, sensitive, and customized. The marketplace for biosensors is expanding as a result of their widespread application in health care and medicine. The world biosensor market is increasing at a breakneck pace, with projections of $50 billion by 2025. It is no surprise that biosensors have a bright future because they can be used to identify life-threatening diseases in vital sections of the human body like the heart, brain, lungs, and kidneys. Soon, wearable biosensors will dominate the worldwide biosensor industry.

Due to their abundant nature, unique structures and compositions, versatility, biocompatibility, biodegradability, low toxicity, renewability, simplicity of fabrication, and low cost. Silk, cellulose, and chitosan are biopolymers that may be produced in a variety of forms, including fibers, films, composites, sheets, textiles, hydrogels, aerogels, foams, and can be used as essential components in sensing and energy devices.

Various advanced technologies and methods should be used to prepare functional biopolymers and biopolymers composites to obtain desirable and high-performance sensing properties. Despite the significant progress made in recent biopolymer and biopolymer-based sensor research, they still need to be enhanced to make them viable opponents to traditional sensing devices. Green processing of natural feedstocks and the development of appropriate methods are required to produce bio-polymer-based sensing devices on a wide scale. Biopolymers, without a doubt, offer an exciting strategy for utilizing new functional, flexible devices critical for improving their implementations in green and sustainable electronic devices and smart electronic equipment.

Author contribution

NN wrote the original draft; DPV and RM contributed to the literature collection and analyzed the data; SC supervised the study; GG and ASY were involved in drafting and critically revising the final manuscript. All authors read and approved the final manuscript.

Data availability

All data analyzed during this study are included in this article.

Declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare no competing interests.