Sustainable material-based biosensors for SARS-CoV-2 detection

In a recent study posted to Sensors International, researchers conducted a brief review on biosensors based on sustainable materials for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection.

Study: Sustainable materials and COVID-19 detection biosensor: A brief review. Image Credit: Willyam Bradberry/Shutterstock
Study: Sustainable materials and COVID-19 detection biosensor: A brief review. Image Credit: Willyam Bradberry/Shutterstock


The coronavirus disease 2019 (COVID-19) pandemic has resulted in billions of infections globally, necessitating an emergency response to contain the spread of the virus. Early detection and immediate medical care are two essential concepts for managing SARS-CoV-2 outbreaks. The novel biosensors used in COVID-19 diagnosis are anticipated to aid in accurate diagnosis. 

The challenges surrounding the materials used in the COVID-19-detecting biosensor are extremely important in clinical material science. While there have been several investigations on new biosensors for COVID-19 diagnosis, there have been few publications on biosensors made of sustainable materials. Additionally, data on systematic reviews for sustainable materials-based biosensors is scarce.

The study

In the present systematic review, the scientists summarized the details of existing sustainable materials and their specific applications in SARS-CoV-2-detecting biosensors. They focused on graphene, paper, and cellulose-based biosensors for SARS-CoV-2 immune response monitoring, ribonucleic acid (RNA) sensing, and antigenic identification.

Cellulose- and paper-based biosensors

Paper and paper-like materials are inexpensive, plentiful, and biodegradable, and they have lately become popular for use in point-of-care (POC) testing devices for COVID-19 diagnosis. Microfluidic paper-based analytical instruments are promising candidates because they are low-cost, easy-to-use, quick, accurate, and long-lasting in a wide range of settings. They are capable of detecting a broad spectrum of viruses. Paper is freely available worldwide, and its properties permit simple liquid conveyance via passive flow. Furthermore, various kinds of paper are compatible with patterning techniques like printing, broadening their use.

Colorimetric, electrochemical, or fluorescence techniques might be the transduction mechanisms for paper-based biosensors for SARS-CoV-2 RNA detection. The applied schemes for paper-based biosensors for SARS-CoV-2 RNA detection include: 1) reverse transcription-recombinase polymerase amplification (RT-RPA) + clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 12 a (cas12a) + biotin-labeled single-strand deoxyribonucleic acid (ssDNA) reporter and 2) loop-mediated isothermal amplification (LAMP) pre-amplification + CRISPR cas12a + biotin-labeled ssDNA reporter. 

Renowned paper-based biosensors for SARS-CoV-2 RNA sensing consist of a paper-based immunoassay centered on 96-well wax-printed paper plate coupled with magnetic beads for sensing virus in saliva established by Fabiani et al. and an antisense oligonucleotide targeting electrochemical biosensor chip created by Alafeef et al.

An alternative way for COVID-19 diagnosis is the identification of SARS-CoV-2-specific antigens, such as the spike (S) glycoprotein and nucleocapsid (N) phosphoprotein. Self-test kits based on the SARS-CoV-2 antigens already exist. Biosensors targeting the S protein in pertinent body fluids detect entire virus particles and N protein diagnoses infection before the symptom onset and initiation of the organism's immune response.

SARS-CoV-2-specific antibodies (Abs) such as immunoglobulin G (IgG), IgA, and IgM are secreted as part of immunological response to COVID-19. Certain studies have focused on the paper-based lateral flow assay (LFA) test strips' applicability in detecting SARS-CoV-2-specific IgM and IgG Abs. This was possible by employing novel approaches of fluorescence optical transduction modalities and alternative reporter particles and standard methods such as gold nanoparticles (AuNP) coupled with SARS-CoV-2-specific antigens. A label-free, paper-based electrochemical platform currently exists that focuses on SARS-CoV-2 Abs without the requirement of a particular Ab.

Biosensors made of cellulose can be especially useful during pandemics since they are renewable, can be produced large-scale using sustainable methods, and are eco-friendly. Despite this, there are few reports of SARS-CoV-2 detection utilizing cellulose-based biosensors. Cellulose-based LFAs for COVID-19 diagnosis are currently available. Nitrocellulose membranes could be utilized to enhance the usefulness of LFA-based diagnostic tools for SARS-CoV-2 detection in a variety of settings. 

An article recently published in Biosensors demonstrates an enhanced cellulose-based LFA SARS-CoV-2 RNA sensing system based on combining two sugar barriers into LFAs. Kim et al. have developed a novel cellulose-based lateral flow immunoassay (LFIA) platform for SARS-CoV-2 antigen detection employing single-chain variable fragment-fragment crystallizable (scFv-Fc) fusion proteins.

Since scFv-Fc Abs specifically bind to the SARS-CoV-2 N antigen with high affinity, they can help with SARS-CoV-2 detection. Further, a novel cellulose-based SARS-CoV-2-specific Ig sensing LFA was established by Elter et al., employing a carbohydrate-binding module-fused strategy.

Graphene-based biosensors

COVID-19 detection using graphene-based biosensors is a novel concept. Many investigations on using graphene nanomaterials to produce novel biosensors for SARS-CoV-2 diagnosis are underway. Traditional LFA and polymerase chain reactions (PCRs) cannot provide rapid, more precise, less costly, or high-throughput results as nano-biosensors can.

Li et al. established a novel graphene-based sensor for SARS-CoV-2 RNA detection in human throat swab specimens. This platform consisted of a graphene field-effect transistor sensor with AuNP. Further, a phosphorodiamidate morpholino oligos (PMO) probe was attached to the AuNP surface. This novel biosensor was an unamplified and rapid (provides results within two minutes) nano sensing platform.

Jia et al. developed a novel graphene-based sensing system for SARS-CoV-2 antigen detection in three minutes. This platform detects SARS-CoV-2 N protein via integrating RNA/DNA oligomers as aptamers. The sensor system of this modality was composed of an optical fiber coated with graphene oxide. Ehsan et al. reported impedance sensors for SARS-CoV-2 antigen sensing, which were screen-printed graphene/carbon electrodes on paper substrates. It identifies SARS-CoV-2 S protein via the anti-SARS-CoV-2 S IgG Ab. 

A highly sensitive graphene-based multiple-layer coated, i.e., BK7/Au/platinum diselenide (PtSe2)/Graphene, surface plasmon resonance biosensor was developed for SARS-CoV-2 Ig identification. This system detects Ig utilizing the SARS-CoV-2 S receptor-binding domain (RBD) as the ligand and the viral anti-S proteins IgG and IgM as analytes. Graphene-based diagnostics for detecting SARS-CoV-2 biomarkers in exhaled breath samples are available now. They offer a non-invasive and rapid technique for monitoring the spread of SARS-CoV-2. Heptanal was identified to be a crucial biomarker that was observed significantly higher in the breath of SARS-CoV-2 patients. The adsorption features of heptanal on transition metal-doped and non-doped graphene could be explored using density functional theory and employed as a biomarker for SARS-CoV-2 diagnosis.

Various strategies, including photolithography, molding, and cutting and printing, are available for the fabrication of microfluidic SARS-CoV-2 detectors. Printing and cutting are usually employed in paper-based biosensors. Three-dimensional (3D) printing produces anatomically comparable specific devices. 3D printing enables designers to print components and assemblies containing a range of materials with different mechanical and physical properties in a single manufacturing process. Further, contact and non-contact printing are the two types of conventional printing strategies.

Grooves engraved on paper by laser could be employed to fasten paper-based microfluidic systems. 3D cutting and printing are presently used widely for the generation of paper-based LFAs for SARS-CoV-2 diagnosis. Stefano et al. developed a graphite-based biosensor for SARS-CoV-2 detection employing printing and cutting fabrication.

Injection and compression molding are widely used for the production of microfluidic devices. However, molding is rarely used in the case of SARS-CoV-2 biosensors. Prabhakar et al. have developed a silver- and AuNP-based SARS-CoV-2 biosensor based on the photolithography fabrication strategy. Nevertheless, there is no data regarding sustainable material-based SARS-CoV-2 biosensors utilizing photolithography.

In addition, advanced sustainable material-based SARS-CoV-2 biosensors include field-effect transistor-based biosensors and wearable biosensors. Biosensors based on the field-effect transistor are triggered by modifications in the surface potential caused by the adhesion of molecules. These kinds of biosensors' efficiency significantly improve when nanotechnology, especially nanomaterials like metal NPs, graphene, and nanowires, is incorporated. Field-effect transistor-based biosensors are the most common screening and sensing platforms due to their large-scale, high-quality manufacturing and commercial availability. 

Seo et al. reported a novel field-effect transistor-based biosensor for SARS-CoV-2 detection in clinical samples that has good analytical performance. Currently, there are some novel field-effect transistor-based biosensors available that can assist with easy SARS-CoV-2 diagnosis using saliva samples. 

Of note, new telemedicine technologies have been developed to solve constraints in SARS-CoV-2 diagnosis, thanks to the advent of mass-fabricated electronics for wearable and portable sensors. Temperature and symptom surveillance are essential when an asymptomatic individual with SARS-CoV-2 exposure is isolated. This surveillance has minimal effectiveness due to SARS-CoV-2-associated symptoms' intermittent nature and heavy dependence on self-discipline. However, due to improvements in biosensor technology, wearable biosensors in a variety of formats could constantly monitor physiological markers linked to COVID-19.


This systematic review raises concerns about the real-world clinical use of sustainable materials–based biosensors. The perspective on material selection and sensor-based clinical concern for the ongoing SARS-CoV-2 pandemic are also unique aspects this paper discussed.

COVID-19 biosensing using sustainable materials will aid in minimizing waste production as numerous diagnostic tests are performed every day. On top of the regular sanitation challenges, infectious waste will become a critical concern that causes environmental pollution during the SARS-CoV-2 pandemic. Waste generated from COVID-19 testing is highly contagious and infectious. Thus, reducing waste as much as feasible is a crucial aspect.

Cellulose- and paper-based biosensors are especially advantageous in pandemic scenarios due to their safe disposal, capacity to mass-produce using sustainable techniques, and recyclability. The modern notion of sustainable materials fits perfectly with the current green and eco-friendly technology revolution. 

The limitations of sustainable biosensing are inadequate storage conditions that might tamper the shelf-life of sustainable diagnostics, unavailability of a system to track the quality of sustainable sensors at various time stamps, and the emergence of mutated SARS-CoV-2 variants. 

Taken together, the study indicates that employing green nanomaterials in optical biosensor systems might lead to SARS-CoV-2 solutions that are more long-lasting and eco-friendlier.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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