Biosensors play a pivotal role in detecting and quantifying biomarkers, which is essential in industries like medical diagnostics and environmental monitoring. Owing to the many unique properties of nanomaterials, they are used in the development of advanced biosensors. Among various nanoparticle-based biosensors, graphene-based nanomaterial biosensors have shown immense potential in biological analysis and clinical medicine.
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The Importance of Biosensors in Medicine
According to the World Health Organization (WHO), by the end of 2035, the world would have experienced around 24 million new cancer cases and 14.5 million deaths due to cancer-related ailments. Therefore, early diagnosis is imperative to improve the survival rate of cancer patients. Clinical diagnosis is based on the detection of specific biomarkers, which are mainly found in body fluids, cells, and tissues. Quantitative detection of biomarkers plays a vital role in early diagnosis, clinical testing, and assessment of therapeutic effects.
Several conventional methods, such as high-performance liquid chromatography, mass spectrometry, and UV absorbance, can accurately diagnose diseases. However, there are certain drawbacks, including very complex operating procedures requiring a skilled individual to operate it. Furthermore, sample preparation for analysis takes a relatively long time, along with utilizing expensive, sophisticated instruments. Advanced nanomaterial-based biosensors were found to be the answer to these common issues.
Biosensors are developed using sensitive biological components such as enzymes, nucleic acids, or antibodies, with a physicochemical detector that can efficiently identify biomarker targets. Detection can occur rapidly and, thereby, help in the early diagnosis of various diseases like cancer.
Characteristic Features of Graphene-based Nanomaterials
Graphene has attracted the attention of scientists owing to its extraordinary properties. It is produced via carbon atom hybridization with sp2 electron orbital and possesses increased specific surface area, strong mechanical strength, excellent electron transport capabilities, adsorption performance, and flexibility. All these characteristic features make graphene an ideal candidate for biosensors.
Generally, graphene-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potential in clinical research associated with drug delivery, photodynamic therapy, and the development of biosensors for biomarker detection.
GO is produced via oxidative stripping of graphite, and compared to graphene, GO comprises various oxygen-containing functional groups, e.g.,–COON, C–O–C, –OH, and C=O. Owing to these functional groups, GO shows robust reactive activity with prominent dispersibility. On the other hand, rGO is obtained by removing oxygen-containing functional groups of GO using chemical or thermal reactions. rGO also contains many advantageous properties such as good thermal conductivity, excellent mechanical properties, large specific surface area ratio, good chemical stability, and high electron mobility.
How Do Graphene Nanoparticles Aid the Development of Advanced Biosensors?
The high surface area ratio of graphene-based nanoparticles provides greater densities of attached biocomponents or analyte molecules which, in turn, ensure high detection sensitivity and the miniaturization of the device. Their extraordinary electronic properties and electron transport capabilities make them an excellent candidate for electrochemical sensing. A single layer of graphene is approximately 0.335 nm thick and is immensely hard and flexible, making it beneficial for developing wearable sensor devices.
From roll to roll: printed biosensors made of graphene
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Applications of Graphene-Based Biosensors
Graphene-based nanomaterials in the development of biosensors are advantageous, especially concerning their miniaturization, high sensitivity, and simplicity of design. Previous studies have shown the application of graphene-based biosensors for the detection and quantification of chemical and biological components and the diagnosis of many harmful diseases by detecting target biomarkers. Some of the types of graphene-based biosensors are discussed below.
Graphene-Based Fluorescent Biosensors
This type of biosensor uses fluorescent tags with labeled targets. It is commonly used in biological monitoring owing to its high sensitivity, great accuracy, and low detection limit. Graphene oxide-based fluorescent sensors are used for the detection of DNA and proteins. Recently, this biosensor was used for the quantitative detection of dopamine in biological matrices and vascular endothelial growth factors.
Graphene-Based Electrochemical Biosensors
The large specific surface area and high electrical conductivity of graphene nanomaterials enable more significant protein adsorption and rapid electron transfer between the electrode's redox centers and the surface. These properties ensure the precise and selective detection of target biomolecules.
Researchers use graphene-based electrochemical biosensors like gold nanoparticles (AuNPs)-toluidine blue-GO nanocomposites to detect DNA. This technique does not require any fluorescent tag for the detection process. This biosensor has also been reported to efficiently detect miRNA, prostate-specific antigen (PSA), and human cervical cancer cells with high specificity.
Graphene-Based Surface Plasmon Resonance (SPR) Biosensors
Scientists used a graphene-Au-based SPR sensor for the detection of thrombin and lysozyme in serum. A graphene-Cu SPR sensor has been developed to identify ssDNA. SPR biosensor based on DNA-GO-AuNPs- can detect miRNA and small molecule adenosine. Also, GO-based SPR immunosensor can identify cytokeratin, a biomarker of lung cancer.
Graphene-Based Surface-Enhanced Raman Scattering (SERS) Biosensors
A graphene-based SERS biosensor is applied for the quantitative detection of different kinds of proteins. Scientists have recently developed nanographene-mediated metallic nanoparticle clusters for SERS biosensing of IgG while a GO-AgNPs-based amplification SERS immunoassay is used to detect PSA. This technique is extremely accurate, rapid, and highly sensitive
Graphene-Based Multifunction Detection Sensor
Researchers have recently developed smart multifunction sensors that can detect multiple targets on one system. An example of this type of biosensor is a graphene-nanodendritic gold-based biosensor, which can perform SERS along with electrochemical and fluorescence. This biosensor is used for the detection of miRNA and also could be applied for various clinical diagnoses and real-time monitoring.
References and Further Reading
Zhang, W., et al. (2021) Highly Sensitive Uric Acid Detection Based on a Graphene Chemoresistor and Magnetic Beads. Biosensors. 11(9), pp. 304. Available at: https://doi.org/10.3390/bios11090304
Bai, Y., et al. (2020) Graphene-Based Biosensors for Detection of Biomarkers. Micromachines, 11(1), pp. 60. Available at: https://doi.org/10.3390/mi11010060
Kim, Y.J. and Jeong B. (2018) Graphene-Based Nanomaterials and Their Applications in Biosensors. Advances in Experimental Medicine and Biology.064, pp. 61-71. Available at: https://doi.org/10.1007/978-981-13-0445-3_4
Pumera, M. (2011) Graphene in biosensing. Materials Today. 14(7–8), pp.308-315. Available at: https://doi.org/10.1016/S1369-7021(11)70160-2
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