Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> This paper is presented as an overview of the pathogen detection industry. The review ::: includes pathogen detection markets and their prospects for the future. Potential markets include the ::: medical, military, food, and environmental industries. Those industries combined have a market size ::: of $563 million for pathogen detecting biosensors and are expected to grow at a compounded annual ::: growth rate (CAGR) of 4.5%. The food market is further segmented into different food product ::: industries. The overall food pathogen testing market is expected to grow to $192 million and 34 ::: million tests by 2005. The trend in pathogen testing emphasizes the need to commercialize ::: biosensors for the food safety industry as legislation creates new standards for microbial monitoring. ::: With quicker detection time and reusable features, biosensors will be important to those interested in ::: real time diagnostics of disease causing pathogens. As the world becomes more concerned with a ::: safe food and water supply, the demand for rapid detecting biosensors only increases. <s> BIB001 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> The surface area of a single graphene sheet is 2630 m2/g, substantially higher than values derived from BET surface area measurements of activated carbons used in current electrochemical double layer capacitors. Our group has pioneered a new carbon material that we call chemically modified graphene (CMG). CMG materials are made from 1-atom thick sheets of carbon, functionalized as needed, and here we demonstrate in an ultracapacitor cell their performance. Specific capacitances of 135 and 99 F/g in aqueous and organic electrolytes, respectively, have been measured. In addition, high electrical conductivity gives these materials consistently good performance over a wide range of voltage scan rates. These encouraging results illustrate the exciting potential for high performance, electrical energy storage devices based on this new class of carbon material. <s> BIB002 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> We first reported that polyvinylpyrrolidone-protected graphene was dispersed well in water and had good electrochemical reduction toward O2 and H2O2. With glucose oxidase (GOD) as an enzyme model, we constructed a novel polyvinylpyrrolidone-protected graphene/polyethylenimine-functionalized ionic liquid/GOD electrochemical biosensor, which achieved the direct electron transfer of GOD, maintained its bioactivity and showed potential application for the fabrication of novel glucose biosensors with linear glucose response up to 14 mM. <s> BIB003 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> We present a low-temperature (300–400 °C), large-area (23 cm×20 cm) and efficient synthesis method for graphene-based transparent conductive films using surface wave plasma chemical vapor deposition. The films consist of few-layer graphene sheets. Their transparency and conductivity characteristics make them suitable for practical electrical and optoelectronic applications, which have been demonstrated by the proper operation of a touch panel fabricated using the films. The results confirm that our method could be suitable for the industrial mass production of macroscopic-scale graphene-based films. <s> BIB004 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> This review is based on the Theophilus Redwood Medal and Award lectures, delivered to Royal Society of Chemistry meetings in the UK and Ireland in 2012, and presents a personal overview of the field of biosensors. The biosensors industry is now worth billions of United States dollars, the topic attracts the attention of national initiatives across the world and tens of thousands of papers have been published in the area. This plethora of information is condensed into a concise account of the key achievements to date. The reasons for success are examined, some of the more exciting emerging technologies are highlighted and the author speculates on the importance of biosensors as a ubiquitous technology of the future for health and the maintenance of wellbeing. <s> BIB005 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. <s> BIB006 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Left-handed Z-DNA has been identified as a transient structure occurred during transcription. DNA B-Z transition has attracted much attention because of not only Z-DNA biological importance but also their relation to disease and DNA nanotechnology. Recently, photoluminescent carbon dots, especially highly luminescent nitrogen-doped carbon dots, have attracted much attention on their applications to bioimaging and gene/drug delivery because of carbon dots with low toxicity, highly stable photoluminescence and controllable surface function. However, it is still unknown whether carbon dots can influence DNA conformation or structural transition, such as B-Z transition. Herein, based on our previous series work on DNA interactions with carbon nanotubes, we report the first example that photoluminescent carbon dots can induce right-handed B-DNA to left-handed Z-DNA under physiological salt conditions with sequence and conformation selectivity. Further studies indicate that carbon dots would bind to DNA major groove with GC preference. Inspired by carbon dots lighting up Z-DNA and DNA nanotechnology, several types of DNA logic gates have been designed and constructed based on fluorescence resonance energy transfer between photoluminescent carbon dots and DNA intercalators. <s> BIB007 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Abstract Interest in two-dimensional, sheet-like or flake-like carbon forms has expanded beyond monolayer graphene to include related materials with significant variations in layer number, lateral dimension, rotational faulting, and chemical modification. Describing this family of “graphene materials” has been causing confusion in the Carbon journal and in the scientific literature as a whole. The international editorial team for Carbon believes that the time has come for a discussion on a rational naming system for two-dimensional carbon forms. We propose here a first nomenclature for two-dimensional carbons that could guide authors toward a more precise description of their subject materials, and could allow the field to move forward with a higher degree of common understanding. <s> BIB008 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Graphene materials have entered a phase of maturity in their development that is characterized by their explorative utilization in various types of applications and fields from electronics to biomedicine. Herein, we describe the recent advances made with graphene-related materials in the biomedical field and the challenges facing these exciting new tools both in terms of biological activity and toxicological profiling in vitro and in vivo. Graphene materials today have mainly been explored as components of biosensors and for construction of matrices in tissue engineering. Their antimicrobial activity and their capacity to act as drug delivery platforms have also been reported, however, not as coherently. This report will attempt to offer some perspective as to which areas of biomedical applications can expect graphene-related materials to constitute a tool offering improved functionality and previously unavailable options. <s> BIB009 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> A protein-based electrochemical biosensor was developed for detection of tau protein aimed towards electrochemically sensing misfolding proteins. The electrochemical assay monitors tau–tau binding and misfolding during the early stage of tau oligomerization. Electrochemical impedance spectroscopy was used to detect the binding event between solution tau protein and immobilized tau protein (tau–Au), acting as a recognition element. The charge transfer resistance (Rct) of tau–Au was 2.9 ± 0.6 kΩ. Subsequent tau binding to tau–Au decreased the Rct to 0.3 ± 0.1 kΩ (90 ± 3% decrease) upon formation of a tau–tau–Au interface. A linear relationship between the Rct and the solution tau concentration was observed from 0.2 to 1.0 μM. The Rct decrease was attributed to an enhanced charge permeability of the tau–tau–Au surface to a redox probe [Fe(CN)6]3−/4−. The electrochemical and surface characterization data suggested conformational and electrostatic changes induced by tau–tau binding. The protein-based electrochemical platform was highly selective for tau protein over bovine serum albumin and allowed for a rapid sample analysis. The protein-based interface was selective for a non-phosphorylated tau441 isoform over the paired-helical filaments of tau, which were composed of phosphorylated and truncated tau isoforms. The electrochemical approach may find application in screening of the early onset of neurodegeneration and aggregation inhibitors. <s> BIB010 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. <s> BIB011 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Carbon dots (C-dots), since their first discovery in 2004 by Scrivens et al. during purification of single-walled carbon nanotubes, have gradually become a rising star in the fluorescent nanoparticles family, due to their strong fluorescence, resistance to photobleaching, low toxicity, along with their abundant and inexpensive nature. In the past decade, the procedures for preparing C-dots have become increasingly versatile and facile, and their applications are being extended to a growing number of fields. In this review, we focused on introducing the biological applications of C-dots, hoping to expedite their translation to the clinic. <s> BIB012 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> The chemical reduction of graphene oxide is a promising route towards the large scale production of graphene for commercial applications. The current state-of-the-art in graphene oxide reduction, consisting of more than 50 types of reducing agent, will be reviewed from a synthetic chemistry point of view. Emphasis is placed on the techniques, reaction mechanisms and the quality of the produced graphene. The reducing agents are reviewed under two major categories: (i) those which function according to well-supported mechanisms and (ii) those which function according to proposed mechanisms based on knowledge of organic chemistry. This review will serve as a valuable platform to understand the efficiency of these reducing agents for the reduction of graphene oxide. <s> BIB013 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano‑biological events. <s> BIB014 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> In this review, we analyze several types of graphene-based sensors for glucose detection with respect to their preparation, properties and efficiency in electro-chemical processes. Graphene may display different types of defects, which play a role in the electron transfer processes. Oxygenated groups on the edges of graphene planes reduce the graphene in-plane conductivity, but may enhance the heterogeneous electron/proton transfer constant. Other positive effects of defects are related to the shortening of the distance between active centers and electrodes upon enzyme or protein immobilization. However, though by different mechanisms, all types of graphene enhance the electrochemical response at the electrode. <s> BIB015 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Gold-doped graphene combined with a serpentine-shaped bilayer of gold mesh and polymeric microneedles form a wearable patch for sweat-based diabetes monitoring and feedback therapy. <s> BIB016 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Abstract Carbon-based photoluminescent nanodot has currently been one of the promising materials for various applications. The remaining challenges are the carbon sources and the simple synthetic processes that enhance the quantum yield, photostability and biocompatibility of the nanodots. In this work, the synthesis of blue photoluminescent carbon nanodots from limeade via a single-step hydrothermal carbonization process is presented. Lime carbon nanodot (L-CnD), whose the quantum yield exceeding 50% for the 490 nm emission in gram-scale amounts, has the structure of graphene core functionalized with the oxygen functional groups. The micron-sized flake of the as-prepared L-CnD powder exhibits multicolor emission depending on an excitation wavelength. The L-CnDs are demonstrated for rapidly ferric-ion (Fe3 +) detection in water compared to Fe2 +, Cu2 +, Co2 +, Zn2 +, Mn2 + and Ni2 + ions. The photoluminescence quenching of L-CnD solution under UV light is used to distinguish the Fe3 + ions from others by naked eyes as low concentration as 100 μM. Additionally, L-CnDs provide exceptional photostability and biocompatibility for imaging yeast cell morphology. Changes in morphology of living yeast cells, i.e. cell shape variation, and budding, can be observed in a minute-period until more than an hour without the photoluminescent intensity loss. <s> BIB017 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Graphene-based materials have attracted increasing attention due to their atomically-thick two-dimensional structures, high conductivity, excellent mechanical properties, and large specific surface areas. The combination of biomolecules with graphene-based materials offers a promising method to fabricate novel graphene–biomolecule hybrid nanomaterials with unique functions in biology, medicine, nanotechnology, and materials science. In this review, we focus on a summarization of the recent studies in functionalizing graphene-based materials using different biomolecules, such as DNA, peptides, proteins, enzymes, carbohydrates, and viruses. The different interactions between graphene and biomolecules at the molecular level are demonstrated and discussed in detail. In addition, the potential applications of the created graphene–biomolecule nanohybrids in drug delivery, cancer treatment, tissue engineering, biosensors, bioimaging, energy materials, and other nanotechnological applications are presented. This review will be helpful to know the modification of graphene with biomolecules, understand the interactions between graphene and biomolecules at the molecular level, and design functional graphene-based nanomaterials with unique properties for various applications. <s> BIB018 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Hydrogels consisting of three-dimensional (3D) polymeric networks have found a wide range of applications in biotechnology due to their large water capacity, high biocompatibility, and facile functional versatility. The hydrogels with stimulus-responsive swelling properties have been particularly instrumental to realizing signal transduction in biosensors and bioelectronics. Graphenes are two-dimensional (2D) nanomaterials with unprecedented physical, optical, and electronic properties and have also found many applications in biosensors and bioelectronics. These two classes of materials present complementary strengths and limitations which, when effectively coupled, can result in significant synergism in their electrical, mechanical, and biocompatible properties. This report reviews recent advances made with hydrogel and graphene materials for the development of high-performance bioelectronics devices. The report focuses on the interesting intersection of these materials wherein 2D graphenes are hybridized with 3D hydrogels to develop the next generation biosensors and bioelectronics. <s> BIB019 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Wearable electronics have been utilized for a number of applications including for ocular use, although their use has been limited to a single function. Here, the authors developed a multifunctional contact lens with wireless electronics for measurement of glucose and intraocular pressure. <s> BIB020 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Graphene and its derivatives have become the most explored materials since Novoselov and Geim (Nobel Prize winners for Physics in 2010) achieved its isolation in 2004. The exceptional properties of graphene have attracted the attention of the scientific community from different research fields, generating high impact not only in scientific journals, but also in general-interest newspapers. Optical fibre sensing is one of the many fields that can benefit from the use of these new materials, combining the amazing morphological, chemical, optical and electrical features of graphene with the advantages that optical fibre offers over other sensing strategies. In this document, a review of the current state of the art for optical fibre sensors based on graphene materials is presented. <s> BIB021 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> The development of new sensors for the accurate detection of biomarkers in biological fluids is of utmost importance for the early diagnosis of diseases. Next to advanced laboratory techniques, there is a need for relatively simple methods which can significantly broaden the availability of diagnostic capability. Here, we demonstrate the successful application of a sensor platform based on graphene oxide and upconversion nanoparticles (NPs) for the specific detection of mRNA-related oligonucleotide markers in complex biological fluids. The combination of near-infrared light upconversion with low-background photon counting readout enables reliable detection of low quantities of small oligonucleotide sequences in the femtomolar range. We demonstrate the successful detection of analytes relevant to mRNAs present in Alzheimer’s disease as well as prostate cancer in human blood serum. The high performance and relative simplicity of the upconversion NP-graphene sensor platform enables new opportunities in early... <s> BIB022 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> This article reviews recent progress in the development of nanomaterial-based electrochemical biosensors for cancer biomarkers. Because of their high electrical conductivity, high affinity to biomolecules, and high surface area-to-weight ratios, nanomaterials, including metal nanoparticles, carbon nanotubes, and graphene, have been used for fabricating electrochemical biosensors. Electrodes are often coated with nanomaterials to increase the effective surface area of the electrodes and immobilize a large number of biomolecules such as enzymes and antibodies. Alternatively, nanomaterials are used as signaling labels for increasing the output signals of cancer biomarker sensors, in which nanomaterials are conjugated with secondary antibodies and redox compounds. According to this strategy, a variety of biosensors have been developed for detecting cancer biomarkers. Recent studies show that using nanomaterials is highly advantageous in preparing high-performance biosensors for detecting lower levels of cancer biomarkers. This review focuses mainly on the protocols for using nanomaterials to construct cancer biomarker sensors and the performance characteristics of the sensors. Recent trends in the development of cancer biomarker sensors are discussed according to the nanomaterials used. <s> BIB023 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> This work reports a convenient and real-time assay of alkaline phosphatase (ALP) in living cells based on a fluorescence quench-recovery process at a physiological pH using the boron-doped graphene quantum dots (BGQDs) as fluorophore. The fluorescence of BGQDs is found to be effectively quenched by Ce3+ ions because of the coordination of Ce3+ ions with the carboxyl group of BGQDs. Upon addition of adenosine triphosphate (ATP) into the system, the quenched fluorescence can be recovered by the ALP-positive expressed cells (such as MCF-7 cells) due to the removal of Ce3+ ions from BGQDs surface by phosphate ions, which are generated from ATP under catalytic hydrolysis of ALP that expressed in cells. The extent of fluorescence signal recovery depends on the level of ALP in cells, which establishes the basis of ALP assay in living cells. This approach can also be used for specific discrimination of the ALP expression levels in different type of cells and thus sensitive detection of those ALP-positive expressed cells (for example MCF-7 cells) at a very low abundance (10±5 cells mL-1). The advantages of this approach are that it has high sensitivity because of the significant suppression of the background due to the Ce3+ ion quenching the fluorescence of BGQDs, and has the ability of avoiding false signals arising from the nonspecific adsorption of non-target proteins because it operates via a fluorescence quench-recovery process. In addition, it can be extended to other enzyme systems, such as ATP-related kinases. <s> BIB024 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> With the increasing concern of potential health and environmental risk, it is essential to develop reliable methods for transgenic soybean detection. Herein, a simple, sensitive and selective assay was constructed based on homogeneous fluorescence resonance energy transfer (FRET) between CdTe quantum dots (QDs) and multiwalled carbon nanotubes@graphene oxide nanoribbons (MWCNTs@GONRs) to form the fluorescent "on-off-on" switching for simultaneous monitoring dual target DNAs of promoter cauliflower mosaic virus 35s (P35s) and terminator nopaline synthase (TNOS) from transgenic soybean. The capture DNAs were immobilized with corresponding QDs to obtain strong fluorescent signals (turning on). The strong π-π stacking interaction between single-stranded DNA (ssDNA) probes and MWCNTs@GONRs led to minimal background fluorescence due to the FRET process (turning off). The targets of P35s and TNOS were recognized by dual fluorescent probes to form double-stranded DNA (dsDNA) through the specific hybridization between target DNAs and ssDNA probes. And the dsDNA were released from the surface of MWCNTs@GONRs, which leaded the dual fluorescent probes to generate the strong fluorescent emissions (turning on). Therefore, this proposed homogeneous assay can be achieved to detect P35s and TNOS simultaneously by monitoring the relevant fluorescent emissions. Moreover, this assay can distinguish complementary and mismatched nucleic acid sequences with high sensitivity. The constructed approach has the potential to be a tool for daily detection of genetically modified organism with the merits of feasibility and reliability. <s> BIB025 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Abstract This paper presents a “turn-on” fluorescence biosensor based on graphene quantum dots (GQDs) and molybdenum disulfide (MoS 2 ) nanosheets for rapid and sensitive detection of epithelial cell adhesion molecule (EpCAM). PEGylated GQDs were used as donor molecules, which could not only largely increase emission intensity but also prevent non-specific adsorption of PEGylated GQD on MoS 2 surface. The sensing platform was realized by adsorption of PEGylated GQD labelled EpCAM aptamer onto MoS 2 surface via van der Waals force. The fluorescence signal of GQD was then quenched by MoS 2 nanosheets via fluorescence resonance energy transfer (FRET) mechanism. In the presence of EpCAM protein, the stronger specific affinity interaction between aptamer and EpCAM protein could detach GQD labelled EpCAM aptamer from MoS 2 nanosheets, leading to the restoration of fluorescence intensity. By monitoring the change of fluorescence signal, the target EpCAM protein could be detected sensitively and selectively with a linear detection range from 3 nM to 54 nM and limit of detection (LOD) around 450 pM. In addition, this nanobiosensor has been successfully used for EpCAM-expressed breast cancer MCF-7 cell detection. <s> BIB026 </s> Graphene-Based Materials for Biosensors: A Review <s> Introduction <s> Abstract Graphene has contributed to the fabrication of sensitive sensors and biosensors due to its physical and electrochemical properties. This review discusses the role of graphene and graphene related materials for the improvement of the analytical performance of sensors and biosensors. This paper also provides an overview of recent graphene based sensors and biosensors (2012–2016), comparing their analytical performance for application in clinical, environmental, and food sciences research, and comments on future and interesting research trends in this field. <s> BIB027
A biosensor is an analytical device which can detect a biomolecule-related element with an appropriate transducer to generate a measurable signal from the sample  BIB005 . The biosensor system illustrated in Figure 1 shows a typical platform, consisting of a bioreceptor interfaced with a transducer. The bioreceptor has to be capable of recognizing the biomolecule element, for instance, enzymes, antibodies, DNA, RNA, and cells. In an incorporation, the biological signal that can be detected in various quantities by the receptor is transduced by physical, chemical, optical, thermal or electrochemical actions into observable information and analyzed quantitatively. The first generation of biosensor devices was introduced by Clark and Lyons  to monitor chemical components in the blood of a surgical patient and to record quantitative biomolecule contents in blood. Since then, the applications of biosensors in the biomedical field and global healthcare have become indispensable for human life improvements in order to spatially analyze diseases through a patient BIB010 BIB011 BIB019 , to detect and to diagnose biomolecules BIB014 BIB020 BIB003  BIB016 , to integrate with drug delivery BIB006   and food safety BIB001 . In many efforts of the investigations, major requirements of biosensors are that the receptor has to not only be highly selective and specific to the biomolecular element, but also that the transducer needs to be ultrasensitive and with sufficient reproducibility for reliable real-time measurements. For more precision, the presence of chemical binding or biological specificity to an analyte in a labeled technique is used to ensure that only the labeled biological activities give a strong signal. However, this technique requires a labeling process in preparation and involves the fluorescent dyes, chemiluminescent molecules, photoluminescent nanoparticles and quantum dots BIB021 BIB007 BIB012 BIB022 BIB023 BIB024 BIB025 BIB026 BIB017 . Alternatively, the label-free technique uses molecular, physical, mechanical, electrical, optical properties and charge interaction to monitor binding activities. The label-free methods can provide real-time tracking in biomolecular events and give more direct information about the target biomolecules without interference effects from the labeling procedure. Currently, label-free biosensors are essential cancer diagnostics, and drug development   25] where the sensitivity is one of the key requirements that needs to be engineered for state-of-the-art biosensors BIB018 . The emergence of graphene, a two-dimensional (2D) nanomaterial, has played a tremendous role in the electronic and sensor communities. Graphene is defined as "a single-atom-thick sheet of hexagonally arranged, sp 2 -bonded carbon atoms occurring within a carbon material structure" BIB008 . The nano-thickness graphene film with 100 μm of lateral size is observed as carbon planes connected together by van der Waals forces acting over a distance of about 0.335 nm. The properties of graphene are those of a semi-metal and are stable under ambient circumstances. This contradicts the general belief that a 2D material could not exist and be thermodynamically stable. The charge transport and electronic properties of graphene are due to its unique electronic band structure. In particular, among existing nanomaterials graphene has a large surface area (2630 m 2 /g) BIB002 BIB004 being available for direct interaction in a wide range of biomolecules BIB018 . Graphene can be engineered with structural defects using low-cost fabrication methods due to the migration of heteroatoms, oxidation, and reduction by chemical modification  BIB013 . The uses of graphene-based materials for biosensing involve two points of view. One is based on charge-biomolecule interactions at π-π domains, electrostatic forces and charge exchange leading to electrical variations in the pristine graphene. The other uses are the effect of defects, disorder, the chemical functionalization to immobilize the molecular receptors onto the surface of graphene oxide (GO), reduced graphene oxide (RGO) and graphene-based quantum dots (GQDs). Recently, several excellent reviews have focused on the interactions of graphene, GO and RGO-based biosensors with their biomolecular targets BIB018 BIB027 BIB015 BIB009 . In this review, we focus on the graphene-based material properties due to their fabrication process, surface chemistry and the photoluminescent graphene socalled GQDs. These graphene properties are utilized and integrated in biosensors for biological and medical applications.