A Breif Review of Glucose Based Biosensors

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Graphene-based Glucose Sensors:

A Brief Review
Feifei Wang, Lianqing Liu, Member, IEEE, and Wen J. Li, Fellow, IEEE
Abstract—Since the existence of graphene, a material only a which has been cited more than 18,352 times as of 2015, has
single atomic layer thick, was demonstrated about a decade ago, allowed them and others to perform fundamental
it has caught the attention of researchers worldwide. This paper characterizations of the novel mechanical, electronic and
begins with a historical overview of graphene since its discovery, optical properties of this 2-D material.
in 2004, and focuses on a citation-weighted review of
graphene-based sensors developed for the detection of biological
The characteristics that make graphene a promising
targets. Based on this statistical analysis, we categorize recent biosensor material are (1) its extraordinary electrical
developments in graphene-based biosensors (GBBs) as optimized conductivity at room temperature and (2) its large specific
for detecting (1) proteins, (2) nucleic acids (3) carbohydrates, or surface area that is optically and chemically active.
(4) compounds generated by metabolic processes. Existing Theoretically, the attachment of a single biomolecule to the
detection methods employed by these sensors include electrical, chemically reactive surface of a graphene layer can be detected
electrochemical, and photonic approaches with respect to
detecting labeled (or enzyme-assisted) and label-free (or as a measureable change in electrical conductivity.
enzyme-free) probe structures. Herein, we focus on Furthermore, the optical spectrum of graphene can change
graphene-based glucose sensors because glucose-monitoring dramatically with the attachment of biomolecules and hence
technology is extremely important in the management of diabetes offers another non-electrical, sensing modality.
and many practical examples of these carbohydrate sensors have Over the past eight years, researchers have explored the
been developed using the aforementioned detection methods. physical, electrical, optical, and chemical characteristics of
graphene and promoted the application of graphene in many
Index Terms—Graphene, Biosensor, Glucose sensor,
Enhancement mechanisms, Bio-detection principles different fields. Applications for graphene have emerged in
energy conversion and storage, field emission display
technology, touchscreen displays, ultrafast photodetectors,
I. INTRODUCTION supercapacitors, information storage and
physical/chemical/biological sensors.
A. Background on Graphene In Section II, we introduce the major properties of graphene
C ARBON is the basis for life on Earth, so there is a certain

sense of symmetry that graphene, a novel two-dimensional
form of carbon that is only one atomic layer thick, has enabled
used in biosensors and elaborate on how these unique
properties enhance overall sensor performance. In Section III,
we summarize the main mechanisms used in graphene-based
recent advances in sensitivity and specificity for detecting biosensors (GBBs) through a statistical analysis of the citation
various biomolecules. Although Geim and Novoselov reported results and specifically discuss how graphene enhances the
that ultrathin graphitic planes (and possibly single-plane detection mechanisms for glucose. We also detail how each of
graphene) had been epitaxially grown by other researchers on the main sensing mechanisms can be applied to detect glucose.
various substrates prior to 2004, these researchers were the first We discuss the survey results in Section V and provide
to mechanically isolate individual graphene planes [1]. The conclusions in Section VI.
flakes obtained using their “Scotch® tape method” allowed
them to characterize the unique electronic properties of this 2-D B. Survey Search Process and Methodology
metastable material. Their straightforward isolation method, We categorized six subtypes of GBB in our literature surveys
as representative examples of the four generic categories of
target molecules. Specifically, we chose biosensors that target
Manuscript received May 12, 2015; revised July 27, 2015; accepted August glucose, thrombin, dopamine, a cancer tumor marker (e.g.,
28, 2015. This work was supported by the National Natural Science Foundation
of China (Project No. 61375107), CAS International Cooperation Key Issues
alpha fetoprotein, AFP), hydrogen peroxide (H 2O2) and
(Project No. 173321KYSB20130006), the CAS-Croucher Funding Scheme for deoxyribonucleic acid (DNA) as practical examples of GBBs
Joint Laboratories (Project No. 9500011), the Hong Kong Innovation and that can detect carbohydrates, proteins, metabolites, and nucleic
Technology Commission (ITF Project No. ITS/143/13), and the CAS FEA acids. This paper presents surveyed results only for glucose
International Partnership Program for Creative Research Teams.
Feifei Wang and Lianqing Liu are with the State Key Laboratory of sensors. Briefly, the literature survey method used in this
Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences review is based on the Web of Science (WOS®) database [2],
(CAS), 110016, China. Feifei Wang is also with the University of the Chinese statistical analysis using HistCite software [3], and manual
Academy of Sciences, Beijing, China, 100049, China.
Wen J. Li is with the Dept. of Mechanical and Biomedical Engineering, City filtering of the irrelevant references along with grouping of the
University of Hong Kong, Hong Kong. Wen J. Li is also an affiliated professor citation results by technical relevance. The search process for
at the Shenyang Institute of Automaton, CAS. graphene-based glucose sensors is summarized below.
Corresponding author: wenjli@cityu.edu.hk.
1536-1241 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/TNB.2015.2475338, IEEE
1) Preliminary searching incomplete results.

Using graphene-based glucose biosensors as an example, we 5) The final search query for graphene-based glucose sensors
first searched by keywords via the advanced search function in The final search query used to search for all citations of
the graphical user interface of WOS®. In this case, “glucose,” graphene-based glucose biosensors was TS=Graphene AND
“biosensor,” “sensor” and “graphene” were selected. After the TS="glucose" AND (TS=biosensor OR TS= sensor OR
initial WOS® search results, we needed to change the search TS=detection OR TS=detecting OR TS=detect OR TS=assay
query to exclude irrelevant results, for example, by narrowing
the search domain. Next, information about citations of the
relevant papers was downloaded from WOS®.
2) Importing data into HistCite and refreshing the WOS ®
search query
After importing the citations into HistCite, we acquired other
keywords from a statistical analysis using HistCite, which
resulted in new relevant keywords. This process allowed us to
graph the relationship of citations, which helped filter and focus
the search results on the target subtopic domain. We then used
these newly generated keywords for another advanced search
query of the WOS®.
3) Repeating steps 1) and 2) until the number of keywords
Fig. 1. Within the past 5 years, there have been at least 1,743 published papers
generates all of the relevant results. related to GBBs and indexed by the WOS® database.
4) Manually excluding search results
Following the process steps in 1), 2), and 3) above, the search OR TS=determination OR TS=determine) NOT (TS=cancer
results were highly relevant, but some unwanted results needed OR TS=(Ion NEAR/5 Sensor) OR TS=immuno OR
to be manually excluded based on our understanding of TS=immunosensor OR TS=immunoassay OR
graphene and biosensors. Thus, we removed these irrelevant TS=erythromycin OR TS=acetylcholine OR TS=solar cell OR
citation results manually. The final search query string used for TS=caffeine OR TS=H2O2 OR TS=Hydrogen peroxide OR
an advanced search of WOS® for graphene-based glucose TS=hydrazine OR TS=nitric oxide OR TS=midecamycin OR
biosensors is provided in the next section. Note that some TS=dopamine OR TS=REVIEW OR TS=ractopamine OR
studies detected glucose and H2O2 simultaneously. For this TS=CEA OR TS=oxalate OR TS=phenolic OR TS=Protein OR
situation, it was necessary to either perform another search TS=amino acid OR TS=salbutamol OR TS=(Cu NEAR/5 Ions)
query or search for both glucose and H2O2 biosensors in the OR TS=cholesterol OR TS=acetaminophen OR
same search query. Furthermore, care had to be taken to avoid a TS=hydroquinone OR TS=quintozen OR
very narrow search domain, which could lead to partial or TS=acetylcholinesterase OR TS=Rutin OR TS=ethanol OR
Fig. 2. HistCite mapping of the 45 papers on GBBs with the highest local citation score (LCS). Various types of GBBs were reported on: those for detecting
glucose, thrombin, dopamine, hydrogen peroxide, alpha fetoprotein and DNA (corresponding to the colored legend in the upper-left corner). The numbers in
the colored circles correspond to the bibliographical reference number for the citation. The line and arrow directions represent the citation relationship
between two papers. The diameter of a circle is a qualitative representation of the LCS, with larger diameters indicating a higher LCS.
TS=(guanine NEAR/4 DNA)). doping will affect the density and mobility of charge carriers;
hence, the electrical conductivity of graphene will change.
C. Summary of the Literature Survey
Another advantage is that owing to graphene’s high
Based on the WOS® database citation results and two conductivity, relatively few crystal defects [58] and
parameters in HistCite—namely, the Global Citation Score demonstrated self-healing of lattice defects [66], electronic
(GCS) and the Local Citation Score (LCS) [3]—our search devices based on graphene are expected to have a low Johnson
yielded relevant data from 1,743 journal papers for noise and 1/f noise [58]. The 1/f noise is further decreased in
graphene-based biosensors, as charted in Fig. 1. Published from bilayer graphene because of the effective screening of external
2008 to June 2015, the 45 papers with the highest LCS are charge impurities induced by band structure scattering [67].
mapped in Fig. 2. This impact map is based on the highest LCS The noise in bilayer graphene can be further decreased by
rankings for the six subtypes of GBB from our WOS® database improvements in surface passivation and the quality of the
survey and was graphed using HistCite. electrical contacts [68]. Robinson et al. [69] studied the
relationship between the level of chemical reduction and the
II. PROPERTIES OF GRAPHENE APPLICABLE TO BIOSENSING conductance and 1/f noise for RGO. The authors noted that the
Owing to its unique properties, two-dimensional 1/f noise was reduced as the reduction time increased.
honeycomb-like graphene has attracted the attention of many Another method to enhance the response current is the
researchers since it was first characterized in 2004 [1]. Herein, doping of graphene. The two main doping categories are
we concentrate on the properties of graphene that make it a electrical doping and chemical doping [70]. Substitutional
unique biosensor. Like other nanomaterials, one of the most doping of graphene with heteroatoms (such as boron [71] and
attractive properties of graphene with respect to sensing is its nitrogen [25], [71]) can intrinsically modulate graphene’s
high specific surface area—i.e., ~2,600 m2/g [49]. This high properties while maintaining high mobility and conductivity
area-to-volume ratio promotes the attachment and [72]. Compared to pristine graphene, a large number of defects
hybridization of molecules or nanoparticles to the graphene will be induced onto an N-doped graphene (N-graphene)
surface, which enhances graphene’s overall sensitivity as a surface [73]. Defects function as scattering sites, which will
biosensor. affect the mobility of N-graphene. However, their existence
also promotes electrocatalytic activity for biosensor use.
A. Mechanical Properties
When graphene is used to modify the surface of an electrode C. Optical Properties
or used in a field effect transistor (FET), its mechanical strength Loh et al. [74] provided a detailed description of the optical
becomes a key advantage. Although the layer structure of properties of graphene oxide (GO) and RGO in terms of
graphene is only a single atom thick, graphene exhibits a very applications relevant to biosensing. Bonaccorso et al. [75]
high Young’s modulus, ~1.1 TPa [50], [51], with an extremely provided a detailed description of optoelectronic devices based
high tensile strength, 130 GPa [50]. Furthermore, owing to the on graphene. Because it is essentially a single atomic layer
natural flexibility of reduced oxide graphene (RGO), even after thick, graphene is highly transparent to visible-light
5,000 bending cycles, the electrical properties of an wavelengths. Only 2.3% of incident visible light is adsorbed by
RGO-based device do not show any obvious changes [52]. monolayer graphene, and the absorption of light linearly
increases with the number of layers [76]. According to Loh et al.
B. Electrical Properties
[74], the most notable and unexpected consequence of the
One way to enhance the performance of an electrochemical atomic structure of RGO is the observation of near-infrared,
biosensor is to promote electron transfer between the electrode visible and ultraviolet fluorescence [77], [78]. Furthermore,
and the target biomolecule. Graphene has a very high mobility graphene can improve the performance of optical sensors
of electrons and holes, resulting in high electrical conductivity. because of its enhanced ability to adsorb biomolecules, and the
The values for electron mobility are usually dependent on the higher density of states improves surface electromagnetic wave
measurement method and the process used to produce the propagation. For example, graphene and GO can both adsorb
graphene. Experimental measurements and theory predict that DNA bases (or single stranded (ss-) DNA), but not double
the electronic mobility will range from 103 to 106 cm2/(V·s) [1], stranded (ds-) DNA, via a π-π interaction [79], [80], making
[53]–[58] and that the conductivity will range from 102 to 106 them nucleic acid detectors.
S/m [59]–[62]. At the Dirac point, graphene has a minimum Additionally, the sensitivity of surface plasmon resonance
conductivity of ~4e2/h, where e is the electron charge and h is (SPR) detectors has been shown to increase by up to three-fold
Planck’s constant [63], [64]. The conductivity increases on a graphene substrate [81]. Swathi et al. [82], [83] reported
linearly with the gate voltage regardless of the electrical that the resonance energy transferred from a dye molecule to
polarity [64], and it generally exhibits a metal-like conductivity graphene has a 4th-power dependence on large distances. They
at room temperature [65]. Graphene shows an ambipolar also studied the influence of doping on this transfer process.
electric field effect [63], meaning that its semiconducting This fluorescence-quenching property of graphene, combined
(n-type or p-type) behavior can be switched by controlling the with the interaction between graphene and biomolecules,
gate voltage. shows the possibility of developing new types of biosensors. In
When molecules or ions are adsorbed onto by graphene, this addition to the properties described above, graphene shows
good biocompatibility and therefore has potential applications graphene can provide more sites to anchor molecules. The
at the interface between the detection unit and cells [84]–[86]. presence of ionic groups and aromatic domains enables GO to
interact with biomolecules in diverse ways [74], such as
III. BIOSENSING PRINCIPLES USING GRAPHENE electrostatic interaction with positively charged molecules and
anchors for chemical functional chains.
A. Electron Transfer
However, for EIS-based GBBs, little research related to the
1) Electrochemical influence of graphene’s electrical properties has been
In this section, common techniques for using graphene as an conducted to date.
electrochemical (EC) sensor are introduced. However, this list 3) Field effect transistors (FETs)
of common techniques is not exhaustive. The basic Enhancements introduced previously for impedimetric- and
electrochemistry of graphene is reviewed by Shao et al. [87]. EC-based GBBs can be used to promote the performance of
The first EC technique is to use graphene as a sensing FET-based GBBs. Using a suspended graphene FET structure
material by exploiting its high specific surface area, which also shows an enhancement [94] owing to the charge traps at
exposes all carbon atoms to sense biomolecules. Combined the interface. These traps act as external scattering centers that
with the aforementioned low noise of graphene, the resultant result in the degradation of transport properties, but electrical
GBB will have excellent sensitivity. The second technique is to 1/f noise is consequently suppressed [95].
use graphene as an electron transfer medium, which leverages As shown in Fig. 3, there are two general types of
its high mobility and electrical conductivity. The third FET-based GBBs: namely, back gate FETs [31], [96] and liquid
technique is to use graphene as a higher-affinity intermediary to gate FETs [11], [97]. The “back gate” refers to changes in the
enhance the attachment of the target biomolecule, which is conductivity of the graphene substrate due to the presence of
possible because of graphene’s high specific surface area and biomolecules. Thus, “back” refers to a second gate voltage due
easily functionalized surface, specifically for RGO and GO. to changes in the threshold voltage arising from changes in the
2) Impedimetric source-drain voltage. The liquid gate can be distilled water, an
Electrochemical impedance spectroscopy (EIS) is a powerful electrolyte, or a buffer solution.
measurement technique that provides electrical information in The response of graphene to a surface charge or a change in
the frequency domain and can be used to probe the interface ion density shows its potential application in liquid-gate
properties and biorecognition events at the electrode surface FET-based biosensors [98]. For example, after the graphene
[88]. The basic principles of EIS have been summarized in surface has been functionalized with an antibody/linker, the
excellent reviews [88], [89], and EIS has been used in FET-based GBB will acquire selectivity for a certain
biosensing for many years [88]–[90]. Briefly, in EIS analysis, biomolecule. In an aptamer sandwich on a FET-based GBB,
the charge transfer resistance, which corresponds to the without this functional modification (i.e., modifying the
diameter of the semicircles in a Nyquist plot, is strongly graphene without an appropriate linker), the GBB will lose not
influenced by the modification of the electrode surface [48]. only its selectivity but also its sensitivity to target molecules
The application of graphene to EIS for the detection of because of the Debye shielding effect [97].
biomolecules is concentrated on using the graphene to Two different mechanisms have been used to explain the
functionalize an electrode. Graphene comprises a monolayer of changes in electrical properties (e.g., conductivity and the Dirac
sp2-hybridized carbon atoms joined by covalent bonding [91]. point shift) induced by target biomolecules. One is an
The π-network in graphene provides an excellent platform for electrostatic gating mechanism, and the other is surface transfer
anchoring π-conjugated molecules via a π-π stacking doping [11], [52], [70].
interaction [92], [93], which provides a non-covalent method to The ambipolar electric field effect of pristine graphene
modify graphene while preserving its excellent electrical enables any increase in gate voltage to induce a rapid increase
properties. Additionally, the high specific surface area of
Fig. 3. Two types of FET-based GBB: (a) back gate FET and (b) liquid gate FET (reproduced by permission of The Royal Society of Chemistry [58]).
in conductivity, and the converse can be used as a sensing efficient electron transfer that induces more intermediate
mechanism. The position of the Fermi level can also be molecules to higher excited electron states per unit time. This
changed by the gate voltage [63]. For an electrostatic gating property, combined with the large specific surface area and
mechanism, the electrical properties of graphene would be easily functionalized surface, can provide a large number of
influenced by the (p-/n-) type of graphene and the type of the sites for luminophores and more binding sites for target
charged species or analyte (negative/positive). For instance, for biomolecules, which all effectively increase the resulting ECL
a p-type graphene-FET, the attachment of a negatively (or signal.
positively) charged species will induce an increase (or The second mechanism that can be used to develop a GBB is
decrease) in hole density and thus the conductivity of the based on the capability of GO to quench ECL owing to
graphene [31], [97], [99], [100]. resonance energy transfer [112]. Wang et al. [113] studied the
The second sensing mechanism, surface transfer doping, relationship between ECL intensity and the amount of graphene
occurs through electron exchanges between graphene and in a graphene-CdS nanocomposite, and they showed competing
dopants [11], [52], [70], [101], [102]. In the experiment mechanisms. There is a critical value below which ECL
performed by Dong et al. [11], a negatively charged target intensity will increase as the amount of graphene increases;
DNA hybridized to a probe DNA anchored to the graphene however, when the amount of graphene is larger than this
surface induced a left-shift in the gate voltage, which critical value, the ECL intensity will decrease even as the
corresponds to the minimum conductance (V g,min). This result amount of graphene is further increased. The authors explained
cannot be explained by the electrostatic gating effect; if this that this trend was due to the blackbody effect that also
were the case, this hybridization process would induce a appeared in experiments with a low-density nanotube array
right-shift in Vg,min. The authors explained this left-shift as an [114]. However, this competition between ECL enhancement
electron transfer from the DNA to the graphene. Kwak et al. and ECL quenching of graphene should be further studied.
[101] also elucidated the H2O2-induced left-shift of the Dirac Fan et al. [115] observed that GO nanoparticles could
point by charge transfer from the H2O2 to the graphene. enhance the ECL intensity of tri-n-propylamine. They
In addition to the electrostatic gating mechanism and surface explained this reaction as ECL emission from GO. In contrast,
transfer doping influencing the electric properties of the Guo et al. [108] noted that GO could not generate ECL. Further
FET-based GBB, the binding of the target biomolecule to the study into ECL enhancement methods and ECL quenching
graphene surface or to the functionalized surface might also mechanisms is thus needed.
increase the number of electron scattering centers, resulting in 2) Fluorescence
decreased mobility of the charge carriers [31]. Because both graphene and GO have fluorescence and
Kwak et al. [101] studied the influence of the drain-source fluorescence-quenching capabilities [74], [82], [83], [116],
voltage (VDS) on the Dirac point in a liquid-gate (PBS-buffer) fluorescence-based GBBs can be separated into two categories.
FET GBB. The results showed that as VDS increased, the Dirac The first category, which is based on detecting graphene/GO
point appeared to right-shift. The authors also measured the fluorescence, can be further divided into two subcategories
influence of the electrochemical effect on their liquid-gate FET based on the different fluorescence-quenching
by monitoring the gate leakage current. mechanisms—namely, by photo-induced charge transfer
between GO and the target biomolecule [116] and fluorescence
B. Photon/Phonon Transfer
resonance energy transfer from GO to a quencher such as Au
1) Electrochemiluminescence (ECL) nanoparticles [15]. A generic illustration of a GBB based on
Since electrochemiluminescence (ECL) was first developed fluorescence detection is illustrated in Fig. 4.
in the 1960s, this detection technique has rapidly matured into a On the basis of using different fluorescence donors/signal
powerful analytical technique. Excellent reviews related to
ECL have been published [103]–[105]. Here, we focus on how
graphene can enhance the ECL detection mechanism.
ECL can be produced by two general mechanisms:
annihilation ECL and co-reactant ECL. In both cases, at the
electrode surface, electrochemically generated intermediate
complexes undergo an electron-transfer reaction that promotes
electrons into higher excited states that emit light as they fall
back to lower electron states [104], [105].
Graphene/GO has introduced two seemingly opposing
mechanisms: ECL enhancement [106]–[111] and ECL
quenching [112]. The intensity of the ECL can be enhanced by
increasing the individual quantum yield of the luminophore,
which is usually limited by electron transfer and the number of
linked luminophores [104]. Hence, graphene is an attractive
option because of its excellent intrinsic electrical properties. Its Fig. 4. Illustration of the basic structure of a GBB using fluorescence
high electric mobility and electrical conductivity promote detection.
reporters, this second subcategory using graphene/GO as an IV. GRAPHENE-BASED GLUCOSE SENSORS
energy quencher can be further subdivided into organic Selected glucose biosensors from the literature survey are
fluorophores [17], [117] or nanomaterials such as CdTe summarized in Table I.
quantum dots [118]–[121] and silver nanoclusters [122]. The
quenching mechanism of graphene/GO in these two cases can A. Enzyme-mediated Biosensors
be described as fluorescence resonance energy transfer [17],
[117], [120], [121].
TABLE I
GRAPHENE-BASED BIOLOGICAL SENSORS: GLUCOSE SENSORS
Detection Linear Detection Range (LDR)
Graphene
Technique (or LOD Year/
Production Sensor Structure
Measured (μM) Range R Ref.
Process
Variables)
Hydrazine/Ammonia CV PVP-Protected 2 – 14 mM 0.994 2009
-RGO RGO/GOD/PFIL/GCE [7]
TEGO/OTEG CV GOD/RGO/CHI/GCE 20 0.08 – 12 mM 0.9993 2009
SEN = 37.93μA/(mM·cm2) [8]
TEGO/OTEG I-T GOD/Pt NP/RGO/CHI/GCE 0.6 sub-μM – 5 mM 2009
[9]
Hydrazine CV GOD/RGO/APTES/GCE 0 – 24 mM 2009
vapor-RGO [6]
Hydrazine-RGO CV GOD/AuNP/RGO/CHI/GCE 180 LDR = 2 – 10 mM (at -0.2 V) 0.999 2010
LDR = 2 – 14 mM (at 0.5 V) 0.999 [19]
Hydrazine I-T GOD/RGO/Ppy/GCE 3 ± 0.5 2  10-3 – 0.04 mM 0.9976 2010
hydrate-RGO [37]
CVD FET GOD/modified-G ~ 100 2010
[12]
GO-COOH A GO-COOH; 1 1  10-3 – 0.02 mM 2010
colorimetric GOD [16]
method
N-doped RGO I-T GOD/N-doped RGO-CHI/GCE 10 0.1 – 1.1 mM 0.998 2010
(in the [25]
presence of
interference
)
Hydrazine-RGO I-T (PEI/GOD)m-(PEI/PAA-RGO)n/GC 168 LDR: within 10 mM R2 = 0.999 2010
E SEN = 0.261μA/(mM·cm2) [123]
I-T Nafion/GOD/RGO-AuNP/GCE 1 Up to 30 mM 2010
[27]
Hydrazine/Ammonia I-T GOD/RGO-IL/AuE 376 LDR = 2 – 20 mM 2010
-RGO SEN = 0.64 μA/mM [124]
Hydrazine-RGO CV GOD-RGO/GCE 10 ± 2 LDR = 0.1 – 10 mM 2010
SEN = 110 ± 3μA/(mM·cm2) [26]
Sodium I-T Au-RGO-GOD-Nafion/GCE 5 0.015 – 5.8 mM 0.9997 2010
borohydride-RGO [125]
I-T GOD-GO/Pt electrode LDR: Up to 22 mM 2010
SEN = 8.045 mA/(M·cm2) [126]
Hydrazine/Ammonia ECL intensity GOD/RGO/Nafion/GCE 1 2  10-3 – 0.1 mM 0.9972 2010
-RGO [127]
Electrochemically-R I-T GOD/RGO/IL-SPE 1.0 LDR = 5  10-3 – 10 mM 2011

GO SEN = 22.78 μA/(mM·cm2) [128]
Hydrazine-RGO GOD/AuNP/RGO-IL/GCE 130 SEN = 0.16 μA/mM 2011
[129]
I-T GOD/PB/GO/CHI/GCE 0.343 LDR = 0.1 – 13.5 mM 0.9988 2011
SEN = 15.28 μA/(mM·cm2) [130]
Electrochemically-R DPV GOD/Au-PdNP/RGO/GCE 6.9 LDR = 0.5 – 3.5 mM R2 = 0.99 2011
GO SEN = 266.6 μA/(mM·cm2) [131]
CV GOD/CdS-G/GCE 700 LDR = 2.0 – 16.0 mM R2 = 0.996 2011
SEN = 1.76 μA/(mM·cm2) [132]
Hydrazine-RGO CV GOD/poly(ViBuIm+Br−)-RGO/GCE 267 LDR = 0.8 – 20.0 mM 0.992 2011
SEN = 0.767 A/(mM·cm2) [133]
Hydrazine I-T PdNP/Nafion-RGO/GCE 1 0.01 – 5.00 mM 0.998 2011
hydrate-RGO [45]
CV GOD/AgNP/SiO2/GO/GCE 310 2 – 12 mM 0.996 2011
[134]
Hydrazine I-T GOD/PdNP/CHI-RGO/GCE 0.2 LDR = 1  10-3 – 1 mM 0.991 2011
hydrate-RGO SEN = 31.2 μA/(mM·cm2) [135]
CHI-RGO CV GOD/CHI-RGO/GCE 20 2 – 22 mM 0.9987 2011
[136]
Unzipping-MWCNT CV GOD/FeTMPyP/RGO-NRB/GCE 200 LDR = 0.5 – 10.0 mM 2011
s SEN = 17.3 μA /(mM·cm2) [137]

Electrochemically-R
GO
Electrochemically-R I-T PtNi NP/RGO/GCE 10 LDR: up to 35 mM 2011
GO SEN = 20.42 μA/(mM·cm2) [138]
Hydrazine-RGO I-T GOD-RGO/Nafion 170 LDR = 2 – 20 mM 2011
SEN = 3.8 μA/(mM·cm2) [139]
Sodium I-T GOD/AuNP/CdTe-CdS/RGO-AuN 3 × 10-6 LDR = 1  10-8 – 1  10-5 mM 0.9999 2011
borohydride-RGO P/AuE SEN = 5762.8 nA/(nM·cm2) [140]
Hydrazine-RGO I-T GOD/Hemin-RGO/GCE 0.3 5  10-4 – 0.4 mM 0.9970 2011
Colorimetric 0.03 5  10-5 – 0.5 mM 0.9927 [141]
method
I-T GOD/GO/CHI-Ferrocene/GCE 7.6 LDR = 0.02 – 6.78 mM 2011
SEN = 10 μA/(mM·cm2) [142]
Hydrazine/Ammonia Ni(II)-Quercetin/RGO/GCE 0.5 LDR = 3  10-3 – 0.9 mM 2011
-RGO SEN = 187 nA/μM [143]
QCM ConA/DexP/G/Au Probe 5.0 0.01 – 7.50 mM R2 = 0.996 2011
displacement- [144]
based sensor
I-T GOD/AuNP/G/GCE 35 0.1 – 10.0 mM 0.999 2011
[145]
G-Carbon CV GOD/G-Carbon nanospheres/GCE 100 0.4 – 20.0 mM 0.9909 2011
nanospheres [146]
Hydrazine-RGO CV AuNP/GOD/DNA-RGO/GCE 0.3 LDR = 8  10-4 – 0.05 mM 0.9960 2011
SEN = 2.4 × 104 μA/mM [147]
Hydrazine/Ammonia I-T RGO-Ni(OH)2/GCE 0.6 LDR = 2  10-3 – 3.1 mM 0.9987 2011
-RGO SEN = 11.43 μA/(mM·cm2) [148]
GO Fluorescence UCP/ConA/CHI/GO 0.025 0.56 – 2.00 μM 2011
intensity [149]
SnCl2-RGO CV Au-PtNP/(RGO/SnO2)/GCE LDR = 2 – 20 mM 0.999 2011
SEN = 20.3 μA/mM [150]
LSV AuNP/GO-THI/GCE 0.05 LDR1 = 2  10-4 – 2  10-3 mM 2012
LDR2 = 2  10-3 – 2.2  10-2 mM [151]
Hydrazine-RGO I-T CuNP/RGO/GCE 0.5 up to 4.5 mM 0.9958 2012
[152]
Electrochemically-R I-T CuNP/ROG/GCE 0.2 LDR = 5  10-3 – 1.4 mM 0.998 2012
OG SEN = 607 μA/mM [153]
I-T GOD/ConA/GOD/AuNP/CHI-PB- 10 LDR = 2.5  10-2 – 3.2 mM 0.9979 2012
RGO/GCE SEN = 58.7 mA/(M·cm2) [154]
RGO I-T GOD/PtNP/polyaniline/RGO/GCE 0.18 LDR = 1  10-3 – 4.35 mM 0.998 2012
SEN = 131.7 μA/(mM·cm2) [155]
(75 wt% Pt loading)
Hydrazine-RGO Colorimetric GOD/H3PW12O40/RGO 0.1 1  10-4 – 0.1 mM 0.99113 2012
assay [156]
CVD FET GOD/G 3.3 × 103 3.3 – 10.9 mM 2012
[101]
Thermally-RGO I-T DNA/NiO/RGO/GCE 2.5 LDR = 1  10-3 – 0.2 mM 0.999 2012
LDR = 1  10-3 – 8 mM 0.992 [157]
CVD I-T,CV Cobalt oxide/G < 10 0.05 – 0.30 mM 0.989 2012
[158]
Colorimetric GO/Fe3O4; 0.74 2  10-3 – 0.2 mM 0.9983 2012
detection TMB (Color-label) [159]
I-T FGGE 10 LDR =0.5 – 7.5 mM 0.9962 2012
SEN = 28.4 μA/(mM·cm2) [160]
Thermally-RGO Amperometri GOD/TiO2-RGO/GCE LDR = 0 – 8 mM 2012
c response SEN = 6.2 μA/(mM·cm2) [161]
I-T GOD/GO/Pt-black microelectrode 1 LDR = 1 μM – 2 mM 0.999 2012
[162]
Hydrazine/Ammonia CV GOD/RGO-Pt/Nafion/HOPG 25 Up to 15 mM 2012
-RGO electrode [163]
Modified-RGO I-T (IL-RGO/Sulfonic 3.33 LDR = 0.01 – 0.5 mM 0.9922 2012

acid-RGO)n/GOD/Nafion SEN = 0.0718 ± 0.00648 [164]
nA/μM
CVD I-T Nafion/GOD/AuNP/G/GCE 4 0.010 – 0.366 mM 0.9995 ± 2012
0.002 [165]
Hydrazine-RGO CV IL-RGO-GOD/GCE 2 – 16 mM 0.997 2012
[166]
Hydrazine I-T CHI/GOD/RGO-PAMAM-AgNP/G 4.5 LDR = 0.032 – 1.890 mM 0.996 2012
hydrate-RGO CE SEN = 75.72 μA/(mM·cm2) [167]
Hydrazine-RGO I-T Ni(OH)2-RGO/GCE 0.6 LDR = 1  10-3 – 0.01 mM 0.9990 2012
SEN = 494 μA/(mM·cm2) [168]
LDR = 0.01 – 1 mM 0.9990

SEN = 328 μA/(mM·cm2)
Hydrazine-RGO I-T Ni-RGO/GCE LDR = 1  10-3 – 0.11 mM R2 = 0.9939 2012
SEN = 813 μA/(mM·cm2) [169]
LDR = 1  10-3 – 0.01 mM R2 = 0.9983
Current CV GOD/G/Nafion/GCE 30 0.5 – 14 mM 0.9959 2012
arc-discharge [170]
method
Hydrazine/Ammonia I-T GOD/Metal coordination 5  10-3 LDR1 = 5  10-5 – 0.1 mM 0.993 2012
-RGO polymer-RGO/GCE LDR2 = 0.1 – 1 mM 0.998 [171]
Electrochemically-R I-T Nafion/NiO NF-RGO/GCE 0.77 LDR = 0.002 – 0.6 mM 0.9978 2012
GO SEN = 1100 μA/(mM·cm2) [172]
Thermally-RGO CV,I-T GOD/RGO-CNT/GCE LDR: up to 8 mM 2012
under strongly SEN = 1.27 μA/(mM·cm2) [173]
alkaline conditions
Oleic acid-RGO I-T CHI /GOD/RGO–TDN/GCE 4.8 LDR = 0.032 – 1.67 mM 0.997 2013
SEN = 35.8 μA/(mM·cm2) [174]
Hydrothermal-RGO Fluorescence APBA-GQDs 5 0.1 – 10 mM 0.999 2013
intensity [175]
Modified Hummers I-T CuO/GO/GCE 0.69 LDR = 2.79  10-3 – 2.03 mM 0.9962 2013
Method SEN = 262.52 μA/(mM·cm2) [176]
NaBH4 -RGO Chemilumine Pt-Co/G LDR1 = 3.33 – 27.75  10-3 mM 2013
scence LDR2 = 2.04 – 2.1 mg/mL [177]
intensity
I-T NiO NP/GO/GCE 1 LDR = 3.13 10-3 – 3.05 mM 2013
SEN = 1087 μA/(mM·cm2) [178]
I-T Spherical Cu2O/NiOx/GO/GCE 0.4 LDR1 = 2  10-3 – 0.87 mM R2 = 0.9943 2013
LDR2 = 0.87 – 2.95 mM R2 = 0.9943 [179]
Electrochemically-R CV RGO–GOD/GCE 20 LDR = 2 – 18 mM 0.9978 2013
OG SEN = 7 μA/(mM·cm2) [180]
Modified Hummers EIS ConA-DexP/GO 0.34 LDR = 5  10-3 – 9 mM 2013
method SEN = 3.5 kΩ/(mM·cm2) [181]
Chemilumine GOD/GO 44 0.05 – 5 mM 2013
scence [182]
intensity
Modified Hummers SERS GOD/Ag-Au NP/GO 330 2 – 6 mM 2013
Method [183]
NaBH4 -RGO DPV RGO-CNT-ZnO/GOD/GCE 4.5 (± 0.08) LDR = 10  10-3 – 6.5 mM R2 = 0.983 2014
SEN = 5.362 (± 0.072) μA/(mM [184]
·cm2)
Hydrazine/Ammonia DPV RGO/polyaniline/Au 0.1 0.2 – 11.2 mM 0.9995 2014
-RGO NP/GOD/SPCE [185]
Hydrazine/Ammonia I-T Co2Nx/nitrogen-doped RGO 6.93 LDR = 10  10-3 – 4.75 mM 0.994 2014
-RGO SEN = 1.167 mA/(mM·cm2) [186]
Electrochemically-R DPV GOD-poly(L-lysine)/RGO-ZrO2/ 0.13 (± LDR = 0.29 – 14 mM 0.992 2014
GO GCE 0.021) × SEN = 11.65 (± 0.17) μA/(mM [187]
103 ·cm2)
CVD I-T Ni(OH)2/3D graphene 0.34 LDR = 1  10-3 – 1.17 mM 0.999 2014
SEN = 2.65 mA/(mM·cm2) [188]
Electrochemically-R I-T NiO/Pt/RGO/GCE 0.2 LDR = 0.05 – 5.66 mM 0.9996 2014
OG SEN = 668.2 μA/(mM·cm2) [189]
CV GOD/Au NP-RGO/GCE 10 LDR = 1 – 8 mM R2 = 0.9885 2014
SEN = 0.835 μA/mM [190]
Longitudinal Chronoamper Au NP/GO nanoribbon/carbon sheet 5 LDR1 = 0.5  10-3 – 4.92 mM R1 = 0.9989 2014
unzipping of ometry substrate SEN1 = 59.1 μA/(mM·cm2) R2 = 0.9936 [191]
MWCNTs LDR2 = 4.92 – 10 mM
SEN2 = 31.4 μA/(mM·cm2)
Longitudinal LSV Au NP/GO nanoribbon/carbon sheet 0.5 LDR = 0.5  10-3 – 10 mM 2014
unzipping of substrate SEN = 57.1 μA/(mM·cm2) [191]
MWCNTs
GOD/Pt/RGO/TiO2 LDR = 0.1 – 8 mM 2014
SEN = 0.94 μA/(mM·cm2) [192]
Microwave-assisted I-T CuO NP/S-doped G/GCE 0.08 LDR = 0.1 – 10.5 mM 0.998 2015
solvothermal method SEN = 1298.6 μA/(mM·cm2) [193]
Hummers method I-T Ag NP/GO 4 LDR = 1 – 14 mM R2 = 0.9741 2015
SEN = 11 μA/(mM·cm2·μg) [194]
Ascorbic Acid-RGO CV RGO aerogel-Au NP/Au NP/GCE 4 LDR = 0.01 – 10 mM 0.998 2015
[195]
Hydrazine-RGO I-T GOD/Pt NP-RGO/Nafion/GCE 2 LDR = 0.005 – 1.1 mM 0.9989 2015

SEN = 20.31 μA/(mM·cm2) [196]
Hydrazine/Ammonia I-T PVP/G nanosheets/Ni NP/CHI 0.03 LDR = 0.1  10-3 – 0.5 mM 0.9953 2015
-RGO SEN = 103.8 μA/(mM·cm2) [197]
Notation:
G = Graphene CV = Cyclic Voltammetry
GO = Graphene Oxide NP = Nanoparticles
NF = Nanofibers PB = Prussian Blue
RT = Response Time I-T = Current-Time
CHI = Chitosan CVD = Chemical Vapor Deposition
DPV = Differential Pulse Voltammetry GCE = Glassy Carbon Electrode
GOD = Glucose Oxidase Gqds = Graphene Quantum Dots
LSV = Linear Sweep Voltammetry PAA = Poly(acrylic acid)
PEI = Poly(ethyleneimine) Ppy = Polypyrrole
PVP = Poly(N-vinylpyrrolidone) QCM = Quartz Crystal Microbalance
Rgo = Reduced Graphene Oxide Sen = Sensitivity
THI = Thionine TDN = Titanium Dioxide Nanocluster
TMB = 3, 3, 5, 5-Tetramethylbenzidine UCP = Upconverting Phosphors
ConA = Concanavalin A APBA = 3-Aminobenzeneboronic Acid
DexP = 1,2-Epoxy-3-phenoxypropane-derivated dextran FGGE = functionalized graphene modified graphite electrode
SPCE = Screen-Printed Carbon Electrode HOPG = Highly Oriented Pyrolytic Graphite
OTEG = Oxidation and Thermal Expansion of Graphite [198] PFIL = Polyethylenimine-Functionalized Ionic Liquid
SERS = Surface-enhanced Raman spectroscopy TEGO = Thermal Exfoliation Of Graphite Oxide [199]
APTES = 3-Aminopropyltriethoxysilane FeTMPyP = Iron(III) meso-tetrakis(N-methylpyridinum-4-yl) porphyrin
poly(ViBuIm+Br−) = Poly(1-vinyl-3-butylimidazolium bromide)
Enzyme use can improve the GBB’s specific detection electrocatalytic activity to H2O2 and further attached to GOD.
performance and the limit of detection (LOD). Enzymatic The amperometric response of this sensor to glucose had a
biosensors are based on the direct electron transfer (DET) linear range from 2 – 10 mM (at -0.2 V) and 2 – 14 mM (at 0.5
between redox enzymes and the electrode surface [8], [25]. V) with an LOD of 180 μM
Thus, accelerating the DET will greatly improve the sensitivity Like horseradish peroxidase (HRP), carboxyl modified GO
of this type of biosensor. Another point is to increase the (GO-COOH) showed an intrinsic peroxidase-like activity [16],
enzyme concentration. Because graphene has a high intrinsic [159], [200]. This quality can be used to catalyze a reaction
mobility of electrons and holes, high conductivity and specific between the peroxidase substrate 3,3,5,5-tetramethylbenzidine
surface area, it has many advantages in this type of biosensor. (TMB) in the presence of H2O2 to produce an observable
Kang et al. [8] used an RGO-CHI nanocomposite to modify blue-colored reaction [16], [159]. Based on this principle, Song
GCE that had a high loading of glucose oxidase (GOD) (1.12 × et al. [16] designed a colorimetric method for glucose
10-9 mol/cm2). A linear detection range (0.08 – 12 mM) with an detection. By detecting this catalytic reaction via monitoring
LOD of 0.02 mM was obtained. To sufficiently disperse the the change in TMB absorbance at 652 nm, glucose can be
RGO and immobilize the negatively charged GOD, Shan et al. detected linearly in the range of 1 × 10 -6 – 2 × 10-5 mol/L with
[7] introduced a polyethylenimine-functionalized ionic liquid an LOD of 1 × 10-6 mol/L. Dong et al. [159] also developed a
(PFIL), with a high ionic conductivity, to design a colorimetric method to detect glucose based on a similar
polyvinylpyrrolidone (PVP)-protected principle (e.g., also monitoring the absorbance of converted
RGO/GOD/PFIL-modified GCE. The linear detection range of TMB). They introduced a GO-Fe3O4 magnetic nanocomposite,
this biosensor for glucose was 2 – 14 mM, with a good which can be effectively separated using a strong magnetic
reproducibility (the relative standard deviation (RSD) was 3.2 field, into their biosensor. Both Fe3O4 NP [201] and GO have
% for 10 successive measurements at 6 mM glucose). The an intrinsic enzymatic activity similar to that of HRP, and the
response current changed over time (increasing by 3.8 % of the GO-Fe3O4 enhanced this property. The linear detection range
initial response after 3 days and by 4.9 % after 1 week). Wang was 2 – 200 μM with an LOD of 0.74 μM [159].
et al. [6] reduced GO, which adhered to the surface of a To further leverage graphene’s intrinsic advantage as a
3-aminopropyltriethoxysilane (APTES)-modified GCE biosensor, Wang et al. [25] doped RGO with nitrogen (N-RGO)
(APTES-GCE), using an electrochemical method. After using a nitrogen plasma treatment. They noted that the resulting
immobilizing GOD on the electrode by covalent bonding N-RGO has a high electrocatalytic activity for reducing H2O2
between N-succinimidyl acrylate and GOD, this biosensor [25], [202] and fast EDT kinetics for GOD by increasing the
showed a linear detection range of 0 – 24 mM. density of electronic states around the Fermi level. All of these
Wu et al. [9] modified RGO/CHI/GCE with PtNP by using factors contributed to enhancing the reductive current by as
potentiostatic electrodeposition, which enzymatically degrades much as ~20-fold more than a bare GCE. A biosensor with a
hydrogen peroxide. An LOD of 0.6 μM with a linear detection structure of GOD/N-RGO-CHI/GCE was built to detect
range from sub-μM to 5 mM was obtained. Instead of using glucose with a linear detection range from 0.1 – 1.1 mM and an
PtNP, Shan et al. [19] introduced AuNP to modify an LOD of 0.01 mM [25].
RGO/CHI/gold electrode, which also showed good By using CVD graphene, Kwak et al. [101] designed a liquid
gate FET biosensor on a flexible polyethyleneterephthalate respectively).

(PET) substrate. After functionalizing with GOD, this FET As shown in Table II, using a combination of ECL and labels
biosensor was used to detect glucose with a linear detection has the advantage of improving the LOD to an extremely low
range of 3.3 – 10.9 mM with an LOD of ~ 3.3 mM. After the level and helps increase the selectivity. Particularly for
sensor was flexibly deformed, the transfer curves change little, detection of tumor markers, a biosensor with sufficient
but the Dirac points shifted left and the current levels declined sensitivity and specificity will minimize measurement errors
slightly [101]. due to the preparation protocol. Enzyme-mediated and
enzyme-free sensors have their own advantages. A glucose
B. Non-enzyme-mediated Biosensors
biosensor with enzyme can decrease the detection limit to 10 -6
By using GO as an energy acceptor and upconverting μM. However, the advantage of enzyme-induced enhancement
phosphors (UCPs) acting as energy donors, Zhang et al. [149] in performance can also be weakened by a complex preparation
reported a biosensor based on fluorescence resonance energy protocol and storage requirements. Therefore, an enzyme-free
transfer (FRET) to detect glucose with a linear detection range biosensor would be more suitable for portable detection
from 0.56 – 2.0 μM and an LOD of 0.025 μM. devices.
The majority of GBBs with the lowest reported LOD were
V. DISCUSSION OF THE SURVEY RESULTS published very recently (Table II). These results showed that
The parameters usually used to directly evaluate and lowering the LOD can be a target for researchers. For certain
compare a given GBB’s performance are the LOD, linear practical situations (e.g., clinical diagnostics), a low LOD is
detection range (LDR), sensitivity, selectivity, reproducibility, essential, but another important factor that influences the
stability, recovery, and response time. We compiled and listed practical application of a biosensor is to have a sufficiently
the minimum LOD and maximum upper limit of the LDR for broad linear detection range. The biosensors in Table III are
each type of GBB (shown in Table II and Table III, summarized by the maximum upper limit of their LDR.
TABLE II
THE MINIMUM LOD FOR EACH TYPE OF GBB
Production Detection Technique
Analyte LOD LDR Year/Ref.
Process (or Variables)
AFP ECL Label-based 2 × 10-5 pg/mL 5 × 10-8 – 5 × 10-4 ng/mL 2012 [203]
CEA ECL Label-based 2 × 10-3 pg/mL 5 × 10-6 – 5 × 10-4 ng/mL 2012 [204]
PSA Conductance Label-free 4 × 10-4 pg/mL 4 × 10-7 – 4 × 103 ng/mL 2012 [95]
IgG DPV Label-based 5 × 10-4 pg/mL 5.0 × 10-7 – 10 ng/mL 2011 [205]
Thrombin ECL Label-based 3.3 × 10-4 pM 1 × 10-6 – 1 nM 2012 [110]
DNA DPV Label-free 9.4 × 10 pM
-9
1 × 10-7 – 1× 107 nM 2012 [206]
Glucose I-T Enzyme-based 3 × 10-6 μM 1 × 10-8 – 1 × 10-5 mM 2011 [140]
H2O2 I-T Enzyme-free 5 × 10-3 μM 5 – 4 × 103 μM 2012 [207]
Dopamine SWV Label-free 1.98 × 10 μM
-6
7 × 10-6 – 0.09 μM 2012 [208]
TABLE III
THE MAXIMUM UPPER LIMIT OF THE LDR FOR EACH TYPE OF GBB
Production Detection Technique
Analyte LOD LDR Year/Ref.
Process (or Variables)
AFP DPV Label-based 5 pg/mL 0.05 – 400 ng/mL 2011 [209]
CEA CV Label-based 10 pg/mL 0.05 – 350 ng/mL 2010 [20]
PSA Conductance Label-free 4 × 10-4 pg/mL 4 × 10-7 – 4 × 103 ng/mL 2012 [95]
IgG FET Label-free 2 × 103 pg/mL 2 – 2 × 104 ng/mL 2010 [31]
Thrombin SPR angle Label-free 50 pM 0.08 – 200 nM 2011 [210]
DNA DPV Label-free 9.4 × 10-9 pM 1 × 10-7 – 1× 107 nM 2012 [206]
Glucose I-T Enzyme-free 10 μM Up to 35 mM 2011 [138]
H2O2 I-T Enzyme-free 4 μM 100 – 2.6 × 105 μM 2011 [134]
Dopamine CV Label-free 120 μM 400 – 6 × 103 μM 2010 [211]
A comparison of each type of GBB reveals that the For reviewing the percentage of each sensor mechanism
electrochemical-based mechanism is the most researched elaborated in Section III, the percentage of papers reported
method for detecting biomolecules, as shown in Fig. 5 (a). This using each type of sensor from our survey results is shown in
figure also summarizes which type of detection mechanism was Fig. 5 (b), which also illustrates the development trends to some
used in each GBB reported in our survey results. For the degree. Owing to their high sensitivity in detecting
detection of a certain target biomolecule, not all detection electroactive molecules, electrochemical GBBs are the most
mechanisms are appropriate. The electrochemical-based popular type, as shown in Table II. The ECL-based biosensors
mechanism has shown its general appeal in each category of are also a popular type with the advantage of their ability to
biosensors (see Table II and Table III), but this may be detect protein molecules with great sensitivity. FET-based
deceiving because other detection mechanisms are not as well biosensors have unique advantages because they can be
developed. integrated with mature IC fabrication technology.
Fig. 5. Based on our literature survey results, (a) the percentages of each detection mechanism as a function of target biomolecule for each type of biosensor;
(b) the percentages of each type of biosensor (separated by mechanism) listed in the tables.
To accurately characterize each detection mechanism, many associated enhancement mechanisms have been
reproducibility and stability are two key parameters for a GBB developed. These enhancement mechanisms might also be
in practical applications. The data for evaluating these two applied to GBBs. To the best of our knowledge, a photon
parameters will change with changes in analyte concentrations, response-based GBB using the photoelectric effect of graphene
the number of detection cycles, the number of available has not yet been developed. Perhaps this sensing modality
biosensors, the time between two measurements, storage time warrants future research.
and storage temperature. However, no universal standard exists Given the explosion in research activities related to GBBs
to constrain these conditions. From this survey result, however, and the subsequent dramatic increase in published results, one
researchers reported coefficients of variation/RSD below 5 – 10 review cannot possibly include all relevant subcategories of
% and were able to retain at least 90 % of the GBB’s initial GBBs. This review is intended to summarize only the major
response signal after 1 month (or longer) of storage. trends and to discuss examples of the prominent sensing
modalities of GBBs.
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Feifei WANG received his B. Eng.

degree from the Agriculture University of
Hebei, China, in 2011. He is currently
working toward a Ph.D. at the State Key
Laboratory of Robotics, Shenyang
Institute of Automation, Chinese
Academy of Sciences, Shenyang, China.
His research interests include
OEHK-based micro/nano fabrication and
three-dimensional super-resolution imaging.
Lianqing LIU is a Professor at the State

Key Laboratory of Robotics, Shenyang
Institute of Automation, Chinese
Academy of Sciences. He received his B.
Eng. degree in automation from
Zhengzhou University and his Ph.D. in
pattern recognition and intelligent systems
from the Shenyang Institute of
Automation, Chinese Academy of
Sciences, China.
Wen J. LI (F’11) is a Chair Professor in

the Department of Mechanical and
Biomedical Engineering, City University
of Hong Kong. He received BS and MS
degrees from the University of Southern
California, Los Angeles, in 1987 and
1989, respectively, and his Ph.D. in
aerospace engineering from the University
of California, Los Angeles, in 1997. From
September 1997 to October 2011, he was with the Department
of Mechanical and Automation Engineering, The Chinese
University of Hong Kong. His industrial experience includes
The Aerospace Corporation (El Segundo, CA), NASA Jet
Propulsion Laboratory (Pasadena, CA), and Silicon
Microstructures, Inc. (Fremont, CA). His research interests
include nanoscale fabrication, sensing, and manipulation. Dr.
Li served as the Editor-in-Chief of the IEEE Nanotechnology
Magazine from 2007 to 2013 and is President-Elect of the IEEE
Nanotechnology Council.

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Graphene-based Glucose Sensors:

C ARBON is the basis for life on Earth, so there is a certain

1) Preliminary searching incomplete results.

Electrochemically-R I-T GOD/RGO/IL-SPE 1.0 LDR = 5  10-3 – 10 mM 2011

s SEN = 17.3 μA /(mM·cm2) [137]

Modified-RGO I-T (IL-RGO/Sulfonic 3.33 LDR = 0.01 – 0.5 mM 0.9922 2012

LDR = 0.01 – 1 mM 0.9990

Hydrazine-RGO I-T GOD/Pt NP-RGO/Nafion/GCE 2 LDR = 0.005 – 1.1 mM 0.9989 2015

gate FET biosensor on a flexible polyethyleneterephthalate respectively).

Feifei WANG received his B. Eng.

Lianqing LIU is a Professor at the State

Wen J. LI (F’11) is a Chair Professor in

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