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mater.scichina.com link.springer.com Published online 29 December 2020 | https://doi.org/10.1007/s40843-020-1577-y
Sci China Mater 2021, 64(3): 739–747

An accurate, high-speed, portable bifunctional


electrical detector for COVID-19
1,2† 2† 2† 3 3 4 5
Guojun Ke , Dingkai Su , Yu Li , Yu Zhao , Honggang Wang , Wanjian Liu , Man Li ,
4 6 7 1* 3* 5*
Zhiting Yang , Fang Xiao , Yao Yuan , Fei Huang , Fanyang Mo , Peng Wang and
2*
Xuefeng Guo

ABSTRACT Coronavirus disease 2019 (COVID-19), caused INTRODUCTION


by SARS-CoV-2, has rapidly spread and caused a severe global In the past 20 years, humans have suffered several serious
pandemic. Because no specific drugs are available for COVID- epidemics from emerging viruses, such as SARS, swine
19 and few vaccines are available for SARS-CoV-2, accurate flu, Ebola, MERS and (most recently) SARS-CoV-2 [1–3].
and rapid diagnosis of COVID-19 has been the most crucial During each epidemic, an accurate, rapid, and accessible
measure to control this pandemic. Here, we developed a por-
molecular diagnostic test is highly essential for the control
and prevention of viral diseases. In particular, a cluster of
table bifunctional electrical detector based on graphene field-
cases of pneumonia resulting from a new coronavirus,
effect transistors for SARS-CoV-2 through either nucleic acid
SARS-CoV-2, was initially described in late 2019 (or
hybridization or antigen-antibody protein interaction, with
−1
earlier); this disease was later named as COVID-19 [4].
ultra-low limits of detection of ∼0.1 and ∼1 fg mL in phos- During the epidemic, the Chinese government and people
phate buffer saline, respectively. We validated our method by implemented approaches to aid in the diagnosis, isola-
assessment of RNA extracts from the oropharyngeal swabs of tion, and treatment of affected patients; they also strictly
ten COVID-19 patients and eight healthy subjects, and the restricted the flow of people, which constituted the so-
IgM/IgG antibodies from serum specimens of six COVID-19 called “people’s war”. Therefore, the outbreak and spread
patients and three healthy subjects. Here we show that the of COVID-19 in China was largely contained after ap-
diagnostic results are in excellent agreement with the findings proximately 1.5 months. However, in most other coun-
of polymerase chain reaction-based optical methods; they also tries, the disease has spread rapidly since late February
exhibit rapid detection speed (∼10 min for nucleic acid de- 2020; on 12 March 2020, the World Health Organization
tection and ∼5 min for immunoassay). Therefore, our assay
recognized the COVID-19 as a global pandemic [5]. As of
30 August 2020, over 24 million confirmed cases and
provides an efficient, accurate tool for high-throughput point-
838,924 deaths had been reported worldwide [6]. Thus
of-care testing.
far, effective specific drugs and vaccines specific for
Keywords: COVID-19, biosensor, nucleic acid detection, COVID-19 are unavailable; accordingly, rapid and accu-
immunoassay, point-of-care testing rate early detection of the COVID-19 causative virus (i.e.,

1
Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of
Technology, Guangzhou 510640, China
2
Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of
Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
3
Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100871, China
4
Qingdao Shuojing Biological Technology Co., Ltd., Qingdao 266112, China
5
Department of Pathology, Beijing Ditan Hospital Capital Medical University, Beijing 100015, China
6
Institute of Digital Economy Industry, Hangzhou 310015, China
7
Beijing Sylincom Technology Co., Ltd., Beijing 100081, China

These authors contributed equally to this work.
*
Corresponding authors (emails: [email protected] (Huang F); [email protected] (Mo F); [email protected] (Wang P);
[email protected] (Guo X))

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SARS-CoV-2) is expected to aid in controlling the on- the use of graphene FETs (G-FETs) for detection of RNA
going pandemic and support resumption of normal life from COVID-19 patients. As shown in Fig. 1, the de-
and economic conditions. tection system mainly consists of two parts: a plug-and-
SARS-CoV-2 mainly consists of a single-stranded RNA play packaged biosensor chip and a home-developed
genome (approximately 30,000 nucleotides) and four electrical measurement machine. Each packaged chip
structural proteins that include the spike surface glyco- contains ten G-FETs; specific ss-DNA probes are im-
protein (S), envelope protein (E), membrane protein (M), mobilized onto the graphene surface via π-π stacking of a
and nucleocapsid protein (N). There are generally two typical linker (1-pyrenebutyric acid N-hydro-
strategies for identification of the virus: (1) detection of xysuccinimide ester, PBASE) [22–24]. The unique feature
viral RNA and (2) detection of host antibodies. Currently, of this method is that the extent of hybridization between
the presence of specific viral RNA sequences in the pa- the ss-DNA probe and viral RNA can be directly con-
tient samples is considered definitive proof of COVID-19, verted to the current change of graphene channels with-
while immunodetection is regarded as a useful auxiliary out repetition of the PCR process. Our G-FET biosensors
technique. Reverse transcriptase quantitative polymerase exhibited excellent performance for the detection of the
chain reaction (RT-qPCR) is the primary method for RNA-dependent RNA polymerase (RdRp) gene target of
detection of nucleic acid-based genetic sequences from SARS-CoV-2 with an ultra-low limit of detection (LOD)
−1
any organism, including SARS-CoV-2 [7–11]. Because of of ∼0.1 fg mL . Furthermore, we validated our method
the labor-intensive sample preparation, which must be using clinical samples collected from ten patients with
conducted in a biological laboratory by professionals COVID-19 infection and eight healthy individuals, and
using specialized instruments, the typical turn-around the testing results were in full agreement with those of
time of the RT-qPCR method is longer than 24 h. The PCR-based optical methods. The entire process, pre-
complex sample preparation steps prior to testing might cluding the extraction of detection targets from or-
also reduce clinical sensitivity (the percentage of actual opharyngeal swabs, requires approximately 10 min.
positive individuals identified as positive individuals), Because it does not involve time-consuming PCR step nor
resulting in false negative results [12,13]. In addition, expensive instruments, our detection system has the po-
point-of-care detection is not accessible by the RT-qPCR tential to enable massive point-of-care testing of COVID-
method. Hence, the development of highly sensitive and 19, outside of specialized diagnostic laboratories, with the
specific nucleic acid testing methods, in combination with advantage of high sensitivity and low cost.
the characters of fewer sample preparation steps and the Notably, false negative results are inevitable in the
use of a portable detection instrument, is an extremely course of nucleic acid testing; thus, the use of im-
attractive prospect for accurate and rapid diagnosis of munodetection as an auxiliary technique is important in
COVID-19. the diagnosis of COVID-19 patients, especially those with
Biosensors, as an alternative and reliable solution for suspected diseases [25–28]. By replacing the ss-DNA
the analysis of biomolecules, has been drawing con- probe with a SARS-CoV-2 antigen protein, our detection
siderable research interest [14–17]. Among different system can also detect SARS-CoV-2 IgM and IgG anti-
−1
kinds of optical and electrical biosensing technologies bodies with an ultra-low LOD of ∼1 fg mL . Im-
currently avalaible, field-effect transisitor (FET)-based munoassays of serum specimens of six COVID-19
biosensors are particularly attractive because of their re- patients and three healthy subjects matched excellently
markable features, including no fluorescent labeling re- with those of PCR-based optical methods.
quirement, highly sensitive detection, mass-production
capability and low cost. The types of the FET biosensors EXPERIMENTAL SECTION
mainly include silicon nanowire FETs, graphene/carbon
nanotube FETs, organic FETs, compound-semiconductor Fabrication of graphene-based biosensor chips
FETs and ion sensitive FETs [18–20]. Graphene materials High-quality chemical vapor deposition (CVD)-grown
possess excellent properties of large surface area, high monolayer graphene on 4-inch silicon dioxide (300 nm)
electronic conductivity and high carrier mobility, making /Si wafer substrate was purchased from Jiangsu XFNANO
the graphene FET an ideal platform for biomolecule de- Materials Tech Co., Ltd. The source/drain metal electrode
tection [14,21]. arrays (8 nm Cr/600 nm Au) were patterned by photo-
In the present study, we developed an unprecedented lithography and thermal evaporation, followed by elec-
accurate, rapid, and portable electrical detector based on tron beam evaporation of 40-nm-thick SiO2 to passivate

740 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 March 2021 | Vol. 64 No. 3
SCIENCE CHINA Materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ARTICLES

Figure 1 Schematic diagram of the operation procedure of our G-FET-based biosensing system for COVID-19. Top left: Extraction of viral RNA.
Bottom left: from Si wafer to plug-and-play graphene packaged chips. Top right: home-developed portable electrical detector. Bottom right:
illustration of the ss-DNA probe immobilization onto graphene using a typical PBASE linker, followed by hybridization with an RNA target.

the electrode surface (Fig. S1a, b). comprising the S and N protein of SARS-CoV-2, de-
Then, the 4-inch G-FET wafer was packaged into bio- veloped by Qingdao Hightop Biotech Co., Ltd. (For S
sensor chips through Plastic Quad Flat Package (PQFP) protein, the receptor-binding domain (RBD) was chosen.
in the following steps: (1) cut into approximately 425 The coincidence rates of N protein to those of SARS or
small chips (4 mm × 4 mm); (2) bond the chip with MERS were ∼78.12% and ∼39.67%, respevtively. Although
QFP64 ceramic package (Fig. S1c); (3) cover the contact the coincidence rate bwteen SARS-CoV-2 and SARS is
point with glue to protect the electrical circuit. high, SARS has almost dissappeared. There are abuntant
antigenic determinants in N protein with high specificity,
Modification of the graphene surface which can avoid missing inspection. Therefore, the full
The freshly as-fabricated G-FET biosensor chips were length of N protein was chosen and recombined with the
−1
immersed in 1 mmol L PBASE (Sigma-Aldrich) in RBD domain of S protein.).
CH3CN at room temperature for 6 h, then rinsed several
times with CH3CN and dried using mild stream of N2 Surface characterization and electrical measurements
flow [22,23]. Subsequently, the PBASE-modified chips The morphology of the G-FET devices was determined by
−1
were exposed to either 10 μg mL ss-DNA probe (Beijing optical microscopy (Nikon Eclipse LV100 POL Micro-
−1
RuiBiotech Co., Ltd.) or 100 μg mL antigen protein in scope). Raman spectroscopy was performed on a confocal
PBS solution at room temperature overnight; they were Raman spectrograph (JY Horiba HR800) in the back-
then being dried by a mild stream of N2 gas, yielding ss- scattering geometry; the laser (532 nm) was focused on
DNA probe-immobilized chips and antigen protein-im- the sample by means of a 100× objective lens (numerical
mobilized chips, respectively. The antigen protein em- aperture (NA) = 0.9). Analysis of the chemical binding
ployed in this study was a recombinant protein component was determined by X-ray photoelectron

March 2021 | Vol. 64 No. 3 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 741
ARTICLES . . . . . . . . . . . . . . . . . . . . . . . . . SCIENCE CHINA Materials

spectroscopy (XPS, Kratos Analytical Ltd., AXIS Supra),


with the incident beam produced by an Al X-ray source
(150 W) and a pass energy of 160 eV. Surface roughness
analysis was conducted by atomic force microscopy
(AFM, Bruker, Dimension Icon with Nanoscope V con-
troller). Electrical characterizations, including the transfer
curves and current-voltage (ID-VD) curves, were carefully
carried out at room temperature using a Keysight B1500A
semiconductor device analyzer (direct-current measure-
ments) and a Karl Suss (PM5) manual probe station. IgG
antibody protein was purchased from Beijing Sino Bio-
logical Inc. (isoelectrical point of ∼6.47 and negetively
charged at pH 7).

Extraction of viral RNA and detection of clinical samples


RNA samples from both COVID-19 patients and healthy
subjects were extracted from oropharyngeal swabs using
QiAamp Viral RNA Mini Kits (Qiagene), which required
approximately about 15 min for each sample. The ex-
tracted RNA solution (25 μL) was directly added to the
packaged chip surface, and heated at 85°C for 9 min.
Afterwards, the chip was gently washed with deionized
(DI) water to remove the unbonded RNA and dried be-
fore measurements with our home-developed electrical
detector (Fig. S2). Similarly, for immunoassays, each
serum specimen (25 μL) was added to the packaged chip
surface at room temperature for 4 min; the surface was
rinsed with DI water and dried with a stream of N2 gas
before electrical measurements were taken.
Figure 2 Surface analyses of pristine, PBASE-modified, ss-DNA-im-
RESULTS AND DISCUSSION mobilized, and antigen-immobilized graphene using Raman spectro-
scopy, XPS, and AFM. (a) Optical image of a G-FET array in a packaged
biosensor chip. (b) Raman spectra of pristine and PBASE-modified
Surface characterization graphene. (c, d) High-resolution XPS spectra and enlarged N 1s region
Fig. 2a displays an optical image of the ten G-FETs in one for pristine and PBASE-modified graphene. (e–h) AFM images of
packaged biosensor chip. The dimensions of the sensing pristine graphene (e), PBASE-modified graphene (f), ss-DNA probe-
area are 40 μm × 8 μm (Length × Width) for each G-FET. immobilized graphene (g) and antigen protein-immobilized graphene
(h). Scale bar = 2 μm.
To avoid undesired adsorption of nucleic acids on the
surface of gold electrodes and reduce interference during
electrical measurements, the electrodes were protected by The single Lorentz type 2D peak and the high integrated
evaporation of an insulating layer of 40 nm SiO2. Details peak area ratio value of ∼2.52 between 2D and G peaks
of the fabrication process of a G-FET array and the indicated high-quality monolayer graphene [29]. While in
packaging procedure of the chip are provided in the the Raman spectrum of PBASE-modified graphene, D
EXPERIMENTAL SECTION and Supplementary in- and D’ peaks apparently appeared, stemming from the
formation. As displayed in Fig. 2b–d, Raman spectrum binding between the pyrene group and graphene. Fig. 2d
analysis and high-resolution XPS were performed to de- shows the comparison of the N 1s region before and after
monstrate that PBASE were efficiently modified onto the the PBASE functionalization of graphene, enlarged from
graphene surface. In the Raman spectrum of pristine the XPS spectrum (Fig. 2c). For pristine graphene, the
graphene, two typical major peaks (G and 2D peaks) were N 1s peak is nearly absent; the obviously increased in-
observed, which corresponded to the lattice vibration tensity of the N 1s peak after modification indicates
mode and second-order Raman scattering, respectively. successful immobilization of PBASE on the graphene

742 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 March 2021 | Vol. 64 No. 3
SCIENCE CHINA Materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ARTICLES

surface. phosphate buffer saline (PBS), with VD ranging from −50


We further exploited AFM to visualize the quality of to 50 mV (Fig. 3a, inset is the partially enlarged image).
surface functionalization. Fig. 2e–h are AFM images of The sequences of the ss-DNA probe, RdRp target, and
pristine graphene, PBASE-modified graphene, ss-DNA mismatched DNA are shown in Table S1. An excellent
probe-immobilized graphene, and antigen protein-im- linear relationship between ID and VD was observed over
mobilized graphene, respectively. The corresponding the entire VD scanning range. Therefore, the values of the
height profiles and surface roughness (RMS) of graphene ID change ratio, in comparison with the origin of ss-DNA
are depicted in Fig. S3. After PBASE assembly, the RMS probe-modified biosensors (ΔID/I0) at VD = 50 mV, was
of graphene slightly increased from ∼0.21 to ∼0.40 nm, extracted and plotted as a function of the concentration
further reaching ∼0.77 and ∼1.25 nm with following im- of RdRp target, as displayed in Fig. 3b. As the con-
mobilization of the ss-DNA probe and antigen protein, centration of RdRp target increased, the slope of the curve
respectively. The AFM results are in consistence with the gradually decreased, such that it reached a close equili-
larger antigen protein size, compared with the ss-DNA brium between the hybridization and electrostatic repul-
probe. These findings confirmed the successful mod- sion of ss-DNA probe and RdRp target at high
ification of graphene. concentrations. For control experiments, the G-FET
biosensor was exposed to different concentrations of a
Electrical characterization mismatched DNA chain of identical length of or to PBS
Transfer curves of G-FETs were also measured to confirm solution, a slight reduction in the value of ΔID/I0 was
efficient immobilization of the ss-DNA probe on the observed (Fig. S5), revealing that the ss-DNA probe-
graphene surface and to monitor the specific interaction modified biosensor was highly specific to its com-
between the ss-DNA probe and its complementary gene plementary RdRp target. Remarkably, our G-FET bio-
sequence (i.e., RdRp target). Ionic liquid as the dielectric sensor exhibited very high sensitivity with an LOD as low
−1
layer has been proven to constitute an effective strategy as ∼0.1 fg mL , which constituted approximately 1800
for modulation of charge transport in semiconductor copies per mL; this was comparable to the LOD of the
devices [30,31]. Here, we employed ionic liquid con- RT-qPCR method. Notably, our electrical method does
taining N,N-diethyl-N-(2-methoxyethyl)-N-methy- not require the amplification steps inherent to RT-qPCR;
lammonium bis(trifluoromethylsulfonyl)imide (DEME- it can also directly measure the gene target, which reduces
TFSI), to prepare an ionic liquid-gated FET (structure the delay for results and lowers the possibility of inter-
shown in Fig. S4a). For pristine graphene, the transfer ference. To examine the reusability of the G-FETs bio-
curve (Fig. S4b, black line) exhibits the typical ambipolar sensor, the ss-DNA probe-RdRp target hybridization and
character of graphene with the Dirac point localized at a dehybridization processes were conducted sequentially
gate voltage of ∼0.38 V (VDirac). The positive value of three times, as shown in Fig. 3e. The values of ΔID/I0 were
VDirac indicates that the graphene is p-doped, resulting ∼7.2%, ∼5.4%, and ∼4.4% for the first, second, and third
from chemical doping by the residues of the processing cycles, respectively, indicating that the G-FET biosensor
chemicals; this phenomenon is common in CVD-grown could be reused multiple times. The reusability of the
graphene processed via wet transfer [32]. After im- devices will enable cost reduction for each test, which is of
mobilization of the ss-DNA probe and hybridization with considerable importance to the future commercialization
the complementary RdRp target, the value of VDirac shifted of our product.
by ∼0.38 and ∼0.31 V, sequentially. These results are in In addition to nucleic acid detection, we investigated
consistence with findings reported in previous literatures the performance of antigen protein-modified G-FET
[33,34]. The transfer curve measurements of the pristine, biosensors in dynamic response to the SARS-CoV-2-
antigen protein-modified, and antibody-bound graphene specific IgG antibody protein. Similarly, the ID value of
show a similar tendency (Fig. S4c). the graphene channel increased gradually with increasing
IgG antibody protein concentration; a good linear re-
Sensitivity and reusability characterizations lationship was preserved with VD ranging from −50 to
−1
To evaluate the performance of the as-fabricated G-FET 50 mV, thereby providing an excellent LOD of ∼1 fg mL
biosensors, we measured the ID–VD curves of ss-DNA (Fig. 3c, d), which ranks the highest among all im-
probe-modified devices in response to various con- munodetection techniques and at least three orders of
centrations of fully complementary RdRp target (frag- magnitude higher than the immune colloidal gold tech-
ment of the RdRp gene sequence in SARS-CoV-2) in nique [25,28]. Collectively, these results indicated that our

March 2021 | Vol. 64 No. 3 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 743
ARTICLES . . . . . . . . . . . . . . . . . . . . . . . . . SCIENCE CHINA Materials

Figure 3 Sensitivity and reusability. (a, c) ID−VD curves of G-FET biosensors responding to different concentrations of RdRp target (a) and antibody
protein (c). Insets are partially enlarged curves. (b, d) Values of ΔID/I0 at VD = 50 mV extracted and plotted as a function of the concentration of RdRp
target (b) and antibody protein (d). (e) Hybridization and dehybridization cycles of the same device.

G-FET biosensors have the potential to rapidly and sen- performance of ss-DNA probe (RdRp gene) in detection
sitively detect both the gene RNA sequence of SARS- of viral RNA in clinical samples, we firstly developed a
CoV-2 and an IgG antibody protein specific for the virus, DNA-RNA in-site hybridization (RNA-ISH) method to
thus laying the foundation for the following clinical di- detect SARS-CoV-2 virus in tissue slides (Fig. S6). RNA-
agnostic assay. ISH is a non-amplification genetic test and a specific test
due to long probe design (100 bps in our RNA-ISH sys-
SARS-COV-2 detection from clinical samples tem). Fluorescent image (Fig. S6b) of the bronchial brush
Because our G-FET biosensors displayed excellent per- specimen of COVID-19 patients clearly indicated effec-
formance for detection of both SARS-CoV-2 RNA and tiveness of the RdRp probe in detection of viral RNA.
SARS-CoV-2-specific IgG antibody protein in PBS, we Afterwards, with ss-DNA probe 01, concentration-
tested their performance for detection of viral RNA in dependent measurements of viral RNA of clinical samples
clinical samples, which were provided by Beijing Ditan were perfomed, indicating an LOD of 1000 copies per mL
Hospital Capital Medical University. To evaluate the (Fig. S7). For clinical detection, both COVID-19 patients

744 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 March 2021 | Vol. 64 No. 3
SCIENCE CHINA Materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ARTICLES

and healthy subjects underwent sampling with orophar- qPCR approach, this method avoids the time-consuming
yngeal swabs, followed by the extraction of viral RNA. step of viral RNA amplification, in combination with the
Then, the viral RNA was diluted by 100 folds before home-developed portable detector. Future development
testing, without further sample processing. All tests of of our portable detector will be focused on point-of-care
clinical samples were performed using the packaged testing outside of specialized diagnostic laboratories,
biosensor chips in our home-developed portable COVID- which is of considerable importance for large-scale nu-
19 detector (Fig. S8). To achieve maximum accuracy, we cleic acid detection of COVID-19 and the ability of large
designed and integrated ten G-FETs in each packaged populations to return to work and school.
biosensor chip. The resistance of ss-DNA probe-modified As an auxiliary measure to complement nucleic acid
graphene was recorded as Rn (n = 1–10); the resistance detection of COVID-19, we assessed the efficiency of
was then recorded as R'n after the addition of clinical immunodetection by validating the performance of our
samples from either COVID-19 patient or healthy sub- method in the immunoassays of clinical samples. The
ject. Subsequently, the value of the relative change in serum specimens of six COVID-19 patients and three
resistance (R'n−Rn)/Rn of each graphene channel was healthy subjects (provided by Beijing Ditan Hospital
calculated and averaged (defined as ΔR/R0) as the basis to Capital Medical University) were diluted 100-fold before
determine whether a sample yielded positive or negative assessment using our G-FET biosensors. Analysis of each
results. Table 1 summarizes the test results of ten COV- sample required approximately 5 min. As summarized in
ID-19 patients and eight healthy subjects. The cutoff va- Table 2, the testing results were in excellent agreement,
lue of ΔR/R was set at −2; thus results with ΔR/R ≤ −2 indicating our biosensors provided accurate, rapid im-
were considered positive and those with ΔR/R > −2 were munological diagnosis of COVID-19.
considered negative. All ten COVID-19 patients were
correctly identified as COVID-19 infected individuals CONCLUSIONS
while eight healthy individuals were correctly identified as In summary, we developed an unprecedented reliable G-
healthy, indicating that our G-FET biosensors possess FET-based detection system for convenient diagnosis of
both high sensitivity and specificity in clinical diagnosis COVID-19, which consists of two parts: a plug-and-play
of COVID-19 patients. The detection process requires packaged biosensor chip and a portable electrical mea-
only 10 min after the extraction of viral RNA from or- surement machine. This detecting system exhibits ob-
opharyngeal swabs (Fig. S9). In comparison with the RT- vious advantages of high sensitivity, rapid speed (∼10 min

a
Table 1 Nucleic acid analysis of COVID-19 patients and healthy subjects
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9
ΔR/R0 (%) −9 −5.8 −2.8 −3.6 −5.9 −8.9 −6.2 −3.1 −6.1
G-FET results + + + + + + + + +
Agreement Yes Yes Yes Yes Yes Yes Yes Yes Yes
Patient 10 Health 1 Health 2 Health 3 Health 4 Health 5 Health 6 Health 7 Health 8
ΔR/R0 (%) −5.4 1.6 −0.3 2 3.2 4.1 5.3 2.9 2.2
G-FET results + − − − − − − − −
Agreement Yes Yes Yes Yes Yes Yes Yes Yes Yes
a) “Cutoff value” was set at −2; “+” represents positive, and “−” represents negative; “Yes” indicates that the G-FET result is in consistence with the
clinical standard samples.

a
Table 2 Antibody analysis of COVID-19 patients and healthy subjects
Number Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Health 1 Health 2 Health 3
ΔR/R0 (%) −2.6 −4.5 −4.5 −2.8 −1.3 −2.6 0.7 0.2 1.1
G-FETs results + + + + + + − − −
Agreement Yes Yes Yes Yes Yes Yes Yes Yes Yes
a) “Cutoff value” was set at −1; “+” represents positive, and “−” represents negative; “Yes” indicates that the G-FET result is in consistence with the
clinical standard samples.

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746 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 March 2021 | Vol. 64 No. 3
SCIENCE CHINA Materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ARTICLES

Project of Basic and Applied Basic Research (2019B030302007), and Xuefeng Guo received his PhD degree in 2004
from the Institute of Chemistry, Chinese Acad-
Beijing National Laboratory for Molecular Sciences (BNLMS201901).
emy of Sciences. From 2004 to 2007, he was a
postdoctoral research scientist at the Columbia
Author contributions Guo X, Mo F, Wang P and Huang F conceived University Nanocenter. He joined the faculty as a
and designed the experiments; Ke G, Su D and Li Y fabricated the professor under the “Peking 100-Talent” Pro-
devices and performed the device measurements; Zhao Y, Wang H, Xiao gram at Peking University in 2008. His research
F and Yuan Y designed and built the measurement machines; Liu W and focuses on functional nanometer/molecular de-
Yang Z provided the antigen protein; Li M and Wang P provided the vices.
clinical samples; Guo X, Mo F, Wang P, Ke G and Su D analyzed the
data and wrote the paper. All authors discussed the results and com-
mented on the manuscript.

Conflict of interest The authors declare that they have no conflict of 一种针对新型冠状病毒肺炎的准确、快速、便携
interest. 式双功能电检测仪
1,2† 2† 2† 3 3 4 5
Supplementary Information Experimental details and supporting 柯国骏 , 苏鼎凯 , 李渝 , 赵钰 , 王宏刚 , 刘万键 , 李慢 ,
4 6 7 1* 3* 5* 2*
data are available in the online version of this paper. 杨志廷 , 肖放 , 袁尧 , 黄飞 , 莫凡洋 , 王鹏 , 郭雪峰
摘要 新型冠状病毒肺炎(COVID-19)正在多个国家快速传播, 已
Guojun Ke received his BS degree in 2012 and 经导致了严重的全球大流行. 由于目前没有针对此类病人的特效
PhD degree in 2017 from the School of Chem- 药和针对此病毒的疫苗, 准确、快速地进行新冠病人检测成为了
istry, Sun Yat-Sen University, respectively. From 控制大流行最有效的措施. 本文中我们开发了一种基于石墨烯场
2013 to 2016, he was a visiting student at the 效应晶体管的便携式双功能电检测仪, 其通过核酸互补杂交或者
University of Basel. He is currently working as a
抗原-抗体特异性结合作用, 能分别进行病毒核酸序列检测和抗体
postdoctoral fellow in South China University of −1
Technology. His current research focuses on 检测, 检测限分别低至0.1和1 fg mL . 我们通过临床样品检测进一
device physics of single-molecule junctions. 步评估了此方法: 从10个新冠病人和8个正常人咽拭子中提取RNA
直接用于核酸检测; 从6个新冠病人和3个正常人血清中提取抗体
用于抗体检测. 临床样品检测结果和基于聚合酶链反应的光学方
法结果完全吻合, 同时此方法拥有超快的检测速度(核酸检测需
10 min, 抗体检测需5 min). 因此, 我们的实验提供了一种有效、准
Dingkai Su received his BS degree in 2017 from
确、高通量的新冠现场即时检测工具.
the College of Nano Science and Technology,
Soochow University. He is currently a PhD
candidate at the College of Chemistry and Mo-
lecular Engineering, Peking University, under the
guidance of Prof. Xuefeng Guo. His research
interest focuses on single-molecule devices and
dynamics.

March 2021 | Vol. 64 No. 3 © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 747

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