Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection

• 

  This publication is Open Access under the license indicated. Learn More

ACS Nano

research-article

Abstract

Click to copy section linkSection link copied!

The ongoing outbreak of the novel coronavirus disease (COVID-19) has spread globally and poses a threat to public health in more than 200 countries. Reliable laboratory diagnosis of the disease has been one of the foremost priorities for promoting public health interventions. The routinely used reverse transcription polymerase chain reaction (RT-PCR) is currently the reference method for COVID-19 diagnosis. However, it also reported a number of false-positive or -negative cases, especially in the early stages of the novel virus outbreak. In this work, a dual-functional plasmonic biosensor combining the plasmonic photothermal (PPT) effect and localized surface plasmon resonance (LSPR) sensing transduction provides an alternative and promising solution for the clinical COVID-19 diagnosis. The two-dimensional gold nanoislands (AuNIs) functionalized with complementary DNA receptors can perform a sensitive detection of the selected sequences from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through nucleic acid hybridization. For better sensing performance, the thermoplasmonic heat is generated on the same AuNIs chip when illuminated at their plasmonic resonance frequency. The localized PPT heat is capable to elevate the in situ hybridization temperature and facilitate the accurate discrimination of two similar gene sequences. Our dual-functional LSPR biosensor exhibits a high sensitivity toward the selected SARS-CoV-2 sequences with a lower detection limit down to the concentration of 0.22 pM and allows precise detection of the specific target in a multigene mixture. This study gains insight into the thermoplasmonic enhancement and its applicability in the nucleic acid tests and viral disease diagnosis.

At the end of 2019, the first case of pneumonia of unknown origin was detected in Wuhan, China. (1) High-throughput sequencing revealed that this was a new severe acute respiratory syndrome β-coronavirus (SARS-CoV-2) and a novel coronavirus disease (COVID-19). (2) Through 1 April 2020, the rapid spread of COVID-19 has impacted more than 200 countries with more than 900000 laboratory-confirmed cases and 45000 deaths (with high numbers in China, United States, Spain, and Italy). (3,4) COVID-19 is the third large-scale pandemic caused by coronavirus in the last two decades after severe acute respiratory syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012. (5,6) These two coronaviruses have caused about 10000 cumulative cases, with mortality rates of 10% for SARS-CoV and 37% for MERS-CoV. Regarding the SARS-CoV-2, the laboratory-confirmed COVID-19 cases have already been more than 90 times higher than the total confirmed cases of SARS and MERS. (7) There is no doubt that fast and accurate identification of a novel virus can greatly contribute to the control of an emerging pandemic.

Reliable laboratory diagnosis has been one of the foremost priorities for promoting epidemic prevention and control. In acute respiratory infection, the molecular method reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect causative viruses using samples from respiratory secretions. (8) According to the latest version of “WHO interim guidance for laboratory testing for COVID-19 in humans”, several molecular assays that detect the COVID-19 have been developed. (9) The gene targets for RT-PCR molecular assays selected by different countries are genetically similar, including the RNA-dependent RNA polymerase (RdRp) sequence and the open reading frame 1ab (ORF1ab) sequence. Generally, RT-PCR is currently the most sensitive method of viral RNA detection by rapidly making many copies of a specific sequence. The sensitivity of a recent SARS-CoV-2 study has reached 3.7 RNA copies on detecting the RdRp sequence. (8) However, RT-PCR can also fail for various reasons, such as its amplification of spurious nucleic acid contaminations. The RT-PCR assays for SARS-CoV-2 detection have reported a number of false-negative results on confirmed infection cases. (10) In clinical diagnosis, a single negative PCR result does not rule out COVID-19 infection as the reported positive rate was only 30–50% for laboratory-confirmed COVID-19 cases at the early stage of the outbreak, (11) particularly if the sample is from an upper respiratory tract (URT) specimen. A recent study of 167 COVID-19 infection patients showed that five (3%) patients had positive chest computed tomography (CT) findings but false-negative results from the RT-PCR testing. These five patients were eventually confirmed with COVID-19 infection by repeated swab tests. (10) In addition, the current RT-PCR-based detection methods demand high manpower and long processing time, which may not be able to provide the capacity to test all the suspected cases during full-scale outbreaks. Other approaches such as CT scan and culture methods are apparently not suitable for fast-response detection and real-time analysis. (12) Therefore, it is advantageous to thoroughly investigate suspected patients by another reliable diagnosis system.

Biosensors are ideal for providing an alternative and reliable solution to clinical diagnosis, real-time detection, and continuous monitoring. (13,14) Among the different biosensing techniques, localized surface plasmon resonance (LSPR) biosensing systems are applicable to different classes of analytes of clinical interests. (15) LSPR is a strong photon-driven coherent oscillation of the surface conduction electrons, which can be modulated when coupling occurs at the surface of the plasmonic materials. (16) Owing to the enhanced plasmonic field in the vicinity of the nanostructures, LSPR sensing systems demonstrate high sensitivity to local variation, including the refractive index change and molecular binding. (17) Thus, LSPR is an ideal candidate for real-time and label-free detection of micro- and nanoscale analytes. (18,19) A latest research has utilized SPR to test the biophysical properties of SARS-CoV-2 spike protein and found that the SARS-CoV-2 spike glycoprotein bound angiotensin-converting enzyme 2 (ACE2) with much higher affinity than SARS-CoV spike protein. (20) In addition, several SARS-CoV receptor-binding domains (RBDs)-specific monoclinal antibodies were also tested in this study and demonstrated that these antibodies did not have appreciable binding to the spike protein of SARS-CoV-2. The key property of nucleic acids that renders them so useful for clinical diagnosis, therapy and bionanotechnology is the predictable and specific hybridization of complementary bases. (21) Thus, the LSPR technique for genetic testing and nucleic acid detection in clinical practices could be an interesting alternative for SARS-CoV-2 detection and COVID-19 diagnosis.

The novel SARS-CoV-2 virus is a positive sense, single-stranded RNA virus. The DNA–RNA hybridization has been widely used in RT-PCR as well as various biomedical sensors. The criteria for hybridization are based on nucleic acid strand melting. (22,23) Two complementary strands can specifically hybridize with each other when the temperature is slightly lower than their melting temperature, while a single mismatch can cause the melting temperature to decrease significantly. (24) It is worth noting that the plasmonic nanoparticles normally exhibit large optical cross sections and the absorbed light can be nonradiatively relaxed resulting in a significant heating energy. (25,26) The converted plasmonic photothermal (PPT) heat energy, also known as the thermoplasmonic effect is highly localized near the nanoparticles, which can be used as a stable in situ heat source for controllable and uniform thermal processing. (26−29) In this work, we developed a dual-functional LSPR biosensor through combining the photothermal effect and plasmonic sensing transduction for SARS-CoV-2 viral nucleic acid detection. The plasmonic chip with the two-dimensional distribution of nanoabsorbers (AuNIs) is capable to generate the local PPT heat and transduce the in situ hybridization for highly sensitive and accurate SARS-CoV-2 detection.

The dual-functional plasmonic performances were systematically studied in the aspects of LSPR sensing transduction and PPT heating. The common-path differential phase-sensitive LSPR system, as shown in Figure 1a, was adopted to measure the local refractive index changes or the binding events. In the LSPR sensing transduction unit, the sensing beam was generated by a wide spectrum LED source and operated in the ATR (attenuated total reflection) mode at the interface between the glass substrate and liquid environment. When reaching the two-dimensional AuNI sensing layer, the measured optical power of the beam was found to be 32.58 μW. The local plasmonic responses were retrieved from the ATR spectral interferograms by using the windowed Fourier transform phase extraction method, as described elsewhere. (30) This phase response, reported in radian units, is more prominent than the conventional spectral and angular responses. Therefore, it has been utilized for improving the sensitivity of plasmonic sensors. (31) In order to generate a stable and intense thermoplasmonic field, an excitation laser with 532 nm peak wavelength and 40 mW maximum optical power was applied onto the AuNI chip in the normal incident angle (Figure 1b). In addition, optimizing the AuNI chip so that its peak absorbance wavelength was exactly at 532 nm can significantly improve the conversion efficiency of thermoplasmonic. By adjusting the Au nanofilm thickness before dewetting, the absorption peak (under normal incident angle) can be accurately controlled within a wavelength range from 523.4 to 539.7 nm as shown in Figure 1c,d and Figure S1. In this work, the AuNIs that matched the laser excitation wavelength at 532.2 nm (±0.2 nm) were utilized for the PPT heating. (32) It is worth noting that under the ATR conditions with a 72° inclined incident angle the plasmonic resonance wavelength for LSPR sensing transduction red-shifted to 580 nm due to the prism coupling and the inclined angle of incidence (Figure 1e). (30) The phase changes caused by a local variation of LSPR conditions were confined in a narrow wavelength region from 578 to 582 nm. Moreover, after addition of a long-pass filter (LPF) with a cut-on wavelength at 552 nm, the 532 nm photothermal excitation laser from the PPT unit did not influence the stability of the real-time LSPR sensing transduction.

In the thermoplasmonic testing, the direct absorption of laser irradiation at 532 nm decayed nonradiatively by generating more hot electrons in AuNIs. (33) The photoexcited highly energetic electrons quickly dissipated and released thermal energies to heat the ambient environments. Conversely, the PPT-induced temperature increase was also responsible for a refractive index variation of the surrounding environment, which can be in situ detected by the LSPR detection system as shown in Figure 2a. Specifically, the AuNI chip was exposed to laser excitation for 50 s, as indicated by the shaded region. Then the laser was switched off to reattain the baseline. The generation and equilibrium of local photothermal heating were relatively fast. According to the laser switching tests as shown in Figure S2, the rapid heating process was completed within 1 s after turning on the laser excitation. Subsequently, the dynamic equilibrium process took another 11 s before finally entering the steady state. In our experiments, we calibrated the LSPR phase response under different ambient temperatures. The in situ temperature arising from the PPT effect was characterized based on the measurement of the thermal-induced refractive index variation in the vicinity of AuNIs. (32,34) During the ambient temperature variation, the real-time LSPR phase responses and temperature values were recorded in parallel (Figure 2b), and the correlation was established as shown in Figure 2c. Based on this calibrated LSPR-temperature regression, the localized photothermal temperatures under different laser powers were retrieved as shown in Figure 2d.

To further evaluate the laser-induced PPT effect and the local temperature profile, we utilized the spectrometer to scan the heating area for mapping the LSPR phase responses and actual temperature distribution on the AuNI sensor chips. In the experimental setup as shown in Figure S3, the excitation laser with 32 mW power was applied to the optimal AuNI absorbers with a peak absorption at 532.2 nm (±0.2 nm). At each point of interest, we used the LSPR transducing unit to record two interferometric spectra: one reference without PPT heating and one spectrum with PPT heating. By scanning the laser spot and surrounding area with a 0.5 mm step interval, the spatial distribution of LSPR phase changes was retrieved as shown in Figure 2e. At each scanning pixel, the retrieved phase response was subsequently converted to the local temperature based on the calibration curve in Figure 2c. Therefore, the corresponding temperature distribution around the PPT heating was obtained and illustrated in Figure 2f. The local temperature was significantly elevated from 21.47 °C (room temperature) to 41.08 °C at the center of the laser spot.

We shall now present the sensing results of the SARS-CoV-2 by the proposed dual-functional plasmonic biosensors. The full genome sequence data of the viruses, i.e., SARS-CoV-2 and SARS-CoV, have been retrieved from the GISAID platform. The selected oligonucleotides for specific SARS-CoV-2 detection and their relative positions were given in Figure 3a and Table S1. These viral oligonucleotides refer to sequences used in different countries for COVID-19 diagnosis, and some of them have been published in the latest research. (8,9,35) The basic local alignment search tool (BLAST) was used to compare these viral sequences with the library of SARS-CoV-2 to confirm their representativeness and specificity. In the present case of COVID-19, SARS-CoV-2 isolates or samples from infected patients are challenging to obtain and handle. Thus, the corresponding DNA sequences were artificially synthesized for representative LSPR sensing demonstration of SARS-CoV-2 and SARS-CoV. According to the WHO guideline and local alignment searching results, two specific sequences from SARS-CoV-2 were selected, i.e., the RdRp and the ORF1ab as shown in Figure 3a. Validation and proof of selectivity were demonstrated by choosing the closely related nucleic acid sequence from RdRp of SARS-CoV. In addition, an oligonucleotide sequence from the coronaviral envelope protein gene (E) was also synthesized and tested to aid the virus identification.

Based on the synthetic oligonucleotide receptors with a thiol group (Table S2), the LSPR sensing chips were directly functionalized by forming the Au–S bond between the thiol-cDNA receptor and AuNIs as illustrated in Figure 3b. The surface functionalization process was initially optimized on its amount and concentration in order to achieve proper surface coverage and high sensitivity. During the real-time surface functionalization as shown in Figure 3c, step-by-step injections of 0.1 nmol of thiol-cDNA of RdRp-COVID, (RdRp-COVID-C) caused continuous phase jumps due to the covalent binding between AuNIs and thiol-cDNA. After a total immobilization of 1 nmol (10 × 0.1 nmol) of RdRp-COVID-C as shown in Figure 3c,d, the LSPR response stopped growing and indicated the appropriate amount of cDNA receptors for AuNI functionalization. Hereafter, the solution containing 1 nmol of thiol-cDNA was utilized to functionalize the AuNI microfluidic sensor chips for SARS-CoV-2 sequence detection (Figure S4). The proper surface functionalization that is sufficient to functionalize the entire AuNI sensing surface can increase the sensitivity and suppress the nonspecific binding events. In contrast, the AuNI sensor chip was oversaturated when functionalized with 10 nmol of cDNA and insufficiently covered by using 0.1 nmol of cDNA (Figure S5).

The surface-functionalized AuNI chips were subsequently installed in the LSPR systems for specific viral sequence detection (Figure 4a). The impacts of the localized thermoplasmonic heating on nucleic acids hybridization and LSPR detection were systematically studied. According to the temperature profile shown in Figure 2f, the excited PPT heat with approximately 41 °C nominal temperature was generated on the AuNI sensor. Before the injection of the RdRp sequence, nuclease-free water was flown across the microfluidic sensing chamber and the thermoplasmonic laser (32 mW) was turned on to establish a steady phase reference and baseline. According to the phase-sensing diagram in Figure 4b and S6a, the LSPR response of the dual-functional AuNI biosensor started to increase when the RdRp-COVID genes were injected into the microfluidic chamber at about 200 s and attained the maximum phase value after about 800 s hybridization. The dual-functional AuNI sensing chip was further flushed with nuclease-free water to remove the nonspecific binding items and to check the final LSPR phase response. In the comparison with and without the PPT effect, the hybridization rate and the LSPR sensing response level were obviously suppressed when the PPT unit was shut down as shown in Figure 4b. It proved that the localized photothermal effect can significantly improve the hybridization kinetics of the RdRp-COVID and its cDNA. Thus, the response-slope of the photothermal enhanced LSPR was much steeper than that without the photothermal assistance. Due to the faster hybridization kinetics, the differential phase response levels were also elevated for the RdRp-COVID sequence at different concentrations as shown in Figure 4c and Figure S6. The PPT effect and its derived local heat can effectively promote the fast and sensitive detection of nucleic acids by improving the hybridization kinetics of fully matching strands.

More importantly, the PPT heating was capable of inhibiting the spurious binding of nonmatching sequences by elevating the local temperature at the vicinity of AuNIs. SARS-CoV and SARS-CoV-2 viruses are similar β-coronavirus, and their genetic similarities are high. The specific SARS-CoV-2 genetic target recommended by the WHO, i.e., the RdRp-COVID sequence as shown in Table S1, is very closely related to that of SARS-CoV. Specifically, in the selected gene sequences, only three fixed nucleotide bases were different between RdRp-COVID and RdRp-SARS. A real-time LSPR detection was conducted on the two closely related sequences. The LSPR sensor without the aid of photothermal unit reported a false positive response signal when detecting the RdRp-SARS sequence (Figure S7), which indicated that a similar but not fully complement sequence was also able to interact and partially hybridize with the cDNA receptors at room temperature. Although the hybridization kinetics of RdRp-SARS sequence from SARS-CoV was clearly slower than that of SARS-CoV-2, the nonmatching spurious binding of any closely related sequence can affect the accurate virus detection and discrimination. Therefore, the local heat based on the proposed PPT effect was employed to improve the specificity of hybridization. At the elevated temperature of 41 °C as illustrated in Figure 4d, the standard free energy of hybridization was weaker due to the mismatched base-pairs. Thus, the similar but not fully matched sequences of SARS-CoV can be distinguished. In detail, the calculated association rate constant k_a of RdRp-COVID with PPT heating enhancement was found to be 1.11 × 10⁶ M^–1 s^–1. A detailed discussion and calculations are given in Figure S6c. For a typical biological sensing system, k_a ranges between 10³ and 10⁷ M^–1 s^–1 and a higher associate rate indicates a stronger binding affinity. (36,37) In a comparison experiment including the PPT heat with 32 mW optical power, the 532 nm laser was applied onto the surface of the AuNI sensor from 200 to 700 s as shown in Figure 4e. The local PPT heat was generated immediately to make the LSPR phase jump to about 1.76 rad. After turning off the laser at 700 s, the LSPR phase response of the mismatching RdRp-SARS gene was fully suppressed to the ground state of blank measurement (i.e., the responses from 0 to 200 s) as shown by the black curve in Figure 4e. Since the RdRp-SARS sequences reported a weak response of 0.002 rad, we determined that its association rate constant was lower than 10³ M^–1 s^–1 under the PPT heating. At the same time, the fully matching RdRp-COVID sequence from SARS-CoV-2, showed an apparent phase difference before and after the laser excitation (orange curve in Figure 4e). Thus, we believed that a similar but not fully matched sequence could be distinguished based on their different binding affinity and the PPT heating.

In another set of verification experiments, the RdRp-SARS genes were initially bound to the RdRp-COVID-C receptors at room temperature. Then the 532 nm laser (32 mW) was applied on the AuNI surface to stimulate the local thermoplasmonic effect. In the real-time LSPR sensorgram shown in Figure 4f, we observed the dissociation of the RdRp-SARS genes from the RdRp-COVID-C receptors after the temperature rise. The calculated dissociation rate constant was 8.287 × 10^–3 s^–1 as shown in Figure S8. The dissociation half-life t_1/2, which indicated the time to dissociate half of the hybridized sequences, was 83.3 s. In contrast, the complementary sequence of RdRp-COVID showed a much lower dissociation rate constant at 3.5 × 10^–6 s^–1 and a long dissociation half-life time of 1.97 × 10⁵ s. These results further verified that the thermoplasmonic effect can eliminate the nonmatching hybridization quickly and promote the selective detection of the target sequence, so as to achieve highly accurate nucleic acid detection and virus differentiation. Compared with the conventional plasmonic biosensing system, we demonstrated how this proposed dual-functional plasmonic sensing system can be the basis of a reliable and easy-to-implement thermoplasmonic biosensing technique: it can significantly reduce the false-positive-rate and enhance the reliability in genetic diagnosis.

To quantify the sensing performance, the dual-functional plasmonic detections of RdRp-COVID were further investigated over the concentration range from 0.01 pM to 50 μM as shown in Figure 5a. The AuNI sensing system started to attain the saturation condition when the concentration of the RdRp-COVID sequence reached 1 μM. In contrast, the low RdRp-COVID concentration, i.e., 0.1 pM, only resulted in a weak phase response by 2.90 × 10^–3 radian (Figure 5b), which was close to the system blank measurement of 2.92 × 10^–3 radian. Thus, as illustrated in the sensing calibration curve in Figure 5b, the dual-functional LSPR sensing system exhibited a limit of the range from 0.1 pM to 1 μM for detecting oligonucleotides, covering 7 orders of magnitude. The calibrated regression curve was further used to estimate the limit of detection (LoD), which is defined by IUPAC (International Union of Pure and Applied Chemistry) as the sum of the blank measures, i.e., 2.92 × 10^–3 radian with the nuclease-free water buffer and triple of its standard deviation (Figure S9). Thus, the LoD of the photothermal enhanced LSPR sensing system was found to be (2.92 × 10^–3) + 3 × (3.12 × 10^–3) = 0.0123 rad as shown by the dashed line in Figure 5b. Therefore, the detectable RdRp-COVID sequence concentration corresponding to the systematic LoD was about 0.22 ± 0.08 pM (Figure S9). A 200 μL analyte solution at this LoD concentration contained about 2.26 × 10⁷ copies of the RdRp-COVID sequence. The actual size of SARS-CoV-2 is about 29.9 kilobases in length, which is 1000 times longer than the RdRp-COVID sequence used in this study. Thus, based on the LSPR signal–target size relationship, the estimated LoD for detecting the entire RNA strands from SARS-CoV-2 could be approximately 2.26 × 10⁴ copies. (38) A recent study reported the viral loads of SARS-CoV-2 from different respiratory trace samples including the throat/nasal swabs and the sputum. Based on these clinical specimens collected from 82 infected individuals, the overall viral load soon after onset was higher than 1 × 10⁶ copies/mL. (39) This indicated that our proposed dual-functional LSPR system has the potential for direct analysis of SARS-CoV-2 sequences in respiratory samples.

In addition to the RdRp-COVID sequence, we also validated our dual-functional LSPR sensing system by performing the selective hybridization detection on several different genome sequences from both SARS-CoV-2 and SARS-CoV, i.e., the ORF1ab-COVID sequence and the E sequence from SARS-CoV-2, the RdRp-SARS sequence from SARS-CoV. The corresponding LSPR phase sensing responses with the in situ PPT enhancement are illustrated in Figure 5c. The complementary cDNA sequences, i.e., ORF1ab-COVID-C, E-C, and RdRp-SARS-C, were functionalized onto the AuNI chips, respectively, for the detection of specific viral sequence. Since the physical length and molecular weight were roughly same, the hybridization of these target sequences reported a similar LSPR phase response (Figure 5c). As the concentration increased from 1 pM to 1 nM, the mean LSPR response levels of each sequence also climbed in a proportional manner, which further proved the feasibility of this dual-functional LSPR sensing system for quantitative analysis of viral nucleic acids. Among them, the ORF1ab-COVID sequence produced the strongest responses due to its high molecular weight (8715.6 g/mol) and long length (28 bases), while the responses for E sequence were slightly lower.

In clinical diagnosis, the respiratory trace samples after viral lysis and RNA extraction may contain multiple nucleic acid sequences from the same viral source of SARS-CoV-2. Thus, detecting the accurate concentration of a specific sequence under the interference of multiple nonspecific sequences was beneficial to demonstrate its potential for real clinical applications. In experiments as shown in Figure 5d, the multisequence mixture containing RdRp-COVID sequences (100 pM), E sequences (100 pM), and ORF1ab-COVID sequences (100 pM) was prepared to simulate an actual sample after virus lysis. The ORF1ab-COVID and E sequences in the mixture showed extremely low spurious binding with the immobilized RdRp-COVID-C receptors. Compared with the standard detection of 100 pM RdRp-COVID as shown in Figure 5d, the calculated recovery rate based on the dual-functional LSPR biosensors was found to be 96% in the mixture sample. This experimental result further demonstrated that the dual-functional LSPR system with the in situ PPT enhancement can perform accurate detection of the target sequence and facilitate the highly accurate SARS-CoV-2 detection.

Our developed dual-functional plasmonic system has successfully demonstrated a highly sensitive, fast, and reliable diagnostic capability for SARS-CoV-2 virus detection. This dual-functional plasmonic biosensing concept integrated the PPT effect and the LSPR sensing transduction on a single cost-effective AuNI chip. By using two different angles of incidence, the plasmonic resonances of PPT and LSPR can be excited at two different wavelengths, which significantly enhanced the sensing stability, sensitivity, and reliability. With this configuration, the LSPR sensing unit attained a real-time and label-free detection of viral sequences including RdRp-COVID, ORF1ab-COVID, and E genes from SARS-Cov-2. More importantly, the in situ PPT enhancement on the AuNI chips dramatically improved the hybridization kinetics and the specificity of nucleic acid detection. Similar sequences such as RdRp genes from SARS-CoV and SARS-CoV-2 can be accurately discriminated with the in situ PPT enhancement. Under the outbreak background of COVID-19, this proposed dual-functional LSPR biosensor can provide a reliable and easy-to-implement diagnosis platform to improve the diagnostic accuracy in clinical tests and relieve the pressure on PCR-based tests.

This article references 39 other publications.

1. 1

   Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. Lancet 2020, 395, 497– 506

   Google Scholar

   1

   Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

   Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin

   Lancet (2020), 395 (10223), 497-506CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)

   A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiol., clin., lab., and radiol. characteristics and treatment and clin. outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analyzed data on patients with lab.-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiol. and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. By Jan 2, 2020, 41 admitted hospital patients had been identified as having lab.-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum prodn. (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) Of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was assocd. with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiol., duration of human transmission, and clin. spectrum of disease need fulfilment by future studies. Ministry of Science and Technol., Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technol. Commission.

2. 2

   Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N. Genomic Characterisation and Epidemiology of 2019 Novel Coronavirus: Implications for Virus Origins and Receptor Binding. Lancet 2020, 395, 565– 574

   Google Scholar

   2

   Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

   Lu, Roujian; Zhao, Xiang; Li, Juan; Niu, Peihua; Yang, Bo; Wu, Honglong; Wang, Wenling; Song, Hao; Huang, Baoying; Zhu, Na; Bi, Yuhai; Ma, Xuejun; Zhan, Faxian; Wang, Liang; Hu, Tao; Zhou, Hong; Hu, Zhenhong; Zhou, Weimin; Zhao, Li; Chen, Jing; Meng, Yao; Wang, Ji; Lin, Yang; Yuan, Jianying; Xie, Zhihao; Ma, Jinmin; Liu, William J.; Wang, Dayan; Xu, Wenbo; Holmes, Edward C.; Gao, George F.; Wu, Guizhen; Chen, Weijun; Shi, Weifeng; Tan, Wenjie

   Lancet (2020), 395 (10224), 565-574CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)

   In late Dec., 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions detd. by rapid amplification of cDNA ends. Phylogenetic anal. of these 2019-nCoV genomes and those of other coronaviruses was used to det. the evolutionary history of the virus and help infer its likely origin. Homol. modeling was done to explore the likely receptor-binding properties of the virus. The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic anal. revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homol. modeling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic anal. suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural anal. suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University. These data have been deposited in the ChinaNational Microbiol. Data Center (accession no. NMDC10013002 and genome accession nos. NMDC60013002-01 to NMDC60013002-10) and the datafrom BGI have been deposited in the China National GeneBank (accession nos. CNA000733235).

3. 3

   Rothe, C.; Schunk, M.; Sothmann, P.; Bretzel, G.; Froeschl, G.; Wallrauch, C.; Zimmer, T.; Thiel, V.; Janke, C.; Guggemos, W. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N. Engl. J. Med. 2020, 382, 970,  DOI: 10.1056/NEJMc2001468

   Google Scholar

   3

   Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

   Rothe Camilla; Schunk Mirjam; Sothmann Peter; Bretzel Gisela; Froeschl Guenter; Wallrauch Claudia; Zimmer Thorbjorn; Thiel Verena; Janke Christian; Hoelscher Michael; Guggemos Wolfgang; Seilmaier Michael; Drosten Christian; Vollmar Patrick; Zwirglmaier Katrin; Zange Sabine; Wolfel Roman

   The New England journal of medicine (2020), 382 (10), 970-971 ISSN:.

   There is no expanded citation for this reference.

4. 4

   Stoecklin, S. B.; Rolland, P.; Silue, Y.; Mailles, A.; Campese, C.; Simondon, A.; Mechain, M.; Meurice, L.; Nguyen, M.; Bassi, C. First Cases of Coronavirus Disease 2019 (COVID-19) in France: Surveillance, Investigations and Control Measures, January 2020. Eurosurveillance 2020, 25, 2000094

5. 5

   Wang, L. F.; Anderson, D. E. Viruses in Bats and Potential Spillover to Animals and Humans. Curr. Opin. Virol. 2019, 34, 79– 89,  DOI: 10.1016/j.coviro.2018.12.007

   Google Scholar

   5

   Viruses in bats and potential spillover to animals and humans

   Wang Lin-Fa; Anderson Danielle E

   Current opinion in virology (2019), 34 (), 79-89 ISSN:.

   In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a large number of known and unknown viruses, many of which could spillover into animal and human populations. However, our knowledge into basic bat biology and immunology is very limited and we have little understanding of major factors contributing to the risk of bat virus spillover events. Here we provide a brief review of the latest findings in bat viruses and their potential risk of cross-species transmission.

6. 6

   Ksiazek, T. G.; Erdman, D.; Goldsmith, C. S.; Zaki, S. R.; Peret, T.; Emery, S.; Tong, S. X.; Urbani, C.; Comer, J. A.; Lim, W.; Rollin, P. E.; Dowell, S. F.; Ling, A. E.; Humphrey, C. D.; Shieh, W. J.; Guarner, J.; Paddock, C. D.; Rota, P.; Fields, B.; DeRisi, J. A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N. Engl. J. Med. 2003, 348, 1953– 1966,  DOI: 10.1056/NEJMoa030781

   Google Scholar

   6

   A novel coronavirus associated with severe acute respiratory syndrome

   Ksiazek, Thomas G.; Erdman, Dean; Goldsmith, Cynthia S.; Zaki, Sherif R.; Peret, Teresa; Emery, Shannon; Tong, Suxiang; Urbani, Carlo; Comer, James A.; Lim, Wilina; Rollin, Pierre E.; Dowell, Scott F.; Ling, Ai-Ee; Humphrey, Charles D.; Shieh, Wan-Ju; Guarner, Jeannette; Paddock, Christopher D.; Rota, Paul; Fields, Barry; DeRisi, Joseph; Yang, Jyh-Yuan; Cox, Nancy; Hughes, James M.; LeDuc, James W.; Bellini, William J.; Anderson, Larry J.; Cannon, A. D. L.; Curtis, M.; Farrar, B.; Morgan, L.; Pezzanite, L.; Sanchez, A. J.; Slaughter, K. A.; Stevens, T. L.; Stockton, P. C.; Wagoner, K. D.; Sanchez, A.; Nichol, S.; Vincent, M.; Osborne, J.; Honig, J.; Brickson, B. R.; Holloway, B.; McCaustland, K.; Lingappa, J.; Lowe, L.; Scott, S.; Lu, X.; Villamarzo, Y.; Cook, B.; Chen, Q.; Birge, C.; Shu, B.; Pallansch, M.; Tatti, K. M.; Morken, T.; Smith, C.; Greer, P.; White, E.; McGlothen, T.; Bhatnagar, J.; Patel, M.; Bartlett, J.; Montague, J.; Lee, W.; Packard, M.; Thompson, H. A.; Moen, A.; Fukuda, K.; Uyeki, T.; Harper, S.; Klimov, A.; Lindstrom, S.; Benson, R.; Carlone, G.; Facklam, R.; Fields, P.; Levett, P.; Mayer, L.; Talkington, D.; Thacker, W. L.; Tondella, M. L. C.; Whitney, C.; Robertson, B.; Warnock, D.; Brooks, T.; Schrag, S.; Rosenstein, N.; Arthur, R.; Ganem, D.; Poutanen, S. M.; Chen, T.-J.; Hsiao, C.-H.; Wai-Fu, N. G.; Ho, M.; Keung, T.-K.; Nghiem, K. H.; Nguyen, H. K. L.; Le, M. Q.; Nguyen, H. H. T.; Hoang, L. T.; Vu, T. H.; Vu, H. Q.; Chunsuttiwat, S.

   New England Journal of Medicine (2003), 348 (20), 1953-1966CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)

   A worldwide outbreak of severe acute respiratory syndrome (SARS) was assocd. with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiol. agent of this outbreak. We received clin. specimens from patients in 7 countries and tested them, using virus-isolation techniques, electron-microscopical and histol. studies, and mol. and serol. assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathol. features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examn. revealed ultrastructural features characteristic of coronaviruses. Immunohistochem. and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers the authors identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate were used to demonstrate a virus-specific serol. response. This virus may never before have circulated in the U.S. population. Conclusions: A novel coronavirus is assocd. with this outbreak, and the evidence indicates that this virus has an etiol. role in SARS. Because of the death of Dr. Carlo Urbani, the authors propose that this first isolate be named the Urbani strain of SARS-assocd. coronavirus.

7. 7

   Mahase, E. Coronavirus: COVID-19 Has Killed More People Than SARS and MERS Combined, Despite Lower Case Fatality Rate. Br. Med. J. 2020, M641,  DOI: 10.1136/bmj.m641

8. 8

   Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L. Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR. Eurosurveillance 2020, 25

10. 10

    Xie, X.; Zhong, Z.; Zhao, W.; Zheng, C.; Wang, F.; Liu, J., Chest CT for Typical 2019- nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology 2020, 200343. DOI: 10.1148/radiol.2020200343

    Google Scholar

    10

    Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

    Xie Xingzhi; Zhong Zheng; Zhao Wei; Zheng Chao; Wang Fei; Liu Jun

    Radiology (2020), (), 200343 ISSN:.

    Some patients with positive chest CT findings may present with negative results of real time reverse-transcription-polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening.

11. 11

    Zhang, Q.; Zhao, Q., Inactivating Porcine Coronavirus before Nucleic Acid Isolation with the Temperature Higher Than 56 °C Damages Its Genome Integrity Seriously. BioRxiv , 2020;  DOI: 10.1101/2020.02.20.958785 (accessed March 2, 2020).

12. 12

    Ye, Z.; Zhang, Y.; Wang, Y.; Huang, Z.; Song, B. Chest CT Manifestations of New Coronavirus Disease 2019 (COVID-19): A Pictorial Review. Eur. Radiol. 2020, 1– 9,  DOI: 10.1007/s00330-020-06801-0

13. 13

    Soler, M.; Huertas, C. S.; Lechuga, L. M. Label-Free Plasmonic Biosensors for Point-of-Care Diagnostics: A Review. Expert Rev. Mol. Diagn. 2019, 19, 71– 81,  DOI: 10.1080/14737159.2019.1554435

    Google Scholar

    13

    Label-free plasmonic biosensors for point-of-care diagnostics: a review

    Soler, Maria; Huertas, Cesar S.; Lechuga, Laura M.

    Expert Review of Molecular Diagnostics (2019), 19 (1), 71-81CODEN: ERMDCW; ISSN:1473-7159. (Taylor & Francis Ltd.)

    A review. Introduction: Optical biosensors, particularly those based on nanoplasmonics technol., have emerged in recent decades as a potential soln. for disease diagnostics and therapy follow-up at the point-of-care (POC). These biosensor platforms could overcome some of the challenges faced in conventional diagnosis techniques offering label-free assays with immediate results and employing small and user-friendly devices. Areas covered: In this review, we will provide a crit. overview of the recent advances in the development of nanoplasmonic biosensors for the POC diagnostics. We focus on those systems with demonstrated capabilities for integration in portable platforms, highlighting some of the most relevant diagnostics applications targeting proteins, nucleic acids, and cells as disease biomarkers. Expert commentary: Despite the attractive features of label-free nanoplasmonic sensors in terms of miniaturization and anal. robustness, the route toward an effective clin. implementation involves the integration of fully automated microfluidic systems for sample processing and anal., and the optimization of surface biofunctionalization procedures. Addnl., the development of multiplexed sensors for high-throughput anal. and including specific neoantigens and novel biomarkers in detection panels will provide the means for delivering a powerful anal. technol. for an accurate and improved medical diagnosis.

14. 14

    Masson, J. F. Surface Plasmon Resonance Clinical Biosensors for Medical Diagnostics. ACS Sens 2017, 2, 16– 30,  DOI: 10.1021/acssensors.6b00763

    Google Scholar

    14

    Surface Plasmon Resonance Clinical Biosensors for Medical Diagnostics

    Masson, Jean-Francois

    ACS Sensors (2017), 2 (1), 16-30CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)

    A review. The design and application of sensors for monitoring biomols. in clin. samples is a common goal of the sensing research community. Surface plasmon resonance (SPR) and other plasmonic techniques such as localized surface plasmon resonance (LSPR) and imaging SPR are reaching a maturity level sufficient for their application in monitoring biomols. in clin. samples. In recent years, the first examples for monitoring antibodies, proteins, enzymes, drugs, small mols., peptides, and nucleic acids in biofluids collected from patients afflicted with a series of medical conditions (Alzheimer's, hepatitis, diabetes, leukemia, and cancers such as prostate and breast cancers, among others) demonstrate the progress of SPR sensing in clin. chem. This Perspective reviews the current status of the field, showcasing a series of early successes in the application of SPR for clin. anal. and detailing a series of considerations regarding sensing schemes, exposing issues with anal. in biofluids, and comparing SPR with ELISA, while providing an outlook of the challenges currently assocd. with plasmonic materials, instrumentation, microfluidics, bioreceptor selection, selection of a clin. market, and validation of a clin. assay for applying SPR sensors to clin. samples. Research opportunities are proposed to further advance the field and transition SPR biosensors from research proof-of-concept stage to actual clin. applications.

15. 15

    Haes, A. J.; Chang, L.; Klein, W. L.; Van Duyne, R. P. Detection of a Biomarker for Alzheimer’s Disease from Synthetic and Clinical Samples Using a Nanoscale Optical Biosensor. J. Am. Chem. Soc. 2005, 127, 2264– 2271,  DOI: 10.1021/ja044087q

    Google Scholar

    15

    Detection of a Biomarker for Alzheimer's Disease from Synthetic and Clinical Samples Using a Nanoscale Optical Biosensor

    Haes, Amanda J.; Chang, Lei; Klein, William L.; Van Duyne, Richard P.

    Journal of the American Chemical Society (2005), 127 (7), 2264-2271CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-β derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quant. binding information for both antigen and second antibody detection that permits the detn. of ADDL concn. and offers the unique anal. of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiol. relevant monomer concns. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concn. reveals two ADDL epitopes that have binding consts. to the specific anti-ADDL antibodies of 7.3×1012 M-1 and 9.5×108 M-1. The anal. of human brain ext. and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.

16. 16

    Willets, K. A.; Van Duyne, R. P. Localized Surface Plasmon Resonance Spectroscopy and Sensing. Annu. Rev. Phys. Chem. 2007, 58, 267– 297,  DOI: 10.1146/annurev.physchem.58.032806.104607

    Google Scholar

    16

    Localized surface plasmon resonance spectroscopy and sensing

    Willets, Katherine A.; Van Duyne, Richard P.

    Annual Review of Physical Chemistry (2007), 58 (), 267-297CODEN: ARPLAP; ISSN:0066-426X. (Annual Reviews Inc.)

    A review. Localized surface plasmon resonance (LSPR) spectroscopy of metallic nanoparticles is a powerful technique for chem. and biol. sensing expts. Also, the LSPR is responsible for the electromagnetic-field enhancement that leads to surface-enhanced Raman scattering (SERS) and other surface-enhanced spectroscopic processes. This review describes recent fundamental spectroscopic studies that reveal key relations governing the LSPR spectral location and its sensitivity to the local environment, including nanoparticle shape and size. The authors also describe studies on the distance dependence of the enhanced electromagnetic field and the relation between the plasmon resonance and the Raman excitation energy. Lastly, the authors introduce a new form of LSPR spectroscopy, involving the coupling between nanoparticle plasmon resonances and adsorbate mol. resonances. The results from these fundamental studies guide the design of new sensing expts., illustrated through applications in which researchers use both LSPR wavelength-shift sensing and SERS to detect mols. of chem. and biol. relevance.

17. 17

    Anker, J. N.; Hall, W. P.; Lyandres, O.; Shah, N. C.; Zhao, J.; Van Duyne, R. P. Biosensing with Plasmonic Nanosensors. Nat. Mater. 2008, 7, 442– 453,  DOI: 10.1038/nmat2162

    Google Scholar

    17

    Biosensing with plasmonic nanosensors

    Anker, Jeffrey N.; Hall, W. Paige; Lyandres, Olga; Shah, Nilam C.; Zhao, Jing; Van Duyne, Richard P.

    Nature Materials (2008), 7 (6), 442-453CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)

    A review. Light incident on metallic nanoparticles can induce a collective motion of electrons that can lead to a strong amplification of the local electromagnetic field. As reviewed here, these plasmonic resonances have important applications in biosensing where they push resoln. and sensitivity towards the single-mol. detection limit. Recent developments have greatly improved the sensitivity of optical sensors based on metal nanoparticle arrays and single nanoparticles. The authors introduce the localized surface plasmon resonance (LSPR) sensor and describe how its exquisite sensitivity to size, shape and environment can be harnessed to detect mol. binding events and changes in mol. conformation. The authors then describe recent progress in three areas representing the most significant challenges: pushing sensitivity towards the single-mol. detection limit, combining LSPR with complementary mol. identification techniques such as surface-enhanced Raman spectroscopy, and practical development of sensors and instrumentation for routine use and high-throughput detection. This review highlights several exceptionally promising research directions and discusses how diverse applications of plasmonic nanoparticles can be integrated in the near future.

18. 18

    Qiu, G. Y.; Ng, S. P.; Wu, C. M. L. Bimetallic Au-Ag Alloy Nanoislands for Highly Sensitive Localized Surface Plasmon Resonance Biosensing. Sens. Actuators, B 2018, 265, 459– 467,  DOI: 10.1016/j.snb.2018.03.066

    Google Scholar

    18

    Bimetallic Au-Ag alloy nanoislands for highly sensitive localized surface plasmon resonance biosensing

    Qiu, Guangyu; Ng, Siu Pang; Wu, Chi-Man Lawrence

    Sensors and Actuators, B: Chemical (2018), 265 (), 459-467CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)

    In this work, monodispersed bimetallic nanoislands (BMNIs) with various Au-Ag at. ratios, synthesized by solid-state dewetting method, show not only improvement of LSPR sensitivity from that of either Au or Ag, but have also provided chem. stability against spontaneous corrosion. Au-Ag alloying and BMNIs formation were achieved by a one-step self-assembly method. A large tunable plasmonic sensing range from 421 nm to 578 nm was found for all possible Au-Ag at. ratios. By employing the common-path interferometric sensing system, the Au0.6Ag0.4 BMNIs showed the best refractive index sensitivity. The as-synthesized Au-Ag BMNIs sensing chips were functionalized with various protocols for biosensing applications, i.e. thiolate functionalization with 11-Mercaptoundecanoic acid and dielec. functionalization with aminosilanes. The dielec. functionalized Au-Ag BMNIs LSPR biosensors can detect sub-picomolar concn. of human IgG with wide dynamic range from 0.89 pM to 1000 pM, whereas thiolate functionalization actually degrades the sensing performance due to Ag degrdn. Moreover, the dielec. functionalization layer also provided anti-degrdn. coverage to protect Au-Ag BMNIs from etchant agents, e.g. H2O2, which indicated the potential in wide biosensing applications. In virtue of the dielec. functionalization method, Au-Ag BMNIs can be utilized as a desirable alternative plasmonic medium in the biosensing community.

19. 19

    Qiu, G.; Thakur, A.; Xu, C.; Ng, S. P.; Lee, Y.; Wu, C. M. L. Detection of Glioma-Derived Exosomes with the Biotinylated Antibody-Functionalized Titanium Nitride Plasmonic Biosensor. Adv. Funct. Mater. 2019, 29, 1806761,  DOI: 10.1002/adfm.201806761

20. 20

    Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263,  DOI: 10.1126/science.abb2507

    Google Scholar

    20

    Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

    Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.

    Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)

    The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

21. 21

    Zhang, D. Y.; Chen, S. X.; Yin, P. Optimizing the Specificity of Nucleic Acid Hybridization. Nat. Chem. 2012, 4, 208,  DOI: 10.1038/nchem.1246

    Google Scholar

    21

    Optimizing the specificity of nucleic acid hybridization

    Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

    Nature Chemistry (2012), 4 (3), 208-214CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)

    The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biol. and biotechnol. reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temp. Here, we anal. derived the thermodn. properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temp., salt and concn. conditions. We rationally designed 'toehold exchange' probes that approx. these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogs with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg2+ to 47 mM Mg2+, and with nucleic acid concns. from 1 nM to 5 μM. Expts. with RNA also showed effective single-base change discrimination.

22. 22

    Stehr, J.; Hrelescu, C.; Sperling, R. A.; Raschke, G.; Wunderlich, M.; Nichtl, A.; Heindl, D.; Kürzinger, K.; Parak, W. J.; Klar, T. A. Gold Nanostoves for Microsecond DNA Melting Analysis. Nano Lett. 2008, 8, 619– 623,  DOI: 10.1021/nl073028i

    Google Scholar

    22

    Gold NanoStoves for Microsecond DNA Melting Analysis

    Stehr, Joachim; Hrelescu, Calin; Sperling, Ralph A.; Raschke, Gunnar; Wunderlich, Michael; Nichtl, Alfons; Heindl, Dieter; Kuerzinger, Konrad; Parak, Wolfgang J.; Klar, Thomas A.; Feldmann, Jochen

    Nano Letters (2008), 8 (2), 619-623CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)

    In traditional DNA melting assays, the temp. of the DNA-contg. soln. is slowly ramped up. In contrast, we use 300 ns laser pulses to rapidly heat DNA bound gold nanoparticle aggregates. We show that double-stranded DNA melts on a microsecond time scale that leads to a disintegration of the gold nanoparticle aggregates on a millisecond time scale. A perfectly matching and a point-mutated DNA sequence can be clearly distinguished in less than one millisecond even in a 1:1 mixt. of both targets.

23. 23

    Zhang, J. X.; Fang, J. Z.; Duan, W.; Wu, L. R.; Zhang, A. W.; Dalchau, N.; Yordanov, B.; Petersen, R.; Phillips, A.; Zhang, D. Y. Predicting DNA Hybridization Kinetics from Sequence. Nat. Chem. 2018, 10, 91– 98,  DOI: 10.1038/nchem.2877

    Google Scholar

    23

    Predicting DNA hybridization kinetics from sequence

    Zhang, Jinny X.; Fang, John Z.; Duan, Wei; Wu, Lucia R.; Zhang, Angela W.; Dalchau, Neil; Yordanov, Boyan; Petersen, Rasmus; Phillips, Andrew; Zhang, David Yu

    Nature Chemistry (2018), 10 (1), 91-98CODEN: NCAHBB; ISSN:1755-4330. (Nature Research)

    Hybridization is a key mol. process in biol. and biotechnol., but so far there is no predictive model for accurately detg. hybridization rate consts. based on sequence information. Here, we report a weighted neighbor voting (WNV) prediction algorithm, in which the hybridization rate const. of an unknown sequence is predicted based on similarity reactions with known rate consts. To construct this algorithm we first performed 210 fluorescence kinetics expts. to observe the hybridization kinetics of 100 different DNA target and probe pairs (36 nt sub-sequences of the CYCS and VEGF genes) at temps. ranging from 28 to 55 °C. Automated feature selection and weighting optimization resulted in a final six-feature WNV model, which can predict hybridization rate consts. of new sequences to within a factor of 3 with ∼91% accuracy, based on leave-one-out cross-validation. Accurate prediction of hybridization kinetics allows the design of efficient probe sequences for genomics research.

24. 24

    Harris, N. C.; Kiang, C.-H. Defects Can Increase the Melting Temperature of DNA– Nanoparticle Assemblies. J. Phys. Chem. B 2006, 110, 16393– 16396,  DOI: 10.1021/jp062287d

    Google Scholar

    24

    Defects Can Increase the Melting Temperature of DNA-Nanoparticle Assemblies

    Harris, Nolan C.; Kiang, Ching-Hwa

    Journal of Physical Chemistry B (2006), 110 (33), 16393-16396CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)

    DNA-gold nanoparticle assemblies have shown promise as an alternative technol. to DNA microarrays for DNA detection and RNA profiling. Understanding the effect of DNA sequences on the melting temp. of the system is central to developing reliable detection technol. We studied the effects of DNA base-pairing defects, such as mismatches and deletions, on the melting temp. of DNA-nanoparticle assemblies. We found that contrary to the general assumption that defects lower the melting temp. of DNA, some defects increase the melting temp. of DNA-linked nanoparticle assemblies. The effects of mismatches and deletions were found to depend on the specific base pair, the sequence, and the location of the defects. Our results demonstrate that the surface-bound DNA exhibit hybridization behavior different from that of free DNA. Such findings indicate that a detailed understanding of DNA-nanoparticle assembly phase behavior is required for quant. interpretation of DNA-nanoparticle aggregation.

25. 25

    Jauffred, L.; Samadi, A.; Klingberg, H.; Bendix, P. M.; Oddershede, L. B. Plasmonic Heating of Nanostructures. Chem. Rev. 2019, 119, 8087– 8130,  DOI: 10.1021/acs.chemrev.8b00738

    Google Scholar

    25

    Plasmonic Heating of Nanostructures

    Jauffred, Liselotte; Samadi, Akbar; Klingberg, Henrik; Bendix, Poul Martin; Oddershede, Lene B.

    Chemical Reviews (Washington, DC, United States) (2019), 119 (13), 8087-8130CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

    A review. The absorption of light by plasmonic nanostructures and their assocd. temp. increase are exquisitely sensitive to the shape and compn. of the structure and to the wavelength of light. Therefore, much effort is put into synthesizing novel nanostructures for optimized interaction with the incident light. The successful synthesis and characterization of high quality and biocompatible plasmonic colloidal nanoparticles has fostered numerous and expanding applications, esp. in biomedical contexts, where such particles are highly promising for general drug delivery and for tomorrow's cancer treatment. We review the thermoplasmonic properties of the most commonly used plasmonic nanoparticles, including solid or composite metallic nanoparticles of various dimensions and geometries. Common methods for synthesizing plasmonic particles are presented with the overall goal of providing the reader with a guide for designing or choosing nanostructures with optimal thermoplasmonic properties for a given application. Finally, the biocompatibility and biol. tolerance of structures are critically discussed along with novel applications of plasmonic nanoparticles in the life sciences.

26. 26

    Lee, J. H.; Cheglakov, Z.; Yi, J.; Cronin, T. M.; Gibson, K. J.; Tian, B. Z.; Weizmann, Y. Plasmonic Photothermal Gold Bipyramid Nanoreactors for Ultrafast Real-Time Bioassays. J. Am. Chem. Soc. 2017, 139, 8054– 8057,  DOI: 10.1021/jacs.7b01779

    Google Scholar

    26

    Plasmonic photothermal gold bipyramid nanoreactors for ultrafast real-time bioassays

    Lee, Jung-Hoon; Cheglakov, Zoya; Yi, Jaeseok; Cronin, Timothy M.; Gibson, Kyle J.; Tian, Bozhi; Weizmann, Yossi

    Journal of the American Chemical Society (2017), 139 (24), 8054-8057CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Nucleic acid amplification techniques have been among the most powerful tools for biol. and biomedical research, and the vast majority of the bioassays rely on thermocycling that uses time-consuming and expensive Peltier-block heating. Here, we introduce a plasmonic photothermal method for quant. real-time PCR, using gold bipyramids and light to achieve ultrafast thermocycling. Moreover, we successfully extend our photothermal system to other biol. assays, such as isothermal nucleic acid amplification and restriction enzyme digestion.

27. 27

    Son, J. H.; Cho, B.; Hong, S.; Lee, S. H.; Hoxha, O.; Haack, A. J.; Lee, L. P. Ultrafast Photonic PCR. Light: Sci. Appl. 2015, 4, e280  DOI: 10.1038/lsa.2015.53

    Google Scholar

    27

    Ultrafast photonic PCR

    Son, Jun Ho; Cho, Byungrae; Hong, Soon Gweon; Lee, Sang Hun; Hoxha, Ori; Haack, Amanda J.; Lee, Luke P.

    Light: Science & Applications (2015), 4 (7), e280CODEN: LSAIAZ; ISSN:2047-7538. (Nature Publishing Group)

    Nucleic acid amplification and quantification via polymerase chain reaction (PCR) is one of the most sensitive and powerful tools for clin. labs., precision medicine, personalized medicine, agricultural science, forensic science and environmental science. Ultrafast multiplex PCR, characterized by low power consumption, compact size and simple operation, is ideal for timely diagnosis at the point-of-care (POC). Although several fast/ultrafast PCR methods have been proposed, the use of a simple and robust PCR thermal cycler remains challenging for POC testing. Here, we present an ultrafast photonic PCR method using plasmonic photothermal light-to-heat conversion via photon-electron-phonon coupling. We demonstrate an efficient photonic heat converter using a thin gold (Au) film due to its plasmon-assisted high optical absorption (approx. 65% at 450 nm, the peak wavelength of heat source light-emitting diodes (LEDs)). The plasmon-excited Au film is capable of rapidly heating the surrounding soln. to over 150 °C within 3 min. Using this method, ultrafast thermal cycling (30 cycles; heating and cooling rate of 12.79±0.93 °C s-1 and 6.6±0.29 °C s-1, resp.) from 55 °C (temp. of annealing) to 95 °C (temp. of denaturation) is accomplished within 5 min. Using photonic PCR thermal cycles, we demonstrate here successful nucleic acid (λ-DNA) amplification. Our simple, robust and low cost approach to ultrafast PCR using an efficient photonic-based heating procedure could be generally integrated into a variety of devices or procedures, including on-chip thermal lysis and heating for isothermal amplifications.

28. 28

    Kim, M.; Lee, J. H.; Nam, J. M. Plasmonic Photothermal Nanoparticles for Biomedical Applications. Adv. Sci. 2019, 6, 1900471,  DOI: 10.1002/advs.201900471

    Google Scholar

    28

    Plasmonic Photothermal Nanoparticles for Biomedical Applications

    Kim, Minho; Lee, Jung-Hoon; Nam, Jwa-Min

    Advanced Science (Weinheim, Germany) (2019), 6 (17), n/a1900471CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)

    A review. Recent advances of plasmonic nanoparticles include fascinating developments in the fields of energy, catalyst chem., optics, biotechnol., and medicine. The plasmonic photothermal properties of metallic nanoparticles are of enormous interest in biomedical fields because of their strong and tunable optical response and the capability to manipulate the photothermal effect by an external light source. To date, most biomedical applications using photothermal nanoparticles have focused on photothermal therapy; however, to fully realize the potential of these particles for clin. and other applications, the fundamental properties of photothermal nanoparticles need to be better understood and controlled, and the photothermal effect-based diagnosis, treatment, and theranostics should be thoroughly explored. This Progress Report summarizes recent advances in the understanding and applications of plasmonic photothermal nanoparticles, particularly for sensing, imaging, therapy, and drug delivery, and discusses the future directions of these fields.

29. 29

    Wang, S.; Huang, P.; Nie, L.; Xing, R.; Liu, D.; Wang, Z.; Lin, J.; Chen, S.; Niu, G.; Lu, G. Single Continuous Wave Laser Induced Photodynamic/Plasmonic Photothermal Therapy Using Photosensitizer-Functionalized Gold Nanostars. Adv. Mater. 2013, 25, 3055– 3061,  DOI: 10.1002/adma.201204623

    Google Scholar

    29

    Single Continuous Wave Laser Induced Photodynamic/Plasmonic Photothermal Therapy Using Photosensitizer-Functionalized Gold Nanostars

    Wang, Shouju; Huang, Peng; Nie, Liming; Xing, Ruijun; Liu, Dingbin; Wang, Zhe; Lin, Jing; Chen, Shouhui; Niu, Gang; Lu, Guangming; Chen, Xiaoyuan

    Advanced Materials (Weinheim, Germany) (2013), 25 (22), 3055-3061CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Chlorin e6 conjugates nanostars (GNS-PEG-Ce6) are used to perform simultaneous photodynamic/plasmonic photothermal therapy (PDT/PPTT) upon single laser irradn. The early-phase PDT effect is coordinated with the late-phase PPTT effect to obtain synergistic anticancer efficiency. The prepd. GNS-PEG-Ce6 shows excellent water dispersibility, good biocompatibility, enhanced cellular uptake and remarkable anticancer efficiency upon irradn. in vivo.

30. 30

    Qiu, G. Y.; Ng, S. P.; Wu, C. M. L. Differential Phase-Detecting Localized Surface Plasmon Resonance Sensor with Self-Assembly Gold Nano-Islands. Opt. Lett. 2015, 40, 1924– 1927,  DOI: 10.1364/OL.40.001924

    Google Scholar

    30

    Differential phase-detecting localized surface plasmon resonance sensor with self-assembly gold nano-islands

    Qiu, Guangyu; Ng, Siu Pang; Wu, Chi Man Lawrence

    Optics Letters (2015), 40 (9), 1924-1927CODEN: OPLEDP; ISSN:0146-9592. (Optical Society of America)

    Self-assembly (SAM) gold nano-islands are fabricated by two-step thin-film deposition-annealing method. Despite random distribution of the SAM, the p-polarized light after total internal reflection shows significant phase transition at the extinction wavelengths upon refractive index variation due to localized surface plasmon resonance (LSPR) effect. It resembles the sharp phase transition obsd. in conventional surface plasmon resonance (SPR) biosensors, so that the bulk sensitivity of the SAM-LSPR sensor is improved via the phase interrogation method. In this Letter, we present both computational and exptl. investigations to the SAM-LSPR sensor and the results show excellent agreement with each other. With bulk refractive index resoln. to 9.75 × 10-8 RIU, we believe the phase-detecting SAM-LSPR sensor would be an essential step toward low-cost label-free sensing applications.

31. 31

    Smolyaninov, A.; El Amili, A.; Vallini, F.; Pappert, S.; Fainman, Y. Programmable Plasmonic Phase Modulation of Free-Space Wavefronts at Gigahertz Rates. Nat. Photonics 2019, 13, 431– 435,  DOI: 10.1038/s41566-019-0360-3

    Google Scholar

    31

    Programmable plasmonic phase modulation of free-space wavefronts at gigahertz rates

    Smolyaninov, Alexei; El Amili, Abdelkrim; Vallini, Felipe; Pappert, Steve; Fainman, Yeshaiahu

    Nature Photonics (2019), 13 (6), 431-435CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)

    Space-variant control of optical wavefronts is important for many applications in photonics, such as the generation of structured light beams, and is achieved with spatial light modulators. Com. devices, at present, are based on liq.-crystal and digital micromirror technologies and are typically limited to kilohertz switching speeds. To realize significantly higher operating speeds, new technologies and approaches are necessary. Here we demonstrate two-dimensional control of free-space optical fields at a wavelength of 1,550 nm at a 1 GHz modulation speed using a programmable plasmonic phase modulator based on near-field interactions between surface plasmons and materials with an electrooptic response. High χ(2) and χ(3) dielec. thin films of either aluminum nitride or silicon-rich silicon nitride are used as an active modulation layer in a surface plasmon resonance configuration to realize programmable space-variant control of optical wavefronts in a 4 × 4 pixel array at high speed.

32. 32

    Chen, Z. X.; Shan, X. N.; Guan, Y.; Wang, S. P.; Zhu, J. J.; Tao, N. J. Imaging Local Heating and Thermal Diffusion of Nanomaterials with Plasmonic Thermal Microscopy. ACS Nano 2015, 9, 11574– 11581,  DOI: 10.1021/acsnano.5b05306

    Google Scholar

    32

    Imaging Local Heating and Thermal Diffusion of Nanomaterials with Plasmonic Thermal Microscopy

    Chen, Zixuan; Shan, Xiaonan; Guan, Yan; Wang, Shaopeng; Zhu, Jun-Jie; Tao, Nongjian

    ACS Nano (2015), 9 (12), 11574-11581CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

    Measuring local heat generation and dissipation in nanomaterials is crit. for understanding the basic properties and developing applications of nanomaterials, including photothermal therapy and joule heating of nanoelectronics. Several technologies have been developed to probe local temp. distributions in nanomaterials, but a sensitive thermal imaging technol. with high temporal and spatial resoln. is still lacking. Here, we describe plasmonic thermal microscopy (PTM) to image local heat generation and diffusion from nanostructures in biol. relevant aq. solns. We demonstrate that PTM can detect local temp. change as small as 6 mK with temporal resoln. of 10 μs and spatial resoln. of submicrons (diffraction limit). With PTM, we have successfully imaged photothermal generation from single nanoparticles and graphene pieces, studied spatiotemporal distribution of temp. surrounding a heated nanoparticle, and obsd. heating at defect sites in graphene. We further show that the PTM images are in quant. agreement with theor. simulations based on heat transport theories.

33. 33

    Baffou, G.; Quidant, R.; García de Abajo, F. J. Nanoscale Control of Optical Heating in Complex Plasmonic Systems. ACS Nano 2010, 4, 709– 716,  DOI: 10.1021/nn901144d

    Google Scholar

    33

    Nanoscale Control of Optical Heating in Complex Plasmonic Systems

    Baffou, Guillaume; Quidant, Romain; Garcia de Abajo, F. Javier

    ACS Nano (2010), 4 (2), 709-716CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

    The authors introduce a numerical technique to study the temp. distribution in arbitrarily complex plasmonic systems subject to external illumination. The authors perform both electromagnetic and thermodn. calcns. based upon a time-efficient boundary element method. Two kinds of plasmonic systems are studied to illustrate the potential of such a technique. First, the authors focus on individual particles with various morphologies. In analogy with electrostatics, the authors introduce the concept of thermal capacitance. This geometry-dependent quantity allows one to assess the temp. increase inside a plasmonic particle from the sole knowledge of its absorption cross section. The authors present universal thermal-capacitance curves for ellipsoids, rods, disks, and rings. Addnl., the authors study assemblies of nanoparticles in close proximity and show that, despite its diffusive nature, the temp. distribution can be made highly nonuniform even at the nanoscale using plasmonic systems. A significant degree of nanoscale control over the individual temps. of neighboring particles is demonstrated, depending on the external light wavelength and direction of incidence. The authors illustrate this concept with simulations of Au sphere dimers and chains in H2O. Work opens new possibilities for selectively controlling processes such as local melting for dynamic patterning of textured materials, chem. and metabolic thermal activation, and heat delivery for producing mech. motion with spatial precision in the nanoscale.

34. 34

    Baffou, G.; Bon, P.; Savatier, J.; Polleux, J.; Zhu, M.; Merlin, M.; Rigneault, H.; Monneret, S. Thermal Imaging of Nanostructures by Quantitative Optical Phase Analysis. ACS Nano 2012, 6, 2452– 2458,  DOI: 10.1021/nn2047586

    Google Scholar

    34

    Thermal Imaging of Nanostructures by Quantitative Optical Phase Analysis

    Baffou, Guillaume; Bon, Pierre; Savatier, Julien; Polleux, Julien; Zhu, Min; Merlin, Marine; Rigneault, Herve; Monneret, Serge

    ACS Nano (2012), 6 (3), 2452-2458CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

    The authors introduce an optical microscopy technique aimed at characterizing the heat generation arising from nanostructures, in a comprehensive and quant. manner. Namely, the technique permits (i) mapping the temp. distribution around the source of heat, (ii) mapping the heat power d. delivered by the source, and (iii) retrieving the abs. absorption cross section of light-absorbing structures. The technique is based on the measure of the thermal-induced refractive index variation of the medium surrounding the source of heat. The measurement is achieved using an assocn. of a regular CCD camera along with a modified Hartmann diffraction grating. Such a simple assocn. makes this technique straightforward to implement on any conventional microscope with its native broadband illumination conditions. The authors illustrate this technique on Au nanoparticles illuminated at their plasmonic resonance. The spatial resoln. of this technique is diffraction limited, and temp. variations weaker than 1 K can be detected.

35. 35

    Zhu, N.; Zhang, D. Y.; Wang, W. L.; Li, X. W.; Yang, B.; Song, J. D.; Zhao, X.; Huang, B. Y.; Shi, W. F.; Lu, R. J.; Niu, P. H.; Zhan, F. X.; Ma, X. J.; Wang, D. Y.; Xu, W. B.; Wu, G. Z.; Gao, G. G. F.; Tan, W. J. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727– 733,  DOI: 10.1056/NEJMoa2001017

    Google Scholar

    35

    A novel coronavirus from patients with pneumonia in China, 2019

    Zhu, Na; Zhang, Dingyu; Wang, Wenling; Li, Xingwang; Yang, Bo; Song, Jingdong; Zhao, Xiang; Huang, Baoying; Shi, Weifeng; Lu, Roujian; Niu, Peihua; Zhan, Faxian; Ma, Xuejun; Wang, Dayan; Xu, Wenbo; Wu, Guizhen; Gao, George F.; Tan, Wenjie

    New England Journal of Medicine (2020), 382 (8), 727-733CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)

    In Dec. 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. Complete genome sequences of the three novel coronaviruses were submitted to GISAID (BetaCoV/Wuhan/ IVDC-HB-01/2019, accession ID: EPI_ISL_402119; BetaCoV/Wuhan/IVDC-HB-04/2020, accession ID: EPI_ISL_402120; BetaCoV/Wuhan/IVDC-HB-05/2019, accession ID: EPI_ISL_402121).

36. 36

    Xu, S. C.; Zhan, J.; Man, B. Y.; Jiang, S. Z.; Yue, W. W.; Gao, S. B.; Guo, C. G.; Liu, H. P.; Li, Z. H.; Wang, J. H.; Zhou, Y. Q. Real-Time Reliable Determination of Binding Kinetics of DNA Hybridization Using a Multi-Channel Graphene Biosensor. Nat. Commun. 2017,  DOI: 10.1038/ncomms14902

37. 37

    Schreiber, G.; Haran, G.; Zhou, H. X. Fundamental Aspects of Protein-Protein Association Kinetics. Chem. Rev. 2009, 109, 839– 860,  DOI: 10.1021/cr800373w

    Google Scholar

    37

    Fundamental Aspects of Protein-Protein Association Kinetics

    Schreiber, G.; Haran, G.; Zhou, H.-X.

    Chemical Reviews (Washington, DC, United States) (2009), 109 (3), 839-860CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

    A review. This review focuses on recent advances in deciphering the kinetic pathway of protein complex formation, the nature of the precomplex formed through diffusion (which the authors term the "transient complex"), the transition state and other intermediates (such as the so-called encounter complex) along the assocn. pathway.

38. 38

    Qiu, G.; Yue, Y.; Tang, J.; Zhao, Y.-B.; Wang, J. Total Bioaerosols Detection by a Succinimidyl-Ester-Functionalized Plasmonic Biosensor to Reveal Different Characteristics at Three Locations in Switzerland. Environ. Sci. Technol. 2020, 54, 1353– 1362,  DOI: 10.1021/acs.est.9b05184

    Google Scholar

    38

    Total Bioaerosol Detection by a Succinimidyl-Ester-Functionalized Plasmonic Biosensor To Reveal Different Characteristics at Three Locations in Switzerland

    Qiu, Guangyu; Yue, Yang; Tang, Jiukai; Zhao, Yi-Bo; Wang, Jing

    Environmental Science & Technology (2020), 54 (3), 1353-1362CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    Bioaerosols consisting of biol. originated airborne particles such as microbes, metabolites, toxins, and fragments of microorganisms are present ubiquitously in the living environment. The international interests in bioaerosols have rapidly increased because of their many potential health effects. Thus, accurate and fast detection of total bioaerosols in different environments has become an important task for safeguarding against biol. threats and broadening the pool of bioaerosol knowledge. To quickly evaluate the total bioaerosol concn., the authors developed a localized surface plasmon resonance biosensor based on succinimidyl-ester-functionalized gold nanoislands (SEF-AuNIs) for quant. bioaerosol detection. The detection limit of the proposed SEF-AuNI sensors for model bacteria Escherichia coli and Bacillus subtilis can go to 0.5119 and 1.69 cells/mL, resp. To demonstrate the capability of this bioaerosol sensing technique, the authors tested aerosol samples collected from Bern (urban station), Basel (suburban station), and Rigi mountain (rural and high altitude station) in Switzerland and further investigated the correlation with endotoxin and PM10. The results substantiated that the SEF-AuNI sensors could be a reliable candidate for total bioaerosol detection and air quality assessment.

39. 39

    Pan, Y.; Zhang, D.; Yang, P.; Poon, L. L.; Wang, Q. Viral Load of SARS-CoV-2 in Clinical Samples. Lancet Infect. Dis. 2020, 20, 411,  DOI: 10.1016/S1473-3099(20)30113-4

    Google Scholar

    39

    Viral load of SARS-CoV-2 in clinical samples

    Pan, Yang; Zhang, Daitao; Yang, Peng; Poon, Leo L. M.; Wang, Quanyi

    Lancet Infectious Diseases (2020), 20 (4), 411-412CODEN: LIDABP; ISSN:1473-3099. (Elsevier Ltd.)

    Serial samples (throat swabs, sputum, urine, and stool) from patients in Beijing were collected daily after their hospitalization. Among 30 pairs of throat swab and sputum samples available, viral loads were significantly correlated for days 1-14. Although the viral loads in stool samples were less than those of respiratory samples, precautionary measures should be considered when handling fecal samples.

Load more citations

Cite this: ACS Nano 2020, 14, 5

Click to copy citationCitation copied!

Copyright © 2020 American Chemical Society. This publication is licensed under these Terms of Use.

Learn about these metrics

• Abstract

  

  Figure 1

  

  Figure 2

  

  Figure 3

  

  Figure 4

  

  Figure 5

  

• This article references 39 other publications.

  1. 1

     Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. Lancet 2020, 395, 497– 506

     1

     Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

     Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin

     Lancet (2020), 395 (10223), 497-506CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)

     A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiol., clin., lab., and radiol. characteristics and treatment and clin. outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analyzed data on patients with lab.-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiol. and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. By Jan 2, 2020, 41 admitted hospital patients had been identified as having lab.-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum prodn. (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) Of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was assocd. with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiol., duration of human transmission, and clin. spectrum of disease need fulfilment by future studies. Ministry of Science and Technol., Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technol. Commission.

  2. 2

     Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N. Genomic Characterisation and Epidemiology of 2019 Novel Coronavirus: Implications for Virus Origins and Receptor Binding. Lancet 2020, 395, 565– 574

     2

     Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

     Lu, Roujian; Zhao, Xiang; Li, Juan; Niu, Peihua; Yang, Bo; Wu, Honglong; Wang, Wenling; Song, Hao; Huang, Baoying; Zhu, Na; Bi, Yuhai; Ma, Xuejun; Zhan, Faxian; Wang, Liang; Hu, Tao; Zhou, Hong; Hu, Zhenhong; Zhou, Weimin; Zhao, Li; Chen, Jing; Meng, Yao; Wang, Ji; Lin, Yang; Yuan, Jianying; Xie, Zhihao; Ma, Jinmin; Liu, William J.; Wang, Dayan; Xu, Wenbo; Holmes, Edward C.; Gao, George F.; Wu, Guizhen; Chen, Weijun; Shi, Weifeng; Tan, Wenjie

     Lancet (2020), 395 (10224), 565-574CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)

     In late Dec., 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions detd. by rapid amplification of cDNA ends. Phylogenetic anal. of these 2019-nCoV genomes and those of other coronaviruses was used to det. the evolutionary history of the virus and help infer its likely origin. Homol. modeling was done to explore the likely receptor-binding properties of the virus. The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic anal. revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homol. modeling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic anal. suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural anal. suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University. These data have been deposited in the ChinaNational Microbiol. Data Center (accession no. NMDC10013002 and genome accession nos. NMDC60013002-01 to NMDC60013002-10) and the datafrom BGI have been deposited in the China National GeneBank (accession nos. CNA000733235).

  3. 3

     Rothe, C.; Schunk, M.; Sothmann, P.; Bretzel, G.; Froeschl, G.; Wallrauch, C.; Zimmer, T.; Thiel, V.; Janke, C.; Guggemos, W. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N. Engl. J. Med. 2020, 382, 970,  DOI: 10.1056/NEJMc2001468

     3

     Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

     Rothe Camilla; Schunk Mirjam; Sothmann Peter; Bretzel Gisela; Froeschl Guenter; Wallrauch Claudia; Zimmer Thorbjorn; Thiel Verena; Janke Christian; Hoelscher Michael; Guggemos Wolfgang; Seilmaier Michael; Drosten Christian; Vollmar Patrick; Zwirglmaier Katrin; Zange Sabine; Wolfel Roman

     The New England journal of medicine (2020), 382 (10), 970-971 ISSN:.

     There is no expanded citation for this reference.

  4. 4

     Stoecklin, S. B.; Rolland, P.; Silue, Y.; Mailles, A.; Campese, C.; Simondon, A.; Mechain, M.; Meurice, L.; Nguyen, M.; Bassi, C. First Cases of Coronavirus Disease 2019 (COVID-19) in France: Surveillance, Investigations and Control Measures, January 2020. Eurosurveillance 2020, 25, 2000094

     There is no corresponding record for this reference.

  5. 5

     Wang, L. F.; Anderson, D. E. Viruses in Bats and Potential Spillover to Animals and Humans. Curr. Opin. Virol. 2019, 34, 79– 89,  DOI: 10.1016/j.coviro.2018.12.007

     5

     Viruses in bats and potential spillover to animals and humans

     Wang Lin-Fa; Anderson Danielle E

     Current opinion in virology (2019), 34 (), 79-89 ISSN:.

     In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a large number of known and unknown viruses, many of which could spillover into animal and human populations. However, our knowledge into basic bat biology and immunology is very limited and we have little understanding of major factors contributing to the risk of bat virus spillover events. Here we provide a brief review of the latest findings in bat viruses and their potential risk of cross-species transmission.

  6. 6

     Ksiazek, T. G.; Erdman, D.; Goldsmith, C. S.; Zaki, S. R.; Peret, T.; Emery, S.; Tong, S. X.; Urbani, C.; Comer, J. A.; Lim, W.; Rollin, P. E.; Dowell, S. F.; Ling, A. E.; Humphrey, C. D.; Shieh, W. J.; Guarner, J.; Paddock, C. D.; Rota, P.; Fields, B.; DeRisi, J. A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N. Engl. J. Med. 2003, 348, 1953– 1966,  DOI: 10.1056/NEJMoa030781

     6

     A novel coronavirus associated with severe acute respiratory syndrome

     Ksiazek, Thomas G.; Erdman, Dean; Goldsmith, Cynthia S.; Zaki, Sherif R.; Peret, Teresa; Emery, Shannon; Tong, Suxiang; Urbani, Carlo; Comer, James A.; Lim, Wilina; Rollin, Pierre E.; Dowell, Scott F.; Ling, Ai-Ee; Humphrey, Charles D.; Shieh, Wan-Ju; Guarner, Jeannette; Paddock, Christopher D.; Rota, Paul; Fields, Barry; DeRisi, Joseph; Yang, Jyh-Yuan; Cox, Nancy; Hughes, James M.; LeDuc, James W.; Bellini, William J.; Anderson, Larry J.; Cannon, A. D. L.; Curtis, M.; Farrar, B.; Morgan, L.; Pezzanite, L.; Sanchez, A. J.; Slaughter, K. A.; Stevens, T. L.; Stockton, P. C.; Wagoner, K. D.; Sanchez, A.; Nichol, S.; Vincent, M.; Osborne, J.; Honig, J.; Brickson, B. R.; Holloway, B.; McCaustland, K.; Lingappa, J.; Lowe, L.; Scott, S.; Lu, X.; Villamarzo, Y.; Cook, B.; Chen, Q.; Birge, C.; Shu, B.; Pallansch, M.; Tatti, K. M.; Morken, T.; Smith, C.; Greer, P.; White, E.; McGlothen, T.; Bhatnagar, J.; Patel, M.; Bartlett, J.; Montague, J.; Lee, W.; Packard, M.; Thompson, H. A.; Moen, A.; Fukuda, K.; Uyeki, T.; Harper, S.; Klimov, A.; Lindstrom, S.; Benson, R.; Carlone, G.; Facklam, R.; Fields, P.; Levett, P.; Mayer, L.; Talkington, D.; Thacker, W. L.; Tondella, M. L. C.; Whitney, C.; Robertson, B.; Warnock, D.; Brooks, T.; Schrag, S.; Rosenstein, N.; Arthur, R.; Ganem, D.; Poutanen, S. M.; Chen, T.-J.; Hsiao, C.-H.; Wai-Fu, N. G.; Ho, M.; Keung, T.-K.; Nghiem, K. H.; Nguyen, H. K. L.; Le, M. Q.; Nguyen, H. H. T.; Hoang, L. T.; Vu, T. H.; Vu, H. Q.; Chunsuttiwat, S.

     New England Journal of Medicine (2003), 348 (20), 1953-1966CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)

     A worldwide outbreak of severe acute respiratory syndrome (SARS) was assocd. with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiol. agent of this outbreak. We received clin. specimens from patients in 7 countries and tested them, using virus-isolation techniques, electron-microscopical and histol. studies, and mol. and serol. assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathol. features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examn. revealed ultrastructural features characteristic of coronaviruses. Immunohistochem. and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers the authors identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate were used to demonstrate a virus-specific serol. response. This virus may never before have circulated in the U.S. population. Conclusions: A novel coronavirus is assocd. with this outbreak, and the evidence indicates that this virus has an etiol. role in SARS. Because of the death of Dr. Carlo Urbani, the authors propose that this first isolate be named the Urbani strain of SARS-assocd. coronavirus.

  7. 7

     Mahase, E. Coronavirus: COVID-19 Has Killed More People Than SARS and MERS Combined, Despite Lower Case Fatality Rate. Br. Med. J. 2020, M641,  DOI: 10.1136/bmj.m641

     There is no corresponding record for this reference.

  8. 8

     Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L. Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR. Eurosurveillance 2020, 25

     There is no corresponding record for this reference.

  10. 10

      Xie, X.; Zhong, Z.; Zhao, W.; Zheng, C.; Wang, F.; Liu, J., Chest CT for Typical 2019- nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology 2020, 200343. DOI: 10.1148/radiol.2020200343

      10

      Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

      Xie Xingzhi; Zhong Zheng; Zhao Wei; Zheng Chao; Wang Fei; Liu Jun

      Radiology (2020), (), 200343 ISSN:.

      Some patients with positive chest CT findings may present with negative results of real time reverse-transcription-polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening.

  11. 11

      Zhang, Q.; Zhao, Q., Inactivating Porcine Coronavirus before Nucleic Acid Isolation with the Temperature Higher Than 56 °C Damages Its Genome Integrity Seriously. BioRxiv , 2020;  DOI: 10.1101/2020.02.20.958785 (accessed March 2, 2020).

      There is no corresponding record for this reference.

  12. 12

      Ye, Z.; Zhang, Y.; Wang, Y.; Huang, Z.; Song, B. Chest CT Manifestations of New Coronavirus Disease 2019 (COVID-19): A Pictorial Review. Eur. Radiol. 2020, 1– 9,  DOI: 10.1007/s00330-020-06801-0

      There is no corresponding record for this reference.

  13. 13

      Soler, M.; Huertas, C. S.; Lechuga, L. M. Label-Free Plasmonic Biosensors for Point-of-Care Diagnostics: A Review. Expert Rev. Mol. Diagn. 2019, 19, 71– 81,  DOI: 10.1080/14737159.2019.1554435

      13

      Label-free plasmonic biosensors for point-of-care diagnostics: a review

      Soler, Maria; Huertas, Cesar S.; Lechuga, Laura M.

      Expert Review of Molecular Diagnostics (2019), 19 (1), 71-81CODEN: ERMDCW; ISSN:1473-7159. (Taylor & Francis Ltd.)

      A review. Introduction: Optical biosensors, particularly those based on nanoplasmonics technol., have emerged in recent decades as a potential soln. for disease diagnostics and therapy follow-up at the point-of-care (POC). These biosensor platforms could overcome some of the challenges faced in conventional diagnosis techniques offering label-free assays with immediate results and employing small and user-friendly devices. Areas covered: In this review, we will provide a crit. overview of the recent advances in the development of nanoplasmonic biosensors for the POC diagnostics. We focus on those systems with demonstrated capabilities for integration in portable platforms, highlighting some of the most relevant diagnostics applications targeting proteins, nucleic acids, and cells as disease biomarkers. Expert commentary: Despite the attractive features of label-free nanoplasmonic sensors in terms of miniaturization and anal. robustness, the route toward an effective clin. implementation involves the integration of fully automated microfluidic systems for sample processing and anal., and the optimization of surface biofunctionalization procedures. Addnl., the development of multiplexed sensors for high-throughput anal. and including specific neoantigens and novel biomarkers in detection panels will provide the means for delivering a powerful anal. technol. for an accurate and improved medical diagnosis.

  14. 14

      Masson, J. F. Surface Plasmon Resonance Clinical Biosensors for Medical Diagnostics. ACS Sens 2017, 2, 16– 30,  DOI: 10.1021/acssensors.6b00763

      14

      Surface Plasmon Resonance Clinical Biosensors for Medical Diagnostics

      Masson, Jean-Francois

      ACS Sensors (2017), 2 (1), 16-30CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)

      A review. The design and application of sensors for monitoring biomols. in clin. samples is a common goal of the sensing research community. Surface plasmon resonance (SPR) and other plasmonic techniques such as localized surface plasmon resonance (LSPR) and imaging SPR are reaching a maturity level sufficient for their application in monitoring biomols. in clin. samples. In recent years, the first examples for monitoring antibodies, proteins, enzymes, drugs, small mols., peptides, and nucleic acids in biofluids collected from patients afflicted with a series of medical conditions (Alzheimer's, hepatitis, diabetes, leukemia, and cancers such as prostate and breast cancers, among others) demonstrate the progress of SPR sensing in clin. chem. This Perspective reviews the current status of the field, showcasing a series of early successes in the application of SPR for clin. anal. and detailing a series of considerations regarding sensing schemes, exposing issues with anal. in biofluids, and comparing SPR with ELISA, while providing an outlook of the challenges currently assocd. with plasmonic materials, instrumentation, microfluidics, bioreceptor selection, selection of a clin. market, and validation of a clin. assay for applying SPR sensors to clin. samples. Research opportunities are proposed to further advance the field and transition SPR biosensors from research proof-of-concept stage to actual clin. applications.

  15. 15

      Haes, A. J.; Chang, L.; Klein, W. L.; Van Duyne, R. P. Detection of a Biomarker for Alzheimer’s Disease from Synthetic and Clinical Samples Using a Nanoscale Optical Biosensor. J. Am. Chem. Soc. 2005, 127, 2264– 2271,  DOI: 10.1021/ja044087q

      15

      Detection of a Biomarker for Alzheimer's Disease from Synthetic and Clinical Samples Using a Nanoscale Optical Biosensor

      Haes, Amanda J.; Chang, Lei; Klein, William L.; Van Duyne, Richard P.

      Journal of the American Chemical Society (2005), 127 (7), 2264-2271CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

      A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-β derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quant. binding information for both antigen and second antibody detection that permits the detn. of ADDL concn. and offers the unique anal. of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiol. relevant monomer concns. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concn. reveals two ADDL epitopes that have binding consts. to the specific anti-ADDL antibodies of 7.3×1012 M-1 and 9.5×108 M-1. The anal. of human brain ext. and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.

  16. 16

      Willets, K. A.; Van Duyne, R. P. Localized Surface Plasmon Resonance Spectroscopy and Sensing. Annu. Rev. Phys. Chem. 2007, 58, 267– 297,  DOI: 10.1146/annurev.physchem.58.032806.104607

      16

      Localized surface plasmon resonance spectroscopy and sensing

      Willets, Katherine A.; Van Duyne, Richard P.

      Annual Review of Physical Chemistry (2007), 58 (), 267-297CODEN: ARPLAP; ISSN:0066-426X. (Annual Reviews Inc.)

      A review. Localized surface plasmon resonance (LSPR) spectroscopy of metallic nanoparticles is a powerful technique for chem. and biol. sensing expts. Also, the LSPR is responsible for the electromagnetic-field enhancement that leads to surface-enhanced Raman scattering (SERS) and other surface-enhanced spectroscopic processes. This review describes recent fundamental spectroscopic studies that reveal key relations governing the LSPR spectral location and its sensitivity to the local environment, including nanoparticle shape and size. The authors also describe studies on the distance dependence of the enhanced electromagnetic field and the relation between the plasmon resonance and the Raman excitation energy. Lastly, the authors introduce a new form of LSPR spectroscopy, involving the coupling between nanoparticle plasmon resonances and adsorbate mol. resonances. The results from these fundamental studies guide the design of new sensing expts., illustrated through applications in which researchers use both LSPR wavelength-shift sensing and SERS to detect mols. of chem. and biol. relevance.

  17. 17

      Anker, J. N.; Hall, W. P.; Lyandres, O.; Shah, N. C.; Zhao, J.; Van Duyne, R. P. Biosensing with Plasmonic Nanosensors. Nat. Mater. 2008, 7, 442– 453,  DOI: 10.1038/nmat2162

      17

      Biosensing with plasmonic nanosensors

      Anker, Jeffrey N.; Hall, W. Paige; Lyandres, Olga; Shah, Nilam C.; Zhao, Jing; Van Duyne, Richard P.

      Nature Materials (2008), 7 (6), 442-453CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)

      A review. Light incident on metallic nanoparticles can induce a collective motion of electrons that can lead to a strong amplification of the local electromagnetic field. As reviewed here, these plasmonic resonances have important applications in biosensing where they push resoln. and sensitivity towards the single-mol. detection limit. Recent developments have greatly improved the sensitivity of optical sensors based on metal nanoparticle arrays and single nanoparticles. The authors introduce the localized surface plasmon resonance (LSPR) sensor and describe how its exquisite sensitivity to size, shape and environment can be harnessed to detect mol. binding events and changes in mol. conformation. The authors then describe recent progress in three areas representing the most significant challenges: pushing sensitivity towards the single-mol. detection limit, combining LSPR with complementary mol. identification techniques such as surface-enhanced Raman spectroscopy, and practical development of sensors and instrumentation for routine use and high-throughput detection. This review highlights several exceptionally promising research directions and discusses how diverse applications of plasmonic nanoparticles can be integrated in the near future.

  18. 18

      Qiu, G. Y.; Ng, S. P.; Wu, C. M. L. Bimetallic Au-Ag Alloy Nanoislands for Highly Sensitive Localized Surface Plasmon Resonance Biosensing. Sens. Actuators, B 2018, 265, 459– 467,  DOI: 10.1016/j.snb.2018.03.066

      18

      Bimetallic Au-Ag alloy nanoislands for highly sensitive localized surface plasmon resonance biosensing

      Qiu, Guangyu; Ng, Siu Pang; Wu, Chi-Man Lawrence

      Sensors and Actuators, B: Chemical (2018), 265 (), 459-467CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)

      In this work, monodispersed bimetallic nanoislands (BMNIs) with various Au-Ag at. ratios, synthesized by solid-state dewetting method, show not only improvement of LSPR sensitivity from that of either Au or Ag, but have also provided chem. stability against spontaneous corrosion. Au-Ag alloying and BMNIs formation were achieved by a one-step self-assembly method. A large tunable plasmonic sensing range from 421 nm to 578 nm was found for all possible Au-Ag at. ratios. By employing the common-path interferometric sensing system, the Au0.6Ag0.4 BMNIs showed the best refractive index sensitivity. The as-synthesized Au-Ag BMNIs sensing chips were functionalized with various protocols for biosensing applications, i.e. thiolate functionalization with 11-Mercaptoundecanoic acid and dielec. functionalization with aminosilanes. The dielec. functionalized Au-Ag BMNIs LSPR biosensors can detect sub-picomolar concn. of human IgG with wide dynamic range from 0.89 pM to 1000 pM, whereas thiolate functionalization actually degrades the sensing performance due to Ag degrdn. Moreover, the dielec. functionalization layer also provided anti-degrdn. coverage to protect Au-Ag BMNIs from etchant agents, e.g. H2O2, which indicated the potential in wide biosensing applications. In virtue of the dielec. functionalization method, Au-Ag BMNIs can be utilized as a desirable alternative plasmonic medium in the biosensing community.

  19. 19

      Qiu, G.; Thakur, A.; Xu, C.; Ng, S. P.; Lee, Y.; Wu, C. M. L. Detection of Glioma-Derived Exosomes with the Biotinylated Antibody-Functionalized Titanium Nitride Plasmonic Biosensor. Adv. Funct. Mater. 2019, 29, 1806761,  DOI: 10.1002/adfm.201806761

      There is no corresponding record for this reference.

  20. 20

      Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263,  DOI: 10.1126/science.abb2507

      20

      Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

      Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.

      Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)

      The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

  21. 21

      Zhang, D. Y.; Chen, S. X.; Yin, P. Optimizing the Specificity of Nucleic Acid Hybridization. Nat. Chem. 2012, 4, 208,  DOI: 10.1038/nchem.1246

      21

      Optimizing the specificity of nucleic acid hybridization

      Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

      Nature Chemistry (2012), 4 (3), 208-214CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)

      The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biol. and biotechnol. reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temp. Here, we anal. derived the thermodn. properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temp., salt and concn. conditions. We rationally designed 'toehold exchange' probes that approx. these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogs with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg2+ to 47 mM Mg2+, and with nucleic acid concns. from 1 nM to 5 μM. Expts. with RNA also showed effective single-base change discrimination.

  22. 22

      Stehr, J.; Hrelescu, C.; Sperling, R. A.; Raschke, G.; Wunderlich, M.; Nichtl, A.; Heindl, D.; Kürzinger, K.; Parak, W. J.; Klar, T. A. Gold Nanostoves for Microsecond DNA Melting Analysis. Nano Lett. 2008, 8, 619– 623,  DOI: 10.1021/nl073028i

      22

      Gold NanoStoves for Microsecond DNA Melting Analysis

      Stehr, Joachim; Hrelescu, Calin; Sperling, Ralph A.; Raschke, Gunnar; Wunderlich, Michael; Nichtl, Alfons; Heindl, Dieter; Kuerzinger, Konrad; Parak, Wolfgang J.; Klar, Thomas A.; Feldmann, Jochen

      Nano Letters (2008), 8 (2), 619-623CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)

      In traditional DNA melting assays, the temp. of the DNA-contg. soln. is slowly ramped up. In contrast, we use 300 ns laser pulses to rapidly heat DNA bound gold nanoparticle aggregates. We show that double-stranded DNA melts on a microsecond time scale that leads to a disintegration of the gold nanoparticle aggregates on a millisecond time scale. A perfectly matching and a point-mutated DNA sequence can be clearly distinguished in less than one millisecond even in a 1:1 mixt. of both targets.

  23. 23

      Zhang, J. X.; Fang, J. Z.; Duan, W.; Wu, L. R.; Zhang, A. W.; Dalchau, N.; Yordanov, B.; Petersen, R.; Phillips, A.; Zhang, D. Y. Predicting DNA Hybridization Kinetics from Sequence. Nat. Chem. 2018, 10, 91– 98,  DOI: 10.1038/nchem.2877

      23

      Predicting DNA hybridization kinetics from sequence

      Zhang, Jinny X.; Fang, John Z.; Duan, Wei; Wu, Lucia R.; Zhang, Angela W.; Dalchau, Neil; Yordanov, Boyan; Petersen, Rasmus; Phillips, Andrew; Zhang, David Yu

      Nature Chemistry (2018), 10 (1), 91-98CODEN: NCAHBB; ISSN:1755-4330. (Nature Research)

      Hybridization is a key mol. process in biol. and biotechnol., but so far there is no predictive model for accurately detg. hybridization rate consts. based on sequence information. Here, we report a weighted neighbor voting (WNV) prediction algorithm, in which the hybridization rate const. of an unknown sequence is predicted based on similarity reactions with known rate consts. To construct this algorithm we first performed 210 fluorescence kinetics expts. to observe the hybridization kinetics of 100 different DNA target and probe pairs (36 nt sub-sequences of the CYCS and VEGF genes) at temps. ranging from 28 to 55 °C. Automated feature selection and weighting optimization resulted in a final six-feature WNV model, which can predict hybridization rate consts. of new sequences to within a factor of 3 with ∼91% accuracy, based on leave-one-out cross-validation. Accurate prediction of hybridization kinetics allows the design of efficient probe sequences for genomics research.

  24. 24

      Harris, N. C.; Kiang, C.-H. Defects Can Increase the Melting Temperature of DNA– Nanoparticle Assemblies. J. Phys. Chem. B 2006, 110, 16393– 16396,  DOI: 10.1021/jp062287d

      24

      Defects Can Increase the Melting Temperature of DNA-Nanoparticle Assemblies

      Harris, Nolan C.; Kiang, Ching-Hwa

      Journal of Physical Chemistry B (2006), 110 (33), 16393-16396CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)

      DNA-gold nanoparticle assemblies have shown promise as an alternative technol. to DNA microarrays for DNA detection and RNA profiling. Understanding the effect of DNA sequences on the melting temp. of the system is central to developing reliable detection technol. We studied the effects of DNA base-pairing defects, such as mismatches and deletions, on the melting temp. of DNA-nanoparticle assemblies. We found that contrary to the general assumption that defects lower the melting temp. of DNA, some defects increase the melting temp. of DNA-linked nanoparticle assemblies. The effects of mismatches and deletions were found to depend on the specific base pair, the sequence, and the location of the defects. Our results demonstrate that the surface-bound DNA exhibit hybridization behavior different from that of free DNA. Such findings indicate that a detailed understanding of DNA-nanoparticle assembly phase behavior is required for quant. interpretation of DNA-nanoparticle aggregation.

  25. 25

      Jauffred, L.; Samadi, A.; Klingberg, H.; Bendix, P. M.; Oddershede, L. B. Plasmonic Heating of Nanostructures. Chem. Rev. 2019, 119, 8087– 8130,  DOI: 10.1021/acs.chemrev.8b00738

      25

      Plasmonic Heating of Nanostructures

      Jauffred, Liselotte; Samadi, Akbar; Klingberg, Henrik; Bendix, Poul Martin; Oddershede, Lene B.

      Chemical Reviews (Washington, DC, United States) (2019), 119 (13), 8087-8130CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

      A review. The absorption of light by plasmonic nanostructures and their assocd. temp. increase are exquisitely sensitive to the shape and compn. of the structure and to the wavelength of light. Therefore, much effort is put into synthesizing novel nanostructures for optimized interaction with the incident light. The successful synthesis and characterization of high quality and biocompatible plasmonic colloidal nanoparticles has fostered numerous and expanding applications, esp. in biomedical contexts, where such particles are highly promising for general drug delivery and for tomorrow's cancer treatment. We review the thermoplasmonic properties of the most commonly used plasmonic nanoparticles, including solid or composite metallic nanoparticles of various dimensions and geometries. Common methods for synthesizing plasmonic particles are presented with the overall goal of providing the reader with a guide for designing or choosing nanostructures with optimal thermoplasmonic properties for a given application. Finally, the biocompatibility and biol. tolerance of structures are critically discussed along with novel applications of plasmonic nanoparticles in the life sciences.

  26. 26

      Lee, J. H.; Cheglakov, Z.; Yi, J.; Cronin, T. M.; Gibson, K. J.; Tian, B. Z.; Weizmann, Y. Plasmonic Photothermal Gold Bipyramid Nanoreactors for Ultrafast Real-Time Bioassays. J. Am. Chem. Soc. 2017, 139, 8054– 8057,  DOI: 10.1021/jacs.7b01779

      26

      Plasmonic photothermal gold bipyramid nanoreactors for ultrafast real-time bioassays

      Lee, Jung-Hoon; Cheglakov, Zoya; Yi, Jaeseok; Cronin, Timothy M.; Gibson, Kyle J.; Tian, Bozhi; Weizmann, Yossi

      Journal of the American Chemical Society (2017), 139 (24), 8054-8057CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

      Nucleic acid amplification techniques have been among the most powerful tools for biol. and biomedical research, and the vast majority of the bioassays rely on thermocycling that uses time-consuming and expensive Peltier-block heating. Here, we introduce a plasmonic photothermal method for quant. real-time PCR, using gold bipyramids and light to achieve ultrafast thermocycling. Moreover, we successfully extend our photothermal system to other biol. assays, such as isothermal nucleic acid amplification and restriction enzyme digestion.

  27. 27

      Son, J. H.; Cho, B.; Hong, S.; Lee, S. H.; Hoxha, O.; Haack, A. J.; Lee, L. P. Ultrafast Photonic PCR. Light: Sci. Appl. 2015, 4, e280  DOI: 10.1038/lsa.2015.53

      27

      Ultrafast photonic PCR

      Son, Jun Ho; Cho, Byungrae; Hong, Soon Gweon; Lee, Sang Hun; Hoxha, Ori; Haack, Amanda J.; Lee, Luke P.

      Light: Science & Applications (2015), 4 (7), e280CODEN: LSAIAZ; ISSN:2047-7538. (Nature Publishing Group)

      Nucleic acid amplification and quantification via polymerase chain reaction (PCR) is one of the most sensitive and powerful tools for clin. labs., precision medicine, personalized medicine, agricultural science, forensic science and environmental science. Ultrafast multiplex PCR, characterized by low power consumption, compact size and simple operation, is ideal for timely diagnosis at the point-of-care (POC). Although several fast/ultrafast PCR methods have been proposed, the use of a simple and robust PCR thermal cycler remains challenging for POC testing. Here, we present an ultrafast photonic PCR method using plasmonic photothermal light-to-heat conversion via photon-electron-phonon coupling. We demonstrate an efficient photonic heat converter using a thin gold (Au) film due to its plasmon-assisted high optical absorption (approx. 65% at 450 nm, the peak wavelength of heat source light-emitting diodes (LEDs)). The plasmon-excited Au film is capable of rapidly heating the surrounding soln. to over 150 °C within 3 min. Using this method, ultrafast thermal cycling (30 cycles; heating and cooling rate of 12.79±0.93 °C s-1 and 6.6±0.29 °C s-1, resp.) from 55 °C (temp. of annealing) to 95 °C (temp. of denaturation) is accomplished within 5 min. Using photonic PCR thermal cycles, we demonstrate here successful nucleic acid (λ-DNA) amplification. Our simple, robust and low cost approach to ultrafast PCR using an efficient photonic-based heating procedure could be generally integrated into a variety of devices or procedures, including on-chip thermal lysis and heating for isothermal amplifications.

  28. 28

      Kim, M.; Lee, J. H.; Nam, J. M. Plasmonic Photothermal Nanoparticles for Biomedical Applications. Adv. Sci. 2019, 6, 1900471,  DOI: 10.1002/advs.201900471

      28

      Plasmonic Photothermal Nanoparticles for Biomedical Applications

      Kim, Minho; Lee, Jung-Hoon; Nam, Jwa-Min

      Advanced Science (Weinheim, Germany) (2019), 6 (17), n/a1900471CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)

      A review. Recent advances of plasmonic nanoparticles include fascinating developments in the fields of energy, catalyst chem., optics, biotechnol., and medicine. The plasmonic photothermal properties of metallic nanoparticles are of enormous interest in biomedical fields because of their strong and tunable optical response and the capability to manipulate the photothermal effect by an external light source. To date, most biomedical applications using photothermal nanoparticles have focused on photothermal therapy; however, to fully realize the potential of these particles for clin. and other applications, the fundamental properties of photothermal nanoparticles need to be better understood and controlled, and the photothermal effect-based diagnosis, treatment, and theranostics should be thoroughly explored. This Progress Report summarizes recent advances in the understanding and applications of plasmonic photothermal nanoparticles, particularly for sensing, imaging, therapy, and drug delivery, and discusses the future directions of these fields.

  29. 29

      Wang, S.; Huang, P.; Nie, L.; Xing, R.; Liu, D.; Wang, Z.; Lin, J.; Chen, S.; Niu, G.; Lu, G. Single Continuous Wave Laser Induced Photodynamic/Plasmonic Photothermal Therapy Using Photosensitizer-Functionalized Gold Nanostars. Adv. Mater. 2013, 25, 3055– 3061,  DOI: 10.1002/adma.201204623

      29

      Single Continuous Wave Laser Induced Photodynamic/Plasmonic Photothermal Therapy Using Photosensitizer-Functionalized Gold Nanostars

      Wang, Shouju; Huang, Peng; Nie, Liming; Xing, Ruijun; Liu, Dingbin; Wang, Zhe; Lin, Jing; Chen, Shouhui; Niu, Gang; Lu, Guangming; Chen, Xiaoyuan

      Advanced Materials (Weinheim, Germany) (2013), 25 (22), 3055-3061CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)

      Chlorin e6 conjugates nanostars (GNS-PEG-Ce6) are used to perform simultaneous photodynamic/plasmonic photothermal therapy (PDT/PPTT) upon single laser irradn. The early-phase PDT effect is coordinated with the late-phase PPTT effect to obtain synergistic anticancer efficiency. The prepd. GNS-PEG-Ce6 shows excellent water dispersibility, good biocompatibility, enhanced cellular uptake and remarkable anticancer efficiency upon irradn. in vivo.

  30. 30

      Qiu, G. Y.; Ng, S. P.; Wu, C. M. L. Differential Phase-Detecting Localized Surface Plasmon Resonance Sensor with Self-Assembly Gold Nano-Islands. Opt. Lett. 2015, 40, 1924– 1927,  DOI: 10.1364/OL.40.001924

      30

      Differential phase-detecting localized surface plasmon resonance sensor with self-assembly gold nano-islands

      Qiu, Guangyu; Ng, Siu Pang; Wu, Chi Man Lawrence

      Optics Letters (2015), 40 (9), 1924-1927CODEN: OPLEDP; ISSN:0146-9592. (Optical Society of America)

      Self-assembly (SAM) gold nano-islands are fabricated by two-step thin-film deposition-annealing method. Despite random distribution of the SAM, the p-polarized light after total internal reflection shows significant phase transition at the extinction wavelengths upon refractive index variation due to localized surface plasmon resonance (LSPR) effect. It resembles the sharp phase transition obsd. in conventional surface plasmon resonance (SPR) biosensors, so that the bulk sensitivity of the SAM-LSPR sensor is improved via the phase interrogation method. In this Letter, we present both computational and exptl. investigations to the SAM-LSPR sensor and the results show excellent agreement with each other. With bulk refractive index resoln. to 9.75 × 10-8 RIU, we believe the phase-detecting SAM-LSPR sensor would be an essential step toward low-cost label-free sensing applications.

  31. 31

      Smolyaninov, A.; El Amili, A.; Vallini, F.; Pappert, S.; Fainman, Y. Programmable Plasmonic Phase Modulation of Free-Space Wavefronts at Gigahertz Rates. Nat. Photonics 2019, 13, 431– 435,  DOI: 10.1038/s41566-019-0360-3

      31

      Programmable plasmonic phase modulation of free-space wavefronts at gigahertz rates

      Smolyaninov, Alexei; El Amili, Abdelkrim; Vallini, Felipe; Pappert, Steve; Fainman, Yeshaiahu

      Nature Photonics (2019), 13 (6), 431-435CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)

      Space-variant control of optical wavefronts is important for many applications in photonics, such as the generation of structured light beams, and is achieved with spatial light modulators. Com. devices, at present, are based on liq.-crystal and digital micromirror technologies and are typically limited to kilohertz switching speeds. To realize significantly higher operating speeds, new technologies and approaches are necessary. Here we demonstrate two-dimensional control of free-space optical fields at a wavelength of 1,550 nm at a 1 GHz modulation speed using a programmable plasmonic phase modulator based on near-field interactions between surface plasmons and materials with an electrooptic response. High χ(2) and χ(3) dielec. thin films of either aluminum nitride or silicon-rich silicon nitride are used as an active modulation layer in a surface plasmon resonance configuration to realize programmable space-variant control of optical wavefronts in a 4 × 4 pixel array at high speed.

  32. 32

      Chen, Z. X.; Shan, X. N.; Guan, Y.; Wang, S. P.; Zhu, J. J.; Tao, N. J. Imaging Local Heating and Thermal Diffusion of Nanomaterials with Plasmonic Thermal Microscopy. ACS Nano 2015, 9, 11574– 11581,  DOI: 10.1021/acsnano.5b05306

      32

      Imaging Local Heating and Thermal Diffusion of Nanomaterials with Plasmonic Thermal Microscopy

      Chen, Zixuan; Shan, Xiaonan; Guan, Yan; Wang, Shaopeng; Zhu, Jun-Jie; Tao, Nongjian

      ACS Nano (2015), 9 (12), 11574-11581CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

      Measuring local heat generation and dissipation in nanomaterials is crit. for understanding the basic properties and developing applications of nanomaterials, including photothermal therapy and joule heating of nanoelectronics. Several technologies have been developed to probe local temp. distributions in nanomaterials, but a sensitive thermal imaging technol. with high temporal and spatial resoln. is still lacking. Here, we describe plasmonic thermal microscopy (PTM) to image local heat generation and diffusion from nanostructures in biol. relevant aq. solns. We demonstrate that PTM can detect local temp. change as small as 6 mK with temporal resoln. of 10 μs and spatial resoln. of submicrons (diffraction limit). With PTM, we have successfully imaged photothermal generation from single nanoparticles and graphene pieces, studied spatiotemporal distribution of temp. surrounding a heated nanoparticle, and obsd. heating at defect sites in graphene. We further show that the PTM images are in quant. agreement with theor. simulations based on heat transport theories.

  33. 33

      Baffou, G.; Quidant, R.; García de Abajo, F. J. Nanoscale Control of Optical Heating in Complex Plasmonic Systems. ACS Nano 2010, 4, 709– 716,  DOI: 10.1021/nn901144d

      33

      Nanoscale Control of Optical Heating in Complex Plasmonic Systems

      Baffou, Guillaume; Quidant, Romain; Garcia de Abajo, F. Javier

      ACS Nano (2010), 4 (2), 709-716CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

      The authors introduce a numerical technique to study the temp. distribution in arbitrarily complex plasmonic systems subject to external illumination. The authors perform both electromagnetic and thermodn. calcns. based upon a time-efficient boundary element method. Two kinds of plasmonic systems are studied to illustrate the potential of such a technique. First, the authors focus on individual particles with various morphologies. In analogy with electrostatics, the authors introduce the concept of thermal capacitance. This geometry-dependent quantity allows one to assess the temp. increase inside a plasmonic particle from the sole knowledge of its absorption cross section. The authors present universal thermal-capacitance curves for ellipsoids, rods, disks, and rings. Addnl., the authors study assemblies of nanoparticles in close proximity and show that, despite its diffusive nature, the temp. distribution can be made highly nonuniform even at the nanoscale using plasmonic systems. A significant degree of nanoscale control over the individual temps. of neighboring particles is demonstrated, depending on the external light wavelength and direction of incidence. The authors illustrate this concept with simulations of Au sphere dimers and chains in H2O. Work opens new possibilities for selectively controlling processes such as local melting for dynamic patterning of textured materials, chem. and metabolic thermal activation, and heat delivery for producing mech. motion with spatial precision in the nanoscale.

  34. 34

      Baffou, G.; Bon, P.; Savatier, J.; Polleux, J.; Zhu, M.; Merlin, M.; Rigneault, H.; Monneret, S. Thermal Imaging of Nanostructures by Quantitative Optical Phase Analysis. ACS Nano 2012, 6, 2452– 2458,  DOI: 10.1021/nn2047586

      34

      Thermal Imaging of Nanostructures by Quantitative Optical Phase Analysis

      Baffou, Guillaume; Bon, Pierre; Savatier, Julien; Polleux, Julien; Zhu, Min; Merlin, Marine; Rigneault, Herve; Monneret, Serge

      ACS Nano (2012), 6 (3), 2452-2458CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

      The authors introduce an optical microscopy technique aimed at characterizing the heat generation arising from nanostructures, in a comprehensive and quant. manner. Namely, the technique permits (i) mapping the temp. distribution around the source of heat, (ii) mapping the heat power d. delivered by the source, and (iii) retrieving the abs. absorption cross section of light-absorbing structures. The technique is based on the measure of the thermal-induced refractive index variation of the medium surrounding the source of heat. The measurement is achieved using an assocn. of a regular CCD camera along with a modified Hartmann diffraction grating. Such a simple assocn. makes this technique straightforward to implement on any conventional microscope with its native broadband illumination conditions. The authors illustrate this technique on Au nanoparticles illuminated at their plasmonic resonance. The spatial resoln. of this technique is diffraction limited, and temp. variations weaker than 1 K can be detected.

  35. 35

      Zhu, N.; Zhang, D. Y.; Wang, W. L.; Li, X. W.; Yang, B.; Song, J. D.; Zhao, X.; Huang, B. Y.; Shi, W. F.; Lu, R. J.; Niu, P. H.; Zhan, F. X.; Ma, X. J.; Wang, D. Y.; Xu, W. B.; Wu, G. Z.; Gao, G. G. F.; Tan, W. J. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727– 733,  DOI: 10.1056/NEJMoa2001017

      35

      A novel coronavirus from patients with pneumonia in China, 2019

      Zhu, Na; Zhang, Dingyu; Wang, Wenling; Li, Xingwang; Yang, Bo; Song, Jingdong; Zhao, Xiang; Huang, Baoying; Shi, Weifeng; Lu, Roujian; Niu, Peihua; Zhan, Faxian; Ma, Xuejun; Wang, Dayan; Xu, Wenbo; Wu, Guizhen; Gao, George F.; Tan, Wenjie

      New England Journal of Medicine (2020), 382 (8), 727-733CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)

      In Dec. 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. Complete genome sequences of the three novel coronaviruses were submitted to GISAID (BetaCoV/Wuhan/ IVDC-HB-01/2019, accession ID: EPI_ISL_402119; BetaCoV/Wuhan/IVDC-HB-04/2020, accession ID: EPI_ISL_402120; BetaCoV/Wuhan/IVDC-HB-05/2019, accession ID: EPI_ISL_402121).

  36. 36

      Xu, S. C.; Zhan, J.; Man, B. Y.; Jiang, S. Z.; Yue, W. W.; Gao, S. B.; Guo, C. G.; Liu, H. P.; Li, Z. H.; Wang, J. H.; Zhou, Y. Q. Real-Time Reliable Determination of Binding Kinetics of DNA Hybridization Using a Multi-Channel Graphene Biosensor. Nat. Commun. 2017,  DOI: 10.1038/ncomms14902

      There is no corresponding record for this reference.

  37. 37

      Schreiber, G.; Haran, G.; Zhou, H. X. Fundamental Aspects of Protein-Protein Association Kinetics. Chem. Rev. 2009, 109, 839– 860,  DOI: 10.1021/cr800373w

      37

      Fundamental Aspects of Protein-Protein Association Kinetics

      Schreiber, G.; Haran, G.; Zhou, H.-X.

      Chemical Reviews (Washington, DC, United States) (2009), 109 (3), 839-860CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

      A review. This review focuses on recent advances in deciphering the kinetic pathway of protein complex formation, the nature of the precomplex formed through diffusion (which the authors term the "transient complex"), the transition state and other intermediates (such as the so-called encounter complex) along the assocn. pathway.

  38. 38

      Qiu, G.; Yue, Y.; Tang, J.; Zhao, Y.-B.; Wang, J. Total Bioaerosols Detection by a Succinimidyl-Ester-Functionalized Plasmonic Biosensor to Reveal Different Characteristics at Three Locations in Switzerland. Environ. Sci. Technol. 2020, 54, 1353– 1362,  DOI: 10.1021/acs.est.9b05184

      38

      Total Bioaerosol Detection by a Succinimidyl-Ester-Functionalized Plasmonic Biosensor To Reveal Different Characteristics at Three Locations in Switzerland

      Qiu, Guangyu; Yue, Yang; Tang, Jiukai; Zhao, Yi-Bo; Wang, Jing

      Environmental Science & Technology (2020), 54 (3), 1353-1362CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

      Bioaerosols consisting of biol. originated airborne particles such as microbes, metabolites, toxins, and fragments of microorganisms are present ubiquitously in the living environment. The international interests in bioaerosols have rapidly increased because of their many potential health effects. Thus, accurate and fast detection of total bioaerosols in different environments has become an important task for safeguarding against biol. threats and broadening the pool of bioaerosol knowledge. To quickly evaluate the total bioaerosol concn., the authors developed a localized surface plasmon resonance biosensor based on succinimidyl-ester-functionalized gold nanoislands (SEF-AuNIs) for quant. bioaerosol detection. The detection limit of the proposed SEF-AuNI sensors for model bacteria Escherichia coli and Bacillus subtilis can go to 0.5119 and 1.69 cells/mL, resp. To demonstrate the capability of this bioaerosol sensing technique, the authors tested aerosol samples collected from Bern (urban station), Basel (suburban station), and Rigi mountain (rural and high altitude station) in Switzerland and further investigated the correlation with endotoxin and PM10. The results substantiated that the SEF-AuNI sensors could be a reliable candidate for total bioaerosol detection and air quality assessment.

  39. 39

      Pan, Y.; Zhang, D.; Yang, P.; Poon, L. L.; Wang, Q. Viral Load of SARS-CoV-2 in Clinical Samples. Lancet Infect. Dis. 2020, 20, 411,  DOI: 10.1016/S1473-3099(20)30113-4

      39

      Viral load of SARS-CoV-2 in clinical samples

      Pan, Yang; Zhang, Daitao; Yang, Peng; Poon, Leo L. M.; Wang, Quanyi

      Lancet Infectious Diseases (2020), 20 (4), 411-412CODEN: LIDABP; ISSN:1473-3099. (Elsevier Ltd.)

      Serial samples (throat swabs, sputum, urine, and stool) from patients in Beijing were collected daily after their hospitalization. Among 30 pairs of throat swab and sputum samples available, viral loads were significantly correlated for days 1-14. Although the viral loads in stool samples were less than those of respiratory samples, precautionary measures should be considered when handling fecal samples.

• Supporting Information

  Supporting Information

  ---

  The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.0c02439.

  • Absorbance spectra of AuNIs; temperature profile of PPT heating; PPT heating system for characterizing the temperature distribution; selected target sequences from SARS-CoV-2 and SARS-CoV; complementary thiol-cDNA for LSPR functionalization; microfluidic detection system; comparison of AuNI surface functionalization; PPT effect on real-time LSPR detection; discrimination of two similar sequences without PPT heat; dissociation rate constant of RdRp-SARS; blank measurement for LoD (PDF)

  • nn0c02439_si_001.pdf (3.4 MB)

  
  

  Terms & Conditions

  Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.