The spread of SARS-CoV-2 virus in the ongoing global pandemic has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is ...crucial for controlling and stopping the pandemic. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. As low as 370 vp/mL were detected in one step within 15 min and the virus concentration can be quantified linearly in the range of 0 to 107 vp/mL. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.
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•15min one step SARS-CoV-2 viral particles detection.•No sample processing and low-cost equipment and biosensor chip.•Sensitive for asymptomatic carriers diagnosis potentially.
Abstract
Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically “cold” tumors, but photo-generated reactive oxygen ...species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.
Technological innovation, cost effectiveness, and miniaturization are key factors that determine the commercial adaptability and sustainability of sensing platforms. Nanoplasmonic biosensors based on ...nanocup or nanohole arrays are attractive for the development of various miniaturized devices for clinical diagnostics, health management, and environmental monitoring. In this review, we discuss the latest trends in the engineering and development of nanoplasmonic sensors as biodiagnostic tools for the highly sensitive detection of chemical and biological analytes. We focused on studies that have explored flexible nanosurface plasmon resonance systems using a sample and scalable detection approach in an effort to highlight multiplexed measurements and portable point-of-care applications.
A fast and reliable method for the detection of molecular interactions in real‐time is necessary for drug screening and control of infections or diseases. Therefore, this study aims to develop a ...high‐throughput portable nanoplasmonic platform. This is done by integrating a nanocup array‐enhanced surface plasmon resonance (NanoSPR) sensor with a standard 96‐well plate or a simple eight‐pillar device, which can offer rapid and label‐free interaction analysis and highly sensitive binding kinetics for drug screening. To fabricate the wafer‐level NanoSPR biosensor, nanoimprint lithography, electron beam evaporation, and bonding technology have been used to offer low‐cost production on a mass scale. Meanwhile, a variety of ready‐to‐use NanoSPR biosensors are separately modified to demonstrate the high‐quality binding kinetics and affinity of different biomolecular interactions. Owing to their unique optical properties, the two developed portable NanoSPR devices provide the possibility of having a portable benchtop molecular interaction instrument that is very promising for meeting the needs of personal and laboratory testing. This study may pave the way for NanoSPR biosensors to achieve high‐throughput and easy‐to‐use molecular interaction analysis with outstanding performance.
Fast, label‐free, and high‐throughput portable NanoSPR devices are produced to be used for drug screening and control of infections or diseases. Various ready‐to‐use NanoSPR biosensors are separately modified to demonstrate the high‐quality binding affinity results, indicating that the cost‐effective platform can be used as a portable benchtop molecular interaction instrument that can meet the needs of personal and laboratory testing.
•A unique asymmetric ERA reaction was developed for SARS-CoV-2 detection.•NanoPEIA platform is based on asymmetric ERA reaction.•The NanoPEIA platform is high throughput and fast real-time and visual ...detection.•The NanoPEIA platform shows very low detection limit and specificity.
The novel mutations attributed by the high mutagenicity of the SARS-CoV-2 makes its prevention and treatment challenging. Developing an ultra-fast, point-of-care-test (POCT) protocol is critical for responding to large-scale spread of SARS-CoV-2 in public places and in resource-poor remote areas. Here, we developed a nanoplasmonic enhanced isothermal amplification (NanoPEIA) strategy that combines a nanoplasmonic sensor with isothermal amplification. The novel strategy provides an ideal easy-to operate detection platform for obtaining accurate, ultra-fast and high-throughput (96 samples can be tested together) data. For clinical samples with viral detection at Ct value <25, the entire process (including sample preparation, virus lysis, detection, and data analysis) can be completed within six minutes. The method is also appropriate for detection of SARS-CoV-2 γ-coronavirus mutants. The NanoPEIA method was validated using clinical samples from 21 patients with SARS-CoV-2 infection and 31 healthy individuals. The detection result on the 52 clinical samples for SARS-CoV-2 showed that the NanoPEIA platform had a 100% sensitivity for N and orf1ab genes, which was higher than those obtained using RT-qPCR (88.9% and 90.0%, respectively). The specificities of 31 clinical negative samples were 92.3% and 91.7% for the N gene and the orf1ab gene, respectively. The limits of detection (LoD) of the clinical samples were 28.3 copies/mL and 23.3 copies/mL for the N gene and the orf1ab gene, respectively. The efficient NanoPEIA detection strategy facilitates real-time detection and visualization within ultrashort durations and can be applied for POCT diagnosis in resource-poor and highly populated areas.
The microRNA21 (miR-21), a specific tumor biomarker, is crucial for the diagnosis of several cancer types, and investigation of its overexpression pattern is important for cancer diagnosis. Herein, ...we report a low-cost, rapid, ultrasensitive, and convenient biosensing strategy for the detection of miR-21 using a nanoplasmonic array chip coupled with gold nanoparticles (AuNPs). This sensing platform combines the surface plasmon resonance effect of nanoplasmonics (NanoSPR) and the localized surface plasmon resonance (LSPR) effect, which allows the real-time monitoring of the subtle optical density (OD) changes caused by the variations in the dielectric constant in the process of the hybridization of the target miRNA. Using this method, the miRNA achieves a broad detection range from 100 aM to 1 μM, and with a limit of detection (LoD) of 1.85 aM. Furthermore, this assay also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this platform has high throughput characteristics (96 samples can be detected simultaneously). This strategy exhibits more than 86.5 times enhancement in terms of sensitivity compared to that of traditional biosensors.
The accumulation of trace amounts of certain small molecules in food poses considerable human health challenges, including the potential for carcinogenesis and mutagenesis. Here, an ultrasensitive ...gold-platinum nanoflower-coupled metasurface plasmon resonance (MetaSPR) (APNMSPR) biosensor, based on a competitive immunoassay, was developed for the multiplexed and rapid quantitative analysis of trace small molecules in eggs, offering timely monitoring of food safety. This one-step biosensor can be integrated into either a newly designed detachable high-throughput MetaSPR chip-strip plate device or a standard 96-well plate for multiplexed small-molecule detection within a single egg. The limits of detection were 0.81, 1.12, and 1.74 ppt for florfenicol, fipronil, and enrofloxacin, respectively, demonstrating up to 1000-fold increased sensitivity and a 15-fold reduction in analysis time compared with those of traditional methods. The results obtained using the APNMSPR biosensor showed a strong correlation with those obtained using liquid chromatography-tandem mass spectrometry. The APNMSPR biosensor holds immense promise for the multiplexed, highly sensitive, and rapid quantitative analysis of small molecules for applications in food safety control, early diagnosis, and environmental monitoring.
A robust serological test is required to detect neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). A nanomaterial‐coupled metasurface plasmon ...resonance (MetaSPR) biosensor is developed for rapid multiplexing quantitative tests of the half maximal inhibitory concentration (IC50) value of SARS‐CoV‐2 NAbs in human sera. This biosensor is applied to a MetaSPR competitive or surrogate virus neutralization test (MSPR VNT) used for quantifying NAb‐mediated blockage of the interaction between the human angiotensin‐converting enzyme 2 (hACE2) receptor and the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein. Novel nanomaterial, gold platinum nanoflowers (Au@Pt NFs), is combined with the optimized MetaSPR chip for dual signal amplification. The clinical utility of this biosensor is validated in 40 participants, and the results are confirmed with the IC50 values calculated using the pseudovirus neutralization test. Similarly, the neutralization titer of Omicron and Delta variants and the ability of NAbs to resist these variants are monitored. The MSPR VNT miniaturized optical biosensor instrument has a high throughput and enables one‐step, rapid, and accurate quantification of SARS‐CoV‐2 variants or viruses causing other infectious diseases, which is applicable in vaccine trials, immune response studies, and epidemiological studies.
In this study, a metasurface plasmon resonance (MetaSPR) competitive or surrogate virus neutralization test (MSPR VNT) is established. Novel nanomaterial is combined with the optimized MetaSPR chip for dual signal amplification. This process has a low non‐specific reaction and can accurately calculate the IC50 value. In addition, the MSPR VNT miniaturized optical biosensor instrument has a high throughput, rapid, and accurate quantification of SARS‐CoV‐2 variants or other infectious diseases.
The formation of high-density silver nanoparticles and a novel method to precisely control the spacing between nanoparticles by temperature are demonstrated for a tunable surface enhanced Raman ...scattering substrates. The high-density nanoparticle thin film is accomplished by self-assembling through the Langmuir−Blodgett (LB) technique on a water surface and transferring the particle monolayer to a temperature-responsive polymer membrane. The temperature-responsive polymer membrane allows producing a dynamic surface enhanced Raman scattering substrate. The plasmon peak of the silver nanoparticle film red shifts up to 110 nm with increasing temperature. The high-density particle film serves as an excellent substrate for surface-enhanced Raman spectroscopy (SERS), and the scattering signal enhancement factor can be dynamically tuned by the thermally activated SERS substrate. The SERS spectra of Rhodamine 6G on a high-density silver particle film at various temperatures is characterized to demonstrate the tunable plasmon coupling between high-density nanoparticles.
Developing plasmonic biosensors that are low‐cost, portable, and relatively simple to operate remains challenging. Herein, a novel metasurface plasmon‐etch immunosensor is described, namely a ...nanozyme‐linked immunosorbent surface plasmon resonance biosensor, for the ultrasensitive and specific detection of cancer biomarkers. Gold‐silver composite nano cup array metasurface plasmon resonance chip and artificial nanozyme‐labeled antibody are used in two‐way sandwich analyte detection. Changes in the biosensor's absorption spectrum are measured before and after chip surface etching, which can be applied to immunoassays without requiring separation or amplification. The device achieved a limit of alpha‐fetoprotein (AFP) detection < 21.74 fM, three orders of magnitude lower than that of commercial enzyme‐linked immunosorbent assay kits. Additionally, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) are used for quantitative detection to verify the universality of the platform. More importantly, the accuracy of the platform is verified using 60 clinical samples; compared with the hospital results, the three biomarkers achieve high sensitivity (CEA: 95.7%; CA125: 90.9%; AFP: 86.7%) and specificity (CEA: 97.3%; CA125: 93.9%; AFP: 97.8%). Due to its rapidity, ease of use, and high throughput, the platform has the potential for high‐throughput rapid detection to facilitate cancer screening or early diagnostic testing in biosensing.
A nanozyme‐linked immunosorbent surface plasmon resonance biosensor integrating the low‐cost nano cup chip with the Au@Pt nanoflowers is developed, which can be used for an ultrasensitive (fM‐scale), rapid (minute‐level), and portable (pocket‐size) test for biomarker diagnosis. In order to verify the universality of the platform, three cancer biomarkers (alpha‐fetoprotein, carcinoembryonic antigen, carbohydrate antigen 125) are selected for quantitative detection. Most importantly, clinical samples are used to verify the accuracy and stability of the platform.
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