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Rapid detection of antibodies to SARS-CoV-2 is critical for COVID-19 diagnostics, epidemiological research, and studies related to vaccine evaluation. It is known that the nucleocapsid (N) is the most abundant protein of SARS-CoV-2 and can serve as an excellent biomarker due to its strong immunogenicity. This paper reports a rapid and ultrasensitive 3D biosensor for quantification of COVID-19 antibodies in seconds via electrochemical transduction. This sensor consists of an array of three-dimensional micro-length-scale electrode architecture that is fabricated by aerosol jet 3D printing, which is an additive manufacturing technique. The micropillar array is coated with N proteins via an intermediate layer of nano-graphene and is integrated into a microfluidic channel to complete an electrochemical cell that uses antibody-antigen interaction to detect the antibodies to the N protein. Due to the structural innovation in the electrode geometry, the sensing is achieved in seconds, and the sensor shows an excellent limit of detection of 13 fm and an optimal detection range of 100 fm to 1 nm. Furthermore, the sensor can be regenerated at least 10 times, which reduces the cost per test. This work provides a powerful platform for rapid screening of antibodies to SARS-CoV-2 after infection or vaccination.
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Técnicas Biossensoriais , COVID-19 , Anticorpos Antivirais , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , Eletrodos , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultrarapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-12 s using a previously reported nanomaterial-based three-dimensional (3D)-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction, where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used to test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at a concentration as low as picomole within 10-12 s in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating the control and prevention of infectious epidemics.
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Técnicas Biossensoriais , COVID-19 , Grafite , Nanopartículas Metálicas , Anticorpos Antivirais , COVID-19/diagnóstico , Ouro , Humanos , Impressão Tridimensional , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
Hybrid carbon fiber reinforced polymer composites are a new breed of materials currently being explored and characterized for next-generation aerospace applications. Through the introduction of secondary reinforcements, such as alumina nanoparticles, hybrid properties including improved mechanical properties-fracture toughness, for example-and stress-sensing capabilities can be achieved. However, problems with manufacturing can arise resulting from the inherent variability of the manufacturing techniques along with the tendency for the nanoparticles to agglomerate. Photoluminescence spectroscopy is used to investigate the effects of adjustments to manufacturing processes and silane functionalization on particle dispersion and sample consistency between samples of the same type. This work finds that application of surface treatments on the nanoparticles improved their dispersion, with the reactive treatment providing for the most consistency among samples. Improvements to dispersion and increased consistency resulting from specific changes in manufacturing processes were shown numerically. Findings provide a manufacturing recommendation to achieve optimum dispersion and mechanical properties of the composite.
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Background: Global longitudinal strain (GLS) imaging is a multifaceted modality that has been utilized in various fields of clinical cardiology in the recent past; however, its implementation for the assessment of ischemia has been limited. Objectives: This study aimed to document the functional changes in GLS secondary to acute myocardial ischemia in patients with chronic chest pain. Methods: In this unblinded, single-center, investigator-initiated, prospective pilot study, the functional changes in GLS at baseline, during, and immediately following coronary percutaneous intervention were monitored in 10 ambulatory patients who underwent elective catheterization. The exclusion criteria included a low ejection fraction, or a history of chemoradiation, myopathy, and congenital heart disease. Results: The average GLS at baseline, during the balloon intervention (BI), and 1-2â¯min after BI was -15.4â¯%⯱â¯3.3â¯%, -10.2â¯%⯱â¯3.6â¯%, and -16.1â¯%⯱â¯4.2â¯%, respectively. The average GLS decreased significantly by 5.1â¯% (95â¯% CI, -7.9â¯% to -2.3; Pâ¯=â¯0.0013) from baseline to BI, increased by 6.3â¯% (95â¯% CI, 3.7â¯% to 8.9â¯%; Pâ¯<â¯0.001) from BI to immediately post-BI, and increased by 0.7â¯% from baseline to post-BI (95â¯% CI, -0.4â¯% to 2.7â¯%; Pâ¯=â¯0.161). Conclusion: Patients undergoing BI showed a significant decrease in the average GLS within 1-2â¯min of BI, with GLS returning to baseline subsequently, clearly demonstrating the efficacy of the modality and the clinical significance of data obtained. These functional changes replicate cardiac perfusion to the segments supplied by respective vessels and its effect with reperfusion or ballooning. The slight increase in GLS from baseline to post-intervention was not statistically significant, which could be attributed to the confounding factors. Analyzing our data, we can safely conclude that GLS is potentially a sensitive, temporal, and quantitative tool for identifying patients with acute ischemia with its limitations and need for further perfection of this modality. Therefore, GLS assessments on 2D echo can be used for risk stratification of patients with subacute to chronic chest pain concerning for ischemia in addition to EKG, troponins and other data obtained by non-invasive testing and evaluation.
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Patients with posterior circulation ischemia due to vertebral artery stenosis account for 20 to 25% of ischemic strokes and have an increased risk of recurrent stroke. In patients treated with medical therapy alone, the risk of recurrence is particularly increased in the first few weeks after symptoms occur, with an annual stroke rate of 10 to 15%. Additionally, obstructive disease of the vertebrobasilar system carries a worse prognosis, with a 30% mortality at 2-years if managed medically without additional surgical or endovascular intervention. Percutaneous transluminal angioplasty and stenting of symptomatic vertebral artery stenosis are promising options widely used in clinical practice with good technical results; however, the improved clinical outcome has been examined in various clinical trials without a sufficient sample size to conclusively determine whether stenting is better than medical therapy. Surgical revascularization is an alternative approach for the treatment of symptomatic vertebral artery stenosis that carries a 10-20% mortality rate. Despite the advances in medical therapy and endovascular and surgical options, symptomatic vertebral artery stenosis continues to impose a high risk of stroke recurrence with associated high morbidity and mortality. This review aims to provide a focused update on the percutaneous treatment of vertebral artery stenosis, its appropriate diagnostic approach, and advances in medical therapies.
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Acidente Vascular Cerebral , Insuficiência Vertebrobasilar , Humanos , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico , Insuficiência Vertebrobasilar/terapia , Insuficiência Vertebrobasilar/complicações , Angioplastia/efeitos adversos , Angioplastia/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , StentsRESUMO
Microelectrode arrays provide the means to record electrophysiological activity critical to brain research. Despite its fundamental role, there are no means to customize electrode layouts to address specific experimental or clinical needs. Moreover, current electrodes demonstrate substantial limitations in coverage, fragility, and expense. Using a 3D nanoparticle printing approach that overcomes these limitations, we demonstrate the first in vivo recordings from electrodes that make use of the flexibility of the 3D printing process. The customizable and physically robust 3D multi-electrode devices feature high electrode densities (2600 channels/cm2 of footprint) with minimal gross tissue damage and excellent signal-to-noise ratio. This fabrication methodology also allows flexible reconfiguration consisting of different individual shank lengths and layouts, with low overall channel impedances. This is achieved, in part, via custom 3D printed multilayer circuit boards, a fabrication advancement itself that can support several biomedical device possibilities. This effective device design enables both targeted and large-scale recording of electrical signals throughout the brain.
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Pseudomonas aeruginosa is a nosocomial pathogen containing various resistance mechanisms. Among them, metallo-ß-lactamase (MBL)-producing Pseudomonas are difficult to treat. Fosfomycin is an older antibiotic that has recently seen increased usage due to its activity against a broad spectrum of multidrug-resistant organisms. Our aim was to evaluate the combination of fosfomycin and meropenem against 20 MBL-producing P. aeruginosa (100% meropenem-resistant and 20% fosfomycin-resistant) using both an Etest minimal inhibitory concentration (MIC): MIC method and time-kill assay. MICs for fosfomycin and meropenem were determined by Etest and by broth microdilution method for the latter. The combination demonstrated synergy by Etest in 3/20 (15%) isolates and 5/20 (25%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 14/20 (70%) of isolates. No antagonism was found. Comparing both methods, Etest MIC: MIC method may be useful to rapidly evaluate other antimicrobial combinations.
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Antibacterianos , Fosfomicina , Meropeném , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Fosfomicina/farmacologia , Meropeném/farmacologia , beta-LactamasesRESUMO
Sensing of clinically relevant biomolecules such as neurotransmitters at low concentrations can enable an early detection and treatment of a range of diseases. Several nanostructures are being explored by researchers to detect biomolecules at sensitivities beyond the picomolar range. It is recognized, however, that nanostructuring of surfaces alone is not sufficient to enhance sensor sensitivities down to the femtomolar level. In this paper, we break this barrier/limit by introducing a sensing platform that uses a multi-length-scale electrode architecture consisting of 3D printed silver micropillars decorated with graphene nanoflakes and use it to demonstrate the detection of dopamine at a limit-of-detection of 500 attomoles. The graphene provides a high surface area at nanoscale, while micropillar array accelerates the interaction of diffusing analyte molecules with the electrode at low concentrations. The hierarchical electrode architecture introduced in this work opens the possibility of detecting biomolecules at ultralow concentrations.
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Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/química , Impressão Tridimensional , Algoritmos , Técnicas Biossensoriais/instrumentação , Dopamina/análise , Dopamina/metabolismo , Técnicas Eletroquímicas/instrumentação , Dispositivos Lab-On-A-Chip , Microscopia Eletrônica de Varredura , Modelos Teóricos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Oxirredução , Reprodutibilidade dos Testes , Prata/químicaRESUMO
Rapid diagnosis is critical for the treatment and prevention of diseases. An advanced nanomaterial-based biosensing platform that detects COVID-19 antibodies within seconds is reported. The biosensing platform is created by 3D nanoprinting of three-dimensional electrodes, coating the electrodes by nanoflakes of reduced-graphene-oxide (rGO), and immobilizing specific viral antigens on the rGO nanoflakes. The electrode is then integrated with a microfluidic device and used in a standard electrochemical cell. When antibodies are introduced on the electrode surface, they selectively bind with the antigens, changing the impedance of the electrical circuit which is detected via impedance spectroscopy. Antibodies to SARS-CoV-2 spike S1 protein and its receptor-binding-domain (RBD) are detected at a limit-of-detection of 2.8 × 10-15 and 16.9 × 10-15 m, respectively, and read by a smartphone-based user interface. The sensor can be regenerated within a minute by introducing a low-pH chemistry that elutes the antibodies from the antigens, allowing successive sensing of test samples using the same sensor. Sensing of S1 and RBD antibodies is specific, which cross-reacts neither with other antibodies such as RBD, S1, and nucleocapsid antibody nor with proteins such as interleukin-6. The proposed sensing platform could also be useful to detect biomarkers for other infectious agents such as Ebola, HIV, and Zika.