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1.
J Mater Chem B ; 9(42): 8851-8861, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1526111

ABSTRACT

Nanomaterial-based optical techniques for biomarker detection have garnered tremendous attention from the nanofabrication community due to their high precision and enhanced limit of detection (LoD) features. These nanomaterials are highly responsive to local refractive index (RI) fluctuations, and their RI unit sensitivity can be tuned by varying the chemical composition, geometry, and dimensions of the utilized nanostructures. To improve the sensitivity and LoD values of these nanomaterials, it is common to increase both dimensions and aspect ratios of the fabricated nanostructures. However, limited by the complexity, prolonged duration, and elevated costs of the available nanofabrication techniques, mass production of these nanostructures remains challenging. To address not only high accuracy, but also speed and production effectiveness in these nanostructures' fabrication, our work reports, for the first time, a fast, high-throughput, and cost-effective nanofabrication protocol for routine manufacturing of polymer-based nanostructures with high sensitivity and calculated LoD in the pM range by utilizing anodized aluminum oxide (AAO) membranes as templates. Specifically, our developed platform consists of arrays of nearly uniform polystyrene nanopillars with an average diameter of ∼185 nm and aspect ratio of ∼11. We demonstrate that these nanostructures can be produced at a high speed and a notably low price, and that they can be efficiently applied for biosensing purposes after being coated with aluminum-doped silver (Ag/Al) thin films. Our platform successfully detected very low concentrations of human C-reactive protein (hCRP) and SARS-CoV-2 spike protein biomarkers in human plasma samples with LoDs of 11 and 5 pM, respectively. These results open new opportunities for day-to-day fabrication of high aspect ratio arrays of nanopillars that can be used as a base for nanoplasmonic sensors with competitive LoD values. This, in turn, contributes to the development of point-of-care devices and further improvement of the existing nanofabrication techniques, thereby enriching the fields of pharmacology, clinical analysis, and diagnostics.


Subject(s)
Aluminum Oxide/chemistry , Biomarkers/blood , High-Throughput Screening Assays/methods , Nanostructures/chemistry , Silver/chemistry , Biosensing Techniques , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/virology , Dimethylpolysiloxanes/chemistry , Humans , Limit of Detection , Point-of-Care Systems , Polystyrenes/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/blood
2.
ACS Sens ; 6(3): 976-984, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1047925

ABSTRACT

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global medical systems and economies and rules our daily living life. Controlling the outbreak of SARS-CoV-2 has become one of the most important and urgent strategies throughout the whole world. As of October 2020, there have not yet been any medicines or therapies to be effective against SARS-CoV-2. Thus, rapid and sensitive diagnostics is the most important measures to control the outbreak of SARS-CoV-2. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. For proof of concept, mimic SARS-CoV-2 consisting of spike proteins and polystyrene beads are used for experiments. Experimental results demonstrate that the proposed approach allows the rapid detection of mimic SARS-CoV-2 with a limit of detection of 0.084 nM (5.9 fmole). The proposed approach has great potential for designing a low-cost and point-of-care device for rapid and sensitive diagnostics of SARS-CoV-2.


Subject(s)
Antibodies, Monoclonal/chemistry , Magnetite Nanoparticles/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Antibodies, Monoclonal/immunology , Biosensing Techniques , Magnetic Phenomena , Polystyrenes/chemistry , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
3.
Talanta ; 225: 122064, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1003087

ABSTRACT

Quantum dots (QDs) based fluorescent nanobeads are considered as promising materials for next generation point-of-care diagnosis systems. In this study, we carried out, for the first time, the synthesis of QDs nanobeads using polystyrene (PS) nanobead as the template. QDs loading on PS nanobead surface in this method can be readily achieved by the use of polyelectrolyte, avoiding the time-consuming and uncontrollable silane reagents-involved functionalization procedure that conventional synthesis of silica-based QDs nanobeads often suffer from. Notably, the application of QDs nanobeads in suspension microarray for H5N1 virus detection leads to a sensitivity lower than 25 PFU/mL. In addition, QDs nanobead was also incorporated into lateral flow assay for SARS-CoV-2 antibody detection, leading to more than one order of magnitude detection sensitivity as compared to that of commercial one based on colloid gold.


Subject(s)
Biosensing Techniques/methods , COVID-19/diagnosis , Influenza, Human/diagnosis , Microspheres , Nanostructures/chemistry , Polystyrenes/chemistry , Quantum Dots , Antibodies, Viral/immunology , COVID-19/virology , Fluorescent Dyes/chemistry , Humans , Influenza A Virus, H5N1 Subtype/physiology , Influenza, Human/virology , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanostructures/ultrastructure , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Sensitivity and Specificity , Silicon Dioxide/chemistry
4.
ACS Appl Mater Interfaces ; 12(52): 58360-58368, 2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-989662

ABSTRACT

The SARS-CoV-2 virus that causes the COVID-19 epidemic can be transmitted via respiratory droplet-contaminated surfaces or fomites, which urgently requires a fundamental understanding of intermolecular interactions of the coronavirus with various surfaces. The corona-like component of the outer surface of the SARS-CoV-2 virion, named spike protein, is a key target for the adsorption and persistence of SARS-CoV-2 on various surfaces. However, a lack of knowledge in intermolecular interactions between spike protein and different substrate surfaces has resulted in ineffective preventive measures and inaccurate information. Herein, we quantified the surface interaction and adhesion energy of SARS-CoV-2 spike protein with a series of inanimate surfaces via atomic force microscopy under a simulated respiratory droplet environment. Among four target surfaces, polystyrene was found to exhibit the strongest adhesion, followed by stainless steel (SS), gold, and glass. The environmental factors (e.g., pH and temperature) played a role in mediating the spike protein binding. According to systematic quantification on a series of inanimate surfaces, the adhesion energy of spike protein was found to be (i) 0-1 mJ/m2 for hydrophilic inorganics (e.g., silica and glass) due to the lack of hydrogen bonding, (ii) 2-9 mJ/m2 for metals (e.g., alumina, SS, and copper) due to the variation of their binding capacity, and (iii) 6-11 mJ/m2 for hydrophobic polymers (e.g., medical masks, safety glass, and nitrile gloves) due to stronger hydrophobic interactions. The quantitative analysis of the nanomechanics of spike proteins will enable a protein-surface model database for SARS-CoV-2 to help generate effective preventive strategies to tackle the epidemic.


Subject(s)
Glass/chemistry , Gold/chemistry , Polystyrenes/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Stainless Steel/chemistry , Adsorption , Fomites/virology , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Microscopy, Atomic Force , Surface Properties , Temperature
5.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-978131

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Subject(s)
COVID-19/therapy , Hemoperfusion/instrumentation , Hemoperfusion/methods , Polymyxin B/chemistry , Polystyrenes/chemistry , Adult , Aged , Aged, 80 and over , Arteries/metabolism , Biomarkers/urine , Blood Gas Analysis , Cytokines/blood , Endothelium, Vascular/metabolism , Female , Hospitalization , Humans , Male , Middle Aged , Oxygen/metabolism , Respiration, Artificial , Retrospective Studies , Risk , beta 2-Microglobulin/urine
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