Nanoconjugated materials as sensors in point-of-care diagnostic tools: Detection of small molecules and viruses

Diagnostic point of care (POC) tools have seen important advances through the many materials introduced to enhance and validate their wide range applications. One of the most used POC tools are paper-based colorimetric formats. These POC are generally based on the use of antibody-antigen pairs interaction for the detection. However, small molecules can be a challenge for these formats and drastically reduce the sensitivity of POC. Therefore, novel conjugated materials using nanoparticles, polymers, and other composites have been developed which helped to tackle the sensitivity issues and, by using these materials, the portable sensors became more trustworthy for the detection of small molecules. These materials can be sculpted into various nanostructures and networks such as nanovesicles and nanogels with high biocompatibility and tunability. These are regarded as promising tools in the current and future lab-on-chip devices due to their accessibility and ease to manufacturing. In addition, the application of portable biosensing devices is of great importance in large-scale screenings of viruses including the coronavirus SARS-CoV-2 (responsible for the COVID-19 pandemic) or road control (i.e., substance of abuse). These approaches were made more accessible using smartphone-assisted analyses allowing for the decentralization of diagnosis. In this chapter, we present the latest findings in the development of polymeric-based materials and biosensors aimed for the detection of viruses and small molecules of drug abuse through simplified approaches including colorimetric paper-based assays and electrochemical sensors. The use of nano-scaled bioconjugated materials became an integral component in sensing applications due to their various structural advantages in producing highly sensitive tools that rival bench-top instruments. New developments in material design opened the door for decentralized dispensation of medicines and public protection that allows effective onsite and point-of-care diagnostics. © 2023 Elsevier B.V.

Comparison of electrochemical immunosensor platforms for indiscriminate SARS-CoV-2 variant detection

Since the first days of the pandemic, diagnosis of patients infected with the SARS-CoV-2 has been one of the most important parameters to control the virus. For this reason, many studies have been carried out to develop various methods for rapid and accurate diagnosis, but mutations and the occurrence of successive variants have made accurate diagnosis difficult. In this study, a screen-printed carbon electrode was used to develop magnetic nanoparticle (MNP)-based electrochemical biosensing systems that selectively detect SARS-CoV-2 virus and its variants (original, alpha, beta, and delta) in nasopharyngeal swabs. These electrodes were modified with MNPs conjugated to SARS-CoV-2 S1, S2 proteins and swab samples. Then, commercially available SARS-CoV-2-specific anti-S1 and anti-S2 antibodies and antibody cocktails purified from serum samples were applied to the surface and the performance of the platforms was compared. Analytical parameters and electrode surface characterizations were performed by electrochemical measurements after each modification step. After optimization studies of the developed biosensor platforms, the detection of limit for the antibody cocktail- based sensors were determined to be 0.53-0.75 ng/mL, while it was calculated to be 0.93-0.99 ng/mL for the anti-S1 and anti- S2-based sensors. The performance of the platforms in real nasopharyngeal swab samples (negative, original, alpha, beta, and delta variants) was evaluated and it was found that the polyclonal antibody cocktail outperformed the commercial anti-S1 and anti-S2 antibodies. As a result, polyclonal antibody cocktail, with an overall sensitivity, specificity, and accuracy of 100%, is a versatile electrochemical biosensor system for the detection of the different variants of SARS-CoV-2. We hope that the biosensor platform modified with polyclonal antibodies can be used as a potential diagnostic tool that can be applied to such epidemics in the future. Synthetic biology.

Acute kidney injury in hospitalized COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in hospitalized patients are not well studied. MATERIALS AND METHODS:  This is a retrospective cohort study conducted in two major university hospitals. Electronic health records of the patients, 18 years or older, hospitalized between 13 April and 1 June 2020 with confirmed COVID-19 were reviewed. We described the incidence and the risk factors for AKI development in COVID-19 patients. Furthermore, we investigated the effects of AKI on the length of hospital and intensive care unit (ICU) stay, the admission rates to ICU, the percentage of patients with cytokine storm and in-hospital mortality rate. RESULTS: Among 770 hospitalized patients included in this study, 92 (11.9%) patients developed AKI. The length of hospitalized days (16 vs 9.9, p < 0.001) and days spent in the hospital until ICU admission (3.5 vs. 2.5, p = 0.003) were higher in the AKI group compared to patients without AKI. In addition, ICU admission rates were also significantly higher in patients with AKI (63% vs. 20.7%, p < 0.001). The percentage of patients with AKI who developed cytokine storm was significantly higher than patients without AKI (25.9% vs. 14%, p = 0.009). Furthermore, the in-hospital mortality rate was significantly higher in patients with AKI (47.2% vs. 4.7%, p < 0.001). CONCLUSIONS: AKI is common in hospitalized COVID-19 patients. Furthermore, we show that AKI increases the admission rates to ICU and in-hospital mortality. Our findings suggest that AKI should be effectively managed to prevent the adverse outcomes in COVID-19 patients.

In vitro studies for BCS classification of an antiviral agent, favipiravir. (COVID-19 dedicated issue.)

Favipiravir (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is a purine nucleic acid analog, which is an antiviral agent used in the treatment of influenza. Since the recent outbreak caused by 2019-novel coronavirus (nCoV), there has been a seek for effective antiviral agents to be used in the treatment of coronavirus disease 2019 (COVID-19), and favipiravir has been one of the options which provides a broad-spectrum therapy. Herein, we studied the aqueous solubility and in vitro permeability characteristics of favipiravir in order to shed light on the BCS classification of this antiviral agent used in COVID-19 therapy. The in vitro solubility was assessed using saturated solution of favipiravir in four different aqueous media and the solubility values were evaluated during 72 h at 37..C. The solubility of favipiravir was between 4.48 to 8.5 mg/ml, which is 5.85 to 10.63 times of calculated solubility limit. Caco-2 cell monolayers were utilized for the permeability assessment, and the drug solutions in three different concentrations including the highest dose required for bioequivalence exemption of the immediate release dosage form were applied. The effect of efflux transporters on the permeability of favipiravir was also determined using a P-gp inhibitor, Verapamil HCl. According to the data obtained from the in vitro studies, favipiravir can be considered as a representative of class I compound.