Simple, rapidly electroassembled thiolated PEG-based sensor interfaces enable rapid interrogation of antibody titer and glycosylation.

Process conditions established during the development and manufacture of recombinant protein therapeutics dramatically impacts their quality and clinical efficacy. Technologies that enable rapid assessment of product quality are critically important. Here, we describe the development of sensor interfaces that directly connect to electronics and enable near real-time assessment of antibody titer and N-linked galactosylation. We make use of a spatially resolved electroassembled thiolated polyethylene glycol hydrogel that enables electroactivated disulfide linkages. For titer assessment, we constructed a cysteinylated protein G that can be linked to the thiolated hydrogel allowing for robust capture and assessment of antibody concentration. For detecting galactosylation, the hydrogel is linked with thiolated sugars and their corresponding lectins, which enables antibody capture based on glycan pattern. Importantly, we demonstrate linear assessment of total antibody concentration over an industrially relevant range and the selective capture and quantification of antibodies with terminal ß-galactose glycans. We also show that the interfaces can be reused after surface regeneration using a low pH buffer. Our functionalized interfaces offer advantages in their simplicity, rapid assembly, connectivity to electronics, and reusability. As they assemble directly onto electrodes that also serve as I/O registers, we envision incorporation into diagnostic platforms including those in manufacturing settings.

Tracking economic activity in response to the COVID-19 crisis using nighttime lights - The case of Morocco.

Over the past decade, nighttime lights have become a widely used proxy for measuring economic activity. This paper examines the potential for high frequency nighttime lights data to provide "near real-time" tracking of the economic impacts of the COVID-19 crisis in Morocco. At the national level, there exists a statistically significant correlation between quarterly movements in Morocco's overall nighttime light intensity and movements in its real GDP. This finding supports the cautious use of lights data to track the economic impacts of the COVID-19 crisis at higher temporal frequencies and at the subnational and city levels, for which GDP data are unavailable. Relative to its pre-COVID-19 trend growth path of lights, Morocco experienced a large drop in the overall intensity of its lights in March 2020 following the country's first COVID-19 case and the introduction of strict lockdown measures, from which it has subsequently struggled to recover. At the subnational and city levels, while all regions and cities examined shared in March's national decline in nighttime light intensity, some suffered much larger declines than others. Since then, the relative effects of the COVID-19 shock across regions and cities appear to have largely persisted. Notwithstanding these findings, however, further research is required to ascertain the exact causes of the observed changes in light intensity and to fully verify that the results are driven by anthropogenic causes.

Development of a prototype device for near real-time surface-enhanced Raman scattering monitoring of biological samples.

With the fast growth of bioanalytical surface-enhanced Raman scattering (SERS), analytical methods have had to adapt to the complex nature of biological samples. In particular, interfering species and protein adsorption onto the SERS substrates have been addressed by sample preparation steps, such as precipitation or extraction, and by smart SERS substrate functionalisation. These additional handling steps however result in irreversible sample alteration, which in turn prevents sample monitoring over time. A new methodology, that enables near real-time, non-invasive and non-destructive SERS monitoring of biological samples, is therefore proposed. It combines solid SERS substrates, benefitting from liquid immersion resistance for extended periods of time, with an original protein filtering device and an on-field detection by means of a handheld Raman analyser. The protein removal device aims at avoiding protein surface fouling on the SERS substrate. It consists of an ultracentrifugation membrane fixed under a cell culture insert for multi-well plates. The inside of the insert is dedicated to containing biological samples. The solid SERS substrate and a simple medium, without any protein, are placed under the insert. By carefully selecting the membrane molecular weight cutoff, selective diffusion of small analytes through the device could be achieved whereas larger proteins were retained inside the insert. Non-invasive SERS spectral acquisition was then carried out through the bottom of the multi-well plate. The diffusion of a SERS probe, 2-mercaptopyridine, and of a neurotransmitter having a less intense SERS signal, serotonin, were first successfully monitored with the device. Then, the latter was applied to distinguish between subclones of cancerous cells through differences in metabolite production. This promising methodology showed a high level of versatility, together with the capability to reduce cellular stress and contamination hazards.

Near real-time analysis of para-cresol in wastewater with a laccase-carbon nanotube-based biosensor.

Para-Cresol is a water-soluble organic pollutant, which is harmful to organisms even at low concentrations. Therefore, it is important to rapidly detect the p-cresol in wastewater as well as natural water. In this work, a new, simple and stable biosensor was developed for on-site quantitatively determination and near real-time monitoring p-cresol in wastewater. The new biosensor was designed and fabricated using a screen-printed carbon electrode (SPCE) modified by waste-derived carbon nanotubes (CNTs) immobilized with laccase (LAC). The fabrication processes and performance of the biosensors were systematically characterized and optimized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM) and electrochemical methods. With improved conductivity, the proposed biosensor could provide the direct quantitation of p-cresol. The linear range of the biosensor is 0.2-25 ppm of p-cresol with a detection limit of 0.05 ppm. Additionally, the biosensor exhibited high reproducibility, stability and reusability during the validation. More importantly, the biosensor was successfully applied for the rapid detection of p-cresol in environmental lab wastewater under the interference of metal ions and other organics, and the results were consistent with high-performance liquid chromatography (HPLC). Finally, the biosensor with a portable potentiostat was approved as an easy-to-use, sensitive and inexpensive platform that could provide near real-time monitoring of p-cresol concentration in wastewater during Fenton oxidation treatment process.

ADVANCE: Towards near real-time monitoring of vaccination coverage, benefits and risks using European electronic health record databases.

BACKGROUND: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private partnership aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using European electronic health record (eHR) databases. This proof-of-concept study aimed to test the feasibility of near real-time (NRT) monitoring of vaccination coverage, benefits and risks based on multiple European eHR databases, using acellular pertussis vaccination in children aged <6 years as test case. METHODS: A qualitative feasibility assessment on NRT monitoring was carried out using a survey and face-to-face discussion with ADVANCE data partners. Subsequently, a dynamic cohort study was conducted containing two distinct observation periods: a first period to establish a baseline (Jan 2014 to Mar 2018) and a subsequent 3-month period to test the actual feasibility of weekly NRT monitoring, based on which data latencies were calculated. An interactive web-application was additionally developed to facilitate the visual monitoring of vaccination coverage, the vaccine preventable disease incidence rates (benefits) and the incidence rates of adverse events (risks). RESULTS: Nine databases from four countries (Denmark, Italy, Spain and UK) participated in the qualitative feasibility assessment. Of them, five databases took part in the dynamic cohort study, with 5 databases providing baseline data and 3 databases participating to the NRT monitoring, providing data extractions on an almost weekly basis. The median data latency (time between event date and data release date) was between 1 and 2 weeks except for the benefit and risk events in one of the databases (latency 16 weeks). CONCLUSION: Three European eHR databases successfully demonstrated the feasibility of providing data for weekly NRT monitoring, with short data latencies of 1-2 weeks for most events.