Highly sensitive detection of malaria biomarker through matching channel and gate capacitance of integrated organic electrochemical transistors.

Organic electrochemical transistors (OECTs) possess versatile advantages for biochemical and electrophysiological applications due to electrochemical gating and ion-to-electron conversion capability. Although OECTs have been successfully applied for biochemical sensing, the effect of relative capacitance for specific sensing events is still unclear. In the present work, we design integrated interdigitated OECTs (iOECTs) with on-plane gold gate and different channel geometries for point-of-care diagnosis of malaria using aptamer as receptor. The transconductance of the iOECTs gated with micro-size gold electrodes decreased with increasing the channel thicknesses, especially for devices with large channel areas, which is inconsistent with devices gated by typical Ag/AgCl electrodes, attributing to the limited gating efficiency of the micro-size gate electrode. The capacitance of gate electrode was heavily suppressed by receptors but increased with the incubation of targets. In addition, the integrated iOECTs with thin channels exhibited superior sensitivity for malaria detection with the detection limit as low as 3.2 aM, much lower than their thick channel counterpart and other state-of-the-art biosensors. These deviations could be caused by the high relative capacitances, with respect to the gate and channel capacitance (Cg/Cch), resulting in a high gate potential drop over the organic channel and thus entirely gating on the thin channel device. These findings provide guidance to optimize the geometry of OECT devices with on-chip integrated gates and the fabrication of miniaturized OECTs for biosensing applications.

Chemical Modifications for a Next Generation of Nucleic Acid Aptamers.

In the past three decades, in vitro systematic evolution of ligands by exponential enrichment (SELEX) has yielded many aptamers for translational applications in both research and clinical settings. Despite their promise as an alternative to antibodies, the low success rate of SELEX (∼30 %) has been a major bottleneck that hampers the further development of aptamers. One hurdle is the lack of chemical diversity in nucleic acids. To address this, the aptamer chemical repertoire has been extended by introducing exotic chemical groups, which provide novel binding functionalities. This review will focus on how modified aptamers can be selected and evolved, with illustration of some successful examples. In particular, unique chemistries are exemplified. Various strategies of incorporating modified building blocks into the standard SELEX protocol are highlighted, with a comparison of the differences between pre-SELEX and post-SELEX modifications. Nucleic acid aptamers with extended functionality evolved from non-natural chemistries will open up new vistas for function and application of nucleic acids.

An electrochemical aptamer-based biosensor targeting Plasmodium falciparum histidine-rich protein II for malaria diagnosis.

Malaria is an infectious disease caused by parasitic protozoans from the genus Plasmodium, with the species P. falciparum causing the highest number of deaths worldwide. Rapid diagnostic tests (RDTs) have become critical in the management of malaria, but current RDTs that detect P. falciparum are primarily antibody-based, which can have drawbacks in cost and robustness. Here, we report the development of an electrochemical aptamer-based (E-AB) biosensing alternative. Through selective evolution of ligands by exponential enrichment, we identify DNA aptamers that bind specifically to P. falciparum histidine-rich protein II (PfHRP2). The aptamer is modified with a methylene blue reporter and attached to a gold sensor surface for square-wave voltammetry interrogation. Through this method we are able to quantify PfHRP2 in human serum with an LOD of 3.73 nM. We further demonstrate the biosensor is stable in serum buffers and reusable for multiple detection rounds. These findings provide a promising alternative to conventional PfHRP2 detection for malaria diagnosis, while also expanding the capabilities of E-AB biosensors.

Polyethylene glycol-mediated blocking and monolayer morphology of an electrochemical aptasensor for malaria biomarker detection in human serum.

Better approaches are critically needed for in situ point-of-care diagnostic biosensors that enable primary care physicians, or even individual patients, to directly analyze biological fluids without complicated sample pretreatments. Additional purification steps consume time, consume reagents, often require other equipment, and can introduce false-negative results. Biosensors have been modified with blocking molecules to reduce biofouling; however, the effectiveness relies on their chemical composition and morphology. Here, we used a polyethylene glycol film to suppress unspecific binding from human serum on an electrochemical malaria aptasensor. A detailed study of the variation of the chemical and morphological composition of the aptamer/polyethylene glycol mixed monolayer as a function of incubation time was conducted. Higher resistance to matrix biofouling was found for polyethylene glycol than for hydrophobic alkanethiol films. The best sensor performance was observed for intermediate polyethylene glycol immobilization times. With prolonged incubation, phase separation of aptamer, and polyethylene glycol molecules locally increased the aptamer density and thereby diminished the analyte binding capability. Remarkably, polyethylene glycols do not affect the aptasensor sensitivity but enhance the complex matrix tolerance, the dynamic range, and the limit of detection. Careful tuning of the blocking molecule immobilization is crucial to achieving high aptasensor performance and biofouling resistance.

COVID-19 - A Covert Catalyst for Pedagogical Stocktake and Transformation: Perspectives of a Global Hub.

This article was migrated. The article was marked as recommended. Education in Hong Kong was shifted online on an abrupt and massive scale as the city faced unprecedented disruptions, first from social unrest in 2019 and then again with the COVID-19 pandemic. Concurrent modernization initiatives since early 2019 in The University of Hong Kong's Medical Faculty (HKUMed), conferred a fortuitous head start for this rapid change. Pre-clinical and clinical teaching were restructured for online delivery through e-learning solutions for didactic teaching, and new innovative approaches were developed to convert bedside to"webside" teaching. E-learning in the current circumstances provided necessary social distancing while being pedagogically sound. Students were also able to develop key communication and collaboration skills via online platforms, developing digital skills critical to their future profession. However, unforeseen issues including socioeconomic inequality, privacy concerns, and social isolation became apparent and should be addressed as medical education progresses further down the digital path. The goal must entail a sustainable and scholarly approach towards optimizing medical education in an increasingly online environment. This will help safeguard the medical curriculum against disruption and empower future medical professionals for tomorrow's practice. Here, we share experiences and perspectives from educators in a global city characterised by land scarcity and income inequality.

DNA Aptamers for the Functionalisation of DNA Origami Nanostructures.

DNA origami has emerged in recent years as a powerful technique for designing and building 2D and 3D nanostructures. While the breadth of structures that have been produced is impressive, one of the remaining challenges, especially for DNA origami structures that are intended to carry out useful biomedical tasks in vivo, is to endow them with the ability to detect and respond to molecules of interest. Target molecules may be disease indicators or cell surface receptors, and the responses may include conformational changes leading to the release of therapeutically relevant cargo. Nucleic acid aptamers are ideally suited to this task and are beginning to be used in DNA origami designs. In this review, we consider examples of uses of DNA aptamers in DNA origami structures and summarise what is currently understood regarding aptamer-origami integration. We review three major roles for aptamers in such applications: protein immobilisation, triggering of structural transformation, and cell targeting. Finally, we consider future perspectives for DNA aptamer integration with DNA origami.

Implementation of an interprofessional team-based learning program involving seven undergraduate health and social care programs from two universities, and students' evaluation of their readiness for interprofessional learning.

BACKGROUND: Interprofessional learning is gaining momentum in revolutionizing healthcare education. During the academic year 2015/16, seven undergraduate-entry health and social care programs from two universities in Hong Kong took part in an interprofessional education program. Based on considerations such as the large number of students involved and the need to incorporate adult learning principles, team-based learning was adopted as the pedagogy for the program, which was therefore called the interprofessional team-based learning program (IPTBL). The authors describe the development and implementation of the IPTBL program and evaluate the effectiveness of the program implementation. METHODS: Eight hundred and one students, who are predominantly Chinese, participated in the IPTBL. The quantitative design (a pretest-posttest experimental design) was utilized to examine the students' gains on their readiness to engage in interprofessional education (IPE). RESULTS: Three instructional units (IUs) were implemented, each around a clinical area which could engage students from complementary health and social care disciplines. Each IU followed a team-based learning (TBL) process: pre-class study, individual readiness assurance test, team readiness assurance test, appeal, feedback, and application exercise. An electronic platform was developed and was progressively introduced in the three IUs. The students' self-perceived attainment of the IPE learning outcomes was high. Across all four subscales of RIPLS, there was significant improvement in student's readiness to engage in interprofessional learning after the IPTBL. A number of challenges were identified: significant time involvement of the teachers, difficulty in matching students from different programs, difficulty in making IPTBL count towards a summative assessment score, difficulty in developing the LAMS platform, logistics difficulty in managing paper TBL, and inappropriateness of the venue. CONCLUSIONS: Despite some challenges in developing and implementing the IPTBL program, our experience showed that TBL is a viable pedagogy to be used in interprofessional education involving hundreds of students. The significant improvement in all four subscales of RIPLS showed the effects of the IPTBL program in preparing students for collaborative practice. Factors that contributed to the success of the use of TBL for IPE are discussed.

Inorganic polyphosphate triggers upregulation of interleukin 11 in human osteoblast-like SaOS-2 cells.

Polyphosphate (polyP) is abundant in bone but its roles in signaling and control of gene expression remain unclear. Here, we investigate the effect of extracellular polyP on proliferation, migration, apoptosis, gene and protein expression in human osteoblast-like SaOS-2 cells. Extracellular polyP promoted SaOS-2 cell proliferation, increased rates of migration, inhibited apoptosis and stimulated the rapid phosphorylation of extracellular-signal-regulated kinase (ERK) directly through basic fibroblast growth factor receptor (bFGFR). cDNA microarray revealed that polyP induced significant upregulation of interleukin 11 (IL-11) at both RNA and protein levels.