New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform

The mechanism of action (MOA) of the first line type-2 diabetes drug metformin remains unclear despite its widespread usage. However, recent evidence suggests that the mitochondrial copper (Cu)-binding action of metformin may contribute toward the drug’s MOA. Here, we present a novel biosensing platform for investigating the MOA of metformin using a magnetic microbead-based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway of metformin’s blood-glucose lowering action. In this assay, cysteine-functionalized magnetic beadswere agglutinated in the presence of Cu due to cysteine’s Cu-chelation property. Addition of clinically relevant doses of metformin resulted in disaggregation of Cu-bridged bead-clusters, whereas the effect of adding a closely related but blood-glucose neutral drug propanediimidamide (PDI) showed completely different responses to the clusters. The entire assay was integrated in an automated microfluidics platform with an advanced optical imaging unit by which we investigated these aggregation–disaggregation phenomena in a reliable, automated, and user-friendly fashion with total assay time of 17 min requiring a sample (metformin/PDI) volume of 30 μL. The marked difference of Cu-binding action between the blood-glucose lowering drug metformin and its inactive analogue PDI thus suggests that metformin’s distinctive Cu-binding properties may be required for its effect on glucose homeostasis. The novel automated platform demonstrating this novel investigation thus holds the potential to be utilized for investigating significant and sensitive molecular interactions via magnetic bead-based agglutination assay

Lab-on-a-disk extraction of PBMC and metered plasma from whole blood: An advanced event-triggered valving strategy

In this paper, we present a centrifugal microfluidic concept employing event-triggered valving for automated extraction of metered plasma and peripheral blood mononuclear cells (PBMCs). This “lab-on-a-disk” system has been developed for retrieving different density layers from a liquid column by “overflowing” the layers sequentially using the pressure exerted by a density-gradient liquid. Defined volumes of plasma and PBMCs were efficiently forwarded into designated microfluidic chambers as a sample preparation step prior to further downstream processing. Furthermore, the extracted PBMCs were counted directly on-disk using an automated optical unit by object-based image analysis, thus eliminating the requirement for the post-processing of the extracted PBMCs. This study is a direct continuation of our previous work1 where we demonstrated combined on-disk detection of C-reactive protein and quantification of PBMCs following on-disk extraction of plasma and PBMCs from a single blood sample using a centrifugo-pneumatic valving mechanism. However, the former valving technique featured limited PBMC extraction efficiency. Here, integrating the novel concept along with event-triggered valving mechanism, we eliminated the occurrence of a specific microfluidic effect, which led us to increase PBMC extraction efficiency to 88%. This extraction method has the potential to be utilized for efficiently separating multiple density layers from a liquid sample in relevant biomedical applications

Strategic & Applied Research & Coordination in Action: Climate Services for Resilient Development (CSRD) in South Asia

A global partnership that is aligned with the Global Framework for Climate Services, Climate Services for Resilient Development (CSRD) works to link climate science, data streams, decision support tools, and training with decision-makers in developing countries. CSRD is led by the United States Government and is supported by the UK Government Department for International Development (DFID), UK Meteorological Office, ESRI, Google, the Inter-American Development Bank, the Asian Development Bank, and the American Red Cross. Led by the International Maize and Wheat Improvement Center (CIMMYT), the CSRD initiative in South Asia works with partners to conduct applied research and facilitate the use of climate information to reduce risk for smallholder farmers. This report details activities of the CSRD project in South Asia during 2018, with emphasis on the second half of 201

Climate Services for Resilient Development in South Asia Mid-Term Report, January - June 2018

Aligned with the Global Framework for Climate Services, Climate Services for Resilient Development (CSRD) is a global partnership that works to link climate science, data streams, decision support tools, and training with decision-makers in developing countries. CSRD is led by the United States Government and is supported by the UK Government Department for International Development (DFID), UK Meteorological Office, ESRI, Google, the Inter-American Development Bank, the Asian Development Bank, and the American Red Cross. Led by the International Maize and Wheat Improvement Center (CIMMYT), the CSRD initiative in South Asia implements applied research and facilitates an expanding network of partners assure that actionable climate information and crop management advisories can be generated, refined, and delivered to smallholder farmers. This report details activities of the CSRD project in South Asia during the first six months of 2018