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Abstract Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces. The model provides the standard monovalent affinity/kinetics and new bivalent parameters, including the molecular reach: the maximum antigen separation enabling bivalent binding. We find large variations in these parameters across antibodies, including reach variations (22–46 nm) that exceed the physical antibody size (~15 nm). By using antigens of different physical sizes, we show that these large molecular reaches are the result of both the antibody and antigen sizes. Although viral neutralisation correlates poorly with affinity, a striking correlation is observed with molecular reach. Indeed, the molecular reach explains differences in neutralisation for antibodies binding with the same affinity to the same RBD-epitope. Thus, antibodies within an isotype class binding the same antigen can display differences in molecular reach, substantially modulating their binding and functional properties. 

Consistent with its title, “An overview of the model container types in physical modeling of geotechnical problems” by Esmaeilpour et al. [1], the essence of the paper is literature review, and hence it is particularly important that the review is accurate. The authors have compiled an extensive list of papers relevant to the design of model containers used to study effects of seismic loading on soil behavior in shake table tests. Of course, many more container types exist for “physical modeling of geotechnical problems” beyond shake table testing. Both the paper and this discussion are focused on containers used to contain soils during shaking table tests, whether performed at 1g or on a centrifuge. Unfortunately, we noticed inaccuracies in the way that the authors have characterized the work of others. We present examples below. 

Biogeotechnics, specifically bio-mediated and bio-inspired geotechnical engineering, has matured rapidly over the past two decades, becoming one of the fastest growing subdisciplines within geotechnical engineering. As typical in most science and engineering fields, biogeotechnics relies on data from physical experiments and field observations to advance technology. Obtaining field data to drive advancement can pose unique challenges, and in many cases may be cost or logistically prohibitive. Physical experiments or models are often preferable and may offer the sole feasible pathway for technology development and upscaling. Hypergravity scaled modeling using centrifuges has been instrumental in biogeotechnics development to support the building of basic science knowledge, the validation of computational and theoretical models, and the advancement of emerging technologies towards field implementation. 

The correct interpretation of the result from a point-of-care device is crucial for an accurate and rapid diagnosis to guide subsequent treatment. Lateral flow tests (LFTs) use a well-established format that was designed to simplify the user experience. However, the LFT device architecture is inherently limited to detecting analytes that can be captured by molecular recognition. Microfluidic paper-based analytical devices (µPADs), like LFTs, have the potential to be used in diagnostic applications at the point of care. However, µPADs have not gained significant traction outside of academic laboratories, in part, because they have often demonstrated a lack of homogeneous shape or color in signal outputs, which consequently can lead to inaccurate interpretation of results by users. Here, we demonstrate a new class of µPADs that form colorimetric signals at the interfaces of converging liquid fronts (i.e., lines) to control where colorimetric signals are formed without relying on capture techniques. We demonstrate our approach by developing assays for three classes of analytes—an ion, an enzyme, and a small molecule—to measure using iron (III), acetylcholinesterase, and lactate, respectively. Additionally, we show these devices have the potential to support multiplexed assays by generating multiple lines in a common readout zone. These results highlight the ability of this new paper-based device architecture to aid the interpretation of assays that create soluble products by using flow to constrain those colorimetric products in a familiar, line-format output.