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Due to their portability, versatility for supporting multiple assay formats, and potential for resulting in low-cost assays, paper-based analytical devices (PADs) are an increasingly popular format as a platform for the development of point-of-care tests. However, very few PADs have been translated successfully to their intended environments outside of academic settings. Often overlooked as a factor that inhibits translation, usability is a vital characteristic of any successful point-of-care test. Recent advancements in PAD design have demonstrated improved usability by simplifying various aspects of user operation, including sample collection, sample processing, device operation, detection, and readout/interpretation. Field testing at various stages of device design can offer critical feedback about device usability, especially when it involves the proposed end-user or other stakeholders. By highlighting advances in usability, we aim to encourage thoughtful and rigorous design at the academic prototyping stage to address one outstanding hurdle that limits the number of PADs that make it from the benchtop to the point-of-care. Image 1 • Paper-based devices have potential for use at the point-of-care. • Devices that are user-friendly are more likely to be translated to the field. • Additional user steps create additional opportunities for user error. • We discuss ways to streamline user operation of paper-based devices. • We highlight three case studies for devices deployed successfully to the field. [ABSTRACT FROM AUTHOR]

Abstract: Periodic outbreaks of pandemic influenza have been a devastating cause of human mortality over the past century. More recently, an avian influenza strain, designated H5N1, has been identified as having the potential to cause a zoogenic pandemic in humans, and a current outbreak of a new H1N1 influenza variant hypothesized to be of swine origin is of considerable concern. In order to facilitate surveillance and the rapid assessment and comparison of vaccination efforts, a high-throughput assay is highly desirable to supplement standard methods, which require high biosafety-level facilities. In this paper, we describe the design, production, and preliminary evaluation of an antigen array incorporating a panel of hemagglutinins as a platform for the detection and rapid quantification of influenza-specific antibodies in human serum by Arrayed Imaging Reflectometry (AIR), a label-free optical biosensor. [ABSTRACT FROM AUTHOR]

Abstract: Assays built upon protein arrays are critical tools in determining the basic nature of biology, and have considerable promise in diagnosing human disease. These protein arrays aid in the elucidation of mapping pathway interactions, disease biomarker discovery, and regulatory processes. The solutions used in these experiments, including cellular lysate and serum, are inherently complex mixtures and are high in total protein content. Therefore, array-based assays must be robust and maintain a high level of selectivity and sensitivity. We report herein that arrayed imaging reflectometry (AIR), a label-free biosensing platform we have previously disclosed, is highly suitable for the detection of human proteins in complex solutions. In particular, we demonstrate array-based detection of cytokines in buffered solutions, and in undiluted human serum. [Copyright &y& Elsevier]

Abstract: The study of proteins and the molecules with which they interact on an organismwide scale is critical to understanding basic biology, and understanding and improving human health. New platform technologies allowing label-free, quantitative array-based analysis of proteins are particularly desirable. We have developed an analytical technology, reflective interferometry (RI), which provides specific, rapid, and label-free optical detection of biomolecules in complex mixtures. In order to evaluate the suitability of RI for proteomics, we have prepared a series of arrays bearing the extracellular domain of the secreted enteropathogenic Escherichia coli (EPEC) protein Translocated Intimin Receptor (Tir). These arrays are able to selectively detect the extracellular domain of the protein Intimin, Tir''s natural binding partner. Furthermore, we demonstrate the use of RI and Tir-functionalized arrays for the selective detection of EPEC directly from culture. [Copyright &y& Elsevier]

• Top/bottom layers of polyelectrolyte multilayers (PEMs) control surface properties. • Surface energy and roughness can be modified independently using model PEM coatings. • Improved cell attachment occurs during first hour up to a day on a PEM surface. • Single layer and uncoated controls show higher spreading and growth after 4 days. • Internal PEM structure has a likely effect on short and long term cell attachment. Polyelectrolyte multilayers (PEMs) are a category of materials commonly used as coatings on surfaces that interact with cells. The properties of PEMs have been established to be controlled by not only polyelectrolyte choice, but by the identity of the initially applied (bottom) layer. In this work, 5-bilayer PEMs consisting of poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium 4-styrenesulfonate) (PSS) were coated on gold-sputtered quartz substrates with different first layer materials. A final poly- l -lysine (PLL) layer was added to all PEMs to provide identical top layers conducive to cell growth. As in previous work, initial layer selection affected PEM roughness. All coated surfaces, including the PLL-only control, showed increased dispersive surface energy but decreased polar surface energy, as compared to uncoated surfaces. When human mesenchymal stem cells (hMSCs) were cultured on these surfaces, analysis through lateral cell imaging for the first 90 min and fluorescent staining after 1 day showed improved attachment on surfaces with a PDADMAC bottom layer. However, after 4 days, a higher cell density was observed on the PLL-only and uncoated control surfaces, indicating that the PEMs negatively affected hMSC proliferation. Both the long and short time period results did not correlate to any of the roughness and surface energy trends, indicating more complex interactions between the cells and the surface relating to charge distribution and functional group density. [ABSTRACT FROM AUTHOR]

Recycling of receptors from the endosomal recycling compartment to the plasma membrane is a critical cellular process, and recycling is particularly important for maintaining invasiveness in solid tumors. In this work, we continue our efforts to inhibit EHD1, a critical adaptor protein involved in receptor recycling. We applied a diversity-oriented macrocyclization approach to produce cyclic peptides with varied conformations, but that each contain a motif that binds to the EH domain of EHD1. Screening these uncovered several new inhibitors for EHD1’s EH domain, the most potent of which bound with a K d of 3.1 μM. Several of the most potent inhibitors were tested in a cellular assay that measures extent of vesicle recycling. Inhibiting EHD1 could potentially slow cancer invasiveness and metastasis, and these cyclic peptides represent the most potent inhibitors of EHD1 to date. [ABSTRACT FROM AUTHOR]