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During embryonic morphogenesis, tissues undergo dramatic deformations in order to form functional organs. Similarly, in adult animals, living cells and tissues are continually subjected to forces and deformations. Therefore, the success of embryonic development and the proper maintenance of physiological functions rely on the ability of cells to withstand mechanical stresses as well as their ability to flow in a collective manner. During these events, mechanical perturbations can originate from active processes at the single-cell level, competing with external stresses exerted by surrounding tissues and organs. However, the study of tissue mechanics has been somewhat limited to either the response to external forces or to intrinsic ones. In this work, we use an active vertex model of a 2D confluent tissue to study the interplay of external deformations that are applied globally to a tissue with internal active stresses that arise locally at the cellular level due to cell motility. We elucidate, in particular, the way in which this interplay between globally external and locally internal active driving determines the emergent mechanical properties of the tissue as a whole. For a tissue in the vicinity of a solid-fluid jamming or unjamming transition, we uncover a host of fascinating rheological phenomena, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening. These model predictions provide a framework for understanding the recently observed nonlinear rheological behaviors in vivo.

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Identification of specific antibodies in patient plasma is an essential part of many diagnostic procedures and is critical for safe blood transfusion. Current techniques require laboratory infrastructure and long turnaround times which limits access to those nearby tertiary healthcare providers. Addressing this challenge, a novel and rapid paper-based antibody test is reported. We validate antibody detection with reverse blood typing using IgM antibodies and then generalise the validity by adapting to detect SARS CoV-2 (COVID-19) antibodies in patient serum samples. Reagent red blood cells (RBC) are first combined with the patient plasma containing the screened antibody and a droplet of the mixture is then deposited onto paper. The light intensity profile is analyzed to identify test results, which can be detected by eye and/or with image processing to allow full automation. The efficacy of this test to perform reverse blood typing is demonstrated and the performance and sensitivity of this test using different paper types and RBC reagents was investigated using clinical samples. As an example of the flexibility of this approach, we labeled the RBC reagent with an antibody-peptide conjugate to detect SARS CoV-2 (COVID-19) antibodies in patient serum samples. This concept could be generalized to any agglutination-based antibody diagnostics with blood plasma.

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Patterns in dried droplets are commonly observed as rings left after spills of dirty water or coffee have evaporated. Patterns are also seen in dried blood droplets and the patterns have been shown to differ from patients afflicted with different medical conditions. This has been proposed as the basis for a new generation of low-cost blood diagnostics. Before these diagnostics can be widely used, the underlying mechanisms leading to pattern formation in these systems must be understood. We analyse the height profile and appearance of dispersions prepared with red blood cells (RBCs) from healthy donors. The red cell concentrations and diluent were varied and compared with simple polystyrene particle systems to identify the dominant mechanistic variables. Typically, a high concentration of non-volatile components suppresses ring formation. However, RBC suspensions display a greater volume of edge deposition when the red cell concentration is higher. This discrepancy is caused by the consolidation front halting during drying for most blood suspensions. This prevents the standard horizontal drying mechanism and leads to two clearly defined regions in final crack patterns and height profile. This article is part of a discussion meeting issue 'A cracking approach to inventing new tough materials: fracture stranger than friction'.

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Pattern formation is a common occurrence in drying colloidal systems. The most common in droplets, is a ring distribution where the constituents have relocated to the edge, which is referred to as a coffee ring. This deposit is unfavourable in many manufacturing processes and is of fundamental interest. In this study, we present a model capable of predicting when a coffee ring will be observed in hard spherical particle systems. Ring profiles are found to be formed at low contact angles with the specific angle predicated upon the initial concentration of the suspension. Modelling results are in agreement with experiments using latex suspensions.

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Paper-based diagnostics are leading the field of low-cost, point of care analytical techniques. However, large scale testing facilities such as hospitals are still primarily using the gel column agglutination technique. This is because paper-based systems are single use tests that are generally more time consuming and less automatable than traditional methods. Here, we present a novel, rapid and scalable, paper-based blood typing method that can produce test results in under ten seconds. We believe this is the fastest blood typing test that is appropriate for large scale automation. The test consists of placing a drop of antibody solution on paper, followed by a drop of blood on the same locus, and measuring the evolution of blood stain area as a function of time. Positive reactions for both forward and reverse tests have significantly slower growth rates and smaller final stain sizes when compared to negatives. We analyse the effect paper type, red blood cell concentration, antibody specificity (A, B and D) and antibody dilution have on the sensitivity and reproducibility of the technique. A high sensitivity is found in papers with a low density and thickness. The optimum red blood cell concentration is determined from a balance between wicking rate, strength of reaction and optical contrast. A and B antibodies give more sensitive results than D; however, the D antigen can still be successfully identified. This technique has the potential to significantly cut down the time and cost of blood typing tests and enable design of a new high throughput and fully automatable system.

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In this study, we analyze stain growth kinetics from droplets of biological fluids such as blood, plasma, and protein solutions on paper both experimentally and numerically. The primary difference of biological fluids from a simple fluid is a significant wetting/dewetting hysteresis in paper. This becomes important in later stages of droplet wicking, after the droplet has been completely absorbed into paper. This is shown by anomalous power dependence of area with time in the later stages of radial wicking. At early stages, current numerical wicking models can predict stain growth of biological fluids. However, at later stages, the introduction of hysteresis complicates modeling significantly. We show that the cause of the observed hysteresis is due to contact angle effects and that this is the dominant mechanism that leads to the anomalous stain growth kinetics measured uniquely in biological fluids. Results presented will streamline the design process of paper-based diagnostics, allowing a modeling approach instead of a trial and error method.

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HYPOTHESIS: The rate of stain growth of a sessile droplet deposited on paper has been previously studied (Kissa, 1981; Danino and Marmur, 1994; Kawase et al., 1986; Borhan and Rungta, 1993) but is not fully understood. In particular, the mechanism by which the abrupt decrease in growth rate occurs is unknown. This process is expected to follow a model where the disappearance of the droplet is represented by a change to the boundary condition at the droplet-paper interface when the volume of the fluid inside the paper is equal to the volume of the simulated droplet. EXPERIMENTS: The stain size of sessile droplets on paper was monitored against time. A series of fluids varying in surface tension and viscosity was studied. The kinetics of stain growth was modelled and compared with experiments and existing models of stain growth. FINDINGS: The measured stain area formed by a sessile droplet deposited on paper follows a two regime mechanism (Danino and Marmur, 1994). In the initial regime, the dynamics are governed by the filling of pores. However, in the later stage, the process is influenced by the emptying/redistribution of fluid. Simulations show that experimental results are well described by a model that identifies the change in boundary conditions after the droplet is no longer present above the paper, coupled with the change to a redistribution dominated mechanism.

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HYPOTHESES: (1) The equilibrium size and characteristics of a radially wicked fluid on porous material such as paper is expected to be dependent on the fluid properties and therefore could serve as a diagnostic tool. (2) The change in wicked stain size between biological fluids is dependent on a change in solid-liquid surface interfacial energy due to protein adsorption. EXPERIMENTS: Sessile droplets of increasing volume of blood, its components, and model fluids were deposited onto paper and the equilibrium stain size after coming to a halt was recorded. The contact angle of fluid droplets on model cellulose surfaces was measured to quantify the effect that blood protein adsorption at the solid-liquid interface has on radially wicked equilibrium size. Finally the significance of droplet evaporation for the time scale of interest was analysed. FINDINGS: The final stain area of all fluids tested on paper scales remarkably linearly with droplet volume. Different fluids were compared and the gradient of this linear relation was measured. Model fluids varying in surface tension and viscosity all behave similarly and exhibit a constant gradient. Blood and its components produce smaller stains, demonstrated by lower gradients. The gradient is a function of protein concentration, thus the mechanism of this phenomenon was identified as protein adsorption at the cellulose-liquid interface. The slope of the area/volume relationship for droplets is an important quantitative mechanistic variable.

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