High-throughput and rapid serology assays to detect the antibody response specific to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in human blood samples are urgently required to improve our understanding of the effects of COVID-19 across the world. Short-term applications include rapid case identification and contact tracing to limit viral spread, while population screening to determine the extent of viral infection across communities is a longer-term need. Assays developed to address these needs should match the ASSURED criteria. We have identified agglutination tests based on the commonly employed blood typing methods as a viable option. These blood typing tests are employed in hospitals worldwide, are high-throughput, fast (10–30 min), and automated in most cases. Herein, we describe the application of agglutination assays to SARS-CoV-2 serology testing by combining column agglutination testing with peptide–antibody bioconjugates, which facilitate red cell cross-linking only in the presence of plasma containing antibodies against SARS-CoV-2. This simple, rapid, and easily scalable approach has immediate application in SARS-CoV-2 serological testing and is a useful platform for assay development beyond the COVID-19 pandemic.

Paper can be used as an alternative blood grouping diagnostic tool for selected blood group phenotypes.

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The gel test is the most prevalent method for the forward and reverse blood typing tests. It relies on the controlled centrifugation of red blood cells (RBCs) and antibodies through a gel column. This noncontinuous matrix is currently based on microbeads that often lack sensitivity. For the first time, nanocellulose hydrogel is demonstrated as a sustainable and reliable medium for gel-based blood typing diagnostics. Gels with a minimum of 0.3 wt % TEMPO-oxidized cellulose nanofibers (0.92 mmol/g of carboxyl content) separate agglutinated and individual RBCs in the forward test. The addition of glycine is able to balance the osmotic pressure and reduce hemolysis to 5%, while retaining the electrostatic repulsion responsible for the gel network structure and its rheological properties. For the reverse typing, cellulose nanofibers are chemically cross-linked with hexamethylenediamine (HMDA), increasing the gel yield point 8-fold. Sodium chloride is added to achieve the osmolality found in the human plasma and limit cell lysis to 15%, without affecting the gel colloidal stability. Nanocellulose hydrogel constitutes a performant, low cost, and green soft material, providing clear and well-defined results for both blood grouping tests.

This work reports the fabrication of biocompatible and pH‐sensitive hybrid polydopamine/bovine serum albumin/calcium carbonate (PDA/BSA/CaCO3) particles via a rapid precipitation method. These hybrid particles generate hyperechogenic carbon dioxide bubbles upon exposure to low pH environments, making them ideal as a contrast agent and detector for tumor cells. This study also highlights the application of red blood cell membrane (RBC)‐derived membranes as a biomimetic coating for PDA/BSA/CaCO3 hybrid particles in order to modulate protein corona formation, a natural physiological response that alters tailored properties of most nanomaterials that are administered systemically. Results of this work demonstrate that the RBC membrane‐coated hybrid particles are ideal for a wide range of biomedical applications, such as noninvasive multimodal imaging, photothermal and photodynamic therapy, and “personalized” drug delivery systems.

A rapid and simple paper-based elution assay for red blood cell antigen typing by the indirect antiglobulin test (IAT) was established. This allows to type blood using IgG antibodies for the important blood groups in which IgM antibodies do not exist. Red blood cells incubated with IgG anti-D were washed with saline and spotted onto the paper assay pre-treated with anti-IgG. The blood spot was eluted with an elution buffer solution in a chromatography tank. Positive samples were identified by the agglutinated and fixed red blood cells on the original spotting area, while red blood cells from negative samples completely eluted away from the spot of origin. Optimum concentrations for both anti-IgG and anti-D were identified to eliminate the washing step after the incubation phase. Based on the no-washing procedure, the critical variables were investigated to establish the optimal conditions for the paper-based assay. Two hundred ten donor blood samples were tested in optimal conditions for the paper test with anti-D and anti-Kell. Positive and negative samples were clearly distinguished. This assay opens up new applications of the IAT on paper including antibody detection and blood donor-recipient crossmatching and extends its uses into non-blood typing applications with IgG antibody-based diagnostics. Graphical abstract A rapid and simple paper-based assay for red blood cell antigen typing by the indirect antiglobulin test.

Fibrinogen is one of the first proteins to be depleted in heavily bleeding patients. In this study, we have developed a new paper-based diagnostic to quantify the fibrinogen concentration in blood at room temperature.

The ability to diagnose and treat critically bleeding patients can save more than 2 million lives a year. Diagnosing hypofibrinogenemia is essential in these patients. Recently, with the development of new handheld diagnostics, fibrinogen concentration can be measured rapidly at the point of care. However, these diagnostics can only work with plasma and hence need blood cells to be separated before use. In this study, we demonstrate a handheld fibrinogen diagnostic that works with whole blood. The test works by (1) forming a premixed droplet of a whole blood sample and thrombin solution on a solid surface, (2) allowing it to clot, and (3) dropping a paper strip on top. The further that blood moves down the strip, the lower the fibrinogen concentration. The diagnostic can easily measure plasma fibrinogen concentrations below 1.6 g/L for blood samples with hematocrits between 40 and 50%. Furthermore, diluting blood samples not only increases the test’s sensitivity but also eliminates the effect of hematocrit and thrombin inhibitors. The test can be completed in 3–4 min, making it suitable for diagnosing early hypofibrinogenemia and allowing for fibrinogen replacement therapy in critically bleeding patients.