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.
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.
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