Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants

Jason Z. Zhang, Hsien Wei Yeh, Alexandra C. Walls, Basile I.M. Wicky, Kaitlin R. Sprouse, Laura A. VanBlargan, Rebecca Treger, Alfredo Quijano-Rubio, Minh N. Pham, John C. Kraft, Ian C. Haydon, Wei Yang, Michelle DeWitt, John E. Bowen, Cameron M. Chow, Lauren Carter, Rashmi Ravichandran, Mark H. Wener, Lance Stewart, David VeeslerMichael S. Diamond, Alexander L. Greninger, David M. Koelle, David Baker

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase–receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.

Original languageEnglish
Pages (from-to)1336-1340
Number of pages5
JournalNature Biotechnology
Issue number9
StatePublished - Sep 2022


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