A universal reagent for detection of emerging diseases using bioengineered multifunctional yeast nanofragments

Accurate and early detection of biomarkers provides the molecular evidence for disease management, allowing prompt actions and timely treatments to save lives. Multivalent biomolecular interactions between the probe and biomarker as well as controlled probe orientation on material surfaces are keys for highly sensitive detection. Here we report the bioengineering of programmable and multifunctional nanoprobes, which can provide rapid, specific and highly sensitive detection of emerging diseases in a range of widely used diagnostic systems. These nanoprobes composed of nanosized cell wall fragments, termed as synthetic bionanofragments (SynBioNFs), are generated by the fragmentation of genetically programmed yeast cells. SynBioNFs display multiple copies of biomolecules for high-affinity target binding and molecular handles for the precisely orientated attachment on surfaces used in diagnostic platforms. SynBioNFs are demonstrated for the capture and detection of SARS-CoV-2 virions using multiple diagnostic platforms, including surface-enhanced Raman scattering, fluorescence, electrochemical and colorimetric-based lateral flow systems with sensitivity comparable with the gold-standard reverse-transcription quantitative polymerase chain reaction. Yeast cells are engineered to prepare multifunctional synthetic biofragments as nanoprobes, which allow multivalent interactions and optimal molecular orientation on material surfaces for the detection of emerging biomarkers in a range of sensor platforms.

Automated summary

Accurate and early detection of biomarkers is crucial for disease management, and programmable and multifunctional nanoprobes have been developed for rapid, specific and highly sensitive detection of emerging diseases. These nanoprobes, composed of synthetic bionanofragments (SynBioNFs), display multiple copies of biomolecules for high-affinity target binding and optimized molecular orientation on diagnostic platform surfaces. The SynBioNFs have been successfully used for the capture and detection of SARS-CoV-2 using various diagnostic systems with sensitivity comparable to the gold-standard reverse-transcription quantitative polymerase chain reaction.