A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics

• Published in: Nature communications Vol. 11; no. 1; pp. 4464 - 11
• Main Authors: Crone, Michael A., Priestman, Miles, Ciechonska, Marta, Jensen, Kirsten, Sharp, David J., Anand, Arthi, Randell, Paul, Storch, Marko, Freemont, Paul S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.09.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 38/56; 38/77; 38/88; 38/90; 631/1647/2163; 631/61/32; 631/61/338/552; 692/699/255; Automation; Betacoronavirus - genetics; Betacoronavirus - isolation & purification; Biological Assay; Clinical Laboratory Techniques - instrumentation; Clinical Laboratory Techniques - methods; Clinical Laboratory Techniques - standards; Coronavirus Infections - diagnosis; Coronavirus Infections - virology; COVID-19; COVID-19 Testing; CRISPR; CRISPR-Cas Systems; Diagnostic systems; Gene amplification; Humanities and Social Sciences; Humans; Molecular Diagnostic Techniques - methods; multidisciplinary; Nucleic Acid Amplification Techniques - methods; Pandemics; Pneumonia, Viral - diagnosis; Pneumonia, Viral - virology; Reagents; Real-Time Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA, Viral - analysis; RNA, Viral - genetics; RNA, Viral - isolation & purification; SARS-CoV-2; Science; Science (multidisciplinary); Sensitivity and Specificity; Severe acute respiratory syndrome coronavirus 2; Viral diseases; Virus-like particles; Viruses; Workflow
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18130-3

The SARS-CoV-2 pandemic has shown how a rapid rise in demand for patient and community sample testing can quickly overwhelm testing capability globally. With most diagnostic infrastructure dependent on specialized instruments, their exclusive reagent supplies quickly become bottlenecks, creating an urgent need for approaches to boost testing capacity. We address this challenge by refocusing the London Biofoundry onto the development of alternative testing pipelines. Here, we present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled. Using an in-house-generated, open-source, MS2-virus-like particle (VLP) SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two detection assays based on CRISPR-Cas13a and RT-loop-mediated isothermal amplification (RT-LAMP). In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and detection of SARS-CoV-2 in patient samples using RT-qPCR, CRISPR-Cas13a, and RT-LAMP. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs, increasing testing capacity by 1000 samples per day. The SARS-CoV-2 pandemic has created large demand on global testing capability. Here the authors use the London Biofoundry, an automated synthetic biology platform, and develop an open-source virus-like particle to implement high-throughput diagnostics.