bioRxivMolecular BiologyPreprint
LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding
Jonathan Leo Schmid-BurgkiD, Ricarda Maria SchmithauseniD, David LiiD, Ronja Hollstein, Amir Ben-Shmuel, Ofir Israeli, Shay WeissiD, Nir Paran, Gero Wilbring, Jana Liebing, David Feldman, Mikolaj Michal SlabickiiD, Bärbel Lippke, Esther Sib, Jacob de Riba BorrajoiD, Jonathan G. StreckeriD, Julia Reinhardt, Per HoffmanniD, Brian ClearyiD, Michael HölzeliD, Markus M. NötheniD, Martin Exner, Kerstin U. LudwigiD, Aviv RegeviD, Feng ZhangiD
Abstract
The ongoing SARS-CoV-2 pandemic has already caused devastating losses. Exponential spread can be slowed by social distancing and population-wide isolation measures, but those place a tremendous burden on society, and, once lifted, exponential spread can re-emerge. Regular population-scale testing, combined with contact tracing and case isolation, should help break the cycle of transmission, but current detection strategies are not capable of such large-scale processing. Here we present a protocol for LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method that is highly scalable. Individual samples are stabilized, inactivated, and amplified in three isothermal heat steps, generating barcoded amplicons that can be pooled and analyzed en masse by sequencing. Using unique barcode combinations per sample from a compressed barcode space enables extensive pooling, potentially further reducing cost and simplifying logistics. We validated LAMP-Seq on 28 clinical samples, empirically optimized the protocol and barcode design, and performed initial safety evaluation. Relying on world-wide infrastructure for next-generation sequencing, and in the context of population-wide sample collection, LAMP-Seq could be scaled to analyze millions of samples per day.
Abstract summary
Claude Opus 5.5 · xhigh effort · 2 Nov 2026 · from the abstract · CC BY-NC-ND 4.0
LAMP-Seq combines three-step isothermal RT-LAMP amplification with combinatorial barcoding to pool and sequence SARS-CoV-2 clinical samples en masse for scalable diagnostics.
Breaking SARS-CoV-2 transmission cycles without relying solely on population-wide isolation requires regular population-scale testing, which existing detection methods cannot process at sufficient scale. LAMP-Seq addresses this bottleneck by introducing combinatorial barcoding into Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP), allowing massive sample pooling for next-generation sequencing.
Key results
ShownLAMP-Seq was experimentally validated on clinical samples along with empirical optimization of its barcode design, protocol parameters, and initial safety evaluation.
Tested on 28 clinical samples using three isothermal heat steps for sample stabilization, inactivation, and barcoded amplification (specific sensitivity or specificity figures are not stated in the abstract). · Abstract
ClaimedCombinatorial barcoding from a compressed barcode space enables extensive sample pooling that could scale LAMP-Seq to population-level throughput.
Using existing next-generation sequencing infrastructure, the authors project the assay could scale to millions of samples per day, though large-scale pooling throughput is not empirically demonstrated in the abstract. · Abstract
Methods, data and reproducibility
LAMP-Seq stabilizes, inactivates, and amplifies individual samples across three isothermal heat steps using barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP). Assigning each sample a unique barcode combination from a compressed barcode space allows barcoded amplicons to be pooled and analyzed together via next-generation sequencing.
- Clinical samples tested during LAMP-Seq validation · SARS-CoV-2 · n = 28
- Methods & tools
- LAMP-Seq, Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP)
- Reproducibility gaps
- The abstract does not include links to protocol repositories, barcode sequences, raw sequencing data, or software tools.
Limitations (2)
- Empirical validation in the abstract is limited to a small cohort of 28 clinical samples, with no quantitative sensitivity or specificity metrics reported in the abstract. · noted in this summary
- The throughput projection of millions of samples per day is theoretical and relies on population-wide collection logistics and global sequencing infrastructure. · noted in this summary
Read this if you are designing high-throughput molecular diagnostics and want a combinatorially barcoded RT-LAMP protocol for pooled next-generation sequencing.
- Citations
- 82
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