Analytical benchmarking of extraction-free lysis devices for molecular detection of tuberculosis.

Sample preparation remains a barrier for decentralized, swab-based molecular testing of tuberculosis (TB). Extraction-free workflows offer a simpler alternative, but systematic benchmarking against standard methods is lacking. We evaluated five novel lysis devices, BLINK Shaker Prototype, nPOC-BB, SPS-1, Truelyse, and Thermolyse, against a heat- and bead-beating reference method using contrived M. tuberculosis -spiked tongue and sputum swabs. The primary outcome was lysis efficiency, measured as the relative DNA recovery compared with the reference workflow. Secondary outcomes included nuclease inactivation, biosafety, and usability. In the reference buffer, lysis efficiencies ranged from 51-63% to 95- 154% on tongue swabs and 12-54% to 280-644% on sputum swabs across the five devices. In proprietary buffers, performance varied more widely, with lysis efficiencies of 2-4% to 64- 80% on tongue swabs and 1% to 94-398% on sputum swabs. Complete biosafety inactivation was achieved by three devices; two showed residual growth (<0.02%). Lysis efficiency of several devices met or exceeded the reference, supporting the feasibility of extraction-free workflows for TB diagnosis, with further optimization of buffer compatibility and biosafety profiles expected to enhance performance.