ABSTRACT
Lipid nanoparticles (LNPs) for RNA and DNA delivery have gained considerable attention to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality under low stress conditions added to fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow-rates, a degradation of performances in terms of size, size monodispersivity and encapsulation efficiency. In this study we focus on the ring micromixer, well adapted to high throughputs. We reveal three regimes - side-by-side, transitionnal and highly mixed – which control the mixing performance of the device. Further, on using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We underline the important role of the flow-rate ratio and propose a physical criterion, based on the onset of temporal instabilities, coupled to a stochiometric one, for producing LNPs with optimal characteristics, in term of geometry, monodispersivity and encapsulation yield. These criteria are general.
ABSTRACT
Objectives: Determine the sensitivity and specificity of a Point-Of-Care test (COVIDISC) for SARS-COV2. The novelty of the test is to integrate, on the same (low-cost) compact plastic/paper device, solid phase RNA extraction and RT-LAMP amplification, all reagents being freeze-dried on it. Method: Retrospective study with a cohort of 99 patients characterized by real-time RT-PCR. The 37 positive naso-pharyngeal samples cover a broad range of viral loads (from 5 gc /microL to 2 10^6 gc/ microL of sample) . Results: The COVIDISC found 36 positives (out of 37 by IP4 RT-PCR protocols) and 63 negatives (out of 62 by RT-PCR). Conclusion: The sensitivity of the COVIDISC, found in this 99-patient retrospective study, is 97% and the specificity 100%.