SYnthetic MEmbraneS With VErtically Aligned Long CArbon Nanotubes for Noiseless miRNA Screening/Sequencing
https://iramis.cea.fr/wp-content/uploads/2026/02/YESWECAN.pdf
MiRNA (RiboNucleic Acid) are short noncoding RNA (≃20 nucleotides) regulating gene expression. As their expression level is correlated with various pathologies including cancers, they are identified as potential biomarkers. Effective methods to identify them in the blood stream remain scarce and biologists face a need for sufficiently selective and sensitive methods. The YESWECAN project (TRL 3) addresses the screening then sequencing of miRNAs by i) the use of a CNT-based (Carbon NanoTube) porous synthetic membrane ii) filled with an Ionic Liquid (IL) and iii) a nanopore sensing strategy using not a thin pore but a long tube. The noiseless system we propose is the route to the sensitivity needed for miRNA sequencing. Objective: A notorious limitation of the nanopore technique is an elevated error rate (up to 25%). This is due to i) the use of nanometric thin membranes (to increase sensitivity), ii) the conduction noise induced by salts (KCl) and iii) the fragility of these biologic membranes. In this framework, we propose a paradigm change: use a thick (1 to 100 microns) porous polymer composite vertically-aligned CNT-based membrane (stable and long-lived). This is already on hand. Here, we will deliver a prototype made of a CNT membrane decorated by a-hemolysin (HL), a canonic screening mediating transport protein. The CNTs interior will be filled with an IL known i) to be a good solvent of NA and ii) to show no conduction noise under confinement. We have a dual objective: first to achieve miRNA screening through a non HL-decorated single CNT using machine learning and then to evaluate the miRNA sequencing potential through a HL-functionalized single CNT tube. Strategy: We have already shown by a nanopore technique that under confinement in a nanometric tube the relative “Pink Noise” amplitude vs electric current for a single tube filled with an IL shows a noise lower than KCl by one order of magnitude. The miRNA flow through an IL filled CNT will make it possible to turn into a fluid transport process (small noise) the usual thin pore jammed (large noise) conduction. Impact for CEA: We propose a paradigm change in the fast-growing field of NA screening and sequencing, then expect publications in high-impact journals i.e. high scientific visibility for CEA. In the long term, after industrialization of screening/sequencing devices based on the YESWECAN seminal concept could be an element in setting France in a market from which it is out at the moment.