Abstract
<jats:p>The search for extraterrestrial life involves finding biosignatures that can take the form of information carrying macromolecules. On Earth, these are polymers assembled from nucleic acids building blocks. Label-free single molecule techniques capable of identifying and characterizing such polymers in small, lightweight format factor instruments, would be valuable for space science. Solid-state nanopores offer a promising platform for this task. In this study, we demonstrate the capability of solid-state nanopores to detect and differentiate a variety of potential biosignatures. We characterized single-stranded RNA (ssRNA) homopolymers (poly(A) and poly(U)), observing distinct translocation profiles for each. Furthermore, by mixing the complementary strands, we confirmed the formation of double-stranded RNA (dsRNA) through the appearance of significantly longer and deeper current blockages, indicative of hybridization. We also detected polymers synthesized de novo from mononucleotides using prebiotic-like hot wet-dry cycles, which produced unique signals corresponding to a heterogeneous population of short oligomers. These findings establish that solid-state nanopores can effectively identify and characterize a range of charged polymeric structures without prior knowledge of their chemical composition. This work highlights the utility of nanopore sensing as a tool for future astrobiology missions aimed at detecting life or proto-life on other worlds.</jats:p>