MicroRNAs (miRNAs) have emerged as promising diagnostic biomarkers. We introduce a kinetic fingerprinting approach called Single Molecule Recognition through Equilibrium Poisson Sampling (SiMREPS) for the amplification-free counting of single unlabeled miRNA molecules, which circumvents thermodynamic limits of specificity and virtually eliminates false positives. We demonstrate high-confidence single-molecule detection of synthetic and endogenous miRNAs in both buffer and minimally treated biological liquids, as well as >500-fold discrimination between single nucleotide polymorphisms.

Developing simple and general approaches for the synthesis of nanometer-sized DNAm aterials with specific morphologies and functionalities is important for various applications.H erein, an ovel approachf or the synthesis of anew set of DNA-based nanoarchitectures through coordination-driven self-assembly of Fe II ions and DNAm olecules is reported. By fine-tuning the assembly,F e-DNAn anospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNAt oc ells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as at ool for directing the assembly of DNA architectures,w hichc onceptualizes an ew pathway to expand the repertoire of DNA-based nanomaterials.This methodology will advance both the fields of DNAn anobiotechnology and metal-ligand coordination chemistry.The past decade has witnessed worldwide interest in the construction of DNA-based nanomaterials due to their numerous applications ranging from biomedicine to biotechnology. [1][2][3][4][5] Because DNAi su nable to penetrate cell membranes,integration of DNAwith functional nanocarriers (e.g. cationic polymeric and liposomal systems) to promote the delivery is of interest. [2] Recently,D NA-nanotechnologyenabled nanomaterials (e.g., DNAo rigami and spherical nucleic acids), which enable delicate structure tailoring and good biocompatibility, [3][4][5] have shown great potential to transport therapeutic nucleic acids or molecular cargos into cells for various applications. [1] However,t he current approaches are often limited by sophisticated materials synthesis and formulation processes.S trategies aiming at reducing complexity in the synthesis process and increasing scalability and functionality remain ac entral theme in the field of DNA-based nanomaterials.Coordination-driven self-assembly has proven to be one of the most attractive strategies in supramolecular chemistry for the bottom-up construction of functional molecular architectures and materials. [6] Examples of such ensembles range from coordination polymers (CPs), [7] metal-organic frameworks (MOFs), [8] to supramolecular polymer gels. [9] The integration of organic and inorganic components into these materials at the molecular level could increase their structural complexity and endow them with advanced functionalities and broader applications. [6][7][8][9] In particular, nanoscale CPs are rapidly emerging as one of the most active research fields among the chemistry and materials communities,a sd emonstrated by versatile applications for catalysis,o ptical and magnetic materials,a nd nanomedicine. [7] To date,m ost of such systems are built from small organic molecules and metal ions. [7a-f] Most recently,s mall biomolecules (e.g,t annic acid and dipeptides) have been explored for the assembly of functional CP nanoparticles (NPs) for potential bioimaging and drug delivery applications. [7g-i] Despite successful attempts,t oo ur knowledge,c ontrolled syn...

Although numerous strategies are now available to generate rudimentary forms of synthetic cell-like entities, minimal progress has been made in the sustained excitation of artificial protocells under non-equilibrium conditions. Here we demonstrate that the electric field energization of coacervate microdroplets comprising polylysine and short single strands of DNA generates membrane-free protocells with complex, dynamical behaviours. By confining the droplets within a microfluidic channel and applying a range of electric field strengths, we produce protocells that exhibit repetitive cycles of vacuolarization, dynamical fluctuations in size and shape, chaotic growth and fusion, spontaneous ejection and sequestration of matter, directional capture of solute molecules, and pulsed enhancement of enzyme cascade reactions. Our results highlight new opportunities for the study of non-equilibrium phenomena in synthetic protocells, provide a strategy for inducing complex behaviour in electrostatically assembled soft matter microsystems and illustrate how dynamical properties can be activated and sustained in microcompartmentalized media.