Solid-state nanopores allow high-throughput single-molecule detection but identifying and even registering all translocating small molecules remain key challenges due to their high translocation speeds. We show here the same electric field that drives the molecules into the pore can be redirected to selectively pin and delay their transport. A thin high-permittivity dielectric coating on bullet-shaped polymer nanopores permits electric field leakage at the pore tip to produce a voltage-dependent surface field on the entry side that can reversibly edge-pin molecules. This mechanism renders molecular entry an activated process with sensitive exponential dependence on the bias voltage and molecular rigidity. This sensitivity allows us to selectively prolong the translocation time of short single-stranded DNA molecules by up to 5 orders of magnitude, to as long as minutes, allowing discrimination against their double-stranded duplexes with 97% confidence.

No abstract

Nucleic acid biomarkers have enormous potential in non-invasive diagnostics and disease management. In medical research and in the near future in the clinics, there is a great demand for accurate miRNA, mRNA, and ctDNA identification and profiling. They may lead to screening of early stage cancer that is not detectable by tissue biopsy or imaging. Moreover, because their cost is low and they are non-invasive, they can become a regular screening test during annual checkups or allow a dynamic treatment program that adjusts its drug and dosage frequently. We briefly review a few existing viral and endogenous RNA assays that have been approved by the Federal Drug Administration. These tests are based on the main nucleic acid detection technologies, namely, quantitative reverse transcription polymerase chain reaction (PCR), microarrays, and next-generation sequencing. Several of the challenges that these three technologies still face regarding the quantitative measurement of a panel of nucleic acids are outlined. Finally, we review a cluster of microfluidic technologies from our group with potential for point-of-care nucleic acid quantification without nucleic acid amplification, designed to overcome specific limitations of current technologies. We suggest that integration of these technologies in a modular design can offer a low-cost, robust, and yet sensitive/selective platform for a variety of precision medicine applications.

We describe the role of functional polymer surfactants in the construction and triggered collapse of droplet-based fibers and the use of these macroscopic supracolloidal structures for reagent compartmentalization. Copolymer surfactants containing both zwitterionic and tertiary amine pendent groups were synthesized for stabilization of oil-in-water droplets, in which the self-adherent properties of the selected zwitterions impart interdroplet adherence, while the amine groups provide access to pH-triggered coalescence. Macroscopic fibers, obtained by droplet extrusion, were prepared with reagents embedded in spatially distinct components of the fibers. Upon acidification of the continuous aqueous phase, protonation of the polymer surfactants increases their hydrophilicity and causes rapid fiber disruption and collapse. Cross-linked versions of these supracolloidal fibers were stable upon acidification and appeared to direct interdroplet passage of encapsulants along the fiber length. Overall, these functional, responsive emulsions provide a strategy to impart on-demand chemical reactivity to soft materials structures that benefits from the interfacial chemistry of the system.

We study the spatiotemporal dynamics of a microfluidic system with a non-selective microfluidic channel gated by an ion-selective membrane which separates the ion flux paths of cations and anions. To preserve electro-neutrality, the ionic concentration in the system is shown to converge to a specific inhomogeneous distribution with robust constant current fluxes. A circuit scaling theory that collapses measured asymptotic currents verifies that this is a generic and robust mechanism insensitive to channel geometry, ion-selectivity and electrolyte ionic strength. This first temporally stationary but spatially inhomogeneous depletion front can be used for modulating ionic current and for isotachophoretic isolation of low-mobility molecules and exosomes on small diagnostic chips for various medical applications that require robust high-throughput and integrated platforms.