Nanofabrication techniques for achieving dimensional control at the nanometer scale are generally equipment-intensive and time-consuming. The use of energetic beams electrons or ions has placed fabrication nanopores in thin solid-state membranes within reach some academic laboratories, yet these tools not accessible to many researchers poorly suited mass-production. Here we describe a fast simple approach fabricating single nanopore down 2-nm size with sub-nm precision, directly solution, by...

The electrical noise characteristics of ionic current through organic and synthetic nanopores have been investigated. Comparison to proteinaceous alpha-Hemolysin pores reveals two dominant sources in silicon nitride nanometre-scale pores: a high-frequency associated with the capacitance support chip (dielectric noise), low-frequency fluctuation 1/fα (flicker noise). We present technique for reducing dielectric by curing polydimethylsiloxane (PDMS) on nanopore chip. This greatly improves...

The surface stress induced during the formation of alkanethiol self-assembled monolayers (SAMs) on gold from vapor phase was measured using a micromechanical cantilever-based chemical sensor. Simultaneous in situ thickness measurements were carried out ellipsometry. Ex scanning tunneling microscopy performed air to ascertain final monolayer structure. evolution coverage-dependent structural transitions reveals features not apparent average ellipsometric measurements. These results show that...

We demonstrate the automated and reproducible fabrication of sub-2-nm nanopores in 10-nm thick silicon nitride membranes, through controlled dielectric breakdown solution. Our results reveal that under appropriate conditions, can be fabricated with a size no larger than 2.0 ± 0.5-nm diameter for sample N = 23 nanopores, an average standard deviation 1.3 0.6-nm. The dimensions these are confirmed by using individual translocating DNA molecules as molecular rulers. show 2.0-nm 2.1-nm nanopore...

Many interactions drive the adsorption of molecules on surfaces, all which can result in a measurable change surface stress. This article compares contributions various possible to overall induced stress for cantilever-based sensing applications. The resulting from adsorption-induced changes electronic density underlying is up 2–4 orders magnitude larger than that intermolecular electrostatic or Lennard-Jones interactions. We reveal associated with formation high quality alkanethiol...

Abstract Serum neurofilament light chain (NfL) is emerging as an important biomarker in multiple sclerosis (MS). Our objective was to evaluate the prognostic value of serum NfL levels obtained close time MS onset with long-term clinical outcomes. In this prospective cohort study, we identified patients collected within 5 years first symptom (baseline) more than 15 routine follow-up. Levels were quantified and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix)....

Biological and solid-state nanometer-scale pores are the basis for numerous emerging analytical technologies use in precision medicine. We developed Modular Single-Molecule Analysis Interface (MOSAIC), an open source analysis software that improves accuracy throughput of nanopore-based measurements. Two key algorithms implemented: ADEPT, which uses a physical model nanopore system to characterize short-lived events do not reach their steady-state current, CUSUM+, version cumulative sum...

Nanopore fabrication by controlled breakdown (CBD) overcomes many of the challenges traditional nanofabrication techniques, reliably forming solid-state nanopores sub-2 nm in size a low-cost and scalable way for nucleic acid analysis applications. Herein, kinetics thin dielectric membranes immersed liquid environment are investigated order to gain deeper insights into mechanism nanopore formation high electric fields. For various conditions, we demonstrate that time is Weibull-distributed,...

Single-molecule counting is the most accurate and precise method for determining concentration of a biomarker in solution leading to emergence digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores-fully electronic sensors with single-molecule sensitivity-are well suited task. Here we present immunoassay scheme capable reliably quantifying target protein complex biofluids that overcomes specificity, sensitivity, consistency challenges associated use...

We present a methodology for preparing silicon nitride nanopores that provides in situ control of size with sub-nanometer precision while simultaneously reducing electrical noise by up to three orders magnitude through the cyclic application high electric fields an aqueous environment. Over 90% treated this technique display desirable characteristics and readily exhibit translocation double-stranded DNA molecules. Furthermore, previously used degraded properties can be rejuvenated further...

We report the use of an array electrically gated ~200 nm solid-state pores as nanofluidic transistors to manipulate capture and passage DNA. The devices are capable reversibly altering rate DNA by over 3 orders magnitude using sub-1 V biasing a gate electrode. This efficient gating originates from counter-balance electrophoresis electroosmosis, revealed quantitative numerical simulations. Such reversible electronically tunable biomolecular switch may be used nucleic acid delivery in fluidic...

Functional low-noise nanopore arrays are fabricated by controlled dielectric breakdown in solid-state membranes integrated within microfluidic devices.

To reduce unwanted variation in the passage speed of DNA through solid-state nanopores, we demonstrate nanoscale preconfinement translocating molecules using an ultrathin nanoporous silicon nitride membrane separated from a single sensing nanopore by cavity. We present comprehensive experimental and simulation results demonstrating that presence integrated nanofilter within distances pore eliminates dependence molecular time distributions on size, revealing global minimum coefficient time....

We demonstrate precise positioning of nanopores fabricated by controlled breakdown (CBD) on solid-state membranes spatially varying the electric field strength with localized membrane thinning. show 100 × nm2 precision in standard SiN x (30-100 nm thick) after selective thinning as little 25% a helium ion beam. Control over nanopore position is achieved through strong dependence field-driven CBD mechanism thickness. Confinement pore formation to thinned region confirmed TEM imaging and...

<h3>Objective</h3> To evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- post-treatment immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) examine associations clinical MRI outcomes. <h3>Methods</h3> Paired addition to measures were collected on 23 at baseline 1 3 years post-IAHSCT. An additional 33 sera pairs taken from noninflammatory neurologic controls. NfL quantitated using the Simoa platform...

Using a solid-state nanopore to measure the concentration of clinically relevant target analytes, such as proteins or specific DNA sequences, is major goal research. This usually achieved by measuring capture rate analyte through pore. However, progress hindered sources systematic error that are beyond level control currently achievable with state-of-the-art nanofabrication techniques. In this work, we show process nanopores subject significant variability, both within individual over time...

Weak molecular interactions drive processes at the core of living systems, such as enzyme−substrate interactions, receptor−ligand binding, and nucleic acid replication. Single-molecule force spectroscopy is a remarkable tool for revealing scale energy landscapes noncovalent bonds, by exerting mechanical directly on an individual complex tracking its survival function time applied force. In principle, methods can also be used highly specific recognition assays, characterizing strength bonds...

The promise of portable diagnostic devices relies on three basic requirements: comparable sensitivity to established platforms, inexpensive manufacturing and cost operations, the ability survive rugged field conditions. Solid state nanopores can meet all these requirements, but achieve high yields at low costs, assays must be tolerant fabrication imperfections nanopore enlargement during operation. This paper presents a model for molecular engineering techniques that meets goals with aim...

A method for calculating the surface stress associated with deflection of a micromechanical cantilever is presented. This overcomes some limitations Stoney’s formula by circumventing need to know cantilever’s Young’s modulus, which can have high level uncertainty, especially silicon nitride cantilevers. The calculated using readily measurable properties, such as its geometry, spring constant, and deflection. applicable both rectangular triangular calibration measurement also accurate within 4%–7%.

The surface stress response of micromechanical cantilever-based sensors was studied as a function the morphology, adhesion, and cleanliness gold sensing surface. Two model systems were investigated: adsorption alkanethiol self-assembled monolayers at gas−solid interface potential-controlled anions liquid−solid interface. potential-induced stress, on smooth continuous polycrystalline Au(111)-textured microcantilever in 0.1 M HClO4, is excellent agreement with macroscopic Au(111)...

The capture and translocation characteristics of multi-arm DNA star nanostructures are studied to evaluate their potential as advanced labels for improved solid-state nanopore sensing performance.