Femtosecond photonic viral inactivation probed using solid-state nanopores

We report on detection of virus inactivation using femtosecond laser radiation by measuring the conductance of a solid state nanopore designed for detecting single particles. Conventional methods of assaying for viral inactivation based on plaque forming assays require 24–48 h for bacterial growth. Nanopore conductance measurements provide information on morphological changes at a single virion level.We show that analysis of a time series of nanopore conductance can quantify the detection of inactivation, requiring only a few minutes from collection to analysis. Morphological changes were verified by dynamic light scattering. Statistical analysis maximizing the information entropy provides a measure of the log reduction value. This work provides a rapid method for assaying viral inactivation with femtosecond lasers using solid-state nanopores.First author draf

Femtosecond Photonic Viral Inactivation Probed Using Solid-State Nanopores

We report on the detection of inactivation of virus particles using femtosecond laser radiation by measuring the conductance of a solid state nanopore designed for detecting single virus particles. Conventional methods of assaying for viral inactivation based on plaque forming assays require 24-48 hours for bacterial growth. Nanopore conductance measurements provide information on morphological changes at a single virion level. We show that analysis of a time series of nanopore conductance can quantify the detection of inactivation, requiring only a few minutes from collection to analysis. Morphological changes were verified by Dynamic Light Scattering (DLS). Statistical analysis maximizing the information entropy provides a measure of the Log-reduction value. Taken together, our work provides a rapid method for assaying viral inactivation with femtosecond lasers using solid-state nanopores.Comment: 6 Figures with caption

Nonlinear Free and Forced Vibrations of a Hyperelastic Micro/Nanobeam Considering Strain Stiffening Effect

In recent years, the static and dynamic response of micro/nanobeams made of hyperelasticity materials received great attention. In the majority of studies in this area, the strain-stiffing effect that plays a major role in many hyperelastic materials has not been investigated deeply. Moreover, the influence of the size effect and large rotation for such a beam that is important for the large deformation was not addressed. This paper attempts to explore the free and forced vibrations of a micro/nanobeam made of a hyperelastic material incorporating strain-stiffening, size effect, and moderate rotation. The beam is modelled based on the Euler–Bernoulli beam theory, and strains are obtained via an extended von Kármán theory. Boundary conditions and governing equations are derived by way of Hamilton’s principle. The multiple scales method is applied to obtain the frequency response equation, and Hamilton’s technique is utilized to obtain the free undamped nonlinear frequency. The influence of important system parameters such as the stiffening parameter, damping coefficient, length of the beam, length-scale parameter, and forcing amplitude on the frequency response, force response, and nonlinear frequency is analyzed. Results show that the hyperelastic microbeam shows a nonlinear hardening behavior, which this type of nonlinearity gets stronger by increasing the strain-stiffening effect. Conversely, as the strain-stiffening effect is decreased, the nonlinear frequency is decreased accordingly. The evidence from this study suggests that incorporating strain-stiffening in hyperelastic beams could improve their vibrational performance. The model proposed in this paper is mathematically simple and can be utilized for other kinds of micro/nanobeams with different boundary conditions

Genetic linkage Analysis of DFNB1)GJB6 (and DFNB4 (SLC26A4) loci with Autosomal Recessive Non-Syndromic Hearing Loss (ARNSHL) in Kermanshah, a western province of Iran

Background: Hearing Loss (HL) is the most common sensory disorder in human with an incidence of about one in 650 alive neonates. It is estimated that at least 50% of pre-lingual HL has a genetic basis. Almost 70% of genetic HL are non-syndromic (NSHL) and of NSHL cases, the autosomal recessive form (ARNSHL) comprises about 80%. Iranian population especially the Kurdish ethnicity with high consanguinity rate offers suitable opportunity for the study of ARNSHL. The aim of this study was to clarify the role of DFNB1 (GJB6) and DFNB4 (SLC26A4) loci in ARNSHL in Kermanshah, Iran. Methods: DFNB1 (GJB6) and DFNB4 (SLC26A4) loci were analysed in a cohort study on 28 ARNSHL families (GJB2- negative) from Kermanshah province in Iran. Genetic linkage analysis was applied on 140 samples from 140 individuals by polymerase chain reaction – polyacrylamide gel electrophoresis (PCR-PAGE) technique. Silver staining was used for visualizing the bands. At least, two informative screening markers were analyzed for each locus. Haplotypes were analyzed to determine linkage.Results: None of the families studied showed linkage to DFNB1 and DFNB4 loci.Conclusions: Our experiment, similar to previous studies, imply the absence of GJB6 mutations in Iran. None of the families showed linkage to DFNB4 locus. As it normally ranks second after DFNB1 in Iran and other parts of the world, more studies are warranted on more families to elucidate the role of this locus as well as other loci in etiogy of ARNSHL

Hyperelastic Microcantilever AFM: Efficient Detection Mechanism Based on Principal Parametric Resonance

The impetus of writing this paper is to propose an efficient detection mechanism to scan the surface profile of a micro-sample using cantilever-based atomic force microscopy (AFM), operating in non-contact mode. In order to implement this scheme, the principal parametric resonance characteristics of the resonator are employed, benefiting from the bifurcation-based sensing mechanism. It is assumed that the microcantilever is made from a hyperelastic material, providing large deformation under small excitation amplitude. A nonlinear strain energy function is proposed to capture the elastic energy stored in the flexible component of the device. The tip–sample interaction is modeled based on the van der Waals non-contact force. The nonlinear equation governing the AFM’s dynamics is established using the extended Hamilton’s principle, obeying the Euler–Bernoulli beam theory. As a result, the vibration behavior of the system is introduced by a nonlinear equation having a time-dependent boundary condition. To capture the steady-state numerical response of the system, a developed Galerkin method is utilized to discretize the partial differential equation to a set of nonlinear ordinary differential equations (ODE) that are solved by the combination of shooting and arc-length continuation method. The output reveals that while the resonator is set to be operating near twice the fundamental natural frequency, the response amplitude undergoes a significant drop to the trivial stable branch as the sample’s profile experiences depression in the order of the picometer. According to the performed sensitivity analysis, the proposed working principle based on principal parametric resonance is recommended to design AFMs with ultra-high detection resolution for surface profile scanning

Picomolar Fingerprinting of Nucleic Acid Nanoparticles Using Solid-State Nanopores

Nucleic acid nanoparticles (NANPs) are an emerging class of programmable structures with tunable shape and function. Their promise as tools for fundamental biophysics studies, molecular sensing, and therapeutic applications necessitates methods for their detection and characterization at the single-particle level. In this work, we study electrophoretic transport of individual ring-shaped and cube-shaped NANPs through solid-state nanopores. In the optimal nanopore size range, the particles must deform to pass through, which considerably increases their residence time within the pore. Such anomalously long residence times permit detection of picomolar amounts of NANPs when nanopore measurements are carried out at a high transmembrane bias. In the case of a NANP mixture, the type of individual particle passing through nanopores can be efficiently determined from analysis of a single electrical pulse. Molecular dynamics simulations provide insight into the mechanical barrier to transport of the NANPs and corroborate the difference in the signal amplitudes observed for the two types of particles. Our study serves as a basis for label-free analysis of soft programmable-shape nanoparticles