Extracellular RNA in a single droplet of human serum reflects physiologic and disease states.

Extracellular RNAs (exRNAs) are present in human serum. It remains unclear to what extent these circulating exRNAs may reflect human physiologic and disease states. Here, we developed SILVER-seq (Small Input Liquid Volume Extracellular RNA Sequencing) to efficiently sequence both integral and fragmented exRNAs from a small droplet (5 μL to 7 μL) of liquid biopsy. We calibrated SILVER-seq in reference to other RNA sequencing methods based on milliliters of input serum and quantified droplet-to-droplet and donor-to-donor variations. We carried out SILVER-seq on more than 150 serum droplets from male and female donors ranging from 18 y to 48 y of age. SILVER-seq detected exRNAs from more than a quarter of the human genes, including small RNAs and fragments of mRNAs and long noncoding RNAs (lncRNAs). The detected exRNAs included those derived from genes with tissue (e.g., brain)-specific expression. The exRNA expression levels separated the male and female samples and were correlated with chronological age. Noncancer and breast cancer donors exhibited pronounced differences, whereas donors with or without cancer recurrence exhibited moderate differences in exRNA expression patterns. Even without using differentially expressed exRNAs as features, nearly all cancer and noncancer samples and a large portion of the recurrence and nonrecurrence samples could be correctly classified by exRNA expression values. These data suggest the potential of using exRNAs in a single droplet of serum for liquid biopsy-based diagnostics

Nonlinear dynamics of shape memory alloys actuated bistable beams

The phenomenon of bi-stable behaviour has been widely used in the structural design, as it can provide large deformation by switching between two stable equilibrium positions. This paper aims to investigate the intrinsic nonlinear dynamic characteristics of an actively controlled bistable beam using a simplified spring-mass model. The dynamic model for an active (heated) SMA wire driven bistable beam is established based on a polynomial constitutive equation to describe the thermomechanical behaviour of the shape memory alloy. The actively controlled bistable beams are designed, fabricated and experimentally tested to achieve the morphing behaviour snapping-through form one position to another. The results obtained from the experimental testing and the theoretical simulation are compared to validate the proposed model. Dynamic behavior of the proposed SMA wires actuated bistable beam under varying external excitation is investigated to show the influence of the thermomechanical loadings. Analysis of the experimental data and simulation results shows that the SMA wires actuated bistable structure can be well-performed for the bistable switching. It also approved that the different behaviours of the system, including periodic responses, complex responses and chaos can be accurately predicted using the proposed simplified model

Dynamic instability of variable angle tow composite plates with delamination

In this paper, the dynamic instability of variable angle tow (VAT) plates with a single rectangular delamination is studied using an analytical model. The analytical model is derived from the principle of potential energy based on the classical laminated plate theory. Both global and local behavior of delaminated VAT plates in the dynamic instability analysis are accurately captured by the use of multiple Legendre polynomial series. The equations for the motion in dynamic instability problem are derived using Hamilton’s principle. The dynamic instability regions are determined from the resulting Mathieu differential equations, which are solved using Bolotin’s approach. To validate the proposed analytical model, both critical buckling loads and natural frequencies of delaminated VAT plates are evaluated and compared with FEM results. The influence of delamination on the buckling load, natural frequency and dynamic instability region (DIR) of delaminated VAT plates is examined by numerical examples. A parametric study is subsequently carried out to analyze the effect of linearly varying fibre orientation angles on the dynamic instability response of delaminated VAT plates. Finally, the mechanism of applying variable angle tows to improve the dynamic stability performance of delaminated composite plates is studied

Evidence theory-based reliability optimization for cross-scale topological structures with global stress, local displacement, and micro-manufacturing constraints

An uncertainty-oriented cross-scale topology optimization model with global stress reliability constraint, local displacement constraint, and micro-manufacturing control based on evidence theory is presented. The model is oriented to two-dimensional porous material structure, which concurrently designs the material distribution of both the macrostructure and the cell microstructure. During the optimization process, the homogenization method is used to solve the equivalent elastic modulus of the cell microstructure, which is then endowed to the macro-elements for subsequent analysis. The local stress constraints are converted to a global constraint by P-norm to reduce the computational consumption. Considering the uncertainty factors, the evidence theory is utilized to process the uncertainty parameters and evaluate the reliability of the structural strength performance. Minimum length-scale constraint is imposed on the cell microstructure by a density projection method for better manufacturability. Three numerical examples are presented to illustrate the availability of the proposed model

Buckling analysis of variable angle tow composite plates with one circular delamination

Advanced carbon-fibre composite materials are increasingly used as primary structural components in aviation and aerospace industries due to their high stiffness-to-density ratio. The design of composite aerostructures is required to meet a number of safety criteria, in particular, the damage tolerance. Delaminations, which are caused by the impact of foreign objects (tool drops, runway debris, bird strikes etc) or the manufacture process, are one of the most common damage defects of laminated composite structures. The delaminations may lead to the occurrence of the local buckling and/or the global buckling before the ultimate design load, and therefore reduce the load-carrying capacity of composite structures. The mechanics of laminated composite structures containing delaminations had been extensively studied by many researchers in last two decades. With an increased understanding of the failure mechanism due to the delaminations, the damage tolerance constraints can be considered in the optimal design of composite structures. However, a finite element method using the cohesive elements or the Virtual Crack Closure Technique (VCCT) is normally very time-consuming to perform the damage analysis of composite laminates. Therefore, developing an analytical modelling to compute the residual buckling or postbuckling strength after the delaminations remains importance, not only for the availability of an efficient design tool but also for the study of physical insights of delaminations. A number of previous works had applied the analytical modelling to study the effect of a delamination or delaminations on buckling and postbuckling strength of constant stiffness composite plates. This work developed a Rayleigh-Ritz modelling to analyse the buckling behaviour of VAT plates with one circular delamination. Taking advantages of the advanced VAT laminates to improve the damage tolerance of composite structures remains great potential. However, the damage mechanics and the failure mechanism of VAT composite laminates containing delaminations have never been well studied. This work performed the parametric study of the compressive buckling load of the VAT laminates with linear variation of fibre angles. The results reveal the benefits of utilizing the variable stiffness tailoring to improve the delaminated buckling resistance of composite structures

Acoustic separation of circulating tumor cells

Circulating tumor cells (CTCs) are important targets for cancer biology studies. To further elucidate the role of CTCs in cancer metastasis and prognosis, effective methods for isolating extremely rare tumor cells from peripheral blood must be developed. Acoustic-based methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contact-free sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients owing to technical constraints, insufficient throughput, and lack of long-term device stability. In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients. Our method uses tilted-angle standing surface acoustic waves. Parametric numerical simulations were performed to design optimum device geometry, tilt angle, and cell throughput that is more than 20 times higher than previously possible for such devices. We first validated the capability of this device by successfully separating low concentrations (~100 cells/mL) of a variety of cancer cells from cell culture lines from WBCs with a recovery rate better than 83%. We then demonstrated the isolation of CTCs in blood samples obtained from patients with breast cancer. Our acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.National Institutes of Health (U.S.) (Grant 1 R01 GM112048-01A1)National Institutes of Health (U.S.) (Grant 1R33EB019785-01)National Science Foundation (U.S.)Penn State Center for Nanoscale Science (Materials Research Science and Engineering Center Grant DMR-0820404)National Institutes of Health (U.S.) (Grant U01HL114476