Ming Dao

Computational modeling of the forward and reverse problems in instrumented sharp indentation

A comprehensive computational study was undertaken to identify the extent to which elasto- plastic properties of ductile materials could be determined from instrumented sharp indentation and to quantify the sensitivity of such extracted properties to variations in the measured indentation data. Large deformation finite element computations were carried out for 76 different combinations of elasto-plastic properties that encompass the wide range of parameters commonly found in pure and alloyed engineering metals: Youngs modulus, E, was varied from 10 to 210 GPa, yield strength, sy, from 30 to 3000 MPa, and strain hardening exponent, n, from 0 to 0.5, and the Poissons ratio, n, was fixed at 0.3. Using dimensional analysis, a new set of dimensionless functions were constructed to characterize instrumented sharp indentation. From these functions and elasto-plastic finite element computations, analytical expressions were derived to relate inden- tation data to elasto-plastic properties. Forward and reverse analysis algorithms were thus established; the forward algorithms allow for the calculation of a unique indentation response for a given set of elasto-plastic properties, whereas the reverse algorithms enable the extraction of elasto-plastic properties from a given set of indentation data. A representative plastic strain er was identified as a strain level which allows for the construction of a dimensionless description of indentation loading response, independent of strain hardening exponent n. The proposed reverse analysis provides a unique solution of the reduced Youngs modulus E*, a representative stress sr, and the hardness pave. These values are somewhat sensitive to the experimental scatter and/or error commonly seen in instrumented indentation. With this information, values of sy and n can be determined for the majority of cases considered here, provided that the assumption of power law hardening adequately represents the full uniaxial stress-strain response. These plastic properties, however, are very strongly influenced by even small variations in the parameters extracted from instrumented indentation experiments. Comprehensive sensitivity analyses were carried out for both forward and reverse algorithms, and the computational results were compared with experimental data for two materials.  2001 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Some critical experiments on the strain-rate sensitivity of nanocrystalline nickel

Systematic experiments have been performed to investigate the rate sensitivity of deformation in fully dense nanocrystalline Ni using two different experimental techniques: depth-sensing indentation and tensile testing. Results from both types of tests reveal that the strain-rate sensitivity is a strong function of grain size. Specifically microcrystalline and ultra-fine crystalline pure Ni, with grain size range of 1 µm and 100–1000 nm, respectively, exhibit essentially rateindependent plastic flow over the range 3 × 10 4 to 3 × 10 1 s 1 , whereas nanocrystalline pure Ni with a grain size of approximately 40 nm, exhibits marked rate sensitivity over the same range. A simple computational model, predicated on the premise that a rate-sensitive grain-boundary affected zone exists, is shown to explain the observed effect of grain size on the rate-dependent plastic response.  2003 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Study of mechanical deformation in bulk metallic glass through instrumented indentation

Instrumented sharp indentation experiments at the nano- and micro-length scales were carried out in an attempt to quantify the deformation characteristics of Vitreloy 1  bulk metallic glass. The experiments were accompanied by detailed three-dimensional finite element simulations of instrumented indentation to formulate an overall constitutive response. By matching the experimentally observed continuous indentation results with the finite element predictions, a general Mohr-Coulomb type constitutive description was extracted to capture the dependence of multiaxial deformation on both shear stresses and normal stresses. This constitutive response is able to provide accurate predictions of the evolution of shear bands seen in uniaxial compression tests. Constrained deformation of the material around the indenter results in incomplete circular patterns of shear bands whose location, shape and size are also captured well by the numerical simulations. The analysis is also able to predict the extent of material pile-up observed around the indenter. The surface deformation features are also consistent with mechanisms such as localized shear flow, serrated yielding and adiabatic heating, which are observed during macroscopic mechanical tests.  2001 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Depth-sensing instrumented indentation with dual sharp indenters

A methodology for interpreting instrumented sharp indentation with dual sharp indenters with different tip apex angles is presented by recourse to computational modeling within the context of finite element analysis. The forward problem predicts an indentation response from a given set of elasto-plastic properties, whereas the reverse analysis seeks to extract elasto-plastic properties from depth-sensing indentation response by developing algorithms derived from computational simulations. The present study also focuses on the uniqueness of the reverse algorithm and its sensitivity to variations in the measured indentation data in comparison with the single indentation analysis on Vickers/Berkovich tip (Dao et al. Acta Mater 49 (2001) 3899). Finite element computations were carried out for 76 different combinations of elasto-plastic properties representing common engineering metals for each tip geometry. Young’s modulus, E, was varied from 10 to 210 GPa; yield strength, sy, from 30 to 3000 MPa; and strain hardening exponent, n, from 0 to 0.5; while the Poisson’s ratio, n, was fixed at 0.3. Using dimensional analysis, additional closedform dimensionless functions were constructed to relate indentation response to elasto-plastic properties for different indenter tip geometries (i.e., 50° ,6 0° and 80° cones). The representative plastic strain er, as defined in Dao et al. (Acta Mater 49 (2001) 3899), was constructed as a function of tip geometry in the range of 50° and 80°. Incorporating the results from 60° tip to the single indenter algorithms, the improved forward and reverse algorithms for dual indentation can be established. This dual indenter reverse algorithm provides a unique solution of the reduced Young’s modulus E ∗ , the hardness pave and two representative stresses (measured at two corresponding representative strains), which establish the basis for constructing power-law plastic material response. Comprehensive sensitivity analyses showed much improvement of the dual indenter algorithms over the single indenter results. Experimental verifications of these dual indenter algorithms were carried out using a 60° half-angle cone tip (or a 60° cone equivalent 3-sided pyramid tip) and a standard Berkovich indenter tip for two materials: 6061-T6511 and 7075-T651 aluminum alloys. Possible extensions of the present results to studies involving multiple indenters are also suggested.  2003 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Acoustic separation of circulating tumor cells

Significance The separation and analysis of circulating tumor cells (CTCs) provides physicians a minimally invasive way to monitor the response of cancer patients to various treatments. Among the existing cell-separation methods, acoustic-based approaches provide significant potential to preserve the phenotypic and genotypic characteristics of sorted cells, owing to their safe, label-free, and contactless nature. In this work, we report the development of an acoustic-based device that successfully demonstrates the isolation of rare CTCs from the clinical blood samples of cancer patients. Our work thus provides a unique means to obtain viable and undamaged CTCs, which can subsequently be cultured. The results presented here offer unique pathways for better cancer diagnosis, prognosis, therapy monitoring, and metastasis research. 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.

Cell separation using tilted-angle standing surface acoustic waves

Significance We have developed a unique approach for the separation of particles and biological cells through standing surface acoustic waves oriented at an optimum angle to the fluid flow direction in a microfluidic device. This experimental setup, optimized by systematic analyses, has been used to demonstrate effective separation based on size, compressibility, and mechanical properties of particles and cells. The potential of this method for biological–biomedical applications was demonstrated through the example of isolating MCF-7 breast cancer cells from white blood cells. The method offers a possible route for label-free particle or cell separation for many applications in research, disease diagnosis, and drug-efficacy assessment. Separation of cells is a critical process for studying cell properties, disease diagnostics, and therapeutics. Cell sorting by acoustic waves offers a means to separate cells on the basis of their size and physical properties in a label-free, contactless, and biocompatible manner. The separation sensitivity and efficiency of currently available acoustic-based approaches, however, are limited, thereby restricting their widespread application in research and health diagnostics. In this work, we introduce a unique configuration of tilted-angle standing surface acoustic waves (taSSAW), which are oriented at an optimally designed inclination to the flow direction in the microfluidic channel. We demonstrate that this design significantly improves the efficiency and sensitivity of acoustic separation techniques. To optimize our device design, we carried out systematic simulations of cell trajectories, matching closely with experimental results. Using numerically optimized design of taSSAW, we successfully separated 2- and 10-µm-diameter polystyrene beads with a separation efficiency of ∼99%, and separated 7.3- and 9.9-µm-polystyrene beads with an efficiency of ∼97%. We illustrate that taSSAW is capable of effectively separating particles–cells of approximately the same size and density but different compressibility. Finally, we demonstrate the effectiveness of the present technique for biological–biomedical applications by sorting MCF-7 human breast cancer cells from nonmalignant leukocytes, while preserving the integrity of the separated cells. The method introduced here thus offers a unique route for separating circulating tumor cells, and for label-free cell separation with potential applications in biological research, disease diagnostics, and clinical practice.

Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum

During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasite-exported proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature.

Cytoskeletal dynamics of human erythrocyte

The human erythrocyte (red blood cell, RBC) demonstrates extraordinary ability to undergo reversible large deformation and fluidity. Such mechanical response cannot be consistently rationalized on the basis of fixed connectivity of the cell cytoskeleton that comprises the spectrin molecular network tethered to phospholipid membrane. Active topological remodeling of spectrin network has been postulated, although detailed models of such dynamic reorganization are presently unavailable. Here we present a coarse-grained cytoskeletal dynamics simulation with breakable protein associations to elucidate the roles of shear stress, specific chemical agents, and thermal fluctuations in cytoskeleton remodeling. We demonstrate a clear solid-to-fluid transition depending on the metabolic energy influx. The solid networks plastic deformation also manifests creep and yield regimes depending on the strain rate. This cytoskeletal dynamics model offers a means to resolve long-standing questions regarding the reference state used in RBC elasticity theory for determining the equilibrium shape and deformation response. In addition, the simulations offer mechanistic insights into the onset of plasticity and void percolation in cytoskeleton. These phenomena may have implication for RBC membrane loss and shape change in the context of hereditary hemolytic disorders such as spherocytosis and elliptocytosis.

Cold spray coating: review of material systems and future perspectives

Abstract Cold gas dynamic spray or simply cold spray (CS) is a process in which solid powders are accelerated in a de Laval nozzle toward a substrate. If the impact velocity exceeds a threshold value, particles endure plastic deformation and adhere to the surface. Different materials such as metals, ceramics, composites and polymers can be deposited using CS, creating a wealth of interesting opportunities towards harvesting particular properties. CS is a novel and promising technology to obtain surface coating, offering several technological advantages over thermal spray since it utilizes kinetic rather than thermal energy for deposition. As a result, tensile residual stresses, oxidation and undesired chemical reactions can be avoided. Development of new material systems with enhanced properties covering a wide range of required functionalities of surfaces and interfaces, from internal combustion engines to biotechnology, brought forth new opportunities to the cold spraying with a rich variety of material combinations. As applications multiply, the total number of studies on this subject is expanding rapidly and it is worth summarizing the current state of knowledge. This review covers different material systems that have been studied up to now with an emphasis on potential innovative applications. This includes metallic, ceramic and metal matrix composite (MMC) coatings and their applications. Polymer (both as substrate and coating) and metal embedment in the polymer are also covered. CS has emerged as a promising process to deposit nanostructured materials without significantly altering their microstructure whereas many traditional consolidation processes do. Relevant material systems containing nanostructured powders are also considered. A critical discussion on the future of this technology is provided at the final part of the paper focusing on the microstructural bonding mechanisms for those relatively less explored material systems. These include MMCs involving more than one constituent, ceramics, polymers and nanostructured powders. Future investigations are suggested especially to quantitatively link the process parameters and the behaviour of the material systems of interest during impact.

High-resolution three-dimensional imaging of red blood cells parasitized by Plasmodium falciparum and in situ hemozoin crystals using optical diffraction tomography

Abstract. We present high-resolution optical tomographic images of human red blood cells (RBC) parasitized by malaria-inducing Plasmodium falciparum (Pf)-RBCs. Three-dimensional (3-D) refractive index (RI) tomograms are reconstructed by recourse to a diffraction algorithm from multiple two-dimensional holograms with various angles of illumination. These 3-D RI tomograms of Pf-RBCs show cellular and subcellular structures of host RBCs and invaded parasites in fine detail. Full asexual intraerythrocytic stages of parasite maturation (ring to trophozoite to schizont stages) are then systematically investigated using optical diffraction tomography algorithms. These analyses provide quantitative information on the structural and chemical characteristics of individual host Pf-RBCs, parasitophorous vacuole, and cytoplasm. The in situ structural evolution and chemical characteristics of subcellular hemozoin crystals are also elucidated.