Abstract-A comprehensive computational study was undertaken to identify the extent to which elastoplastic 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: Young's modulus, E, was varied from 10 to 210 GPa, yield strength, s y , from 30 to 3000 MPa, and strain hardening exponent, n, from 0 to 0.5, and the Poisson's 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 indentation 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 e r 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 Young's modulus E*, a representative stress s r , and the hardness p ave . These values are somewhat sensitive to the experimental scatter and/or error commonly seen in instrumented indentation. With this information, values of s y 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. 

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Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosomebased biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contactfree manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro-and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contactfree, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine. extracellular vesicles | exosomes | blood-borne vesicles | surface acoustic waves | acoustic tweezers

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. Acousticbased methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contactfree 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.circulating cancer cells | cell separation | rare-cell sorting | acoustic tweezers | microfluidics