Michela Geri

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.

Thermokinematic memory and the thixotropic elasto-viscoplasticity of waxy crude oils

The effect of thermal and shear history on the rheology of waxy crude oils is studied in detail. A protocol sequence is presented, which enables us to systematically extract the main thixotropic features of a model waxy oil by a series of steady state and transient experiments at different temperatures. The importance of the underlying microstructure formed by a loosely aggregated and percolated network of wax crystals is discussed and quantified through differential scanning calorimetry and rheological measurements. The microstructural morphology can be described by relevant concepts used previously in the literature for concentrated suspensions of fractal aggregates and is augmented with evolution equations to capture the transient rearrangement of the microstructure, resulting in a thermokinematic memory of the shearing history and thermal history of the sample. Finally, a complete constitutive framework is derived that is able to quantitatively describe and predict a number of rheological features of the model waxy oil, such as viscoelasticity at small deformations and plasticity at large deformations, with both the yield stress and viscosity exhibiting thermokinematic memory. Direct comparison with rheometric data is used to determine the model constants and evaluate the predictive ability of the constitutive relations. The proposed model provides a new framework that can be used to describe not only waxy crude oils, but also other materials characterized by similar microstructural components, i.e., solid non-Brownian interacting particles of arbitrary shape that form a percolated sample-spanning network and convey thixotropy as well as elasto-viscoplasticity.The effect of thermal and shear history on the rheology of waxy crude oils is studied in detail. A protocol sequence is presented, which enables us to systematically extract the main thixotropic features of a model waxy oil by a series of steady state and transient experiments at different temperatures. The importance of the underlying microstructure formed by a loosely aggregated and percolated network of wax crystals is discussed and quantified through differential scanning calorimetry and rheological measurements. The microstructural morphology can be described by relevant concepts used previously in the literature for concentrated suspensions of fractal aggregates and is augmented with evolution equations to capture the transient rearrangement of the microstructure, resulting in a thermokinematic memory of the shearing history and thermal history of the sample. Finally, a complete constitu...

Computing the linear viscoelastic properties of soft gels using an optimally windowed chirp protocol

We use molecular dynamics simulations to investigate the linear viscoelastic response of a model three-dimensional particulate gel. The numerical simulations are combined with a novel test protocol (the optimally windowed chirp or OWCh), in which a continuous exponentially varying frequency sweep windowed by a tapered cosine function is applied. The mechanical response of the gel is then analyzed in the Fourier domain. We show that (i) OWCh leads to an accurate computation of the full frequency spectrum at a rate significantly faster than with the traditional discrete frequency sweeps, and with a reasonably high signal-to-noise ratio, and (ii) the bulk viscoelastic response of the microscopic model can be described in terms of a simple mesoscopic constitutive model. The simulated gel response is in fact well described by a mechanical model corresponding to a fractional Kelvin-Voigt model with a single Scott-Blair (or springpot) element and a spring in parallel. By varying the viscous damping and the particle mass used in the microscopic simulations over a wide range of values, we demonstrate the existence of a single master curve for the frequency dependence of the viscoelastic response of the gel that is fully predicted by the constitutive model. By developing a fast and robust protocol for evaluating the linear viscoelastic spectrum of these soft solids, we open the path toward novel multiscale insight into the rheological response for such complex materials.We use molecular dynamics simulations to investigate the linear viscoelastic response of a model three-dimensional particulate gel. The numerical simulations are combined with a novel test protocol (the optimally windowed chirp or OWCh), in which a continuous exponentially varying frequency sweep windowed by a tapered cosine function is applied. The mechanical response of the gel is then analyzed in the Fourier domain. We show that (i) OWCh leads to an accurate computation of the full frequency spectrum at a rate significantly faster than with the traditional discrete frequency sweeps, and with a reasonably high signal-to-noise ratio, and (ii) the bulk viscoelastic response of the microscopic model can be described in terms of a simple mesoscopic constitutive model. The simulated gel response is in fact well described by a mechanical model corresponding to a fractional Kelvin-Voigt model with a single Scott-Blair (or springpot) element and a spring in parallel. By varying the viscous damping and the parti...