Encapsulated Cell Dynamics in Droplet Microfluidic Devices with Sheath Flow.

In this paper we study the dynamics of single cells encapsulated in water-in-oil emulsions in a microchannel. The flow field of a microfluidic channel is coupled to the internal flow field of a droplet through viscous traction at the interface, resulting in a rotational flow field inside the droplet. An encapsulated single cell being subjected to this flow field responds by undergoing multiple orbits, spins, and deformations that depend on its physical properties. Monitoring the cell dynamics, using a high-speed camera, can lead to the development of new label-free methods for the detection of rare cells, based on their biomechanical properties. A sheath flow microchannel was proposed to strengthen the rotational flow field inside droplets flowing in Poiseuille flow conditions. A numerical model was developed to investigate the effect of various parameters on the rotational flow field inside a droplet. The multi-phase flow model required the tracking of the fluid-fluid interface, which deforms over time due to the applied shear stresses. Experiments confirmed the significant effect of the sheath flow rate on the cell dynamics, where the speed of cell orbiting was doubled. Doubling the cell speed can double the amount of extracted biomechanical information from the encapsulated cell, while it remains within the field of view of the camera used.

Modeling of Droplet Generation in a Microfluidic Flow-Focusing Junction for Droplet Size Control.

In this paper, we study the parameters that affect the generation of droplets in a microfluidic flow-focusing junction. Droplets are evaluated based on the size and frequency of generation. Droplet size control is essential for microfluidic lab-on-a-chip applications in biology, chemistry, and medicine. We developed a three-dimensional numerical model that can emulate the performance of the physical system. A numerical model can help design droplet-generation chips with new junction geometries, different dispersed and continuous phase types, and different flow rates. Our model uses a conservative level-set method (LSM) to track the interface between two immiscible fluids using a fixed mesh. Water was used for the dispersed phase and mineral oil for the continuous phase. The effects of the continuous-to-dispersed flow rate ratio (Qo/Qw) and the surfactant concentration on the droplet generation were studied both using the numerical model and experimentally. The numerical model was found to render results that are in good agreement with the experimental ones, which validates the LSM model. The validated numerical model was used to study the time effect of changing Qo/Qw on the generated droplet size. Properly timing when the flow rates are changed enables control over the size of the next generated droplet, which is useful for single-droplet size modulation applications.

Modeling of a Symmetric Five-Bar Displacement Amplification Compliant Mechanism for Energy Harvesting.

This paper presents an analytical model to determine a closed form mathematical representation for the output displacement of a displacement amplification compliant mechanism used for energy harvesting. A symmetric five-bar compliant mechanism with right-circular and corner-filleted flexure hinges was mathematically modeled and its displacement was determined using the Castigliano energy theorem. The stresses within the flexure joints, the weakest points in the mechanism body, were calculated. The mathematical model expresses both the displacement amplification and the stresses as functions of the design parameters and the load caused by the harvester. The developed model can be used to optimize the mechanism dimensions for maximum harvested power, while minimizing its structural stresses. The mechanism was also modeled numerically using finite element methods; both the analytical and numerical models were verified experimentally. The mathematical model of the mechanism was integrated with a model representing a piezoelectric energy harvester to calculate the open-circuit voltage. As a proof of concept, experiments were performed using an unimorph piezoelectric cantilever at low-frequency (less than 1 Hz) harmonic excitation inputs. The measured open-circuit voltage was found to be in agreement with that calculated using the proposed model, when integrated with the model representing the piezoelectric beam. The power generated by the piezoelectric harvester, equipped with the proposed displacement amplification mechanism, was more than a hundred times that without amplification.

Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells.

Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system's capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates.