UC Santa Barbara

Although high strain and strain-rate impacts to the human body have been the subject of substantial research at both the systemic and tissue levels, little is known about the cell-level ramifications of such assaults. This is largely due to the lack of high throughput, dynamic compression devices capable of simulating such traumatic loading conditions on individual cells. Understanding the mechanical response to impact on the cellular level is important, since it can elucidate the fundamental mechanisms of damage following impact to vulnerable tissue like the brain and cartilage, providing a window into potential targets for therapy. To fill this gap, my collaborators and I have developed and characterized a high speed, high actuation force, magnetically driven MEMS chip to apply compression to biological cells with an unprecedented combination of strain (10% to 90%), strain rate (30,000 to 200,000 s-1), and throughput (10,000 to 1,000,000 cells/experiment). To demonstrate the cell-impact capabilities of the μHammer, we applied biologically relevant strains and strain rates to human leukemic K562 cells and then monitored their viability for up to 8 days. We observed significantly repressed proliferation of the hit cells compared to both unperturbed and sham-hit control cells, accompanied by minimal cell death. This indicates success in applying cellular damage without compromising the overall viability of the population.

Once we validated the µHammer's ability to impact cells, we sought to fully leverage the high-throughput capabilities of the device by optimizing the experimental conditions of the fluid and cells (or other particles) flowing through it. Parameters such as flow velocity and particle size are known to affect the trajectories of particles in microfluidic systems and have been studied extensively, but the effects of temperature and buffer viscosity are not as well understood. To explore the effects of these parameters on the performance of the µHammer, we first tracked the velocity of polystyrene beads through the device and then visualized the impact of these beads. Through these assays, we find that the timing of our device is sensitive to changes in the ratio of inertial forces to viscous forces that particles experience while traveling through the µHammer. This sensitivity provides a set of parameters that can serve as a robust framework for optimizing the performance of microfluidic devices under various experimental conditions. Using this framework, we achieved an effective throughput over 360 particles/s with the µHammer and proposed geometric redesigns which could further improve device performance in future experiments. In the end, the impact parameters applied by the µHammer to each of these particles align with those experienced by individual cells during traumatic impacts in the brain and cartilage, allowing us to conclude that this device is well-suited to study the subtle effects of impact on large populations of inherently heterogeneous cells.