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.

The adhesive systems of climbing animals have served as inspiration for a new class of temporary adhesive utilizing surface microstructure in place of intrinsically soft and viscoelastic materials. These have the potential to address requirements for robust, releasable, and reusable bonding. Efforts to characterize synthetic dry adhesives, as well as to scale adhesive patches to large areas while maintaining performance, necessitate consideration of features of the system across length scales. This work addresses two topics which require that the behavior of individual microfibrils be accounted for explicitly within large-scale loading configurations.

Under ideal conditions the strength of fibril arrays is known to be controlled by an array edge load concentration associated with compliance of the backing layer. Laboratory experiments have revealed that the strength is sensitive to the alignment of the adhesive and substrate surfaces, however no systematic investigation of the response to these perturbations in the loading configuration has been performed. A contact mechanics model is developed, considering the role of backing layer compliance in addition to misalignment. A monotonic decay in the adhesive strength of the array with increasing misalignment angle is confirmed. More interestingly, regimes of dominance of backing layer compliance and misalignment in control of the adhesive strength are revealed. Where circumferential detachment gives way to peel-like detachment, compliance of the backing layer is found to be beneficial to performance. This is the result of shielding of the peel-front load concentration by backing layer deformation. Subsequent experimental characterization of a mushroom-tipped synthetic fibril array shows that this regime is dominant for misalignment angles of just ~ 0.2° over a patch size of 2 mm. These results can be utilized to anticipate the performance of fibrillar adhesive patches on flat surfaces without precise control of alignment, or of sub-arrays within a larger hierarchy where surface undulations may lead to local misalignment.

While the potential importance of the variability in fibril adhesive strength in controlling the performance of microstructure arrays has been highlighted in past work, there has been no effort to systematically characterize the strength distribution or understand its effect on performance further. The capabilities of an experimental platform with in-situ contact visualization are leveraged to provide strength data on a fibril-by-fibril basis. A framework is developed, based upon the statistical theory of fracture, allowing for the decoupling of two defect populations and assessment of the impact of fabrication imperfections on performance. A subsequent theoretical investigation is performed with a view to understanding the combined effect of variability in fibril adhesive strength and load concentrations at the array scale. It is shown that, dependent on the severity of the load concentration, increased variability in fibril adhesive strength can modulate the influence of load concentrations and lead to independence of the adhesive strength of the array from properties such as backing layer compliance or substrate curvature. This is highly significant, given that the severity of load concentrations is a key factor in designing hierarchical structures for adhesive strength.

Traumatic Brain Injury (TBI) is a leading cause of death and disability worldwide, making it both a global health and economic problem. Despite extensive studies utilizing tissue-level injury models, there is still no effective neural therapeutic available to counteract the neurodegenerative cascade, or secondary injury mechanism, of TBI. In part, this is due to limited understanding of cell-level response to mechanical injury. Prior research has examined the effects of mechanical strain on individual cells, but these studies have involved low strains and low strain rates (ε < 10%, ε ̇ < 100 s-1 ) leaving a largely unexplored injury regime. Furthermore, many of these tools are low throughput (100s of cells per study) which limits the statistical significance of their findings. To more thoroughly explore the effects of cellular injury, a microfluidic and electromagnetically actuated MEMS device (the ‘µHammer’) was developed to apply high strains and high strain rates (ε > 40%, ε ̇ = 200,000 s-1) to individual cells in a high throughput manner (36,000 cells per minute). With this device, compressive strain was applied to human Neural Progenitor Cells (NPCs), which were then monitored for changes in viability and gene expression. Compression studies revealed TBI secondary injury mechanisms (cell death and apoptosis), mechanically sensitive neuroinflammation signaling elements, and a previously unexplored global expression signature. These results suggest that the µHammer device can be an invaluable tool for furthering the understanding of cellular response to mechanical injury.