Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation.

High-frequency irreversible electroporation (H-FIRE) is a technique that uses pulsed electric fields that have been shown to ablate malignant cells. In order to evaluate the clinical potential of H-FIRE to treat glioblastoma (GBM), a primary brain tumor, we have studied the effects of high-frequency waveforms on therapy-resistant glioma stem-like cell (GSC) populations. We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes. This selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric field thresholds, significantly lower than that of healthy astrocytes. However, neural stem cell (NSC) populations also exhibit a similar sensitivity to these pulses. This observation may suggest that different considerations be taken when applying these therapies in younger versus older patients, where the importance of preserving NSC populations may impose different restrictions on use. We also demonstrate variability in threshold among the three patient-derived GSC lines studied, suggesting the need for personalized cell-specific characterization in the development of potential clinical procedures. Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.

Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures.

Experimental tools to model cell-tissue interactions will likely lead to new ways to both understand and treat cancer. While the mechanical properties and regulation of invasion have been recently studied for tumor cells, they have received less attention in the context of tumor vascular dynamics. In this article, we have investigated the interaction between the surfaces of structures encountered by endothelial cells invading their surrounding extracellular matrix (ECM) during angiogenesis. For this purpose, we have fabricated round and sharp geometries with various curvature and sharpness indices in collagen hydrogel over a wide range of stiffness to mimic different microenvironments varying from normal to tumor tissues. We have then cultured endothelial cells on these structures to investigate the bi-directional interaction between the cells and ECM. We have observed that cell invasion frequency is higher from the structures with the highest sharpness and curvature index, while interestingly the dependence of invasion on the local micro-geometry is strongest for the highest density matrices. Notably, structures with the highest invasion length are linked with higher deformation of side structures, which may be related to traction force-activated signaling suggesting further investigation. We have noted that round structures are more favorable for cell adhesion and in some cases round structures drive cell invasion faster than sharp ones. These results highlight the ability of endothelial cells to sense small variations in ECM geometry, and respond with a balance of matrix invasion as well as deformation, with potential implications for feedback mechanisms that may enhance vascular abnormality in response to tumor-induced ECM alterations.

High-Q nanomechanics via destructive interference of elastic waves.

Mechanical dissipation poses a ubiquitous challenge to the performance of nanomechanical devices. Here we analyze the support-induced dissipation of high-stress nanomechanical resonators. We develop a model for this loss mechanism and test it on Si(3)N(4) membranes with circular and square geometries. The measured Q values of different harmonics present a nonmonotonic behavior which is successfully explained. For azimuthal harmonics of the circular geometry we predict that destructive interference of the radiated waves leads to an exponential suppression of the clamping loss in the harmonic index. Our model can also be applied to graphene drums under high tension.

Anodically bonded submicron microfluidic chambers.

We demonstrate the use of anodic bonding to fabricate cells with characteristic size as large as 7 x 10 mm(2), with height of approximately 640 nm, and without any internal support structure. The cells were fabricated from Hoya SD-2 glass and silicon wafers, each with 3 mm thickness to maintain dimensional stability under internal pressure. Bonding was carried out at 350 degrees C and 450 V with an electrode structure that excluded the electric field from the open region. We detail fabrication and characterization steps and also discuss the design of the fill line for access to the cavity.

Stress and silicon nitride: a crack in the universal dissipation of glasses.

High-stress silicon nitride microresonators exhibit a remarkable room temperature Q factor that even exceeds that of single crystal silicon. A study of the temperature dependent variation of the Q of a 255 micromx255 micromx30 nm thick high-stress Si3N4 membrane reveals that the dissipation Q-1 decreases with lower temperatures and is approximately 3 orders of magnitude smaller than the universal behavior. Stress-relieved cantilevers fabricated from the same material show a Q that is more consistent with typical disordered materials. e-beam and x-ray studies of the nitride film's structure reveal characteristics consistent with a disordered state. Thus, it is shown that stress alters the Q-1, violating the universality of dissipation in disordered materials in a self-supporting structure.