Saturable nonlinear dielectric waveguide with applications to broad-area semiconductor lasers

Self-focusing in a passive dielectric waveguide with a saturable nonlinearity is studied. The eigensolutions constitute a good approximation to the lateral modes of broad-area semiconductor lasers under low-duty-cycle pulsed conditions. The laser modes are predicted to consist of adjacent filaments coupled in phase, leading to a single-lobed far field, and to be stable with increased current injection above saturation intensity. The ultimate filament spacing is inversely proportional to the threshold gain, and thus wider filaments are expected in low-threshold broad-area lasers

Self-stabilized Nonlinear Lateral Modes of Broad Area Lasers

The lateral modes of broad area lasers are investigated theoretically. The nonlinear interaction between optical field and effective refractive index leads to a saturable nonlinearity in the governing field equation, so that self-modulated solutions are found to be stable with increased current injection above saturation intensity. We derive approximate analytical solutions for traveling wave fields within the broad area laser. The field amplitude consists of a small ripple superimposed on a large dc value. Matching fields at the boundary determines the modulation depth and imparts an overall phase curvature to the traveling wave mode. There are multiple lateral modes for a given set of operating conditions, and modes with successively more lobes in the ripple have greater overall phase curvature. In contrast to the linear problem, several lateral modes can achieve the same modal gain, for a given injected current density, by saturating the gain to different extent. Thus, these modes would exhibit slightly different optical powers

Broadband tunability of gain-flattened quantum well semiconductor lasers with an external grating

Quantum well lasers are shown to exhibit flattened broadband gain spectra at a particular pumping condition. The gain requirement for a grating-tuned external cavity configuration is examined and applied to a semiconductor quantum well laser with an optimized length of gain region. The predicted very broadband tunability of quantum well lasers is confirmed experimentally by grating-tuning of uncoated lasers over 85 nm, with single longitudinal mode output power exceeding 200 mW

Modifying Ultrasound Waveform Parameters to Control, Influence, or Disrupt Cells

Ultrasound can be focused into deep tissues with millimeter precision to perform non-invasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit non-selective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here we describe an alternative low intensity pulsed ultrasound approach known as “oncotripsy” that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that when applied at a specific frequency and pulse duration, focused ultrasound selectively disrupts a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to non-selective high intensity ultrasound ablation. In this dissertation, I describe the oncotripsy theory in its initial formulation, the experimental validation and investigation of testable predictions from that theory, and the refinement of said theory with new experimental evidence. Throughout, I describe how careful modifications to the ultrasound waveform directly can significantly impact how the ultrasound bio-effects control, influence, or disrupt cells in a selective and controlled manner.</p

Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification

Ultrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research

Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound

Ultrasound can be focused into deep tissues with millimeter precision to perform noninvasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit nonselective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here, we describe an alternative low intensity (I_(SPTA) 20 ms causes selective disruption of a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to nonselective high intensity ultrasound ablation

Genetically encoded nanostructures enable acoustic manipulation of engineered cells

The ability to mechanically manipulate and control the spatial arrangement of biological materials is a critical capability in biomedicine and synthetic biology. Ultrasound has the ability to manipulate objects with high spatial and temporal precision via acoustic radiation force, but has not been used to directly control biomolecules or genetically defined cells. Here, we show that gas vesicles (GVs), a unique class of genetically encoded gas-filled protein nanostructures, can be directly manipulated and patterned by ultrasound and enable acoustic control of genetically engineered GV-expressing cells. Due to their differential density and compressibility relative to water, GVs experience sufficient acoustic radiation force to allow these biomolecules to be moved with acoustic standing waves, as demonstrated within microfluidic devices. Engineered variants of GVs differing in their mechanical properties enable multiplexed actuation and act as sensors of acoustic pressure. Furthermore, when expressed inside genetically engineered bacterial cells, GVs enable these cells to be selectively manipulated with sound waves, allowing patterning, focal trapping and translation with acoustic fields. This work establishes the first genetically encoded nanomaterial compatible with acoustic manipulation, enabling molecular and cellular control in a broad range of contexts