Nonlinear Aerodynamic Damping of Sharp-Edged Beams at Low Keulegan-Carpenter Numbers

Slender sharp-edged flexible beams such as flapping wings of micro air vehicles (MAVs), piezoelectric fans and insect wings typically oscillate at moderate-to-high values of non-dimensional frequency parameter β with amplitudes as large as their widths resulting in Keulegan–Carpenter (KC) numbers of order one. Their oscillations give rise to aerodynamic damping forces which vary nonlinearly with the oscillation amplitude and frequency; in contrast, at infinitesimal KC numbers the fluid damping coefficient is independent of the oscillation amplitude. In this article, we present experimental results to demonstrate the phenomenon of nonlinear aerodynamic damping in slender sharp-edged beams oscillating in surrounding fluid with amplitudes comparable to their widths. Furthermore, we develop a general theory to predict the amplitude and frequency dependence of aerodynamic damping of these beams by coupling the structural motions to an inviscid incompressible fluid. The fluid–structure interaction model developed here accounts for separation of flow and vortex shedding at sharp edges of the beam, and studies vortex-shedding-induced aerodynamic damping in slender sharp-edged beams for different values of the KC number and the frequency parameter β. The predictions of the theoretical model agree well with the experimental results obtained after performing experiments with piezoelectric fans under vacuum and ambient conditions

IMECE2005-81318 AERO ELASTIC FLUTTER AT THE FREE EDGES OF UNI-AXIALLY TENSIONED WEBS AND THIN FILMS

ABSTRACT Aero elastic flutter may play an important role in the breakage of thin membrane-like structures (a.k.a. webs) found in paper-handling, textile, sheet-metal and magnetic tapes industry. In this article, we examine the aero elastic stability of a web modeled as a uni-axially tensioned (along the machine direction) low aspect ratio Kirchhoff plate, which is subject to a fluid flow in the cross machine direction. Panel methods based on the distribution of singularity solutions (sources and doublets) on the surface of the web are used to numerically solve the problem of 3D unsteady potential flow surrounding the web. The equation of motion of the plate coupled to a fluid flow is discretized by using Galerkin's method. The discretization is performed in the configuration space formulation of the gyroscopic eigenvalue problem. The linear stability of this reduced order system is investigated. The onset of flutter instability as a function of base fluid flow in the cross machine direction is studied. The effects of fluid coupling on the frequencies and modes of oscillations of the web are also studied

Fluid-structure interactions of flexible structures in different fluid flow regimes

The research presented in this dissertation focuses on fluid-structure interactions of thin flexible structures for three different problems, namely, the aeroelastic flutter of webs and ribbons, the nonlinear aerodynamic damping of slender beams, and the gas damping of microcantilevers. All these problems involve flexible structures at different length scales resulting in different physical regimes for the surrounding fluid flows, which are modeled using simplified fluid flow models. The first part of this dissertation presents a theoretical investigation of the aeroelastic flutter of tensioned wide webs and narrow ribbons commonly used in the paper-handling, textile, and sheet-metal industries. The web or ribbon is modeled as a uni-axially tensioned Kirchhoff plate with vanishingly small bending stiffness and is submerged in an incompressible inviscid fluid flow across its free edges resulting in a coupled non-conservative dynamical system with gyroscopic and circulatory terms. Wide webs mainly destabilize through a divergence instability due to cross-flow-induced, conservative centrifugal effects, and for certain values of applied tension, destabilize via a weak flutter instability, due to the wake-induced non-conservative effects. Contrarily, narrow ribbons in cross flow exhibit either flutter or divergence instability depending on the value of applied tension. Wind tunnel experiments, conducted to qualitatively corroborate these theoretical results, were inconclusive due to the lack of sufficient control over the important physical parameters. Nonetheless, the experiments show interesting dynamical phenomena such as simultaneous occurrence of oscillatory and zero frequency response of ribbons. The second part of this dissertation focuses on the nonlinear aerodynamic damping of slender, sharp-edged beams commonly found in flapping wings of micro-air-vehicles (MAVs), piezoelectric fans and insect wings. When such structures oscillate at moderate to large non-dimensional frequencies with large amplitudes comparable to their widths, vortex-shedding from the beam\u27s sharp edges gives rise to nonlinear aerodynamic damping. In this work, a general theory is developed to predict the amplitude and frequency dependence of this aerodynamic damping by coupling the structural motions to an inviscid, incompressible fluid. The fluid-structure interaction model developed here accounts for separation of flow and studies vortex-shedding-induced aerodynamic damping in slender, sharp-edged beams for different values of the Keulegan-Carpenter number and the non-dimensional frequency parameter. The theoretical predictions are validated against carefully performed experiments with piezoelectric fans under vacuum and atmospheric conditions. The third part of this dissertation studies the gas damping of microcantilevers oscillating in different vibration modes in an unbounded gas at low ambient pressures varying over 6 orders of magnitude. The accurate prediction of gas damping of microcantilevers at low ambient pressures is essential for improving the sensitivity of microcantilever-based sensors and improving the efficiency of microresonators. In this work, solutions of a sub-continuum, quasisteady Boltzmann equation with a simplified ellipsoidal statistical Bhatnagar-Gross-Krook (ES-BGK) collision operator are used to provide a closed-form fit, which can be used to predict the gas damping of different microcantilever vibration modes. The fit is uniformly valid over 5 orders of magnitude of the Knudsen number and spans the free-molecular, the transition, and the lower pressure side of the slip flow regime. For the higher pressure side of the slip flow regime, this work proposes a boundary-integral-method-based approach for including the slip boundary condition in existing continuum regime models. Detailed experimental data on gas damping of silicon microcantilevers obtained from research collaborators shows excellent agreement with the predictions of the ES-BGK-model-based fit

Automated manufacturability analysis for injection-molded and die-cast parts

In this thesis, a mathematical framework to automatically evaluate the manufacturability of injection-molded and die-cast parts is presented. The framework includes both a logical algorithm for the general problem of feature recognition and an implemented mathematical and numerical algorithm to solve key outstanding challenges in feature recognition for manufacturability analysis. --Abstract, page iii

Unified Theory Of Gas Damping Of Flexible Microcantilevers At Low Ambient Pressures

Predicting the gas damping of microcantilevers oscillating in different vibration modes in unbounded gas at low pressures is relevant for increasing the sensitivity of microcantilever-based sensors. While existing free-molecular theories are valid only at very high Knudsen numbers, continuum models are valid only at very low Knudsen numbers. We solve the quasisteady Boltzmann equation and compute a closed-form fit for gas damping of rectangular microcantilevers that is valid over four orders of magnitude of Knudsen numbers spanning the free-molecular, the transition, and the low pressure slip flow regimes. Experiments are performed using silicon microcantilevers under controlled pressures to validate the theory

Nonlinear aerodynamic damping of sharp-edged flexible beams oscillating at low Keulegan-Carpenter numbers

Slender sharp-edged flexible beams such as flapping wings of micro air vehicles (MAVs), piezoelectric fans and insect wings typically oscillate at moderate-to-high values of non-dimensional frequency parameter beta with amplitude as large as their widths resulting in Keulegan-Carpenter (KC) numbers or order one. Their oscillations give rise to aerodynamic damping forces which vary nonlinearly with the oscillation amplitude and frequency; in contrast, at infinitesimal KC numbers the fluid damping coefficient is independent of the oscillation amplitude. In this article, we present experimental results to demonstrate the phenomenon of nonlinear aerodynamic damping in slender sharp-edged beams oscillating in surrounding fluid with amplitudes comparable to their widths. Furthermore, we develop a general theory to predict the amplitude and frequency dependence of aerodynamic damping of these beams by coupling the structural motions to an inviscid incompressible fluid. The fluid-structure interaction model developed here accounts for separation of flow and vortex shedding at sharp edges of the beam, and studies vortex-shedding-induced aerodynamic damping in slender sharp-edged beams for different values of the KC number and the frequency parameter beta. The predictions of the theoretical model agree well with the experimental results obtained after performing experiments with piezoelectric fans under vacuum and ambient conditions

Unified theory of gas damping of flexible microcantilevers at low ambient pressures

Predicting the gas damping of microcantilevers oscillating in different vibration modes in unbounded gas at low pressures is relevant for increasing the sensitivity of microcantilever-based sensors. While existing free-molecular theories are valid only at very high Knudsen numbers, continuum models are valid only at very low Knudsen numbers. We solve the quasisteady Boltzmann equation and compute a closed-form fit for gas damping of rectangular microcantilevers that is valid over four orders of magnitude of Knudsen numbers spanning the free-molecular, the transition, and the low pressure slip flow regimes. Experiments are performed using silicon microcantilevers under controlled pressures to validate the theory

Development of CD46 targeted alpha theranostics in prostate cancer using 134Ce/225Ac-Macropa-PEG4-YS5

Rationale: 225Ac, a long-lived α-emitter with a half-life of 9.92 days, has garnered significant attention as a therapeutic radionuclide when coupled with monoclonal antibodies and other targeting vectors. Nevertheless, its clinical utility has been hampered by potential off-target toxicity, a lack of optimized chelators for 225Ac, and limitations in radiolabeling methods. In a prior study evaluating the effectiveness of CD46-targeted radioimmunotherapy, we found great therapeutic efficacy but also significant toxicity at higher doses. To address these challenges, we have developed a radioimmunoconjugate called 225Ac-Macropa-PEG4-YS5, incorporating a stable PEGylated linker to maximize tumoral uptake and increase tumor-to-background ratios. Our research demonstrates that this conjugate exhibits greater anti-tumor efficacy while minimizing toxicity in prostate cancer 22Rv1 tumors. Methods: We synthesized Macropa.NCS and Macropa-PEG4/8-TFP esters and prepared Macropa-PEG0/4/8-YS5 (with nearly ~1:1 ratio of macropa chelator to antibody YS5) as well as DOTA-YS5 conjugates. These conjugates were then radiolabeled with 225Ac in a 2 M NH4OAc solution at 30 °C, followed by purification using YM30K centrifugal purification. Subsequently, we conducted biodistribution studies and evaluated antitumor activity in nude mice (nu/nu) bearing prostate 22Rv1 xenografts in both single-dose and fractionated dosing studies. Micro-PET imaging studies were performed with 134Ce-Macropa-PEG0/4/8-YS5 in 22Rv1 xenografts for 7 days. Toxicity studies were also performed in healthy athymic nude mice. Results: As expected, we achieved a >95% radiochemical yield when labeling Macropa-PEG0/4/8-YS5 with 225Ac, regardless of the chelator ratios (ranging from 1 to 7.76 per YS5 antibody). The isolated yield exceeded 60% after purification. Such high conversions were not observed with the DOTA-YS5 conjugate, even at a higher ratio of 8.5 chelators per antibody (RCY of 83%, an isolated yield of 40%). Biodistribution analysis at 7 days post-injection revealed higher tumor uptake for the 225Ac-Macropa-PEG4-YS5 (82.82 ± 38.27 %ID/g) compared to other conjugates, namely 225Ac-Macropa-PEG0/8-YS5 (38.2 ± 14.4/36.39 ± 12.4 %ID/g) and 225Ac-DOTA-YS5 (29.35 ± 7.76 %ID/g). The PET Imaging of 134Ce-Macropa-PEG0/4/8-YS5 conjugates resulted in a high tumor uptake, and tumor to background ratios. In terms of antitumor activity, 225Ac-Macropa-PEG4-YS5 exhibited a substantial response, leading to prolonged survival compared to 225Ac-DOTA-YS5, particularly when administered at 4.625 kBq doses, in single or fractionated dose regimens. Chronic toxicity studies observed mild to moderate renal toxicity at 4.625 and 9.25 kBq doses. Conclusions: Our study highlights the promise of 225Ac-Macropa-PEG4-YS5 for targeted alpha particle therapy. The 225Ac-Macropa-PEG4-YS5 conjugate demonstrates improved biodistribution, reduced off-target binding, and enhanced therapeutic efficacy, particularly at lower doses, compared to 225Ac-DOTA-YS5. Incorporating theranostic 134Ce PET imaging further enhances the versatility of macropa-PEG conjugates, offering a more effective and safer approach to cancer treatment. Overall, this methodology has a high potential for broader clinical applications

Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

PurposeRadiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody.Experimental design[225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity.ResultsBiodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line-derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi.Conclusions[225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen-positive and prostate-specific membrane antigen-deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer