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This article presents a miniature shock wave driven micro-jet generator to deliver liquid drugs into human skin, to a controlled depth, with minimal invasion. The device can release the vaccine/drug to the depth of dermal blood vessels, without breaching much of the microcirculation system of dermis. The drug delivery technique is needle-free, which can reduce pain, trauma, and contamination besides minimal dosage and systemic exposure. The device can also be used to deliver liquid or colloidal drugs into soft tissues in human. The mechanical analyses of the device were carried out by analyzing the strength of the impulse of the shock wave, measuring the velocity of the generated jet and capturing the pressure exerted by the jet on the target. The penetrating ability of the jet was investigated by delivering it into sample of human skin and gelatin slabs. Theoretical analyses were carried out on the physics of the delivery and the predicted results had a close agreement with the experimental observations. The development can offer an important cost-effective solution to needle-free health care worldwide. Biotechnol. Bioeng. 2016;113: 2507-2512. © 2016 Wiley Periodicals, Inc.
Assuntos
Ondas de Choque de Alta Energia , Injeções a Jato/instrumentação , Preparações Farmacêuticas/administração & dosagem , Transdutores de Pressão , Vacinas/administração & dosagem , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Agulhas , PressãoRESUMO
An accelerometer-based force balance was designed and developed for the measurement of drag, lift, and rolling moment on a blunt-nosed, flapped delta wing in a short-duration hypersonic shock tunnel. Calibration and validation of the balance were carried out by a convolution technique using hammer pulse test and surface pressure measurements. In the hammer pulse test, a known impulse was applied to the model in the appropriate direction using an impulse hammer, and the corresponding output of the balance (acceleration) was recorded. Fast Fourier Transform (FFT) was operated on the output of the balance to generate a system response function, relating the signal output to the corresponding load input. Impulse response functions for three components of the balance, namely, axial, normal, and angular, were obtained for a range of input load. The angular system response function was corresponding to rolling of the model. The impulse response functions thus obtained, through dynamic calibration, were operated on the output (signals) of the balance under hypersonic aerodynamic loading conditions in the tunnel to get the time history of the unknown aerodynamic forces and moments acting on the model. Surface pressure measurements were carried out on the model using high frequency pressure transducers, and forces and moments were deduced thereon. Tests were carried out at model angles of incidence of 0, 5, 10, and 15 degrees. A good agreement was observed among the results of different experimental methods. The balance developed is a comprehensive force/moment measurement device that can be used on complex, lifting, aerodynamic geometries in ground-based hypersonic test facilities.
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Acelerometria/normas , Algoritmos , CalibragemRESUMO
This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength) ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval) in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles) was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications.
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DNA/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Lasers , Microesferas , Gases em Plasma/química , Biolística , Sistemas de Liberação de Medicamentos/instrumentação , Glucuronidase/metabolismo , Terapia a Laser , Cebolas/citologia , Aceleradores de PartículasRESUMO
A chromel-constantan coaxial surface junction thermocouple has been designed, fabricated, calibrated, and tested to measure the temperature-time history on the surface of a body in a hypersonic freestream of Mach 8 in a shock tunnel. The coaxial thermocouple with a diameter of 3.25 mm was flush mounted in the surface of a hemisphere of 25 mm diameter. The hypersonic freestream was of a very low temperature and density, and had a flow time of about a millisecond. Preliminary test results indicate that the thermocouple is quite sensitive to low temperature-rarefied freestreams, and also has a response time of a few microseconds (≈5 µs) to meet the requirements of short duration transient measurements. The sensor developed is accurate, robust, reproducible, and is highly inexpensive.
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OBJECT: A pressure-driven continuous jet of water has been reported to be a feasible tool for neuroendoscopic dissection owing to its superiority at selective tissue dissection in the absence of thermal effects. With respect to a safe, accurate dissection, however, continuous water flow may not be suitable for intraventricular use. The authors performed experiments aimed at solving problems associated with continuous flow by using a pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser-induced liquid jet (LILJ). They present this candidate neuroendoscopic LILJ dissection system, having examined its mechanical characteristics and evaluated its controllability both in a tissue phantom and in a rabbit cadaveric ventricle wall. METHODS: The LILJ generator was incorporated into the tip of a No. 4 French catheter so that the LILJ could be delivered via a neuroendoscope. Briefly, the LILJ was generated by irradiating an internally supplied column of physiological saline with a pulsed Ho:YAG laser (pulse duration time 350 microsec; laser energy 250-700 mJ/pulse) within a No. 4 French catheter (internal diameter 1 mm) and ejecting it from a metal nozzle (internal diameter 100 microm). The Ho:YAG laser energy pulses were conveyed by an optical fiber (core diameter 400 microm) at 3 Hz, whereas physiological saline (4 degrees C) was supplied at a rate of 40 ml/hour. The mechanical characteristics of the pulsed LILJ were investigated using high-speed photography and pressure measurements; thermal effects and controllability were analyzed using an artificial tissue model (10% gelatin of 1 mm thickness). Finally, the ventricle wall of a rabbit cadaver was dissected using the LILJ. Jet pressure increased in accordance with laser energy from 0.1 to 2 bar; this translated into a penetration depth of 0.08 to 0.9 mm per shot in the ventricle wall of the rabbit cadaver. The gelatin phantom could be cut into the desired shape without significant thermal effects and in the intended manner, with a good surgical view. CONCLUSIONS: The present results show that the pulsed LILJ has the potential to become a safe and reliable dissecting method for endoscopic procedures.
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Ventrículos Cerebrais/cirurgia , Dissecação/instrumentação , Lasers , Neuroendoscopia , Fluxo Pulsátil , Animais , Ventrículos Cerebrais/patologia , Desenho de Equipamento , Segurança de Equipamentos , Masculino , Modelos Neurológicos , CoelhosRESUMO
BACKGROUND AND OBJECTIVES: Although water jet technology has been considered as a feasible neuroendoscopic dissection methodology because of its ability to perform selective tissue dissection without thermal damage, problems associated with continuous use of water and the ensuing fountain-effect-with catapulting of the tissue-could make water jets unsuitable for endoscopic use, in terms of safety and ease of handling. Therefore, the authors experimented with minimization of water usage during the application of a pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser-induced liquid jet (LILJ), while assuring the dissection quality and the controllability of a conventional water jet dissection device. We have developed the LILJ generator for use as a rigid neuroendoscope, discerned its mechanical behavior, and evaluated its dissection ability using the cadaveric rabbit ventricular wall. STUDY DESIGN/MATERIALS AND METHODS: The LILJ generator is incorporated into the tip of a stainless steel tube (length: 22 cm; internal diameter: 1.0 mm; external diameter: 1.4 mm), so that the device can be inserted into a commercial, rigid neuroendoscope. Briefly, the LILJ is generated by irradiating an internally supplied water column within the stainless steel tube using the pulsed Ho:YAG laser (wave length: 2.1 microm, pulse duration time: 350 microseconds) and is then ejected through the metal nozzle (internal diameter: 100 microm). The Ho:YAG laser pulse energy is conveyed through optical quartz fiber (core diameter: 400 microm), while cold water (5 degrees C) is internally supplied at a rate of 40 ml/hour. The relationship between laser energy (range: 40-433 mJ/pulse), standoff distance (defined as the distance between the tip of the optical fiber and the nozzle end; range: 10-30 mm), and the velocity, shape, pressure, and average volume of the ejected jet were analyzed by means of high-speed camera, PVDF needle hydrophone, and digital scale. The quality of the dissection plane, the preservation of blood vessels, and the penetration depth were evaluated using five fresh cadaveric rabbit ventricular walls, under neuroendoscopic vision. RESULTS: Jet velocity (7.0-19.6 m/second) and pressure (0.07-0.28 MPa) could be controlled by varying the laser energy, which determined the penetration depth in the cadaveric rabbit ventricular wall (0.07-1.30 mm/shot). The latter could be cut into desirable shapes-without thermal effects-under clear neuroendoscopic vision. The average volume of a single ejected jet could be confined to 0.42-1.52 microl/shot, and there was no accompanying generation of shock waves. Histological specimens revealed a sharp dissection plane and demonstrated that blood vessels of diameter over 100 microm could be preserved, without thermal damage. CONCLUSIONS: The present pulsed LILJ system holds promise as a safe and reliable dissection device for deployment in a rigid neuroendoscope.