The microjet injector system accelerates drugs and delivers them without a needle, which is shown to overcome the weaknesses of existing jet injectors. A significant increase in the delivered dose of drugs is reported with multiple pulses of laser beam at lower laser energy than was previously used in a Nd:YAG system. The new injection scheme uses the beam wavelength best absorbable by water at a longer pulse mode for elongated microjet penetration into a skin target. A 2.9 μm Er:YAG laser at 250 μs pulse duration is used for fluorescent staining of guinea pig skin and for injection controllability study. Hydrodynamic theory confirms the nozzle exit jet velocity obtained by the present microjet system.

Abstract. An Er:YAG laser with 2940-nm wavelength and 250-μs pulse duration is used to generate a microjet that is ejected at ∼50 m∕s in air. The strength of the microjet depends on the bubble dynamics from the beamwater interaction within the driving chamber as well as the discharging of the drug solution underneath the elastic membrane that separates the drug from the driving liquid. The jet characteristics, such as velocity, volume, and level of atomization, are obtained by high-speed camera images taken at 42,000 fps. The enhancements in jet volume (dosage) and repeated jet generation, which are aimed at making the injector suitable for general clinical applications, are achieved. The generation of repeated microjets is achieved with the help of a stepping motor that provides a uniform pressure within the drug reservoir before an ejection occurs through a micro nozzle. Also, two types of human growth hormones are used for monitoring any potential thermal damage to the drug solution due to a repeated laser ablation when driving the microjet. We provide strong evidence to support that the drugs, as they are injected to porcine skins, are free of the damage associated with the present delivery method. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

A breakthrough in the efficient transdermal delivery of drug via the laser-driven microjet is reported. A single source of laser beam is split into two: one beam ablates a targeted spot on a skin and another beam drives the injector for fast microjet ejection into a preablated spot. This combined ablation and microjet injection scheme using a beam splitter utilizes laser energy sharing between generation of the microhole via ablation and the microjet which is generated using the Er:YAG laser beam at a 2940-nm wavelength and pulse duration. A careful analysis of the injection mechanism is carried out by studying the response of the elastic membrane that separates a driving water unit for bubble expansion from a drug unit for a microjet ejection. The efficiency of the present delivery scheme is evaluated by the abdominal porcine skin test using the fluorescein isothiocyanate staining and the confocal microscopy for quantitative delivery confirmation. The depth of penetration and the injected volume of the drug are also confirmed by polyacrylamide gel tests.

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A narrow nozzle ejects a microjet of 150 μm in diameter with a velocity of 140 m/s a by the laser-induced bubble expansion in the designed injector. The pulsed form of the driving force at a period of 10 Hz from the connected Er:YAG laser makes it possible for multiple microjet ejections aimed at delivery of drugs into a skin target. The pulsed actuation of the microjet generation is however susceptible to the air leak which can cause the outside air to enter into the momentarily de-pressurized nozzle, leading to a significant reduction of the microjet speed during the pulsed administering of the drug. In the present study, we designed a ball-check valve injector which is less prone to an unwanted air build up inside the nozzle by controlling the nozzle pressure to remain above ambient pressure at all times. The new device is rigorously compared against the reported performance of the previous injector and has shown to maintain about 97% of the initial microjet speed regardless of the number of shots administered; likewise, the drug penetration depth into a porcine skin is improved to 1.5 to 2.25 times the previously reported penetration depths.

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Fractional-rotational ablation increases number of micro-holes in a unit area, enabling fast reepithelialization and high drug delivery efficiency. Optimization of system parameters such as ablation time, number of ablations, and injection time will eventually ensure a macromolecule delivery technique with the potential to include vaccines, insulins, and growth hormones, all of which require deeper penetration into the skin. Lasers Surg. Med. 49:387-394, 2017. © 2016 Wiley Periodicals, Inc.