Continuous-wave laser generated jets for needle free applications

Berrospe‐Rodriguez, Carla; Visser, Claas Willem; Schlautmann, Stefan; Ramos-Garcı́a, R.; Rivas, David Fernández

doi:10.1063/1.4940038

Cited by 28 publications

(39 citation statements)

References 35 publications

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“…Fast liquid jets carry spatially confined kinetic energy that can penetrate into a tissue 2 . Motivation for this work ranges from the development of needle-free transdermal drug injectors [3][4][5][6][7][8][9] , "liquid scalpel" for soft tissue dissecting [10][11][12] or devices for gene delivery [13][14][15] . The main advantage lies in the smaller extent of collateral damage caused to the tissue, superior lateral precision and addressability of certain depths 16 .…”

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confidence: 99%

Repetitive regime of highly focused liquid microjets for needle-free injection

Krizek

Delrot

Moser

2020

Sci Rep

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fast liquid jets are investigated for use as a needle-free drug delivery system into an elastic tissue such as skin. Using smaller jet diameters in a repetitive regime can mitigate bruising and pain associated with current injectors. in this study, we aim to unravel the potential of the method to deliver liquids into biological tissues having higher elasticity than healthy skin (i.e >60 kPa). To address this challenge, we have implemented a laser-based jetting system capable of generating supersonic liquid microjets in a repetitive regime. We provide insights on the penetration of microjets into hydrogel samples with elastic modulus ranging from 16 kPa to 0.5 MPa. The unprecedented speeds of injection (>680 m/s) together with a newly introduced repetitive regime opens possibilities for usage in needle-free drug administration into materials with elasticity covering the wide spectrum of biological soft tissues like blood vessels, all skin layers, scarred or dried skin or tumors.Development of needle-free delivery systems for distribution of medicines was listed as one of the grand challenges in global health 1 . The goal is to reduce contaminated waste, mitigate the risk of disease spreading or to avoid needle-stick accidents. Fast liquid jets carry spatially confined kinetic energy that can penetrate into a tissue 2 . Motivation for this work ranges from the development of needle-free transdermal drug injectors 3-9 , "liquid scalpel" for soft tissue dissecting 10-12 or devices for gene delivery [13][14][15] . The main advantage lies in the smaller extent of collateral damage caused to the tissue, superior lateral precision and addressability of certain depths 16 .The use of currently available jet injectors is associated with pain and bruising which originates from the relatively large injection depth and volume 4 . This can be addressed by injecting smaller diameter jets in repetitive regime thus compensating for the smaller volume of each jet by its multiplicity. In the context of needle-free drug delivery, this strategy was first implemented by Arora 4 using a piezo actuator system 17 . The Arora study 4 showed that in vivo injection in rats minimized the collateral damage and provided sufficient dosage of insulin. The same technology was used by Römgens et al. 3 who reported a delivery efficiency through the first skin layer (epidermis) as high as 90%. Jets were mostly stopped by the reticular dermis and reached the hypodermis with the efficiency of only 12%. With regard to the diagram presented by Rodríguez et al. 18 we can claim, that such shallow penetration prevents this technology from delivering a drug aimed to reach the hypodermis or muscle tissue.

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confidence: 99%

Repetitive regime of highly focused liquid microjets for needle-free injection

Krizek

Delrot

Moser

2020

Sci Rep

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“…According to the literature, a minimum jet velocity of 13 ∕ should be sufficient to penetrate a typical skin strength of 20 . 9,29 Out of all created jets, 92% were faster or even twice as fast than this velocity.…”

Section: Comparison Of Transdermal Delivery Methodsmentioning

confidence: 97%

“…The fabrication process and design of these devices were previously described elsewhere. 8,9 The microfluidic devices consisted of two rectangular channels with 100 μm depth:…”

Section: Needle-free Micro-jet Injectormentioning

confidence: 99%

“…16,17 From the different energy sources used to power NFIs, a recent example is based on continuous wave (CW) lasers that cause a phenomenon known as thermocavitation to create liquid jets by heating the injectate above its boiling point with an explosive phase transition. 8,9,27,28,35 This work evaluates a CW-based needle-free micro-jet injector as a possible transdermal delivery alternative with minimal damage to the skin structure. For the purpose of this study, the topical solution delivery will be primarily associated with diffusion processes.…”

Section: Introductionmentioning

confidence: 99%

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A Comparison of Drug Delivery into Skin Using Topical Solutions, Needle Injections and Jet Injections

Cu¹,

Bansal

Mitragotri³

et al. 2019

Preprint

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Drug diffusion within the skin with a needle-free micro-jet injection (NFI) device was compared with two well-established delivery methods: topical application and solid needle injection. A permanent make-up (PMU) machine, normally used for dermal pigmentation, was utilized as a solid needle injection method. For NFIs a continuous wave (CW) laser diode was used to create a bubble inside a microfluidic device containing a light absorbing solution. Each method delivered two different solutions into ex-vivo porcine skin. The first solution consisted of a red dye (direct red 81) and rhodamine B in water. The second solution was direct red 81 and rhodamine B in water and glycerol. For PMU experiments, the skin samples were kept stationary and the diffusion depth, width and surface area were measured. The NFI has a higher vertical dispersion velocity of 3 × 10 5 /s compared to topical (0.1 µm/s) and needle injection (53 /s). The limitations and advantages of each method are discussed, and we conclude that the micro-jet injector represents a fast and minimally invasive injection method, while the solid needle injector causes notably tissue damage. In contrast, the topical method had the slowest diffusion rate but causes no visible damage to the skin.

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“…Unlike jetting in cylindrical geometries, this device had a rectangular cross-section channel with high aspect ratio known to produce disk-like cavitation bubbles [4,35], with different self-focusing effects as those observed in capillaries. The tapering angle of the nozzle was varied in a range of 15 • to 40 • , and provided a speed increase of up to 65 % [34].…”

Section: Introductionmentioning

confidence: 99%

Microfluidics control the ballistic energy of thermocavitation liquid jets for needle-free injections

Galvez

Fraters

Offerhaus

et al. 2020

Journal of Applied Physics

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Illuminating a water solution with a focused continuous wave laser produces a strong local heating of the liquid that leads to the nucleation of bubbles, also known as thermocavitation. During the growth of the bubble, the surrounding liquid is expelled from the constraining microfluidic channel through a nozzle, creating a jet. The characteristics of the resulting liquid jet was imaged using ultra-fast imaging techniques. Here, we provide a phenomenological description of the jet shapes and velocities, and compare them with a Boundary Integral numerical model. We define the parameter regime, varying jet speed, taper geometry and liquid volume, for optimal printing, injection and spray applications. These results are important for the design of energy-efficient needle-free jet injectors based on microfluidic thermocavitation. arXiv:2003.00934v1 [physics.flu-dyn]

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Continuous-wave laser generated jets for needle free applications

Cited by 28 publications

References 35 publications

Repetitive regime of highly focused liquid microjets for needle-free injection

Repetitive regime of highly focused liquid microjets for needle-free injection

A Comparison of Drug Delivery into Skin Using Topical Solutions, Needle Injections and Jet Injections

Microfluidics control the ballistic energy of thermocavitation liquid jets for needle-free injections

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