Depth-controlled laser-induced jet injection for direct three-dimensional liquid delivery

Abstract

Needle-free jet injection enables the delivery of drugs into skin or soft tissue by puncturing them with a high-velocity liquid jet. However, precise and efficient drug delivery requires generating such liquid jets with both a controlled velocity and a high throughput, which remains challenging with current spring-and gas-actuated jet injectors. Here, we propose a depth-controlled and high-throughput injection method by adapting laser-induced forward transfer (LIFT), a high-resolution two-dimensional printing technique, for direct three-dimensional liquid delivery into soft tissues.The velocity of thin liquid jets is laser actuated from 10 to 85 m/s so that doses as small as 10 pL, not achievable with other injectors, are injected at a 1 Hz repetition rate into a 300 μm thick soft gelatin substrate with a 25 μm depth precision and 12 μm lateral resolution. We further investigate the potential of this liquid delivery technique as a direct three-dimensional cell-delivery vehicle and show that depth-controlled particle delivery requires high-delivery efficiency. Our direct three-dimensional liquid delivery system opens up more possibilities for pinpoint drug delivery in soft tissues or tissue-engineered constructs.

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

“…That is why we elaborate only on the focused part of the ejected fluid because for the high material stiffnesses we are not able to generate slower tail part fast enough to penetrate in. System avoiding slow-tail are realized by a change in the generation scheme in a way the laser pulse is close to the interface like in Turkoz et al 30 , Delrot et al 16 , or Hayasaka et al 31 . In this paper we elaborate only on the critical values required to achieve certain depths without the assessment of the efficiency.…”

“…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 .…”

“…In this system, a nanosecond laser pulse induces a shockwave that impacts a concave meniscus, thus creating a flow-focused micro-jet tip whose shape remains spatially focused even for high Reynolds number (the highest measured Reynolds number is Re ≈ 10 4 by considering the effective length-scale as the diameter of the tip which is 0.1 of the capillary diameter). Moreover, the thin shape has a positive influence on the penetration performance and lateral positioning of the dose 16,22 .…”

Needle-free delivery of fluids from compact laser-based jet injector

“…11 Such contactless devices provide better dose control, lateral and depth localization and lower collateral damage than the needles. 12,53 In needle-free injection devices, the liquid is pushed out of the nozzle forming a thin jet, which is powerful enough to penetrate into a tissue. The actuation scheme is commonly based on a piezoactuator, [13][14][15] loaded spring, 11,16 gas cartridge, 11 voice coil actuator 17,18 or an electrical discharge.…”

“…Laser induced cavitation has been investigated as the driving mechanism for needle-free injection systems. 12,[21][22][23][24][25][26][27][28][29][30] Tagawa et al 28 demonstrated injection with a new type of highly focused liquid microjets generated by a laser pulse focused by an optical objective from the side of a transparent nozzle. In the recent study by Krizek et al 29 this concept was elaborated on hydrogel models mimicking stiffer materials representing mechanical properties of various soft body tissues up to 0.5 MPa (e.g.…”