Needle-free jet injection using real-time controlled linear Lorentz-force actuators
Introduction
Needle-free drug delivery can be realized using the principle of jet injection, whereby a liquid drug is pressurized and accelerated through a small orifice, creating a narrow, high-speed fluid jet of sufficient velocity to penetrate skin and tissue. Pressures of ∼20 MPa, and forces of ∼200 N are required to accelerate the drug to the requisite velocity of 100–200 m/s; the energy required per injection is ∼10 J. The principle of jet injection was first discovered in the nineteenth century, and has been utilized for drug delivery since the mid-twentieth century [1].
Currently available commercial devices employ a variety of forms of stored energy, including compressed springs [2], [3], [4], [5], [6], compressed gases [5], [7], [8], [9], [10], [11], or explosive chemicals [12], [13], [14]. Because it is not possible to control the actuator during delivery, these techniques provide limited pressure control at best, and poor regulation of injection depth and volume. Piezo-electric actuators offer greater opportunities for active control. Electrically pulsed microjet piezo-electric actuators have been used to deliver injections, albeit to restricted tissue depths (∼200 μm) and at slow rates (100 nL/s) [15]. Others [16], [17] have used piezo-electric stack actuators [18] to effect jet injection via a piston, but deliverable fluid volumes were <10 μL, and scaling this technology is challenging.
There is an evident need for a jet injection system that affords active control of jet speed or drug pressure, while allowing the injection of precisely metered volumes of the order of 1 mL. We have previously used Lorentz-force actuators driven by voltage waveforms in an open-loop jet injection system to deliver volumes of this magnitude [19], [20], [21]. In this paper, we report on the implementation of real-time control of a prototype jet injector that utilizes a linear Lorentz-force motor [21], [22], [23]. Using this device, it is possible reproducibly to create the high pressures and jet speeds necessary to penetrate this skin and then transition smoothly to a lower jet speed for delivery of the remainder of the desired dose [20], [23], [24]. Here, we quantify the performance of our device in terms of its monotonicity, sound production, repeatability and accuracy, and demonstrate its effectiveness in delivering injectate into a tissue analog, and post-mortem animal tissues.
Section snippets
Materials and methods
The servo-controlled jet injection system (Fig. 1) described in this paper comprises a hand-held injector, real-time controller, and a linear power amplifier. This prototype system has been designed for initial use in our laboratory, with a view to developing portable, electronically controllable, high-volume, and/or continuous-throughput jet-injection devices suitable for animal and human drug delivery applications. The hand-held jet injector is designed to be light, but sufficiently robust
Results
The ability of our device to accelerate the injectate gently and controllably is illustrated in Fig. 6 where piston-tip motion of an Injex ampoule driven by our system (Fig. 6, dashed line) is compared with that of the same ampoule being driven by a standard Injex 30 spring-based injector (Fig. 6, solid line). The spring-actuated piston tip exhibited a resonance at approximately 630 Hz; several oscillations are evident in the piston-tip trajectory. The gently accelerated servo-controlled piston
Discussion
Most jet-injection systems comprise a fluid-filled ampoule and a piston that is accelerated by the rapid release of potential energy to produce a step-like increase in jet pressure upon activation of the device. There is limited opportunity to control pressure, or to regulate the depth or volume of injectate delivered by such devices. Moreover, they behave as underdamped resonant systems, reflecting the energy storage method, the mass of the drive mechanism and fluid, and the viscous losses
Conclusions
Our real-time feedback-controlled approach to needle free jet injection has allowed us to demonstrate highly repeatable independent control over injection depth and delivered dose to a range of different tissues and tissue-analogs. Control of injection depth is achieved by modulating the peak jet speed, and the time for which peak jet speed is maintained. Control of injection volume is achieved by real-time feedback control of piston position as it describes a band-limited injection trajectory.
Conflict of interest
Some of the technology presented in this paper is the subject of an issued patent, and of several other patent applications. The authors have no conflict of interest with relation to this study.
Acknowledgements
Guillermo Tirado-Soto, Katie Smyth and Rhys Williams assisted with conducting experiments for device characterization, and Yi Chen provided comparative measurements of the material properties of in vivo skin and acrylamide gels. This publication includes work supported in part by the University of Auckland Vice-Chancellor's Strategic Development Fund #23444.
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