Needle-free small-volume liquid injection system powered by a rotary actuator.

Controllable jet injection could provide a fast, repeatable method for delivery of small volume, high viscosity drugs to the dermis. We have developed a compact, lightweight jet injector that uses a small commercial rotary motor and differential screw to create a jet of fluid with sufficient force to deliver drug into tissue. Clear tissue analogue and ex vivo tissue were used to demonstrate repeatable delivery of <;10 µL of fluid using the device. The fluid when forced through a narrow orifice (108 µm) reaches a velocity of >250 m/s with an injection time of <;3 ms.

High-speed X-ray analysis of liquid delivery during jet injection.

The effect of varying velocity during jet injection on the dispersion of fluid into tissue is investigated using a custom-built X-ray imaging system. Injections are performed into ex-vivo porcine abdominal tissue using a voice coil actuated injection device. Single velocity and two-phase velocity injections reveal the complex nature of the dispersion of the fluid jet in layered tissue and highlight the effects of changing the jet velocity following the initial penetration of the liquid into the tissue.

Ampoule and nozzle development for needle-free injections.

A rigid, compact, multi-piece ampoule has been designed and fabricated as a platform to conveniently house different nozzle inserts one at a time to offer increased jet consistency and functional flexibility. Three different nozzle geometries that respectively produce a single axial jet, radial jets, and intersecting jets are designed and fabricated. Through high-speed imaging and injection into tissue analog and ex vivo porcine tissue, these nozzles are demonstrated to have potential for a range of injection applications including intradermal, intratympanic, and traditional uses. The presented ampoule is more successful than a commercial jet injection ampoule in adhering to desired position and velocity trajectories and the energy efficiencies of jet ejections are compared.

Delivery of immunoreactive antigen using a controllable needle-free jet injector.

Intradermal immunization of mice against hepatitis B surface antigen (HBsAg) using a novel real-time controlled jet injector was assessed by comparison with intradermal and subcutaneous injection of antigen using a 27G needle and syringe. Three doses of aluminium-absorbed HBsAg were delivered at 0, 14, and 28days. Antibodies to HBsAg were detected only in mice injected with antigen with antibody levels increasing with secondary injections. Mice vaccinated by intradermal injection using the jet injector or subcutaneous needle injection exhibited comparable immune responses at day 47. Differences in titer observed between intradermal jet injected and needle injected animals reflect differences in the volume of antigen delivered. With the exception of minor bleeding at the injection site in a few animals injected either by jet injection or needle, no adverse events were observed in any of the mice used in the study.

Analysis of Moving-Coil Actuator Jet Injectors for Viscous Fluids.

OBJECTIVE: A jet injector is a device that can be used to deliver liquid drugs through the skin using a fluid jet, without the use of a needle. Most jet injectors are designed and used for the delivery of inviscid liquids, and are not optimized for the delivery of viscous drug compounds. To better understand the requirements for delivering viscous drugs, we have developed a mathematical model of the electromechanics of a moving-coil actuated jet injector as it delivers viscous fluids. METHODS: The model builds upon previous work by incorporating the nonlinear electrical properties of the motor, compliant elements of the mechanical piston and ampoule system, and the effect of viscosity on injector characteristics. The model has been validated by monitoring the movement of the piston tip and measurements of the jet force. RESULTS: The results of the model indicate that the jet speed is diminished with increasing fluid viscosity, but overshoot and ringing in the jet speed is unaffected. However, a stiffer ampoule and piston will allow for a better control of the jet speed profile during an injection, and reduce ringing. CONCLUSION: We identified that the piston friction coefficient, the compliance of the injector components, and the viscous properties of the fluid are important determinants of performance when jet-injecting viscous fluids. SIGNIFICANCE: By expanding upon previous jet injector models, this study has provided informative simulations of jet injector characteristics and performance. The model can be used to guide the design of future jet injectors for viscous fluids.

A needle-free technique for interstitial fluid sample acquisition using a lorentz-force actuated jet injector.

We present a novel method of quickly acquiring dermal interstitial fluid (ISF) samples using a Lorentz-force actuated needle-free jet injector. The feasibility of the method is first demonstrated on post-mortem porcine tissue. The jet injector is used to first inject a small volume of physiological saline to breach the skin, and the back-drivability of the actuator is utilized to create negative pressure in the ampoule and collect ISF. The effect of the injection and extraction parameters on sample dilution and extracted volumes is investigated. A simple finite element model is developed to demonstrate why this acquisition method results in faster extractions than conventional sampling methods. Using this method, we are able to collect a sample that contains up to 3.5% ISF in 3.1s from post-mortem skin. The trends revealed from experimentation on post-mortem skin are then used to identify the parameters for a live animal study. The feasibility of the acquisition process is successfully demonstrated using live rats; the process is revealed to extract samples that have been diluted by a factor of 111-125.

Jet injection of a monoclonal antibody: A preliminary study.

Monoclonal antibodies (mAbs) represent a major group of biotherapeutics. The high concentration and volume of drug administered together with a shift to administration via the subcutaneous route have generated interest in alternative delivery technologies. The feasibility of using a novel, highly controllable jet injection technology to deliver a mAb is presented. The effect of delivery parameters on protein structure were evaluated and compared with delivery using a conventional needle and syringe. Injection of mAb into a rat model showed that jet injection using the device resulted in more rapid absorption and longer duration of exposure.

Adaptive controller for a needle free jet-injector system.

A nonlinear, sliding mode adaptive controller was created for a needle-free jet injection system. The controller was based on a simplified lumped-sum parameter model of the jet-injection mechanics. The adaptive control scheme was compared to a currently-used Feed-forward+PID controller in both ejection of water into air, and injection of dye into ex-vivo porcine tissue. The adaptive controller was more successful in trajectory tracking and was more robust to the biological variations caused by a tissue load.

The effect of jet shape on jet injection.

The effects of the dispersion pattern of a needle-free jet injector are explored. The shape of the jets were compared using a high-speed video camera and jet injections of collimated and dispersed fluid jets with a Lorentz-force actuated jet injector were made into acrylamide gel and post-mortem porcine tissue. A custom-built high-speed X-ray imaging system was used in order to observe the dynamics of the dispersion mechanism for each injection in real time. We show that a collimated jet stream results in greater tissue penetration than a dispersed jet stream.

Needle-free interstitial fluid acquisition using a Lorentz-force actuated jet injector.

The feasibility of a new method of quickly acquiring interstitial fluid (ISF) samples using a Lorentz-force actuated needle-free jet injector is demonstrated on ex vivo porcine tissue. The jet injector is used to first inject a small volume of physiological saline to breach the skin, and the back-drivability of the actuator is utilized to create a vacuum in the ampoule and collect ISF. Injection and extraction parameters are tested and optimized for minimal acquired sample dilution and extracted volume consistency. Using this method, we are able to collect a sample that contains up to 3.5% ISF in 3.1 s.

Needle-free jet injection using real-time controlled linear Lorentz-force actuators.

Needle-free drug delivery by jet injection is achieved by ejecting a liquid drug through a narrow orifice at high pressure, thereby creating a fine high-speed fluid jet that can readily penetrate skin and tissue. Until very recently, all jet injectors utilized force- and pressure-generating principles that progress injection in an uncontrolled manner with limited ability to regulate delivery volume and injection depth. In order to address these shortcomings, we have developed a controllable jet injection device, based on a custom high-stroke linear Lorentz-force motor that is feed-back controlled during the time-course of an injection. Using this device, we are able to monitor and modulate continuously the speed of the drug jet, and regulate precisely the volume of drug delivered during the injection process. We demonstrate our ability to control injection depth (up to 16mm) and repeatably and precisely inject volumes of up to 250µL into transparent gels and post-mortem animal tissue.

Low-cost, flexible polymer arrays for long-term neuronal culture.

Conducting polymers are promising materials for fabrication of microelectrode arrays for both neural stimulation and recording. Our ability to engineer the morphology and composition of polypyrrole together with its suitability as an electrically addressable tissue/cell substrate have been used to develop an inexpensive, disposable three-dimensional polymeric array for use in neuronal culture and drug discovery. These arrays could be interfaced with a fixed, parallel stimulation and optical imaging system, amenable to automated handling and data analysis.

Development of a Lorentz-force actuated intravitreal jet injector.

Intravitreal injection is a common treatment in ophthalmology, but it can lead to numerous complications. Needle-free jet injection has been shown to successfully deliver fluid to various layers of skin, and, by its nature, may reduce intravitreal injection complications. From injection trials into ex vivo rabbit eyes, we find that needle-free jet injection can be used for intravitreal drug delivery. A custom-designed control scheme, characterized in this study, is crucial to this delivery. The system is capable of delivering 40 µL of fluid to the posterior vitreous humor, with an injection duration less than 100 ms and scleral entry site less than 350 µm in diameter.

A computational model of a controllable needle-free jet injector.

We present a mathematical model of the dynamics of a previously developed needle-free jet injector (NFJI) that is based upon a servo-controlled Lorentz-force motor. The injector creates a fluid jet that can pierce through the skin and deliver a drug to dermal, subcutaneous and muscular tissue. We use the model to predict the jet speed achieved during an injection. The model simulates the electrical response of the motor coil, the mechanical response of the drug piston and ampoule and the friction incident upon the piston during the time course of the injection. High-speed video measurements of piston movement in response to a step input show that the model predicts piston-tip position during an injection within an RMS error of 287 µm. The corresponding jet speed is predicted to be 180 m·s(-1) with a maximum overshoot to 205 m·s(-1).

Intradermal needle-free powdered drug injection by a helium-powered device.

We present a new method for needle-free powdered drug injection via a bench-top gas-powered device. This injector provides an alternative method of vaccine delivery to address the cold chain problem--the cost and risk of transporting temperature sensitive vaccines to developing countries. The device houses interchangeable nozzle inserts to vary orifice geometries and is capable of delivering polymer beads (1-5 µm diameter) into the dermal layer of porcine tissue. Results for injection shape and injection depth versus nozzle orifice diameter demonstrate the device's controllability.

A portable needle-free jet injector based on a custom high power-density voice-coil actuator.

We have constructed a portable needle-free drug injection (NFI) device based upon a custom voice-coil linear actuator. Our actuator is optimized to provide high instantaneous force (>200 N) and power (4 kW) while still allowing a total stroke of 25 mm. The actuator is relatively inexpensive, compact, and lightweight, allowing it to serve as the force generator in a portable, reusable, handheld NFI system. The actuator is capable of accelerating liquid drug in quantities of up to 250 microL to a speed of more than 200 ms(-1). The repeatability of a 50 microL volume ejection is better than +/-1 microL.

Delivery of active collagenase to skin using a lorentz-force actuated needle-free injector.

The development of new therapeutics and the desire to reduce the frequency of needle stick injuries, overcome the improper reuse of needles, improve compliance, and reduce the prohibitive cost of disposal have fueled resurgent efforts to develop alternative drug delivery methods. This report discusses the use of a controllable Lorentz-force actuated needle-free injector to deliver a blend of bacterial collagenases to the skin. Drug ejected/injected using a preprogrammed pressure vs time profile through a 100 or 200 microm orifice showed activity comparable to that observed following ejection/injection using a conventional syringe as determined by a solution based fluorescence assay and zymography. In a live animal trial, necrosis, hair loss, and minimal bruising were observed at drug injected sites regardless of the delivery mode as were changes in tissue morphology.

Real-time PCR measurement by fluorescence anisotropy.

We have developed an instrument for monitoring real-time PCR using fluorescence anisotropy, enabling an assay chemistry in which the fluorescence from a labeled primer elucidates amplification. The instrument holds the sample temperature constant to within +/-0.03 degrees C during measurement in the extension phase of each PCR cycle and achieves 0.116 mP FA resolution. Primer conjugation with Alexa-Fluor 488, when compared with other fluorophores, is shown to provide the greatest FA range between primer and product. Comparable reproducibility and linearity of the crossing point for a range of target copy numbers is observed between the FA-based assay run in our instrument and the SYBR green assay run in commercial instrumentation. Reproducibility is also consistent with Poisson-distributed experimental error in aliquoting starting copies, a theoretical limit to instrument/assay performance.