Share thisIt is generally accepted that ambulatory (tetherless) infusion models are less stressful to lab animals than tethered models. Reduction in stress has a direct impact on the quality of in vivo data and in minimizing the number of animals needed in research studies.
Nevertheless, the tethered infusion model has been a staple in pre-clinical research since its development, decades ago. It was the best option available for continuous infusion in small laboratory animals, since no other technology was available to meet the necessary fluid delivery rates.
With the recent advent of miniature electrochemical pumps, it is now possible to perform tetherless, continuous infusion, in small and large laboratory animals, in a simple, practical manner that is considerably less stressful to the animal.
What are electrochemical pumps?
Electrochemical pumps are based on the controlled electrochemical generation of gases, such as oxygen, hydrogen, and carbon dioxide. The generated gas is used for the performance of mechanical functions, such as the pumping action required for the delivery of fluids (drugs).
In its simplest form, oxygen is extracted from the air to produce a stream of pure, compressed (if need be) oxygen, which is used to produce mechanical work. In this instance the gas generation process is related to the polymer electrolytic membrane (PEM) fuel cell technology, currently a popular topic for the emission-free generation of power for a variety of uses, including vehicular propulsion.
The gas generation process is the result of two individual electrode reactions, conducted by the “heart” of the pumping device, the electrochemical cell.
Electrochemical cells (Figure 1) consist of two electrodes and a PEM capable of moving electrons. The composite structure is less than 0.2 mm thick. A small power source (commercial battery such as a button cell or hearing aid battery) is adequate to deliver up to 50 mL of fluids at rates up to 5 mL/hr.
The process does not involve wet chemistry and the only chemical species either consumed or generated is oxygen. Although it may appear that oxygen is being transferred across the membrane, the transfer takes place via an ionized species (aqueous protons) and not by molecular transfer. The electrochemical process requires a small amount of (battery) energy.
Gas generation takes place immediately upon the application of a current. Conversely, current interruption results in instant cessation of gas generation.
An important property of the electrochemical oxygen generation process is its predictability. Exactly one molecule of oxygen is extracted from the air and regenerated at the counter-electrode for a current input equivalent to four electrons. Therefore, accurate control of the current to the electrochemical cell results in an accurate, continuous generation of gas, which in turn results in an accurate delivery of fluid from the pump.
Infusion devices using electrochemical gas generation
Electrochemical fluid delivery pumps are available in configurations that are often not possible with conventional electromechanical pumping mechanisms. An example of a disposable infusion pump is shown in Figure 2.
A toroidal fluid reservoir surrounds the pumping module containing the battery and electrochemical cell. A small air intake port allows air to enter the module, where it is processed (electrochemically) to produce oxygen, which applies pressure on a diaphragm within the fluid reservoir. The fluid is released through a delivery set, terminated at its distal end by a cannula or luer lock. A fill port, sealed by a septum, is available for filling the pump reservoir.
The key features of a disposable pump are its simplicity and ease-of-use, which consists of a two-step process: 1) filling the reservoir via the fill port, and 2) pushing the start button to start fluid delivery.
The reservoir, housing, and pumping module are medical grade plastics. The complete assembly weighs 11 or 19 grams for devices with 5 or 10 mL reservoirs, respectively. The assembled pumps can be radiation sterilized.
Fluid delivery performance using electrochemical gas generation
Exceptional fluid delivery accuracy can be achieved by regulating the current applied to the electrochemical cell. Disposable, low cost pumps are only controlled by a surface-mount resistor, and yet achieve delivery accuracies comparable to electromechanical pumps.
Typically, the fluid delivery profile is similar to the illustration of Figure 3, obtained from 12 separate 10 mL pumps operating at a nominal rate of 0.40 mL/hr.
Another important requirement in continuous drug delivery is uninterrupted flow. Electrochemical pump mechanisms operate in a pulsatile manner, which results in interrupted flow. Therefore, medical pumps are evaluated by means of “trumpet curves” which measure flow rates using ever decreasing time intervals, thereby measuring delivery accuracy for small quantities of delivered fluid.