A wireless implantable micropump for chronic drug infusion against cancer

Abstract

We present an implantable micropump with a miniature form factor and completely wireless operation that enables chronic drug administration intended for evaluation and development of cancer therapies in freely moving small research animals such as rodents. The low power electrolysis actuator avoids the need for heavy implantable batteries. The infusion system features a class E inductive powering system that provides on-demand activation of the pump as well as remote adjustment of the delivery regimen without animal handling. Micropump performance was demonstrated using a model anti-cancer application in which daily doses of 30 μL were supplied for several weeks with less than 6% variation in flow rate within a single pump and less than 8% variation across different pumps. Pumping under different back pressure, viscosity, and temperature conditions were investigated; parameters were chosen so as to mimic in vivo conditions. In benchtop tests under simulated in vivo conditions, micropumps provided consistent and reliable performance over a period of 30 days with less than 4% flow rate variation. The demonstrated prototype has potential to provide a practical solution for remote chronic administration of drugs to ambulatory small animals for research as well as drug discovery and development applications.

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…An interesting approach in which the electrochemical actuator was based on Parylene bellows containing water and two interdigitated platinum electrodes was described in a series of reports (Gensler et al, 2012;Sheybani et al, 2013a;Cobo et al, 2016). The pressure, increased by application of electrical current to these electrodes, deflected the bellows which were placed inside drug reservoir, turned on a one-way check valve, which was introduced to guarantee appropriate flow regulation, and discharged the drug solution out of the reservoir through an attached catheter to the targeted site ( Figure 5).…”

An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction

“…The pumps developed by Cobo A, Sheybani R, Tu H, et al [ 194 ] and Gensler H, Sheybani R, Li P-Y, et al [ 195 ] appear to be the most suitable for integration into a control system. Both systems run on 3 V DC and have undergone extended testing to verify their precision and performance and would be suitable selections for control by the system outlined in Section VII.…”

Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors

“…By designing a reservoir with an inner diameter close to that of the bellows outer diameter, the dead volume between was minimized to less than 100 μL (Gensler 2013;Cobo et al (2015).…”

“…Following the incorporation of the check valve in the fully integrated wireless system, once again a realistic drug regimen was selected to characterize system performance (Cobo et al (2015)). The micropump reservoir was filled with 10× PBS.…”