Implantable drug delivery device using frequency-controlled wireless hydrogel microvalves

Abstract

This paper reports a micromachined drug delivery device that is wirelessly operated using radiofrequency magnetic fields for implant applications. The controlled release from the drug reservoir of the device is achieved with the microvalves of poly(N-isopropylacrylamide) thermoresponsive hydrogel that are actuated with a wireless resonant heater, which is activated only when the field frequency is tuned to the resonant frequency of the heater circuit. The device is constructed by bonding a 1-mm-thick polyimide component with the reservoir cavity to the heater circuit that uses a planar coil with the size of 5-10 mm fabricated on polyimide film, making all the outer surfaces to be polyimide. The release holes created in a reservoir wall are opened/closed by the hydrogel microvalves that are formed inside the reservoir by in-situ photolithography that uses the reservoir wall as a photomask, providing the hydrogel structures self-aligned to the release holes. The wireless heaters exhibit fast and strong response to the field frequency, with a temperature increase of up to 20°C for the heater that has the 34-MHz resonant frequency, achieving 38-% shrinkage of swelled hydrogel when the heater is excited at its resonance. An active frequency range of ~2 MHz is observed for the hydrogel actuation. Detailed characteristics in the fabrication and actuation of the hydrogel microvalves as well as experimental demonstrations of frequency-controlled temporal release are reported.

Approaches and Challenges of Engineering Implantable Microelectromechanical Systems (MEMS) Drug Delivery Systems for in Vitro and in Vivo Applications

“…In order to maximize the drug reservoir volume of the device, the actuation mechanism has to be minimalistic yet effective. Examples of such minimalistic methods include electrochemical method [30], electrothermal method [35] (Figure 2), and passive method [13]. In general, delivery methods for BioMEMS devices fall into three main categories: (i) actuation-less methods, (ii) single chamber actuation methods and (iii) multi-chamber actuation methods.…”

“…A popular microvalve used for this BioMEMS design is a thermosensitive material known as hydrogel. Rahimi et al [35] have demonstrated that by using radio frequency telemetry, heat can be generated within a coil in contact with the hydrogel microvalves, causing the hydrogel to contract, thus opening the valves for delivering drugs via passive diffusion ( Figure 2). The overall size dimension of the device is approximately 5 mm × 5 mm × 4 mm and has a drug reservoir size of about 78 uL.…”

“…A novel concept of an actuation-less method is proposed by Lo et al [13] that involves a manually actuated BioMEMS device where one will apply pressure onto the device, thus pressurizing the drug reservoir and releasing the drug solution. Illustration of a thermoelectric drug delivery device based on thermal sensitive hydrogel, redrawn from reference [35]. (a) Schematic view of the device.…”

“…Inherently, due to the small size of these implantable BioMEMS, powering the device for a long time is an issue [41]. However, several methods have been investigated to overcome this issue: (i) the adoption of low power actuation mechanisms [33] and/or (ii) increasing the battery life of the device by enabling the internal batteries to be recharged [42][43][44] or using wireless power [35,45].…”

Microwave assisted drug delivery

“…These include, but are not limited to, the use of ultrasound [8], light waves [9], magnetic fields [10] and radio waves below 100 MHz [11]. Complex systems have also been integrated into a drug delivery module consisting of a receiving inductor, control circuitry chip and a drug delivery chip [12].…”