Wirelessly Controlled Soft Robotic Patches for Targeted and Sustained Drug Release

Introduction: : Bladder cancer and other diseases require long-term and targeted drug delivery which is currently a grand challenge. Existing approaches, including bladder instillation, lack of drug retention and specificity to diseased tissue, resulting in frequent hospital visits and side effects for patients. To address these challenges, we propose a soft robotic patch [1] designed to anchor securely to the bladder tissue for extended periods while enabling continuous, remotely controlled drug delivery (Fig. 1). Combining wireless microfluidic techniques, the patch integrates magnetic valves that regulate a soft robotic pump by external magnetic field, leveraging osmotic pressure to achieve precise drug release. An integrated LC circuit with the soft pump allows wireless battery-free real-time monitoring of the liquid release process, ensuring accurate dosage control. To ensure stable attachment, the device incorporates a bioadhesive-based soft robotic adhesive patch, which can be delivered through a catheter for minimally invasive deployment. A customized delivery tool with a steerable sheath and a foldable adapter is developed for precise deployment upon targeted area. Additionally, a wearable magnetic actuation system enables fully wireless operation of the drug release mechanism. The device’s performance is systematically evaluated using phantom models and ex vivo porcine bladders to assess its reliability and effectiveness. This minimally invasive, soft robotic patch presents a transformative solution for targeted, on-demand, and long-term delivery of therapeutic agents, beyond precedented methods.
[1] Xiao, Boyang, Yi Zhu, Jeffrey J. Tosoian, and Xiaoguang Dong. “Wirelessly Controlled Soft Robotic Patches for Targeted and Sustained Drug Release.” Under review.

Materials and

Methods: : The soft robotic patch consists of an osmosis pump, LC circuit for sensing released liquid volume, outer shell with magnetic valves, and adhesive patch for anchoring.
First, the soft pump integrates a foldable chamber, super absorbent fiber (SAF) and a hypodermic needle patch as the outlet. The foldable chamber is made of polydimethylsiloxane (PDMS) combined with soft hinges made of Ecoflex 00-30, which can be folded laterally. After SAF absorbs water and swells, the loaded drug in the foldable chamber will be squeezed out from the 31-gauge needles.
Second, to monitor the released liquid volume, two insulated copper sheets are attached on two sides of the foldable chamber as a capacitor, which is connected to an inductor coil. When the loaded liquid is being released, the capacitance will vary. A vector network analyzer (VNA) is used to capture signal wirelessly.
Third, the magnetic valve includes a magnetic leaf, a magnetic bottom layer, and a microfluidic channel layer. The microfluidic channel layer is coated with hydrogel to allow water being absorbed by SAF. The magnetic leaf and bottom layer are made of magnetic composite and magnetized perpendicularly. When an external magnetic field parallel to the base layer is applied, the magnetic leaf will bend and open the valve due to magnetic torque.
Lastly, two bioadhesive patches are attached to the chamber and the induction coil for tissue anchoring underwater. A customized delivery tool with a steerable sheath and an adapter is used for device deployment like urinary catheters.

Results, Conclusions, and Discussions:: Results (Fig. 2): First, the drug release performance is evaluated when the soft robotic patch is submerged in water. The loaded liquid can be ejected out within 2 minutes. While liquid is being ejected, the distance between the copper sheets reduces, leading to an increase of capacitance as well as the resonant frequency of the LC circuit. The variation of resonant frequency is captured from the inductor coil by a VNA, which is used to fit a prediction model for released liquid volume. In the releasing process, the predicted volume agrees well with the ground truth. Second, with the active control of the magnetic valves, closed-loop drug release regulation can be achieved. By controlling the magnitude and direction of the magnetic field, multiple valves can be opened sequentially and closed simultaneously. The released liquid volume is controlled on-demand by the external magnetic field waveform, combining the information from ejected volume sensing. Third, to retain the soft robotic patch on the bladder tissue for long-term drug release, a bioadhesive patch for underwater adhesion is integrated with the drug chamber. Lastly, a 3D printed steerable delivery tool compatible with urinary catheters is developed for the minimally invasive deployment process. The adapter on the delivery tool can apply pressure to allow the adhesive patch to form stable bonding, as demonstrated on ex vivo porcine tissues.
The intravesical soft robotic patch provides a promising solution for minimally invasive deployed medical patch for long-term, on-demand, and close-loop drug release in a bladder promising for treating bladder cancer and other diseases. The soft robotic patch can also be adapted for other fluid-filled lumens like stomach in the human body as an approach of prolonged treatment. Limitations of the current design include the lack of sensors for other physiological properties to monitor disease progression and adjust dosage. In future work, we will integrate sensors for detecting pH, temperature, pressure, and tissue stiffness which can greatly enhance the capability of extended disease management. In addition, developing the refilling function of the device by a catheter can increase the drug capacity.

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