Postdoctoral Researcher University of Cambridge Cambridge, United Kingdom
Introduction: The use of electrode arrays to interface with peripheral nerves is attracting significant interest for the diagnosis and treatment of various neurological disorders. Existing electrodes, however, require complex placement surgeries that carry a high risk of nerve injury. Here, we leverage recent advances in soft robotic actuators and flexible electronics to develop highly conformable nerve cuffs that allow for extensive and reprogrammable shape morphing into complex three-dimensional (3D) geometries (Fig. 1a). These devices combine electrochemically driven conducting polymer-based soft actuators with low impedance microelectrodes. They enable controlled shape reconfiguration of the electrode arrays into predesigned 3D architectures with applied voltages as small as a few hundreds of millivolts, allowing active grasping or wrapping around delicate nerves. We validate this technology in in vivo rat models, showing that the cuffs form and maintain a self-closing and reliable bioelectronic interface with the sciatic nerve of rats without the use of surgical sutures or glues. Moreover, they provide the flexibility to adjust the fit or release the electrode array as required. This seamless integration of soft electrochemical actuators with neurotechnology offers a path toward minimally invasive intraoperative monitoring of nerve activity and high-quality bioelectronic interfaces.
Materials and
Methods: Soft robots utilize various types of actuators to convert input energies into mechanical motions through controlled deformations stimulated by light, electrical fields, magnetic fields, or heat. We propose using a conducting polymer, polypyrrole doped with dodecylbenzene sulfonate PPy(DBS), as the main actuating material. This polymer exhibits controllable volumetric expansion or contraction in response to safe, low-voltage stimuli, achieved through a reversible electrochemical process involving ion sources like aqueous electrolytes. PPy(DBS) is electrochemically deposited on patterned gold electrodes in a three-electrode electrochemical cell connected to a potentiostat. The devices are fabricated using standard photolithography techniques with thin layers of parylene C as the substrate and encapsulating material. We investigated the electrochemical properties and actuation behaviors of the PPy(DBS) film in phosphate-buffered saline (PBS). All animal procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act, 1986. The experiments were performed under terminal anaesthesia and were conducted on female rats ~250 g in weight. Surgical implantation of devices was carried out under isoflurane anaesthesia. Electrophysiology recordings were carried out by connecting the implant through a custom PCB to an Intan 32-Channel Stim/Recording Headstage (Intan Technologies, Los Angeles, CA, USA). Data was collected at 30 kHz sampling rate from implanted electrodes using an Intan RHS Stim/Recording System (Intan Technologies, Los Angeles, CA, USA), with a ground wire being placed subcutaneously in the contralateral side of the animal. Recordings were performed while the rat hindpaw was gently pressed using a surgical clamp.
Results, Conclusions, and Discussions: As shown in Fig. 1b, the conducting polymer undergoes volumetric expansion when a slightly negative voltage is applied, as solvated cations (e.g., Na+) are drawn into the polymer matrix. Conversely, a positive voltage causes the expulsion of cations, leading to polymer contraction. By leveraging this reversible electrochemical process, bilayer configurations of PPy(DBS)-coated gold exhibit controllable bending behaviour. Fig. 1c displays a merged sequence of photographs illustrating a thin film curling into spirals, highlighting the large strain and the low stiffness of the configuration. In Fig. 1d we show two designs – one depicting a gentle holding of a nerve resembling conventional cuff electrodes, while the other demonstrates a helical wrapping around the nerve. The latter approach enables adaptation to nerves with varying diameters, avoiding communication issues that often occur in conventional cuffs due to poor electrode-nerve bundle alignment. An exploded view of the cuff and overall structure of the device are schematically depicted in Fig. 1e, f. We placed the cuff electrodes to the sciatic nerve of anaesthetised rats for in vivo validation. The device was initially flattened by applying a voltage of -0.5 V, which allowed us to manually position it adjacent to the nerve. Subsequently, upon the removal of the applied voltage, the device gradually self-wrapped around the nerve in a helical manner. This reversible actuation process allowed for repeated retrieval and adjustment until achieving the desired 3D conformal interface (Fig. 1g). The implanted devices were able to record bursts of spikes associated with paw press sensory stimuli, yielding low baseline noise and high, stable spike amplitude in their recordings (Fig. 1h). Once the recording was completed, we applied -0.5 V to the actuators to gently loosen the interface, allowing for easy extraction of the device. These soft actuators can find immediate application in intraoperative nerve monitoring, for example monitoring of nearby nerves during tumour extraction, where a short-term, reconfigurable and removable interface is needed. In other clinical scenarios, such as vagus nerve stimulation, the ability of these implants to be repositioned during implantation for optimal contact, would be a valuable feature.
