Hydrocephalus is a debilitating neurological disorder for which there is no cure. Patients suffering from hydrocephalus require chronically-implanted shunt systems to control intracranial pressure by diverting excess cerebrospinal fluid from brain (Fig. 1). Unfortunately, existing implants have a high rate of failure. Up to 50% of shunt systems are expected to fail within two years of initial implantation. One of the reasons for device failure is cellular obstruction of inlet pores on ventricular catheter. To combat this problem, we are developing micro-fabricated magnetic actuators to be integrated into shunt systems (Fig. 2).
The magnetically-actuated devices facilitate long-term implantation because they do not contain integrated circuit and internal power source. We can design devices to produce large amount of force and deflection required to remove cellular occlusion. Thus far, we have evaluated cell-removal capabilities in static and circulating flow environment, fatigue responses, and MRI compatibility issues of these magnetic microdevices. Preliminary data demonstrate good cell-clearing in both static and circulating environments, excellent mechanical robustness, and no RF-heating concerns (See video below). We are currently developing processing techniques to integrate these microdevices into silicone catheters for in vivo evaluation. In addition, we are looking to integrate wireless pressure sensors to measure intracranial pressure and monitor device functionality.
For patients who are unresponsive to pharmaceutical treatment of glaucoma, an implantable glaucoma drainages devices (GDD) are often used to manage the debilitating eye disease. However, the microscale channel that removes excess aqueous humor from the eye often gets obstructed due to biofouling, which necessitates additional surgical intervention.
Here we are using rapidly-prototyped microscale magnetic actuators to create smart self-clearing drainage devices. The microactuators are integrated in the lumen of the microtubes and can be activated on-demand using external magnetic field to remove proteinaceous film disputed on device surface (Fig. 3). We have shown that it can effectively remove up to 90% of non-specifically adsorbed protein material on both the device and the inner wall of the drainage devices. We are currently working on evaluating the in vivo safety and efficacy of this novel medical devices with our collaborators from Purdue Mechanical Engineering (Dr. Arezoo Ardekani) and the Jackson Laboratory (Dr. Simon John).
Platinum-based stimulation electrodes are widely used in the neuromodulation industry. For safe electrical stimulation of nervous tissues, each device has certain charge-injection limit. For years, many companies have adopted the safe charge-injection limit described in Shannon Plot, which is based on several in vivo cortical studies. It is important to evaluate the applicability of Shannon Plot as the gold standard for all neurostimulation application especially with the increasing number of indications (e.g., chronic pain, Parkinson’s disease, hearing and vision impairments, urinary incontinence, obesity, etc.) that target different neural tissues. We are working with collaborators from FDA to better understand the tissue-electrode charge-transfer process and the impact of electrochemical byproducts to improve the safety and efficacy of neurostimulation. We are constantly evaluating novel electrode materials and designs to improve the performance of these chronically implantable neurostimulation electrodes. Recently, we identified that a fractal-shaped electrodes can improve the charge injection capacity by more than 74% compared to conventional circular electrodes (Fig. 4).
Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanism, which further aggravates the damage in traumatic spinal cord injury. Conventional bioanalytical technique such as micro-dialysis used to characterize glutamate level in vivo has a low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this work, we are creating an amperometric biosensor fabricated using a 3D printing technique for the purpose of in vivo electrochemical monitoring. The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate (Fig. 5). The sensor is designed to measure extracellular dynamics of glutamate and other biomarkers after traumatic spinal cord injury event. Thus far, we have demonstrated a sensitive and selective amperometric glutamate detection. Furthermore, the glutamate biosensor exhibits a useful linear range, repeatability, and stability.