Flexible and Wireless Bioelectronics for Continuous Monitoring of Intracranial Pressure

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Project Summary: This proposal describes a five-year research and career development program to prepare Dr. Razieh Khalifehzadeh for a career as an independent investigator. This program will build upon Dr. Khalifehzadeh’s multidisciplinary background as a bioengineer scientist, trained in bioelectronics, biomaterials and basic cancer research, by providing expertise in designing flexible and highly sensitive pressure sensors for continuous wireless monitoring of intracranial pressure (ICP) associated with brain tumors. The PI will be mentored at Stanford Schools of Engineering and Medicine by Drs. Zhenan Bao (Main mentor, flexible and wearable bioelectronics), Sanjiv S. Gambhir (co-mentor, cancer diagnosis, cancer bioengineering and cancer nanotechnology), Heike Daldrup-Link (co-mentor, brain cancer imaging and therapy, and a leader in promoting diversity), Ada Poon (collaborator, wireless bioelectronics), Melanie Hayden (collaborator, neurosurgery and neurology) and Eric Appel (collaborator, biomaterials and biocompatibility). Brain tumors are usually associated with increased ICP. Delayed diagnosis and treatment of the elevated ICP often results in irreversible neurological damage and even death. The overall goal of the proposed research is to design highly sensitive and brain compatible pressure sensors that can wirelessly detect ICP variations, as a generally neglected neurological marker in brain tumor patients. Recently, I developed ultrasmall (3×3×0.1 mm3), flexible, and implantable pressure sensors that were effective for wireless monitoring of the ICP variations in mice models of growing U87 brain tumor over their 30 day survival period. The key component of these pressure sensors is an intermediate elastomer layer with a specific pressure-responsive micropattern that defines the consistent sensitivity of these devices for long-term accurate measurements in the brain. In Aim 1 of this project, I will study new designs for this elastomer layer, in order to further improve the sensitivity and long- term electro-mechanical stability of my pressure sensors. Additionally, I will use experiments and simulations to find alternative designs for more efficient wireless signal transfer (i.e., higher signal-to-noise ratios) from these sensors. I will also develop a handheld wireless signal recording setup to enable recording and rapid analysis of the wireless pressure data using a smartphone, for easier in vivo measurements and future point-of-care applications. Aim 2 is focused on extending the post-implantation lifetime and brain compatibility of the sensors by coating them with parylene (thickness ~ 1-4 µm). Parylene has been broadly used as a protective coating for neuro-interface and cardiac assist devices to enhance their post-implantation lifetime. Finally, I will use these sensors for continuous wireless monitoring of ICP variations in different mice models of brain tumors, with various survival periods, depending on invasiveness of the tumor (Aim 3). MRI, simulations and histology will be used to verify ICP measurements. These sensors are clinically needed for monitoring ICP in different brain diseases, including tumors, and we envision that their versatile design will facilitate their clinical applications.