Multifunctional Neural Probes for Electrochemical Sensing, Chemical Delivery and Optical Stimulation
- Author(s): Wen, Ximiao
- Advisor(s): Chiou, Pei-Yu
- et al.
Implantable neural probes are one of the most important technologies for neuroscientists to detect and stimulate neural activities inside the brain to advance the understanding of brain function and behavior, especially in the deep brain regions where other non-invasive approaches cannot reach. With the development of microelectromechanical systems (MEMS) in the past few decades, a great amount of efforts has been made to improve the neural probes to provide reliable and versatile tools to enable neuroscience studies that otherwise impossible to conduct.
In this dissertation, I focused on three important objectives to improve the current neural probe platform: 1) to incorporate optical stimulation capability on top of the current silicon-based microelectrode arrays (MEAs) with electrochemical sensing function for optogenetics applications; 2) to integrate microfluidic channels with the current silicon platform for chemical deliveries; and 3) to develop a soft neural probe to reduce the brain damage and foreign body response. All the probes developed in this work are capable of deep brain implantation (>5 mm) and equipped with various electrochemical biosensors to study neural activities in deep brain regions.
For the first objective, an ultra-thin silicon nitride waveguide was integrated on top of the silicon probe using grating couplers to couple light in and out of the waveguide. PECVD silicon nitride film was optimized to reduce the waveguide propagation loss to ~ 3dB/cm at 450 nm wavelength. The probe is capable of delivering ~40 μW light power to the probe tip with ~2 mW input light power from a 3 μm polarization maintaining optical fiber coupled with a pigtailed laser diode. The average light intensity is ~200 mW/mm2 which is sufficient for Channelrhodopsin-2 excitation. Using this probe, we have detected optically-evoked glutamate release in the rat nucleus accumbens several weeks after injection of channelrhodopsin-expressing AAV into the above region.
For the second objective, PDMS microfluidic channels were transferred to the front and backside of the current Si probes using a novel PDMS thin-film transfer process. With this process, microfluidic channels can be easily bonded to Si probes as an add-on module to provide a simple solution to integrate chemical delivery functions into existing silicon-based probes, providing another level of control of the brain activities. Local injection of drug solution with nanoliter precision can be controlled by the pumping pressure and duration. The system was validated in vivo by local glucose injection through the fluidic channel and detection by biosensors in rat striatum.
For the third objective, a multifunctional neural probe with Ultra-Large Tunable Stiffness (ULTS) was developed for chemical sensing, delivery and deep brain implantation, whose stiffness can be tuned by 5 orders of magnitude before and after brain implantation. ULTS probe is stiff enough to penetrate 2 cm deep into a gel with similar mechanical properties as the brain tissue and becomes soft and flexible within few minutes to minimize brain damage due to the brain movements in all directions. With appropriate coatings, the electrodes on ULTS were converted into different biosensors which exhibits similar sensing performance as previous Si probes. The integration of microfluidic channels permits delivery of chemicals in the local vicinity of the sensing sites. Acute stimulation and sensing experiments were conducted in rats, in which potassium induced glutamate release was recorded demonstrating the capability of in vivo application. The chronic immune response was compared between ULTS and silicon probes with similar geometry, which shows a reduced immune response indicated by the lower astrocytes density around ULTS.