382353 The Injectrode: Simultaneous Chemical and Electrical Interfacing with Neural Circuits
The recently announced BRAIN initiative highlights the importance of understanding neural function and, ultimately, identifying strategies to treat and cure brain diseases. Our lab is working on a micro-scale device, which we call the “injectrode,” to employ chemical and electrical interfacing with neural circuits. The ability to measure neural activity as well as respond with chemical and electrical cues will provide researchers with a “mechanical neuron” to better understand brain activity and provide insight into device design for therapeutic medical devices.
Our device is built around custom, multi-lumen capillaries that provide channels for fluid flow and metal microelectrodes. The current injectrode houses one 90 micron lumen for housing electrodes and two 30 micron lumens for fluidics. Other groups have used traditional silicon microfabrication techniques to make similar probes suitable for use in rodents (brain structures typically 2-3 mm deep); our injectrode can target brain structures several centimeters deep in non-human primates and are currently being used in experimental behavioral models. We have fabricated injectrodes with tungsten microelectrodes and are developing protocols for incorporating carbon fiber electrodes than can be used to measure endogenous neurotransmitter concentrations (e.g. dopamine) using fast-scan cyclic voltammetry. These capabilities, combined with on-demand microdosing of drugs to specific regions of the brain provide a platform to interrogate neural circuits in large and small animal models.
Intravital live animal imaging was employed to evaluate in vivo device performance. We have evaluated several near-infrared fluorescent dyes as infusion tracers. Using these tracers, we have identified parameters (volume, flow rate) that provide neural-circuit-sized microdoses in the brain. Effective diffusion constants can also be extracted from serial imaging experiments, allowing us to examine the effects of glial scarring on infusions. We are also testing the hypothesis that mechanical matching of probe interfaces with surrounding brain tissue can improve chronic biocompatibility of neural implants. The injectrode can be coated with poly(ethylene glycol) hydrogels with various thickness and moduli. The cushioning effect of these gels is measured using particle tracking velocimetry in tissue phantoms after applying physiologically relevant micromotion using an Arduino-controlled manipulator. We are optimizing gel parameters to minimize the strain field on surrounding tissue and testing coating formulations in rodent models.
The injectrode is a platform technology that allows multimodal interrogation and stimulation of brain tissue at the circuit level. Ongoing animal research is exploring pathways to improve long term biocompatibility in rodents as well as basic neuroscience of behavior and decision making in non-human primates. We ultimately hope that the injectrode will become a valuable tool for neuroscientists and serve as a template for potential therapeutic devices to treat neuropsychiatric disorders.
Acknowledgements: Work is funded by the National Institutes of Health [K99EB016690 (JCS), R01EB016101 (RSL/MJC)] and the Institute for Soldier Nanotechnologies at MIT. The authors wish to acknowledge the Swanson Biotechnology Center at MIT for assistance with live animal imaging.