2, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
3, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Neurological disorders affect up to a billion people worldwide. However, our ability to understand and to treat disorders is currently limited by the lack of tools capable of interfacing with the brain over extended periods of time. This is hypothesized to stem from the mismatch in mechanical and chemical properties between the neural probes and the neural tissues. To address the challenge, we developed a sensing and actuation platform mimicking the properties of the brain tissue while integrating thermally drawn polymer fibers and a tough alginate-based hydrogel.
To fabricate the hybrid probes, fibers including a waveguide, three electrode arrays, and three hollow channels were first thermally drawn and assembled by hydrogel dip-coating process. The optical waveguides consisted of a polycarbonate (PC) core and cyclic olefin copolymer (COC) cladding due to their high refractive index contrast, and the recording electrodes were composed of seven tin cores (10 µm) in poly(etherimide) (PEI) insulation. Hollow PEI microtubes served as the microfluidic channels. To establish strong bonding of resilient hydrogels onto polymer-based neural probes, their surfaces were treated with hexamethylenediamine (HMDA), which allowed the use of straightforward carbodiimide chemistry to covalently graft Ca-alginate/polyacrylamide hydrogels from the surfaces of the fibers.
To test the hypothesis that our probes reduce the mechanical damage of the brain tissue, we used finite element models to calculate the bending stiffness of the probes and the stress fields of brain tissue. The results indicated that our devices containing hydrogel bodies exhibited significantly lower bending stiffness than polymer fibers. This also resulted in lower stresses on the brain tissue during micromotion. Interestingly, dried hydrogel body rendered these hybrid structures an order of magnitude stiffer, which facilitated the fiber implantation into deep brain regions without buckling.
Lastly, the long-term performance of devices was assessed. The probes were implanted into the mouse basolateral amygdala (BLA) and ventral hippocampus (vHPC), as the neural projection between these regions is established in the context of anxiety-related behaviors. In this circuity, optogenetic experiments with viral injection, optical stimulation, and electrophysiological recording were conducted with simultaneous behavioral experiments. The foreign-body responses in the probe vicinity were also quantified by immunohistochemistry.
In summary, we designed hydrogel hybrid probes that will enable long-term studies of brain circuits in freely moving subjects. Our results provide an experimental evaluation of the hypothesis that matching the properties of neural tissue minimizes foreign-body response and extends the lifetime of neural interfaces. Our research offer a promising pathway for development of brain-machine interfaces needed to accelerate understanding and treatments of progressive neurological disorders.