Currently available interface technologies for mapping of neural circuits suffer from fundamental limitations of low resolution, inability to perform multiple functions (recording, stimulation, drug delivery, chemical sensing etc.) simultaneously, and limited application space (i.e. cortex). Furthermore, the difference between the elastic and chemical properties of the neural tissues and the implanted probes results in a profound foreign body response and the formation of glial scars that isolate the devices from healthy tissue resulting in a loss of useful signal. By employing flexible and biocompatible neural probes we intend to address both the mechanical and chemical issues of neural recording devices. Furthermore, using simultaneous processing of multiple materials we can incorporate capabilities inaccessible to existing lithographically defined devices, such as simultaneous optical or pharmacological stimulation combine with high-resolution neural recording.
By leveraging recent advances in multi-material fiber-drawing processing traditionally used in telecommunications industry as well as photonics research, we combine polymers, metals and conductive composites to produce flexible probes incorporating conductive electrodes, optical waveguides and microfluidic channels (Nat. Biotechnol. 2015; Nat. Neurosci. 2017). These multifunctional fiber-based probes with features as small as 5 µm allow, for the first time, for concomitant neural recording, optogenetic stimulation and drug delivery in the brain of freely moving mice, a set of capabilities indispensable in systems neuroscience, a field that aims to connect the dynamics of neural circuits to the observed behaviors. We are also working towards extending our fiber-probe technology to the applications in the peripheral nervous system and the spinal cord, which demand high flexibility and extremely low dimensions. Specifically, we were the first lab to demonstrate simultaneous neural recording and optogenetic stimulation in a mouse spinal cord that enabled direct optical control of lower limb muscles (Adv. Funct. Mater. 2014; Sci. Adv. 2017). Most recently, we have extended our flexible fiber-based tools to manipulation and monitoring of the circuits in the enteric (gut) nervous system (bioRxiv 2020), paving way to understanding the communication between the gut and the brain and to developing early diagnostics and treatments for conditions ranging from obesity to Parkinson’s disease.
To advance the studies of chemical neurotransmission, we are combining fiber-based tools with principles of photopharmacology and electrochemistry to achieve spatiotemporally precise generation of neuro-active compounds within specific regions of the nervous system. For instance, photoswitchable compounds have been instrumental in studies of receptors in neurons, but their potential in linking receptor function to behavior was not realized due to lack of tools for simultaneous light and drug delivery in moving subjects. To facilitate applications of photopharmacology in systems neuroscience, we have demonstrated control of reward behaviors in mice using miniature polymer fibers integrating waveguides and microfluidics (bioRxiv 2020). Gaseous neurochemicals such as a secondary messenger nitric oxide (NO) present a greater challenge to delivery into the brain. Inspired by catalysis of a metabolite nitrite into NO by enzymes containing iron-sulfur clusters in their cores, we have designed electrocatalytic fibers comprising cathodes decorated with platinum doped Fe3S4 nanoclusters and platinum anodes in addition to microfluidic channels. The Fe3S4-Pt nanoclusters within the electrocatalytic fibers were able to catalyze the generation of NO from the sodium nitrite solutions delivered via the same devices. We have applied these fibers to locally generate NO and control NO-mediated neural signaling in vitro and in vivo, paving way for studies of the role of this gaseous messenger in synaptic plasticity and metabolism (Nat. Nanotechnol. 2020).