Multifunctional Fibers | Bioelectronics at MIT

Area II: Multifunctional interfaces with central and peripheral nervous systems

Tue, 03 Oct 2023 00:00:00 +0000

To understand the signaling complexity in neural circuits, while matching the mechanical and chemical properties of tissues and organs, we design miniature, soft, and flexible multifunctional devices capable of electrical, optical, and chemical interrogation of neuronal activity. Devices capable of interfacing with organs as diverse as the brain, spinal cord, and the gastrointestinal tract, demand versatility in materials, designs, and fabrication approaches to adapt to the target organ anatomy and physiology. We combine scalable fiber drawing with additive/subtractive manufacturing and traditional lithographic techniques to seamlessly integrate polymers, metals, composites, and solid-state microelectronics into multifunctional probes with microscale features. Our fiber-based probes have enabled optogenetics, electrophysiology, and drug and gene delivery in the brain (Nat. Biotech.) and spinal cord (Sci. Adv.) of behaving rodents (Nat. Neurosci.) and have recently permitted multifunctional interrogation of neuronal signaling (Sci. ADv.) in non-human primates performing complex tasks. More recently, we have created wireless probes that enabled optical neuromodulation and physiological recordings across gut and the brain, allowing for long-term studies of gut-brain circuits in behaving subjects (Nat. Biotech.). Our current work seeks to expand the palette of functional features in diverse device architectures to advance the basic understanding of brain-body neural circuits as well as develop bioelectronic therapies for neurobiological disorders.

Multifunctional Fibers

Sun, 20 Sep 2020 00:00:00 +0000

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).

Controlling drug activity with light

Thu, 17 Dec 2020 00:00:00 +0000

Hormones and nutrients bind to receptors on cell surfaces by a lock-and-key mechanism that triggers intracellular events linked to that specific receptor. Drugs that mimic natural molecules are widely used to control these intracellular signaling mechanisms for therapy and in research.

In a recent publication, a team led by MIT Associate Professor Polina Anikeeva, a McGovern Institute for Brain Research Associate Investigator, and Oregon Health and Science University (OHSU) Research Assistant Professor James Frank introduce a microfiber technology to deliver and activate a drug that can be induced to bind its receptor by exposure to light.

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