(2io) Ultra-Flexible Endovascular Probes for Brain Recording through Micron-Scale Vasculature

Implantable neuroelectronic interfaces have enabled advances in both fundamental research and treatment of neurological diseases, yet traditional intracranial depth electrodes require invasive surgery to place and can disrupt the neural networks during implantation. I developed an ultra-small and flexible endovascular neural probe that can be implanted into sub-100-micron scale blood vessels in the brains of rodents without damaging the brain or vasculature. In vivo electrophysiology recording of local field potentials and single-unit spikes have been selectively achieved in the cortex and the olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases. (See attached figure, accepted for publication in Science)

Research Interests:

My long-term goal is to achieve clinical translation of neuroelectronic interfaces capable of long-term monitoring and treatment of neurological diseases. I was originally trained as a materials scientist, my research interests later expanded dramatically to encompass biology, medicine, and neuroscience. Specifically, I am most interested in using my interdisciplinary knowledge to manufacture novel engineered devices to research, monitor, and treat neurological diseases.

Aim 1: Minimally invasive endovascular neural interfaces for brain recording and modulation

(See the above abstract and the attached figure for introduction and the preliminary data.) In my own laboratory, my short-term goals include extending this platform technology to achieve controllable implantation into common therapeutic targets, demonstrating endovascular stimulation, and developing stretchable endovascular probes for chronic recording. In the long term, I plan to achieve the detection and treatment of many chronic and progressive neurological diseases, such as Parkinson’s disease, Alzheimer’s disease, epilepsy, and stroke, and clinical translation to neurology, neurosurgery, and interventional radiology practice.

Aim 2: Biochemically functionalized probes for cell type-specific electrophysiology in the brain

Selective targeting and modulation of distinct cell types and neuron subtypes is central to understanding complex neural circuitry, and could enable electronic treatments that target specific circuits while minimizing off-target effects. In my previous work (under review), I functionalized ultra-flexible mesh electronic probes with antibodies or peptides to target specific cell markers, and demonstrated selective accumulation of the targeted cell types. In vivo chronic electrophysiology further yielded results consistent with selective targeting of neurons, astrocytes and microglia, as well as a dopaminergic neuron subtype. In my own laboratory, my short-term goals are to use these probes with recording/stimulation electrodes to decode the local excitation/inhibition circuitries. In addition, I plan to extend the targeting capabilities with genetically targeted biorthogonal chemistry, which could introduce artificial functional groups on the cell surface. In the long term, I plan to use these probes to study Parkinson’s disease, selective targeting and stimulation of dopaminergic neuron subtypes may have a beneficial therapeutic effect.

Aim 3: Constructing life: building functional materials in living brains

Multicellular biological systems, particularly living neural networks, exhibit highly complex organizations that pose difficulties for building cell-specific and seamless interfaces. In my previous works (in revision at Science Advances, accepted for publication in Nature Reviews Bioengineering), I developed a genetic targeting approach to program neurons to assemble functional materials on their membranes in situ, and demonstrated broad generalizability of this method across a range of design strategies. In my own laboratory, I will continue working on genetically targeted photosensitizers enabled 3D in vivo photolithography, a field that I initiated, which allows for arbitrarily constructed neural networks in situ. In the long term, I plan to explore potential clinical applications where the excitation-inhibition balance is important, such as autism.

Teaching Interests:

My previous research experience has given me rigorous and highly interdisciplinary training in chemistry, materials sciences, genetic engineering, neuroscience, neurosurgery, and computation. When I was a Ph.D. student at Harvard, I served as a Teaching Fellow for two courses, Quantum and Statistical Foundations of Chemistry, and Organic Chemistry of Life, and received teaching awards for both courses. I also took courses in other fields, including Electronic Devices and Circuits, Microfabrication Laboratory, The Missing Matlab course: An Introduction to Programming and Data Analysis, Cellular Neurophysiology, and Experimental Approaches to Developmental Biology. After I transition to an independent position, I am interested in teaching basic courses in chemistry, materials sciences, or biology, or laboratory courses in microfabrication.