Research

Neurological disorders are the leading cause of disability and the second-most common cause of death worldwide. Conditions like epilepsy, stroke, and neurodegenerative diseases affect many, particularly the elderly. Accurate detection and treatment of abnormal neural activity are crucial. Neuroelectronics offers targeted interventions through electrical recording and stimulation, which can help modulate neural activity, alleviate symptoms, and restore functions. The Zhang Research Group aims to combine innovative electronic, chemical, and genetic tools to develop minimally invasive, targeted treatments, bringing these advances from the lab to clinical practice.

Endovascular neural interfaces

Implantable neuroelectronic interfaces have enabled advances in both fundamental research and the treatment of neurological disease, yet traditional intracranial depth electrodes require invasive surgery to place and can damage the brain. We developed a flexible endovascular probe and demonstrated acute recording from sub-100-micron scale vessels in the rat cortex and olfactory bulb. This technology could be extended to the detection and treatment of many neurological diseases as a research tool and could lead to clinical translation of minimally invasive neuroelectronic interfaces.

Related recent publication:

A. Zhang†, E.T. Mandeville, L. Xu, C.M. Stary, E.H. Lo, C.M. Lieber†, Ultraflexible endovascular probes for brain recording through micron-scale vasculature. Science. 2023, 381, 306-312. (†corresponding authors)

Cell type-specific neural interfaces

The ability to record and modulate specific neural cell types and subtypes is essential for understanding complex neural circuitry, and could enable electronic treatments that target specific circuits while minimizing off-target effects. We developed brain-implanted ultra-flexible mesh electronic probes that did not elicit an inflammatory immune response and showed minimal effect on the natural distribution of cells post-implantation, functionalized the probe surface with antibodies or peptides to target specific cell markers, and demonstrated selective accumulation and recording of the targeted cells. These cell targeting capabilities could be significantly expanded to treat neurological diseases associated with specific cell types.

Related recent publication:

A. Zhang*, T.J. Zwang*, C.M. Lieber, Biochemically-functionalized probes for cell-type–specific targeting and recording in the brain. Science Advances. 2023, 9, eadk1050. (*equal contribution)

Bottom-up assembled neural interfaces

In situ assembly within biological tissues is a novel strategy for fabricating functional materials and devices for interfacing with living tissues. As an example, we have developed an approach to genetically program cells to assemble conductive polymers from the neuron membrane surface. Such functional electronic materials constructed from the bottom-up hold the potential for seamless integration of electronic devices into the nervous system.

Related recent publications:

A. Zhang, K.Y. Loh, C.S. Kadur, L. Michalek, J. Dou, C. Ramakrishnan, Z. Bao, K. Deisseroth, Genetically targeted chemical assembly of polymers specifically localized extracellularly to surface membranes of living neurons. Science Advances. 2023, 9, eadi1870.

A. Zhang, Y. Jiang, K.Y. Loh, Z. Bao, K. Deisseroth, Genetically targeted chemical assembly. Nature Reviews Bioengineering. 2024, 2, 82-94.

A. Zhang, S. Zhao, J. Tyson, K. Deisseroth, Z. Bao, Applications of synthetic polymers directed toward living cells. Nature Synthesis. 2024, doi: 10.1038/s44160-024-00560-2.