Three-dimensional -3D- nanosensors array for measurement of the electrical activity of microscale human brain tissue
Abstract
Project Summary Abstract - Three-dimensional (3D) nanosensors array for measurement of the electrical activity of microscale human brain tissue. The Research Problem. For decades, the electrical properties of neurons have been investigated by using glass micropipette patch-clamp electrodes and ion/voltage sensitive dyes. However, multisite, simultaneous, three-dimensional (3D), and long term electrophysiological investigation of a human brain tissue has not been possible. Specifically, (1) voltage/ion sensitive dyes are toxic to the cells and limited in volume (3D) measurements, (2) patch clamp technique is limited by its recording sites, (3) patch clamp and voltage sensitive dyes are limited to few minutes to hours anddo not allow long term electrophysiological investigation, and (4) multisite electrical stimulation is currently unavailable. Currently, there is a critical need to develop new ways to measure (and affect) how neurons electrically communicate in a native 3D organization at the cellular level with exquisite spatial-temporal (a few ~m and sec) resolution.The Technical Approach. Here we propose a novel approach for electrophysiology measurements in 3D (surface and body) of microscale brain tissue (~brain) engineered from human induced pluripotent stem cells derived neurons (iPS-N) with greater sensitivity, high spatio-temporal resolution (a few m and sec), and simultaneous multiplexed intracellular measurements and stimulation (Input/Output). The technical goal is to engineer a two-way interface between human brain tissue and a 3D electrophysiological recording platform. Studying the mechanism of cell-cell communication and understanding electrical signal propagation will further our knowledge of device neuronal tissue interfaces formation (and alteration) toward the creation of smartprosthetics. This application proposes an innovative interdisciplinary approach to address the material properties of the synthesized nanosensors and their assembly to form a 3D recording platform. It will require in depth engineering of the nanosensor/cell interactions to form direct access of the nanosensor to the cell~s cytosol to enable intracellular measurements. The anticipated outcome of the research and impact on DoD capabilities. Our research will provide high spatial-temporal resolution interfaces with cells, multiplexed communication, and complex materials assemblies that form the interfaces. Knowing how electrical informationpropagates in a brain tissue will greatly impact basic understanding of signals transduction in complex cellular assemblies and will create new avenues for bidirectional communication (sensing and stimulation) with electrically active brain tissue. This knowledge will have societal impact by shedding light on the relationship between electrical signals and reported diseases such asAlzheimer and Parkinson~s disease, and will enable the development of new prosthetics for motion and vision restoration which is of great interest for the DoD. This novel measurement platform will be transformative and will address broader challenges, such as recording electrical activity of stem cells, cardiomyocytes and neurons. The ONR YIP will support the needed solidfoundation to initiate additional immensely challenging bioelectronics projects.If successful, this proposal would lead to:1. A platform for investigation of developing human iPS-N ~brain tissue in-situ under various physiological conditions such as chemical stimulants or applied electrical fields.2. A platform for the investigation of I/O communication with human brain tissue, toward the formation of smart prosthetics.3. The tools and procedures to allow the immediate development of I/O systems in additional tissues of interest such as cardiac tissue.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 05, 2017
- Source ID
- N000141712368
Entities
People
- Tzahi Cohen Karni
Organizations
- Massachusetts Institute of Technology
- Office of Naval Research
- United States Navy