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We use both the top-down and bottom-up synthesis approaches to synthesize new materials and nanostructures to investigate the biophysical properties of tissue and cells. We are mainly interested in the mechanism by which cellular arrangements communicate.

Our grand aim with this work is to utilize our novel materials and platforms to incorporate inorganic elements into a tissue to allow for the development of a smart tissue, which can allow for key biological questions to be answered through the acquisition of data from our device.

Three-dimensional self-rolling biosensor arrays

The Cohen-Karni lab designed and demonstrated the first direct, multisite electrophysiological platform to investigate tissues in 3D cell cultures. The use of 3D platforms greatly improves the translation of findings to the human body, as cell-cell communication in 2D varies greatly from that in 3D in structure and function. Our novel platform has filled the gap in the field of being able to investigate the electrophysiological properties of tissues in 3D.

The organ-on-electronic-chip biosensor takes advantage of prestress in material thin films to self-roll around a spheroid and directly record electrical activity with high spatiotemporal resolution.

The organ-on-a-chip can be used to investigate the electrical activity of any electrically active 3D multicellular assemblies, such as cardiac organoids, mini-brains, or pancreatic islets.

With the development of this platform, investigation of 3D tissues will now be possible in the following areas:

• Signal propagation and network function
• Tissue development and maturation
• Pharmaceutical screening and testing

Together, these capabilities support deeper investigation of fundamental biological questions.

Pushing the limits of electrophysiological recordings using ultra-microelectrodes

Microelectrode arrays (MEAs) have enabled the investigation of cellular networks at sub-millisecond temporal resolution. However, current MEAs are limited by the large electrode footprint since reducing the electrode’s geometric area to sub-cellular dimensions leads to a significant increase in impedance, thus affecting its recording capabilities.

We have developed a breakthrough ultra-microelectrodes platform by leveraging the outstanding surface-to-volume ratio of nanowire-templated out-of-plane synthesized three-dimensional fuzzy graphene (NT-3DFG).

We demonstrated the recording of the electrical activity of excitable cells using ultra-microelectrodes ranging from 10 down to 2 μm.

The out-of-plane morphology and enormous surface area of NT-3DFG enables fabrication of ultra-microelectrodes, as small as an axon, thus opening up possibilities to:

1. Probe at sub-cellular scale
2. Investigate distribution of ion channels
3. Investigate propagation of electrical activity within a single cell

Furthermore, miniaturization of microelectrodes down to 2 μm will enable fabrication of high-density electrode arrays to study network dynamics in dense cellular networks, minimize signal averaging, and reduce the foreign body response in an in vivo environment.

The presented platform pushes the limits of the current MEA technology, thus will help advance and accelerate our understanding of complex cellular networks, both in health and diseas,e and enable diagnosis as well as screening of therapeutics for various cardiac and neurological diseases.

Transparent graphene MEAs

Cell-cell communication plays a pivotal role in biological systems’ coordination and function. Electrical properties have been linked to specification and differentiation of stem cells into targeted progeny, such as neurons and cardiomyocytes.

Electrophysiological studies of cells and tissues have been carried out using a variety of recording techniques, including:

1. Glass micropipette patch-clamp electrodes
2. Voltage and Ca2+ sensitive dyes
3. Multielectrode arrays (MEAs)
4. Planar field-effect transistors (FETs).

Complementing electrical recording with optical imaging using fluorescent indicators such as Ca2+ sensitive dyes can leverage the temporal resolution and spatial advantages of both techniques.  

Commonly used metal-based MEAs have high opacity, which hinders simultaneous optical and electrical recordings. Currently, there is a critical need to develop new ways to complement fluorescent indicators, such as Ca2+ sensitive dyes, for direct electrophysiological measurements of cells and tissue.

We developed a unique transparent and biocompatible graphene-based electrical platform that enables electrical and optical investigation of human embryonic stem cell-derived cardiomyocytes’ (hESC-CMs) intracellular processes and intercellular communication.

The transparent graphene platform enables the investigation of both intracellular and intercellular communication processes and will create new avenues for bidirectional communication (sensing and stimulation) with electrically active tissues and will set the ground for investigations of reported diseases such as Alzheimer's disease, Parkinson’s disease, and arrhythmias.