park_nano_research_grant.jpg

Cyborg organoids offer rare view into early stages of development


The nanoelectronics seamlessly reconfigured themselves with stem cells, resulting in fully-grown 3D organoids with embedded sensors. The stem cells were then differentiated into cardiomyocytes -- heart cells -- and the researchers were able to monitor and record the electrophysiological activity for 90 days. @ Harvard SEAS

What happens in the early days of organ development? How do a small group of cells organize to become a heart, a brain, or a kidney? This critical period of development has long remained the black box of developmental biology, in part because no sensor was small or flexible enough to observe this process without damaging the cells.


Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have grown simplified organs known as organoids with fully integrated sensors. These so-called cyborg organoids offer a rare glimpse into the early stages of organ development.


The research was published in Nano Letters.


"I was so inspired by the natural organ development process in high school, in which 3D organs start from few cells in 2D structures. I think if we can develop nanoelectronics that are so flexible, stretchable, and soft that they can grow together with developing tissue through their natural development process, the embedded sensors can measure the entire activity of this developmental process," said Jia Liu, Assistant Professor of Bioengineering at SEAS and senior author of the study. "The end result is a piece of tissue with a nanoscale device completely distributed and integrated across the entire three-dimensional volume of the tissue."


This type of device emerges from the work that Liu began as a graduate student in the lab of Charles M. Lieber, the Joshua and Beth Friedman University Professor. In Lieber's lab, Liu once developed flexible, mesh-like nanoelectronics that could be injected in specific regions of tissue.


Building on that design, Liu and his team increased the stretchability of the nanoelectronics by changing the shape of the mesh from straight lines to serpentine structures (similar structures are used in wearable electronics). Then, the team transferred the mesh nanoelectronics onto a 2D sheet of stem cells, where the cells covered and interwove with the nanoelectronics via cell-cell attraction forces. As the stem cells began to morph into a 3D structure, the nanoelectronics seamlessly reconfigured themselves along with the cells, resulting in fully-grown 3D organoids with embedded sensors.


The stem cells were then differentiated into cardiomyocytes -- heart cells -- and the researchers were able to monitor and record the electrophysiological activity for 90 days.


"This method allows us to continuously monitor the developmental process and understand how the dynamics of individual cells start to interact and synchronize during the entire developmental process," said Liu. "It could be used to turn any organoid into cyborg organoids, including brain and pancreas organoids."


In addition to helping answer fundamental questions about biology, cyborg organoids could be used to test and monitor patient-specific drug treatments and potentially used for transplantations.


Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology

Qiang Li, Kewang Nan, Paul Le Floch, Zuwan Lin, Hao Sheng, Thomas S. Blum, Jia Liu

Nano Letter 2019

DOI: 10.1021/acs.nanolett.9b02512


Contact information:

Jia Liu

Assistant Professor of Bioengineering at Harvard SEAS

jia_liu@seas.harvard.edu

Phone: (617) 599-7582

Harvard's Liu Lab


Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS)

 

STAY CURRENT WITH THE NWA NEWSLETTER DELIVERED TO YOUR INBOX.

FOUNDING MEMBERS

Rice lab's bright idea is pure gold

Decoding material wear with supercomputers

Light from inside the tunnel

Wearable-tech glove translates sign language into speech in real time

How to store data using 2D materials instead of silicon chips?

Building a harder diamond

Clinical-grade wearables offer continuous monitoring for COVID-19