3D cardiac spheroid labeled with Ca2+ indicator dye encapsulated by the...
3D cardiac spheroid labeled with Ca2+ indicator dye encapsulated by the self-rolling sensor array.
Source: Carnegie Mellon University
03.09.2019 •

Self-rolling sensors take heart cell readings in 3D

Researchers from Carnegie Mellon University (CMU) and Nanyang Technological University, Singapore (NTU Singapore) have developed an organ-on-an-electronic-chip platform, which uses bioelectrical sensors to measure the electrophysiology of the heart cells in three dimensions. These 3D, self-rolling biosensor arrays coil up over heart cell spheroid tissues to form an “organ-on-e-chip,” thus enabling the researchers to study how cells communicate with each other in multicellular systems such as the heart.

The organ-on-e-chip approach will help develop and assess the efficacy of drugs for disease treatment — perhaps even enabling researchers to screen for drugs and toxins directly on a human-like tissue, rather than testing on animal tissue. The platform will be used to shed light on the connection between the heart’s electrical signals and disease, such as arrhythmias. The research allows the researchers to investigate processes in cultured cells that currently are not accessible, such as tissue development and cell maturation.

“For decades, electrophysiology was done using cells and cultures on two-dimensional surfaces, such as culture dishes,” said Tzahi Cohen-Karni, an associate professor of biomedical engineering and materials science and engineering. “We are trying to circumvent the challenge of reading the heart’s electrical patterns in 3D by developing a way to shrink-wrap sensors around heart cells and extracting electrophysiological information from this tissue.”

The “organ-on-e-chip” platform starts out as a small, flat rectangle, not unlike a microscale slap bracelet. A slap bracelet starts out as a rigid, ruler-like structure, but when you release the tension it quickly coils up to band around the wrist.

A spheroid encapsulated by 3D self-rolling biosensor arrays (top) and a...
A spheroid encapsulated by 3D self-rolling biosensor arrays (top) and a spheroid that is not encapsulated (bottom). Imaged at (i) 0 hours (immediately after encapsulation), (ii) 1 hour, (iii) 2 hours, and (iv) 3 hours. Green, red, and blue denote live cells, dead cells, and cell nuclei, respectively.
Source: Carnegie Mellon University

The organ-on-e-chip starts out similarly. The researchers pin an array of sensors made of either metallic electrodes or graphene sensors to the chip’s surface, then etch off a bottom layer of germanium, which is known as the “sacrificial layer.” Once this sacrificial layer is removed, the biosensor array is released from its hold and rolls up from the surface in a barrel-shaped structure.

The researchers tested the platform on cardiac spheroids, or elongated organoids made of heart cells. These 3D heart spheroids are about the width of two to three human hairs. Coiling the platform over the spheroid allows the researchers to collect electrical signal readings with high precision.

“Essentially, we have created 3D self-rolling biosensor arrays for exploring the electrophysiology of induced pluripotent stem cell derived cardiomyocytes,” said Anna Kalmykov, the lead author of the study and a Ph.D. student in biomedical engineering. “This platform could be used to do research into cardiac tissue regeneration and maturation that potentially can be used to treat damaged tissue after a heart attack, for example, or developing new drugs to treat disease.”

Through collaboration with the labs of Adam Feinberg and Jimmy Hsia, the researchers were able to design a proof of concept and test them on 3D micro-mold formed cardiomyocyte spheroids.

“Mechanics analysis of the roll-up process enables us to precisely control the shape of the sensors to ensure conforming contact between the sensors and the cardiac tissue,” said Hsia, professor and dean of the Graduate College of NTU Singapore and former CMU faculty member. “The technique also automatically adjusts the level of the delicate ‘touch’ between the sensors and the tissue such that high quality electric signals are measured without changing in the physiological conditions of the tissue due to external pressure.”

“The whole idea is to take methods that are traditionally done in planar geometry and do them in three dimensions,” Cohen-Karni said. “Our organs are 3D in nature. For many years, electrophysiology was done using just cells cultured on a 2D tissue culture dish. But now, these amazing electrophysiology techniques can be applied to 3D structures.”

Subscribe to our newsletter

Related articles

3D body mapping could identify damaged cells

3D body mapping could identify damaged cells

A Purdue University team has come up with 3D body mapping technology to help treat organs and cells damaged by cancer and other medical issues.

Necklace detects abnormal heart rhythm

Necklace detects abnormal heart rhythm

A necklace which detects abnormal heart rhythm will be showcased for the first time on EHRA Essentials 4 You, a scientific platform of the European Society of Cardiology (ESC).

Sensor predicts worsening heart failure before hospitalization

Sensor predicts worsening heart failure before hospitalization

A wearable sensor could help doctors remotely detect critical changes in heart failure patients days before a health crisis occurs and could prevent hospitalization.

A step towards mending a broken heart

A step towards mending a broken heart

Bioengineers have developed a prototype patch that does the same job as crucial aspects of heart tissue.

Artificial pericardial tissue from the 3D printer

Artificial pericardial tissue from the 3D printer

In the PolyKARD project, biomimetic polymers are being developed that can imitate the mechanical properties of pericardial tissue.

Photonic pH sensor tracks tissue with light

Photonic pH sensor tracks tissue with light

In a proof-of-concept work, scientists demonstrated their photonics-based sensors using fibers and liquid-filled petri dishes.

Microscopy: AI converts 2D images into 3D

Microscopy: AI converts 2D images into 3D

Researchers have devised a technique that extends the capabilities of fluorescence microscopy, which allows scientists to precisely label parts of living cells and tissue with dyes that glow under special lighting.

Activity trackers help manage diabetes

Activity trackers help manage diabetes

Patients with diabetes and cardiovascular disease who used wearable step-counting devices have shown small-to-medium improvements in physical activity.

mhealth: health studies to benefit from Apple watch

mhealth: health studies to benefit from Apple watch

During its latest keynote presentation, tech giant Apple announced cooperations for health studies. The latest model of their smartwatches are to be key in their execution.

Popular articles