The first-of-its-kind nanotechnology is capable of measuring signals within individual cells, as well as between cells. The device even found that signals moving within individual cardiac cells move nearly five times quicker than signals between cardiac cells. The research team believes this technology could also be used to analyze diseased neurons. (Image credit: University of California San Diego/Yue Gu)
Experts from the University of California, San Diego, have invented a remarkable new instrument that uses microscopic “pop-up” sensors to monitor the electrical activity inside heart cells. The device detects the movement and speed of electrical signals within a single heart cell, as well as between various cardiac cells, in real time. It’s also the first time these signals have been measured inside 3D tissue cells.
The newly developed technology could help scientists learn more about heart abnormalities and diseases including arrhythmia (abnormal heart rhythm), heart attack, and myocardial fibrosis (stiffening or thickening of heart tissue).
The paper’s first author, Yue Gu, explained the significance behind the technology, stating, “Studying how an electrical signal propagates between different cells is important to understand the mechanism of cell function and disease…Irregularities in this signal can be a sign of arrhythmia, for example. If the signal cannot propagate correctly from one part of the heart to another, then some part of the heart cannot receive the signal so it cannot contract.”
Fellow author Sheng Xu added, “With this device, we can zoom in to the cellular level and get a very high resolution picture of what’s going on in the heart; we can see which cells are malfunctioning, which parts are not synchronized with the others, and pinpoint where the signal is weak. This information could be used to help inform clinicians and enable them to make better diagnoses.”
The device is made up of a three-dimensional array of tiny field effect transistors (FETs) formed like sharp pointed ends. These small FETs can pierce cell membranes without causing damage and are sensitive enough to detect electrical impulses, even if they are extremely faint, inside the cells. The FETs are covered in a phospholipid bilayer to avoid being recognized as a foreign material and to enable them to reside within the cell for lengthy periods of time. The FETs may simultaneously detect signals from several cells.
The FETs were initially produced as 2D forms, and then selected spots of these shapes were glued to a pre-stretched polymer sheet to create the device. The engineers subsequently loosened the elastomer layer, which buckled the device and caused the FETs to fold into a 3D shape, allowing them to pierce into the cells.
“It’s like a pop-up book,” said Gu. “It starts out as a 2D structure, and with compressive force it pops up at some portions and becomes a 3D structure.”
According to the new research using the new device, signals inside individual heart cells move nearly five times quicker than signals between heart cells. These pieces of information, according to Gu, might give insights about cardiovascular issues at the molecular level.
“Say you’re measuring the signal speed in one cell, and the signal speed between two cells. If there’s a very big difference between these two speeds — that is, if the intercellular speed is much, much smaller than the intracellular speed — then it’s likely that something is wrong at the junction between the cells, possibly due to fibrosis,” he explained.
The study was published in Nature Nanotechnology, on December 23rd, 2021.
Abstract. Electrical impulse generation and its conduction within cells or cellular networks are the cornerstone of electrophysiology. However, the advancement of the field is limited by sensing accuracy and the scalability of current recording technologies. Here we describe a scalable platform that enables accurate recording of transmembrane potentials in electrogenic cells. The platform employs a three-dimensional high-performance field-effect transistor array for minimally invasive cellular interfacing that produces faithful recordings, as validated by the gold standard patch clamp. Leveraging the high spatial and temporal resolutions of the field-effect transistors, we measured the intracellular signal conduction velocity of a cardiomyocyte to be 0.182 m s−1, which is about five times the intercellular velocity. We also demonstrate intracellular recordings in cardiac muscle tissue constructs and reveal the signal conduction paths. This platform could provide new capabilities in probing the electrical behaviours of single cells and cellular networks, which carries broad implications for understanding cellular physiology, pathology and cell–cell interactions.
Gu, Y., Wang, C., Kim, N. et al. Three-dimensional transistor arrays for intra- and inter-cellular recording. Nat. Nanotechnol. (2021). https://doi.org/10.1038/s41565-021-01040-w
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