Two-in-one sensor: Team leader Jun Yao (left) and first author Hongyan Gao, a PhD student in electrical and computer engineering, have developed a new tool for improved cardiac studies. (Courtesy: Jun Yao)
A team of US-based researchers has developed an innovative nanoelectronic sensor that simultaneously measures electrical and mechanical activity in heart cells – paving the way for improved approaches to cardiac disease studies, drug testing and regenerative medicine. So, how exactly does the sensor work? What are its key advantages over existing approaches? And what are the next steps for the research team?
Cardiac diseases remain stubbornly at the top of the list of the leading causes of human mortality, and interest in studying them remains a priority within the scientific community. During such studies, it is generally much more convenient to use in vitro tissue that exists outside the human body – and to be able to constantly monitor tissue status with minimal disruption.
In an effort to optimize such processes, researchers from the University of Massachusetts Amherst and the University of Missouri have created a tiny nanoelectronic sensor, much smaller than a single cell, that is capable of simultaneously measuring electrical and mechanical cellular responses in cardiac tissue. And it does this in such a way that the cell or tissue under investigation does not “feel” anything strange plugged into it.
Because the electrical and mechanical responses from cells are intricately correlated, through the excitation-contraction coupling process, their simultaneous measurement is critical for identifying physiological and pathological mechanisms.
As team leader Jun Yao explains, existing sensors can only detect either the electrical or the mechanical activity in the cardiac tissue or cell. “We needed to detect both signals simultaneously to better monitor tissue status and reveal more mechanistic information,” he says.
The new nanosensors are made from inorganic or organic materials that are rigorously tested to ensure they are biocompatible. The sensor incorporates a suspended semiconducting silicon nanowire that is 100 times smaller than a cell and is non-toxic to the cell. “Imagine that it’s a tiny suspended rope – if you pull it, it can feel the strain,” Yao explains. “So that’s the way that it can detect the mechanical signal from cells. Meanwhile, imagine that it’s a conducting cable, meaning it can also detect the electrical signals from cells.”
Device schematic: The sensor structure and cell–sensor interface; the nanowire is suspended across a microbar. (Courtesy: Jun Yao)
According to Yao, the nanosensors are currently fabricated on a flat biochip-based substrate, with cardiac cells cultured on top. However, in the future, there is possibility that they could be embedded into tissue in a 3D distribution.
“The sensors can be placed in tissue models outside the body, which can be used to test key variables like drug effects, so the sensor provides feedback about the effect of the drug on the cardiac tissue or cells,” Yao explains. “The cardiac tissue is driven by the so-called excitation-contractile mechanism – the former an electrical process and the latter a mechanical process – and we need to monitor both in order to give the most accurate feedback. Previous sensors can only tell one of them; we now can monitor both processes together.”
Looking further ahead, Yao reveals that there is also a possibility that the sensors can be integrated onto what he describes as a “deliverable substrate”, so that they can be patched on a living heart for health monitoring and early disease diagnosis.
“This may sound scary – but imagine that everything is so small that it does not introduce perturbation to the heart,” he says. “The next step is that we will translate the current planar biochip integration into a 3D integration, so that the sensors will reach out to cells in the 3D space. A possible way is to integrate these sensors on a soft, porous tissue scaffold that can naturally embed in the 3D tissue.”
The researchers describe their findings in Science Advances.
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