Scientists at UC Berkeley and Stanford University have recorded the electrical activity of a beating heart in real time by using a graphene plate to record an optical image – almost like a video camera – of the weak electrical fields created by the rhythmic firing of the heart’s muscle cells.
The “graph camera” is a new type of sensor that could prove useful for examining cells and tissues that generate electrical voltages, such as groups of neurons or cardiac muscle cells. Heretofore, electrodes or chemical dyes have been used to measure electrical ignition in these cells. But electrodes and dyes only measure voltage at one point; a graph sheet continuously measures the tension across the entire tissue it touches.
“Since we image all cells simultaneously on one camera, we don’t have to scan and we don’t just have a point measurement. We can map the entire cell network at the same time, ”said Halleh Balch, one of the three first authors of the work and who recently received a doctorate. Recipient in the Department of Physics at UC Berkeley.
The graphene sensor works without having to mark the cells with dyes or tracers, but can easily be combined with standard microscopy to image fluorescence-marked nerve or muscle tissue and at the same time record the electrical signals with which the cells communicate.
“The ease with which you can image an entire region of a sample could be particularly useful when studying neural networks that involve all possible cell types,” said Allister McGuire, another lead author on the study, who recently earned a Ph. received .D. from Stanford. “When you have a fluorescently tagged cell system, you may only be targeting one type of neuron. Our system would allow you to capture the electrical activity in all neurons and their supporting cells with very high integrity, which could really affect the way people conduct these network-level studies. “
“This is perhaps the first example where you can use a visual display of 2D materials to measure biological electric fields,” said senior author Feng Wang, professor of physics at UC Berkeley. “Humans have used 2D materials to detect something with all-electric readings, but this is unique in that it works with microscopy so you can do parallel detection.”
The team calls the tool a critically coupled waveguide-reinforced graphene electric field sensor, or CAGE sensor.
“This study is only a preliminary; We want to show biologists that there is such a tool that you can use and that you can get great imaging. It has fast time resolution and excellent electric field sensitivity, ”said third lead author, Jason Horng, a Ph.D. at UC Berkeley. Recipient who is now a postdoc at the National Institute of Standards and Technology. “Right now it’s just a prototype, but in the future I think we can improve the device.”
Ten years ago, Wang discovered that an electric field affects how graphene reflects or absorbs light. Balch and Horng used this discovery in the design of the graph camera. They received a layer of graphene about 1 centimeter in size on one side, which was produced by chemical vapor deposition in the laboratory of physics professor Michael Crommie at UC Berkeley, and placed on it a living heart from a chicken embryo freshly obtained from a fertilized egg cell. These experiments were carried out in the Stanford laboratory by Bianxiao Cui, who is developing nanoscale tools to study electrical signals in neurons and heart cells.
The team showed that when the graph is properly tuned, the electrical signals flowing along the surface of the heart during a beat are sufficient to change the reflectivity of the graphene sheet.
“When cells contract, they ignite action potentials that create a small electric field outside the cell,” said Balch. “The absorption of graphene directly under this cell is modified so that we will see a change in the amount of light that comes back from this position on the large graphene surface.”
However, in initial studies, Horng found that the change in reflectivity was too small to be easily seen. An electric field reduces the reflectivity of graphene by at most 2%; the effect was much less due to changes in the electric field when the heart muscle cells fired an action potential.
Together, Balch, Horng, and Wang found a way to amplify this signal by adding a thin waveguide under graphene that forces the reflected laser light to internally impact about 100 times before it escapes. This made the change in reflectivity detectable by a normal optical video camera.
“One way of thinking is that the more light is reflected from graphene as it propagates through this small cavity, the more effects the light will feel from the reaction of the graphene, and that allows us to be very, very sensitive to electrical fields and voltages down to microvolts, ”said Balch.
The increased gain necessarily decreases the resolution of the image, but at 10 microns it’s more than enough to examine heart cells tens of microns in diameter, she said.
Another application, according to McGuire, is to test the effects of drug candidates on the heart muscle before these drugs go into clinical trials to see whether they cause, for example, an undesirable arrhythmia. To demonstrate this, he and his colleagues observed the beating chicken heart with CAGE and a light microscope while they infused it with the drug blebistatin, which inhibits the muscle protein myosin. They observed that the heart stopped beating, but CAGE showed that the electrical signals were not affected.
Since graphene foils are mechanically tough, they could also be placed directly on the surface of the brain to get a continuous measurement of electrical activity – for example, to monitor neuron firing in the brains of epilepsy patients or to study basic brain activity. Today’s electrode arrays measure activity at a few hundred points, not continuously above the surface of the brain.
“One of the things that amazes me about this project is that electric fields mediate chemical interactions, mediate biophysical interactions – they mediate all kinds of processes in the natural world – but we never measure them. We measure current and we measure voltage, ”said Balch. “The ability to actually map electric fields gives you insight into a modality that you previously had little insight into.”