Tag Archives: Bianxiao Cui

A graphene ‘camera’ and your beating heart: say cheese

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Comparing it to a ‘camera’, even with the quotes, is a bit of a stretch for my taste but I can’t come up with a better comparison. Here’s a video so you can judge for yourself,

Caption: This video repeats three times the graphene camera images of a single beat of an embryonic chicken heart. The images, separated by 5 milliseconds, were measured by a laser bouncing off a graphene sheet lying beneath the heart. The images are about 2 millimeters on a side. Credit: UC Berkeley images by Halleh Balch, Alister McGuire and Jason Horng

A June 16, 2021 news item on ScienceDaily announces the research,

Bay Area [San Francisco, California] scientists have captured the real-time electrical activity of a beating heart, using a sheet of graphene to record an optical image — almost like a video camera — of the faint electric fields generated by the rhythmic firing of the heart’s muscle cells.

A University of California at Berkeley (UC Berkeley) June 16, 2021 news release (also on EurekAlert) by Robert Sanders, which originated the news item, provides more detail,

The graphene camera represents a new type of sensor useful for studying cells and tissues that generate electrical voltages, including groups of neurons or cardiac muscle cells. To date, electrodes or chemical dyes have been used to measure electrical firing in these cells. But electrodes and dyes measure the voltage at one point only; a graphene sheet measures the voltage continuously over all the tissue it touches.

The development, published online last week in the journal Nano Letters, comes from a collaboration between two teams of quantum physicists at the University of California, Berkeley, and physical chemists at Stanford University.

“Because we are imaging all cells simultaneously onto a camera, we don’t have to scan, and we don’t have just a point measurement. We can image the entire network of cells at the same time,” said Halleh Balch, one of three first authors of the paper and a recent Ph.D. recipient in UC Berkeley’s Department of Physics.

While the graphene sensor works without having to label cells with dyes or tracers, it can easily be combined with standard microscopy to image fluorescently labeled nerve or muscle tissue while simultaneously recording the electrical signals the cells use to communicate.

“The ease with which you can image an entire region of a sample could be especially useful in the study of neural networks that have all sorts of cell types involved,” said another first author of the study, Allister McGuire, who recently received a Ph.D. from Stanford and. “If you have a fluorescently labeled cell system, you might only be targeting a certain type of neuron. Our system would allow you to capture electrical activity in all neurons and their support cells with very high integrity, which could really impact the way that people do these network level studies.”

Graphene is a one-atom thick sheet of carbon atoms arranged in a two-dimensional hexagonal pattern reminiscent of honeycomb. The 2D structure has captured the interest of physicists for several decades because of its unique electrical properties and robustness and its interesting optical and optoelectronic properties.

“This is maybe the first example where you can use an optical readout of 2D materials to measure biological electrical fields,” said senior author Feng Wang, UC Berkeley professor of physics. “People have used 2D materials to do some sensing with pure electrical readout before, but this is unique in that it works with microscopy so that you can do parallel detection.”

The team calls the tool a critically coupled waveguide-amplified graphene electric field sensor, or CAGE sensor.

“This study is just a preliminary one; we want to showcase to biologists that there is such a tool you can use, and you can do great imaging. It has fast time resolution and great electric field sensitivity,” said the third first author, Jason Horng, a UC Berkeley Ph.D. recipient who is now a postdoctoral fellow at the National Institute of Standards and Technology. “Right now, it is just a prototype, but in the future, I think we can improve the device.”

Graphene is sensitive to electric fields

Ten years ago, Wang discovered that an electric field affects how graphene reflects or absorbs light. Balch and Horng exploited this discovery in designing the graphene camera. They obtained a sheet of graphene about 1 centimeter on a side produced by chemical vapor deposition in the lab of UC Berkeley physics professor Michael Crommie and placed on it a live heart from a chicken embryo, freshly extracted from a fertilized egg. These experiments were performed in the Stanford lab of Bianxiao Cui, who develops nanoscale tools to study electrical signaling in neurons and cardiac cells.

The team showed that when the graphene was tuned properly, the electrical signals that flowed along the surface of the heart during a beat were sufficient to change the reflectance of the graphene sheet.

“When cells contract, they fire action potentials that generate a small electric field outside of the cell,” Balch said. “The absorption of graphene right under that cell is modified, so we will see a change in the amount of light that comes back from that position on the large area of graphene.”

In initial studies, however, Horng found that the change in reflectance was too small to detect easily. An electric field reduces the reflectance of graphene by at most 2%; the effect was much less from 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 below graphene, forcing the reflected laser light to bounce internally about 100 times before escaping. This made the change in reflectance detectable by a normal optical video camera.

“One way of thinking about it is that the more times that light bounces off of graphene as it propagates through this little cavity, the more effects that light feels from graphene’s response, and that allows us to obtain very, very high sensitivity to electric fields and voltages down to microvolts,” Balch said.

The increased amplification necessarily lowers the resolution of the image, but at 10 microns, it is more than enough to study cardiac cells that are several tens of microns across, she said.

Another application, McGuire said, is to test the effect of drug candidates on heart muscle before these drugs go into clinical trials to see whether, for example, they induce an unwanted arrhythmia. To demonstrate this, he and his colleagues observed the beating chicken heart with CAGE and an optical microscope while infusing it with a drug, blebbistatin, that inhibits the muscle protein myosin. They observed the heart stop beating, but CAGE showed that the electrical signals were unaffected.

Because graphene sheets are mechanically tough, they could also be placed directly on the surface of the brain to get a continuous measure of electrical activity — for example, to monitor neuron firing in the brains of those with epilepsy or to study fundamental brain activity. Today’s electrode arrays measure activity at a few hundred points, not continuously over the brain surface.

“One of the things that is amazing to me about this project is that electric fields mediate chemical interactions, mediate biophysical interactions — they mediate all sorts of processes in the natural world — but we never measure them. We measure current, and we measure voltage,” Balch said. “The ability to actually image electric fields gives you a look at a modality that you previously had little insight into.”

Here’s a link to and a citation for the paper,

Graphene Electric Field Sensor Enables Single Shot Label-Free Imaging of Bioelectric Potentials by Halleh B. Balch, Allister F. McGuire, Jason Horng, Hsin-Zon Tsai, Kevin K. Qi, Yi-Shiou Duh, Patrick R. Forrester, Michael F. Crommie, Bianxiao Cui, and Feng Wang. Nano Lett. 2021, XXXX, XXX, XXX-XXX OI: https://doi.org/10.1021/acs.nanolett.1c00543 Publication Date: June 8, 2021 © 2021 American Chemical Society

This paper is behind a paywall.

The sense of touch via artificial skin

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Scientists have been working for years to allow artificial skin to transmit what the brain would recognize as the sense of touch. For anyone who has lost a limb and gotten a prosthetic replacement, the loss of touch is reputedly one of the more difficult losses to accept. The sense of touch is also vital in robotics if the field is to expand and include activities reliant on the sense of touch, e.g., how much pressure do you use to grasp a cup; how much strength  do you apply when moving an object from one place to another?

For anyone interested in the ‘electronic skin and pursuit of touch’ story, I have a Nov. 15, 2013 posting which highlights the evolution of the research into e-skin and what was then some of the latest work.

This posting is a 2015 update of sorts featuring the latest e-skin research from Stanford University and Xerox PARC. (Dexter Johnson in an Oct. 15, 2015 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineering] site) provides a good research summary.) For anyone with an appetite for more, there’s this from an Oct. 15, 2015 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

Using flexible organic circuits and specialized pressure sensors, researchers have created an artificial “skin” that can sense the force of static objects. Furthermore, they were able to transfer these sensory signals to the brain cells of mice in vitro using optogenetics. For the many people around the world living with prosthetics, such a system could one day allow them to feel sensation in their artificial limbs. To create the artificial skin, Benjamin Tee et al. developed a specialized circuit out of flexible, organic materials. It translates static pressure into digital signals that depend on how much mechanical force is applied. A particular challenge was creating sensors that can “feel” the same range of pressure that humans can. Thus, on the sensors, the team used carbon nanotubes molded into pyramidal microstructures, which are particularly effective at tunneling the signals from the electric field of nearby objects to the receiving electrode in a way that maximizes sensitivity. Transferring the digital signal from the artificial skin system to the cortical neurons of mice proved to be another challenge, since conventional light-sensitive proteins used in optogenetics do not stimulate neural spikes for sufficient durations for these digital signals to be sensed. Tee et al. therefore engineered new optogenetic proteins able to accommodate longer intervals of stimulation. Applying these newly engineered optogenic proteins to fast-spiking interneurons of the somatosensory cortex of mice in vitro sufficiently prolonged the stimulation interval, allowing the neurons to fire in accordance with the digital stimulation pulse. These results indicate that the system may be compatible with other fast-spiking neurons, including peripheral nerves.

And, there’s an Oct. 15, 2015 Stanford University news release on EurkeAlert describing this work from another perspective,

The heart of the technique is a two-ply plastic construct: the top layer creates a sensing mechanism and the bottom layer acts as the circuit to transport electrical signals and translate them into biochemical stimuli compatible with nerve cells. The top layer in the new work featured a sensor that can detect pressure over the same range as human skin, from a light finger tap to a firm handshake.

Five years ago, Bao’s [Zhenan Bao, a professor of chemical engineering at Stanford,] team members first described how to use plastics and rubbers as pressure sensors by measuring the natural springiness of their molecular structures. They then increased this natural pressure sensitivity by indenting a waffle pattern into the thin plastic, which further compresses the plastic’s molecular springs.

To exploit this pressure-sensing capability electronically, the team scattered billions of carbon nanotubes through the waffled plastic. Putting pressure on the plastic squeezes the nanotubes closer together and enables them to conduct electricity.

This allowed the plastic sensor to mimic human skin, which transmits pressure information as short pulses of electricity, similar to Morse code, to the brain. Increasing pressure on the waffled nanotubes squeezes them even closer together, allowing more electricity to flow through the sensor, and those varied impulses are sent as short pulses to the sensing mechanism. Remove pressure, and the flow of pulses relaxes, indicating light touch. Remove all pressure and the pulses cease entirely.

The team then hooked this pressure-sensing mechanism to the second ply of their artificial skin, a flexible electronic circuit that could carry pulses of electricity to nerve cells.

Importing the signal

Bao’s team has been developing flexible electronics that can bend without breaking. For this project, team members worked with researchers from PARC, a Xerox company, which has a technology that uses an inkjet printer to deposit flexible circuits onto plastic. Covering a large surface is important to making artificial skin practical, and the PARC collaboration offered that prospect.

Finally the team had to prove that the electronic signal could be recognized by a biological neuron. It did this by adapting a technique developed by Karl Deisseroth, a fellow professor of bioengineering at Stanford who pioneered a field that combines genetics and optics, called optogenetics. Researchers bioengineer cells to make them sensitive to specific frequencies of light, then use light pulses to switch cells, or the processes being carried on inside them, on and off.

For this experiment the team members engineered a line of neurons to simulate a portion of the human nervous system. They translated the electronic pressure signals from the artificial skin into light pulses, which activated the neurons, proving that the artificial skin could generate a sensory output compatible with nerve cells.

Optogenetics was only used as an experimental proof of concept, Bao said, and other methods of stimulating nerves are likely to be used in real prosthetic devices. Bao’s team has already worked with Bianxiao Cui, an associate professor of chemistry at Stanford, to show that direct stimulation of neurons with electrical pulses is possible.

Bao’s team envisions developing different sensors to replicate, for instance, the ability to distinguish corduroy versus silk, or a cold glass of water from a hot cup of coffee. This will take time. There are six types of biological sensing mechanisms in the human hand, and the experiment described in Science reports success in just one of them.

But the current two-ply approach means the team can add sensations as it develops new mechanisms. And the inkjet printing fabrication process suggests how a network of sensors could be deposited over a flexible layer and folded over a prosthetic hand.

“We have a lot of work to take this from experimental to practical applications,” Bao said. “But after spending many years in this work, I now see a clear path where we can take our artificial skin.”

Here’s a link to and a citation for the paper,

A skin-inspired organic digital mechanoreceptor by Benjamin C.-K. Tee, Alex Chortos, Andre Berndt, Amanda Kim Nguyen, Ariane Tom, Allister McGuire, Ziliang Carter Lin, Kevin Tien, Won-Gyu Bae, Huiliang Wang, Ping Mei, Ho-Hsiu Chou, Bianxiao Cui, Karl Deisseroth, Tse Nga Ng, & Zhenan Bao. Science 16 October 2015 Vol. 350 no. 6258 pp. 313-316 DOI: 10.1126/science.aaa9306

This paper is behind a paywall.