Tag Archives: University of California at San Diego (UCSD)

Transparent graphene electrode technology and complex brain imaging

Michael Berger has written a May 24, 2018 Nanowerk Spotlight article about some of the latest research on transparent graphene electrode technology and the brain (Note: A link has been removed),

In new work, scientists from the labs of Kuzum [Duygu Kuzum, an Assistant Professor of Electrical and Computer Engineering at the University of California, San Diego {UCSD}] and Anna Devor report a transparent graphene microelectrode neural implant that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. The new class of transparent brain implant is based on monolayer graphene. It offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.

Conventional metal-based microelectrodes cannot be used for simultaneous measurements of multiple optical and electrical parameters, which are essential for comprehensive investigation of brain function across spatio-temporal scales. Since they are opaque, they block the field of view of the microscopes and generate optical shadows impeding imaging.

More importantly, they cause light induced artifacts in electrical recordings, which can significantly interfere with neural signals. Transparent graphene electrode technology presented in this paper addresses these problems and allow seamless and crosstalk-free integration of optical and electrical sensing and manipulation technologies.

In their work, the scientists demonstrate that by careful design of key steps in the fabrication process for transparent graphene electrodes, the light-induced artifact problem can be mitigated and virtually artifact-free local field potential (LFP) recordings can be achieved within operating light intensities.

“Optical transparency of graphene enables seamless integration of imaging, optogenetic stimulation and electrical recording of brain activity in the same experiment with animal models,” Kuzum explains. “Different from conventional implants based on metal electrodes, graphene-based electrodes do not generate any electrical artifacts upon interacting with light used for imaging or optogenetics. That enables crosstalk free integration of three modalities: imaging, stimulation and recording to investigate brain activity over multiple spatial scales extending from single neurons to large populations of neurons in the same experiment.”

The team’s new fabrication process avoids any crack formation in the transfer process, resulting in a 95-100% yield for the electrode arrays. This fabrication quality is important for expanding this technology to high-density large area transparent arrays to monitor brain-scale cortical activity in large animal models or humans.

“Our technology is also well-suited for neurovascular and neurometabolic studies, providing a ‘gold standard’ neuronal correlate for optical measurements of vascular, hemodynamic, and metabolic activity,” Kuzum points out. “It will find application in multiple areas, advancing our understanding of how microscopic neural activity at the cellular scale translates into macroscopic activity of large neuron populations.”

“Combining optical techniques with electrical recordings using graphene electrodes will allow to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity,” she adds.

Next steps for the team involve employing this technology to investigate coupling and information transfer between different brain regions.

This work is part of the US BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative and there’s more than one team working with transparent graphene electrodes. John Hewitt in an Oct. 21, 2014 posting on ExtremeTech describes two other teams’ work (Note: Links have been removed),

The solution [to the problems with metal electrodes], now emerging from multiple labs throughout the universe is to build flexible, transparent electrode arrays from graphene. Two studies in the latest issue of Nature Communications, one from the University of Wisconsin-Madison and the other from Penn [University of Pennsylvania], describe how to build these devices.

The University of Wisconsin researchers are either a little bit smarter or just a little bit richer, because they published their work open access. It’s a no-brainer then that we will focus on their methods first, and also in more detail. To make the arrays, these guys first deposited the parylene (polymer) substrate on a silicon wafer, metalized it with gold, and then patterned it with an electron beam to create small contact pads. The magic was to then apply four stacked single-atom-thick graphene layers using a wet transfer technique. These layers were then protected with a silicon dioxide layer, another parylene layer, and finally molded into brain signal recording goodness with reactive ion etching.

PennTransparentelectrodeThe researchers went with four graphene layers because that provided optimal mechanical integrity and conductivity while maintaining sufficient transparency. They tested the device in opto-enhanced mice whose neurons expressed proteins that react to blue light. When they hit the neurons with a laser fired in through the implant, the protein channels opened and fired the cell beneath. The masterstroke that remained was then to successfully record the electrical signals from this firing, sit back, and wait for the Nobel prize office to call.

The Penn State group [Note: Every reearcher mentioned in the paper Hewitt linked to is from the University of Pennsylvania] in the  used a similar 16-spot electrode array (pictured above right), and proceeded — we presume — in much the same fashion. Their angle was to perform high-resolution optical imaging, in particular calcium imaging, right out through the transparent electrode arrays which simultaneously recorded in high-temporal-resolution signals. They did this in slices of the hippocampus where they could bring to bear the complex and multifarious hardware needed to perform confocal and two-photon microscopy. These latter techniques provide a boost in spatial resolution by zeroing in over narrow planes inside the specimen, and limiting the background by the requirement of two photons to generate an optical signal. We should mention that there are voltage sensitive dyes available, in addition to standard calcium dyes, which can almost record the fastest single spikes, but electrical recording still reigns supreme for speed.

What a mouse looks like with an optogenetics system plugged in

What a mouse looks like with an optogenetics system plugged in

One concern of both groups in making these kinds of simultaneous electro-optic measurements was the generation of light-induced artifacts in the electrical recordings. This potential complication, called the Becqueral photovoltaic effect, has been known to exist since it was first demonstrated back in 1839. When light hits a conventional metal electrode, a photoelectrochemical (or more simply, a photovoltaic) effect occurs. If present in these recordings, the different signals could be highly disambiguatable. The Penn researchers reported that they saw no significant artifact, while the Wisconsin researchers saw some small effects with their device. In particular, when compared with platinum electrodes put into the opposite side cortical hemisphere, the Wisconsin researchers found that the artifact from graphene was similar to that obtained from platinum electrodes.

Here’s a link to and a citation for the latest research from UCSD,

Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays by Martin Thunemann, Yichen Lu, Xin Liu, Kıvılcım Kılıç, Michèle Desjardins, Matthieu Vandenberghe, Sanaz Sadegh, Payam A. Saisan, Qun Cheng, Kimberly L. Weldy, Hongming Lyu, Srdjan Djurovic, Ole A. Andreassen, Anders M. Dale, Anna Devor, & Duygu Kuzum. Nature Communicationsvolume 9, Article number: 2035 (2018) doi:10.1038/s41467-018-04457-5 Published: 23 May 2018

This paper is open access.

You can find out more about the US BRAIN initiative here and if you’re curious, you can find out more about the project at UCSD here. Duygu Kuzum (now at UCSD) was at  the University of Pennsylvania in 2014 and participated in the work mentioned in Hewitt’s 2014 posting.

Humans can distinguish molecular differences by touch

Yesterday, in my December 18, 2017 post about medieval textiles, I posed the question, “How did medieval artisans create nanoscale and microscale gilding when they couldn’t see it?” I realized afterwards that an answer to that question might be in this December 13, 2017 news item on ScienceDaily,

How sensitive is the human sense of touch? Sensitive enough to feel the difference between surfaces that differ by just a single layer of molecules, a team of researchers at the University of California San Diego has shown.

“This is the greatest tactile sensitivity that has ever been shown in humans,” said Darren Lipomi, a professor of nanoengineering and member of the Center for Wearable Sensors at the UC San Diego Jacobs School of Engineering, who led the interdisciplinary project with V. S. Ramachandran, director of the Center for Brain and Cognition and distinguished professor in the Department of Psychology at UC San Diego.

So perhaps those medieval artisans were able to feel the difference before it could be seen in the textiles they were producing?

Getting back to the matter at hand, a December 13, 2017 University of California at San Diego (UCSD) news release (also on EurekAlert) by Liezel Labios offers more detail about the work,

Humans can easily feel the difference between many everyday surfaces such as glass, metal, wood and plastic. That’s because these surfaces have different textures or draw heat away from the finger at different rates. But UC San Diego researchers wondered, if they kept all these large-scale effects equal and changed only the topmost layer of molecules, could humans still detect the difference using their sense of touch? And if so, how?

Researchers say this fundamental knowledge will be useful for developing electronic skin, prosthetics that can feel, advanced haptic technology for virtual and augmented reality and more.

Unsophisticated haptic technologies exist in the form of rumble packs in video game controllers or smartphones that shake, Lipomi added. “But reproducing realistic tactile sensations is difficult because we don’t yet fully understand the basic ways in which materials interact with the sense of touch.”

“Today’s technologies allow us to see and hear what’s happening, but we can’t feel it,” said Cody Carpenter, a nanoengineering Ph.D. student at UC San Diego and co-first author of the study. “We have state-of-the-art speakers, phones and high-resolution screens that are visually and aurally engaging, but what’s missing is the sense of touch. Adding that ingredient is a driving force behind this work.”

This study is the first to combine materials science and psychophysics to understand how humans perceive touch. “Receptors processing sensations from our skin are phylogenetically the most ancient, but far from being primitive they have had time to evolve extraordinarily subtle strategies for discerning surfaces—whether a lover’s caress or a tickle or the raw tactile feel of metal, wood, paper, etc. This study is one of the first to demonstrate the range of sophistication and exquisite sensitivity of tactile sensations. It paves the way, perhaps, for a whole new approach to tactile psychophysics,” Ramachandran said.

Super-Sensitive Touch

In a paper published in Materials Horizons, UC San Diego researchers tested whether human subjects could distinguish—by dragging or tapping a finger across the surface—between smooth silicon wafers that differed only in their single topmost layer of molecules. One surface was a single oxidized layer made mostly of oxygen atoms. The other was a single Teflon-like layer made of fluorine and carbon atoms. Both surfaces looked identical and felt similar enough that some subjects could not differentiate between them at all.

According to the researchers, human subjects can feel these differences because of a phenomenon known as stick-slip friction, which is the jerking motion that occurs when two objects at rest start to slide against each other. This phenomenon is responsible for the musical notes played by running a wet finger along the rim of a wine glass, the sound of a squeaky door hinge or the noise of a stopping train. In this case, each surface has a different stick-slip frequency due to the identity of the molecules in the topmost layer.

In one test, 15 subjects were tasked with feeling three surfaces and identifying the one surface that differed from the other two. Subjects correctly identified the differences 71 percent of the time.

In another test, subjects were given three different strips of silicon wafer, each strip containing a different sequence of 8 patches of oxidized and Teflon-like surfaces. Each sequence represented an 8-digit string of 0s and 1s, which encoded for a particular letter in the ASCII alphabet. Subjects were asked to “read” these sequences by dragging a finger from one end of the strip to the other and noting which patches in the sequence were the oxidized surfaces and which were the Teflon-like surfaces. In this experiment, 10 out of 11 subjects decoded the bits needed to spell the word “Lab” (with the correct upper and lowercase letters) more than 50 percent of the time. Subjects spent an average of 4.5 minutes to decode each letter.

“A human may be slower than a nanobit per second in terms of reading digital information, but this experiment shows a potentially neat way to do chemical communications using our sense of touch instead of sight,” Lipomi said.

Basic Model of Touch

The researchers also found that these surfaces can be differentiated depending on how fast the finger drags and how much force it applies across the surface. The researchers modeled the touch experiments using a “mock finger,” a finger-like device made of an organic polymer that’s connected by a spring to a force sensor. The mock finger was dragged across the different surfaces using multiple combinations of force and swiping velocity. The researchers plotted the data and found that the surfaces could be distinguished given certain combinations of velocity and force. Meanwhile, other combinations made the surfaces indistinguishable from each other.

“Our results reveal a remarkable human ability to quickly home in on the right combinations of forces and swiping velocities required to feel the difference between these surfaces. They don’t need to reconstruct an entire matrix of data points one by one as we did in our experiments,” Lipomi said.

“It’s also interesting that the mock finger device, which doesn’t have anything resembling the hundreds of nerves in our skin, has just one force sensor and is still able to get the information needed to feel the difference in these surfaces. This tells us it’s not just the mechanoreceptors in the skin, but receptors in the ligaments, knuckles, wrist, elbow and shoulder that could be enabling humans to sense minute differences using touch,” he added.

This work was supported by member companies of the Center for Wearable Sensors at UC San Diego: Samsung, Dexcom, Sabic, Cubic, Qualcomm and Honda.

For those who prefer their news by video,

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

Human ability to discriminate surface chemistry by touch by Cody W. Carpenter, Charles Dhong, Nicholas B. Root, Daniel Rodriquez, Emily E. Abdo, Kyle Skelil, Mohammad A. Alkhadra, Julian Ramírez, Vilayanur S. Ramachandran and Darren J. Lipomi. Mater. Horiz., 2018, Advance Article DOI: 10.1039/C7MH00800G

This paper is open access but you do need to have opened a free account on the website.

Mimicking the sea urchin’s mouth and teeth for space exploration

Researchers at the University of California at San Diego (UCSD) have designed a new device for use in space exploration that is based on the structure and mechanics of a sea urchin’s mouth and teeth. From a May 2, 2016 news item on ScienceDaily,

The sea urchin’s intricate mouth and teeth are the model for a claw-like device developed by a team of engineers and marine biologists at the University of California, San Diego to sample sediments on other planets, such as Mars. The researchers detail their work in a recent issue of the Journal of Visualized Experiments.

A May 2, 2016 UCSD press release (also on EurekAlert), which originated the news item, expands on the theme by hearkening back to Aristotle (a Greek philosopher),

The urchin’s mouthpiece was first described in detail by the Greek philosopher Aristotle, earning it the nickname “Aristotle’s lantern.” It is comprised of an intricate framework of muscles and five curved teeth with triangle-shaped tips that can scrape, cut, chew and bore holes into the toughest rocks—a colony of sea urchins can destroy an entire kelp forest by churning through rock and uprooting seaweed.  The teeth are arranged in a dome-like formation that opens outwards and closes inwards in a smooth motion, similar to a claw in an arcade prize-grabbing machine.

The news release goes on to describe the methodology,

Bio-inspiration for the study came from pink sea urchins (Strongylocentrotus fragilis), which live off the West Coast of North America, at depths ranging from 100 to 1000 meters in the Pacific Ocean. The urchins were collected for scientific research by the Scripps Institution of Oceanography at UC San Diego.

Researchers extracted the urchins’ mouthpieces, scanned them with microCT, essentially a 3D microscopy technique, and analyzed the structures at the National Center for Microscopy and Imaging Research at the School of Medicine at UC San Diego. This allowed engineers to build a highly accurate model of the mouthpiece’s geometry.

Researchers also used finite element analysis to investigate the structure of the teeth, a method that allowed them to determine the importance of the keel to the teeth’s performance.

Engineers then turned the microCT data into a user-friendly file that a team of undergraduate engineering students at UC San Diego used to start iterating prototypes of the claw-like device, under the supervision of Ph.D. students in McKittrick’s lab.

The first iteration was very close to the mouthpiece’s natural structure, but didn’t do a very good job at grasping sand.  In the second iteration, students flattened the pointed end of the teeth so the device would scoop up sand better. But the device wasn’t opening quite right. Finally, on the third iteration, they connected the teeth differently to the rest of the device, which allowed it to open much easier. The students were able to quickly modify each prototype by using 3D printers in the UC San Diego Design Studio.

The device was then attached to a remote-controlled small rover. The researchers first tested the claw on beach sand, where it performed well. They then used the claw on sand that simulates Martian soil in density and humidity (or lack thereof). The device was able to scoop up sand efficiently. Researchers envision a fleet of mini rovers equipped with the claw that could be deployed to collect samples and bring them back to a main rover. Frank hopes that this design will be of interest to NASA [US National Aeronautics and Space Administraton] and SpaceX [a private enterprise for designing, manufacturing, and launching craft bound for space].

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

A Protocol for Bioinspired Design: A Ground Sampler Based on Sea Urchin Jaws by Michael B. Frank, Steven E. Naleway, Taylor S. Wirth, Jae-Young Jung, Charlene L. Cheung, Faviola B. Loera, Sandra Medina, Kirk N. Sato, Jennifer R. A. Taylor, Joanna McKittrick. Journal of Visualized Experiments, 2016; (110) DOI: 10.3791/53554 Date Published: 4/24/2016

This paper and its video are behind a paywall. For those unfamiliar with the Journal of Visualized Experiments (JOVE), it is focused largely on videos which demonstrate the various techniques and protocols being described in the accompanying papers.

The researchers have made an introductory video available courtesy of UCSD,