Tag Archives: brain

Body-on-a-chip (10 organs)

Also known as human-on-a-chip, the 10-organ body-on-a-chip was being discussed at the 9th World Congress on Alternatives to Animal Testing in the Life Sciences in 2014 in Prague, Czech Republic (see this July 1, 2015 posting for more). At the time, scientists were predicting success at achieving their goal of 10 organs on-a-chip in 2017 (the best at the time was four organs). Only a few months past that deadline, scientists from the Massachusetts Institute of Technology (MIT) seem to have announced a ’10 organ chip’ in a March 14, 2018 news item on ScienceDaily,

MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.

Such a system could reveal, for example, whether a drug that is intended to treat one organ will have adverse effects on another.

A March 14, 2018 MIT news release (also on EurekAlert), which originated the news item, expands on the theme,

“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation, a professor of biological engineering and mechanical engineering, and one of the senior authors of the study. “With our chip, you can distribute a drug and then look for the effects on other tissues, and measure the exposure and how it is metabolized.”

These chips could also be used to evaluate antibody drugs and other immunotherapies, which are difficult to test thoroughly in animals because they are designed to interact with the human immune system.

David Trumper, an MIT professor of mechanical engineering, and Murat Cirit, a research scientist in the Department of Biological Engineering, are also senior authors of the paper, which appears in the journal Scientific Reports. The paper’s lead authors are former MIT postdocs Collin Edington and Wen Li Kelly Chen.

Modeling organs

When developing a new drug, researchers identify drug targets based on what they know about the biology of the disease, and then create compounds that affect those targets. Preclinical testing in animals can offer information about a drug’s safety and effectiveness before human testing begins, but those tests may not reveal potential side effects, Griffith says. Furthermore, drugs that work in animals often fail in human trials.

“Animals do not represent people in all the facets that you need to develop drugs and understand disease,” Griffith says. “That is becoming more and more apparent as we look across all kinds of drugs.”

Complications can also arise due to variability among individual patients, including their genetic background, environmental influences, lifestyles, and other drugs they may be taking. “A lot of the time you don’t see problems with a drug, particularly something that might be widely prescribed, until it goes on the market,” Griffith says.

As part of a project spearheaded by the Defense Advanced Research Projects Agency (DARPA), Griffith and her colleagues decided to pursue a technology that they call a “physiome on a chip,” which they believe could offer a way to model potential drug effects more accurately and rapidly. To achieve this, the researchers needed new equipment — a platform that would allow tissues to grow and interact with each other — as well as engineered tissue that would accurately mimic the functions of human organs.

Before this project was launched, no one had succeeded in connecting more than a few different tissue types on a platform. Furthermore, most researchers working on this kind of chip were working with closed microfluidic systems, which allow fluid to flow in and out but do not offer an easy way to manipulate what is happening inside the chip. These systems also require external pumps.

The MIT team decided to create an open system, which essentially removes the lid and makes it easier to manipulate the system and remove samples for analysis. Their system, adapted from technology they previously developed and commercialized through U.K.-based CN BioInnovations, also incorporates several on-board pumps that can control the flow of liquid between the “organs,” replicating the circulation of blood, immune cells, and proteins through the human body. The pumps also allow larger engineered tissues, for example tumors within an organ, to be evaluated.

Complex interactions

The researchers created several versions of their chip, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each “organ” consists of clusters of 1 million to 2 million cells. These tissues don’t replicate the entire organ, but they do perform many of its important functions. Significantly, most of the tissues come directly from patient samples rather than from cell lines that have been developed for lab use. These so-called “primary cells” are more difficult to work with but offer a more representative model of organ function, Griffith says.

Using this system, the researchers showed that they could deliver a drug to the gastrointestinal tissue, mimicking oral ingestion of a drug, and then observe as the drug was transported to other tissues and metabolized. They could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down. In a related publication, the researchers modeled how drugs can cause unexpected stress on the liver by making the gastrointestinal tract “leaky,” allowing bacteria to enter the bloodstream and produce inflammation in the liver.

Kevin Healy, a professor of bioengineering and materials science and engineering at the University of California at Berkeley, says that this kind of system holds great potential for accurate prediction of complex adverse drug reactions.

“While microphysiological systems (MPS) featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitro pharmacology. This study beautifully illustrates that multi-MPS “physiome-on-a-chip” approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” says Healy, who was not involved in the research.

Griffith believes that the most immediate applications for this technology involve modeling two to four organs. Her lab is now developing a model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue, which she plans to use to investigate the hypothesis that bacteria found in the gut can influence the development of Parkinson’s disease.

Other applications include modeling tumors that metastasize to other parts of the body, she says.

“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Griffith says. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.”

The research was funded by the U.S. Army Research Office and DARPA.

Caption: MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body. Credit: Felice Frankel

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

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies by Collin D. Edington, Wen Li Kelly Chen, Emily Geishecker, Timothy Kassis, Luis R. Soenksen, Brij M. Bhushan, Duncan Freake, Jared Kirschner, Christian Maass, Nikolaos Tsamandouras, Jorge Valdez, Christi D. Cook, Tom Parent, Stephen Snyder, Jiajie Yu, Emily Suter, Michael Shockley, Jason Velazquez, Jeremy J. Velazquez, Linda Stockdale, Julia P. Papps, Iris Lee, Nicholas Vann, Mario Gamboa, Matthew E. LaBarge, Zhe Zhong, Xin Wang, Laurie A. Boyer, Douglas A. Lauffenburger, Rebecca L. Carrier, Catherine Communal, Steven R. Tannenbaum, Cynthia L. Stokes, David J. Hughes, Gaurav Rohatgi, David L. Trumper, Murat Cirit, Linda G. Griffith. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-22749-0 Published online:

This paper which describes testing for four-, seven-, and ten-organs-on-a-chip, is open access. From the paper’s Discussion,

In summary, we have demonstrated a generalizable approach to linking MPSs [microphysiological systems] within a fluidic platform to create a physiome-on-a-chip approach capable of generating complex molecular distribution profiles for advanced drug discovery applications. This adaptable, reusable system has unique and complementary advantages to existing microfluidic and PDMS-based approaches, especially for applications involving high logD substances (drugs and hormones), those requiring precise and flexible control over inter-MPS flow partitioning and drug distribution, and those requiring long-term (weeks) culture with reliable fluidic and sampling operation. We anticipate this platform can be applied to a wide range of problems in disease modeling and pre-clinical drug development, especially for tractable lower-order (2–4) interactions.

Congratulations to the researchers!

A 3D printed eye cornea and a 3D printed copy of your brain (also: a Brad Pitt connection)

Sometimes it’s hard to keep up with 3D tissue printing news. I have two news bits, one concerning eyes and another concerning brains.

3D printed human corneas

A May 29, 2018 news item on ScienceDaily trumpets the news,

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today [May 29, 2018] in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Here are the proud researchers with their cornea,

Caption: Dr. Steve Swioklo and Professor Che Connon with a dyed cornea. Credit: Newcastle University, UK

A May 30,2018 Newcastle University press release (also on EurekAlert but published on May 29, 2018), which originated the news item, adds more details,

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture – or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

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

3D bioprinting of a corneal stroma equivalent by Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research Volume 173, August 2018, Pages 188–193 and 2018 May 14 pii: S0014-4835(18)30212-4. doi: 10.1016/j.exer.2018.05.010. [Epub ahead of print]

This paper is behind a paywall.

A 3D printed copy of your brain

I love the title for this May 30, 2018 Wyss Institute for Biologically Inspired Engineering news release: Creating piece of mind by Lindsay Brownell (also on EurekAlert),

What if you could hold a physical model of your own brain in your hands, accurate down to its every unique fold? That’s just a normal part of life for Steven Keating, Ph.D., who had a baseball-sized tumor removed from his brain at age 26 while he was a graduate student in the MIT Media Lab’s Mediated Matter group. Curious to see what his brain actually looked like before the tumor was removed, and with the goal of better understanding his diagnosis and treatment options, Keating collected his medical data and began 3D printing his MRI [magnetic resonance imaging] and CT [computed tomography] scans, but was frustrated that existing methods were prohibitively time-intensive, cumbersome, and failed to accurately reveal important features of interest. Keating reached out to some of his group’s collaborators, including members of the Wyss Institute at Harvard University, who were exploring a new method for 3D printing biological samples.

“It never occurred to us to use this approach for human anatomy until Steve came to us and said, ‘Guys, here’s my data, what can we do?” says Ahmed Hosny, who was a Research Fellow with at the Wyss Institute at the time and is now a machine learning engineer at the Dana-Farber Cancer Institute. The result of that impromptu collaboration – which grew to involve James Weaver, Ph.D., Senior Research Scientist at the Wyss Institute; Neri Oxman, [emphasis mine] Ph.D., Director of the MIT Media Lab’s Mediated Matter group and Associate Professor of Media Arts and Sciences; and a team of researchers and physicians at several other academic and medical centers in the US and Germany – is a new technique that allows images from MRI, CT, and other medical scans to be easily and quickly converted into physical models with unprecedented detail. The research is reported in 3D Printing and Additive Manufacturing.

“I nearly jumped out of my chair when I saw what this technology is able to do,” says Beth Ripley, M.D. Ph.D., an Assistant Professor of Radiology at the University of Washington and clinical radiologist at the Seattle VA, and co-author of the paper. “It creates exquisitely detailed 3D-printed medical models with a fraction of the manual labor currently required, making 3D printing more accessible to the medical field as a tool for research and diagnosis.”

Imaging technologies like MRI and CT scans produce high-resolution images as a series of “slices” that reveal the details of structures inside the human body, making them an invaluable resource for evaluating and diagnosing medical conditions. Most 3D printers build physical models in a layer-by-layer process, so feeding them layers of medical images to create a solid structure is an obvious synergy between the two technologies.

However, there is a problem: MRI and CT scans produce images with so much detail that the object(s) of interest need to be isolated from surrounding tissue and converted into surface meshes in order to be printed. This is achieved via either a very time-intensive process called “segmentation” where a radiologist manually traces the desired object on every single image slice (sometimes hundreds of images for a single sample), or an automatic “thresholding” process in which a computer program quickly converts areas that contain grayscale pixels into either solid black or solid white pixels, based on a shade of gray that is chosen to be the threshold between black and white. However, medical imaging data sets often contain objects that are irregularly shaped and lack clear, well-defined borders; as a result, auto-thresholding (or even manual segmentation) often over- or under-exaggerates the size of a feature of interest and washes out critical detail.

The new method described by the paper’s authors gives medical professionals the best of both worlds, offering a fast and highly accurate method for converting complex images into a format that can be easily 3D printed. The key lies in printing with dithered bitmaps, a digital file format in which each pixel of a grayscale image is converted into a series of black and white pixels, and the density of the black pixels is what defines the different shades of gray rather than the pixels themselves varying in color.

Similar to the way images in black-and-white newsprint use varying sizes of black ink dots to convey shading, the more black pixels that are present in a given area, the darker it appears. By simplifying all pixels from various shades of gray into a mixture of black or white pixels, dithered bitmaps allow a 3D printer to print complex medical images using two different materials that preserve all the subtle variations of the original data with much greater accuracy and speed.

The team of researchers used bitmap-based 3D printing to create models of Keating’s brain and tumor that faithfully preserved all of the gradations of detail present in the raw MRI data down to a resolution that is on par with what the human eye can distinguish from about 9-10 inches away. Using this same approach, they were also able to print a variable stiffness model of a human heart valve using different materials for the valve tissue versus the mineral plaques that had formed within the valve, resulting in a model that exhibited mechanical property gradients and provided new insights into the actual effects of the plaques on valve function.

“Our approach not only allows for high levels of detail to be preserved and printed into medical models, but it also saves a tremendous amount of time and money,” says Weaver, who is the corresponding author of the paper. “Manually segmenting a CT scan of a healthy human foot, with all its internal bone structure, bone marrow, tendons, muscles, soft tissue, and skin, for example, can take more than 30 hours, even by a trained professional – we were able to do it in less than an hour.”

The researchers hope that their method will help make 3D printing a more viable tool for routine exams and diagnoses, patient education, and understanding the human body. “Right now, it’s just too expensive for hospitals to employ a team of specialists to go in and hand-segment image data sets for 3D printing, except in extremely high-risk or high-profile cases. We’re hoping to change that,” says Hosny.

In order for that to happen, some entrenched elements of the medical field need to change as well. Most patients’ data are compressed to save space on hospital servers, so it’s often difficult to get the raw MRI or CT scan files needed for high-resolution 3D printing. Additionally, the team’s research was facilitated through a joint collaboration with leading 3D printer manufacturer Stratasys, which allowed access to their 3D printer’s intrinsic bitmap printing capabilities. New software packages also still need to be developed to better leverage these capabilities and make them more accessible to medical professionals.

Despite these hurdles, the researchers are confident that their achievements present a significant value to the medical community. “I imagine that sometime within the next 5 years, the day could come when any patient that goes into a doctor’s office for a routine or non-routine CT or MRI scan will be able to get a 3D-printed model of their patient-specific data within a few days,” says Weaver.

Keating, who has become a passionate advocate of efforts to enable patients to access their own medical data, still 3D prints his MRI scans to see how his skull is healing post-surgery and check on his brain to make sure his tumor isn’t coming back. “The ability to understand what’s happening inside of you, to actually hold it in your hands and see the effects of treatment, is incredibly empowering,” he says.

“Curiosity is one of the biggest drivers of innovation and change for the greater good, especially when it involves exploring questions across disciplines and institutions. The Wyss Institute is proud to be a space where this kind of cross-field innovation can flourish,” says Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Here’s an image illustrating the work,

Caption: This 3D-printed model of Steven Keating’s skull and brain clearly shows his brain tumor and other fine details thanks to the new data processing method pioneered by the study’s authors. Credit: Wyss Institute at Harvard University

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

From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets by Ahmed Hosny , Steven J. Keating, Joshua D. Dilley, Beth Ripley, Tatiana Kelil, Steve Pieper, Dominik Kolb, Christoph Bader, Anne-Marie Pobloth, Molly Griffin, Reza Nezafat, Georg Duda, Ennio A. Chiocca, James R.. Stone, James S. Michaelson, Mason N. Dean, Neri Oxman, and James C. Weaver. 3D Printing and Additive Manufacturing http://doi.org/10.1089/3dp.2017.0140 Online Ahead of Print:May 29, 2018

This paper appears to be open access.

A tangential Brad Pitt connection

It’s a bit of Hollywood gossip. There was some speculation in April 2018 that Brad Pitt was dating Dr. Neri Oxman highlighted in the Wyss Institute news release. Here’s a sample of an April 13, 2018 posting on Laineygossip (Note: A link has been removed),

It took him a long time to date, but he is now,” the insider tells PEOPLE. “He likes women who challenge him in every way, especially in the intellect department. Brad has seen how happy and different Amal has made his friend (George Clooney). It has given him something to think about.”

While a Pitt source has maintained he and Oxman are “just friends,” they’ve met up a few times since the fall and the insider notes Pitt has been flying frequently to the East Coast. He dropped by one of Oxman’s classes last fall and was spotted at MIT again a few weeks ago.

Pitt and Oxman got to know each other through an architecture project at MIT, where she works as a professor of media arts and sciences at the school’s Media Lab. Pitt has always been interested in architecture and founded the Make It Right Foundation, which builds affordable and environmentally friendly homes in New Orleans for people in need.

“One of the things Brad has said all along is that he wants to do more architecture and design work,” another source says. “He loves this, has found the furniture design and New Orleans developing work fulfilling, and knows he has a talent for it.”

It’s only been a week since Page Six first broke the news that Brad and Dr Oxman have been spending time together.

I’m fascinated by Oxman’s (and her colleagues’) furniture. Rose Brook writes about one particular Oxman piece in her March 27, 2014 posting for TCT magazine (Note: Links have been removed),

MIT Professor and 3D printing forerunner Neri Oxman has unveiled her striking acoustic chaise longue, which was made using Stratasys 3D printing technology.

Oxman collaborated with Professor W Craig Carter and Composer and fellow MIT Professor Tod Machover to explore material properties and their spatial arrangement to form the acoustic piece.

Christened Gemini, the two-part chaise was produced using a Stratasys Objet500 Connex3 multi-colour, multi-material 3D printer as well as traditional furniture-making techniques and it will be on display at the Vocal Vibrations exhibition at Le Laboratoire in Paris from March 28th 2014.

An Architect, Designer and Professor of Media, Arts and Science at MIT, Oxman’s creation aims to convey the relationship of twins in the womb through material properties and their arrangement. It was made using both subtractive and additive manufacturing and is part of Oxman’s ongoing exploration of what Stratasys’ ground-breaking multi-colour, multi-material 3D printer can do.

Brook goes on to explain how the chaise was made and the inspiration that led to it. Finally, it’s interesting to note that Oxman was working with Stratasys in 2014 and that this 2018 brain project is being developed in a joint collaboration with Statasys.

That’s it for 3D printing today.

Accelerated healing of the tissue in the blood-brain barrier with gelatin

It’s been a few years since my last brain and gelatin story (Dec. 24, 2014 posting: Gelatin nanoparticles for drug delivery after stroke) and this time they’re trying to make brain surgery easier and to reduce any attendant brain damage according to a Nov. 6, 2017 news item on ScienceDaily,

Researchers already know that gelatin-covered electrode implants cause less damage to brain tissue than electrodes with no gelatin coating. Researchers at the Neuronano Research Centre (NRC) at Lund University in Sweden have now shown that microglia, the brain’s cleansing cells, and the enzymes that the cells use in the cleaning process, change in the presence of gelatin.

“Knowledge about the beneficial effects of gelatin could be significant for brain surgery, but also in the development of brain implants,” say the researchers behind the study.

Our brains are surrounded by a blood brain barrier which protects the brain from harmful substances that could enter it via the bloodstream. When the barrier is penetrated, as in the case of biopsy or brain surgery for example, leaks can occur and cause serious inflammation. Researchers at the NRC have previously shown that gelatin accelerates brain tissue healing and reduces damage to nerve cells in the case of electrode implants, but only now are they starting to understand how.

A November 6, 2017 Lund University press release, which originated the news item, provides more details,

The researchers used sedated rats to investigate how the brain is repaired after an injury. Gelatin-coated needles were used in one group, and needles without gelatin in the other.

“The use of gelatin-coated needles reduced or eliminated the leakage of molecules (which normally don’t get through) through the blood brain barrier within twenty-four hours. Without gelatin, the leakage continued for up to three days”, says Lucas Kumosa, one of the researchers behind the study, which was recently published in the research journal Acta Biomaterialia.

Gelatin

The images in the left-hand column show the healing of an injury caused by a stainless steel needle. The images in the right-hand column show what the process looked like when the researchers used a gelatin-coated needle. Gelatin accelerated the healing process and reduced the leakage of blood-borne molecules capable of passing through the blood brain barrier into the brain and causing inflammation.

FEWER INFLAMMATORY CLEANING CELLS

When there is an injury to the brain, microglial cells – the brain’s cleaning cells – gather at the site. They clean up, but can also damage the nerve cell tissue through enzymes they release. In their study, the researchers observed a change in which cleaning cells moved towards the injury site.

“When we used gelatin, we saw only a small number of the inflammatory microglial cells. Instead, we observed cells of a different kind, that are anti-inflammatory, which we believe could be significant in accelerating healing”, explains Lucas Kumosa.

The hypothesis is that the potentially damaging enzymes are occupied with the gelatin instead.

“Gelatin is a protein and its decomposition releases amino-acids that we believe could promote the reconstruction of blood vessels and tissue”, explains Jens Schouenborg, professor of neurophysiology at Lund University.

SURGICAL SIGNIFICANCE

Research is currently underway on how electrodes implanted in the brain could be used in the treatment of various diseases, such as epilepsy or Parkinson’s. A major challenge has been to find ways of reducing damage to the area when using such implants.

“Although the research field of brain electrodes is promising, it has been a challenge to find solutions that don’t damage the brain tissue. Knowledge of how injuries heal faster with gelatin could therefore be significant for the development of surgical treatment as well,” says Jens Schouenborg.

The research is funded by the Knut and Alice Wallenberg Foundation, the Swedish Research Council, Lund University and the Sven-Olof Jansons livsverk Foundation.

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

Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury by Lucas S. Kumosa, Valdemar Zetterberg, Jens Schouenborg. Acta Biomaterialia https://doi.org/10.1016/j.actbio.2017.10.020 Available online 14 October 2017

This paper is open access.

Mott memristor

Mott memristors (mentioned in my Aug. 24, 2017 posting about neuristors and brainlike computing) gets more fulsome treatment in an Oct. 9, 2017 posting by Samuel K. Moore on the Nanoclast blog (found on the IEEE [Institute of Electrical and Electronics Engineers] website) Note: 1: Links have been removed; Note 2 : I quite like Moore’s writing style but he’s not for the impatient reader,

When you’re really harried, you probably feel like your head is brimful of chaos. You’re pretty close. Neuroscientists say your brain operates in a regime termed the “edge of chaos,” and it’s actually a good thing. It’s a state that allows for fast, efficient analog computation of the kind that can solve problems that grow vastly more difficult as they become bigger in size.

The trouble is, if you’re trying to replicate that kind of chaotic computation with electronics, you need an element that both acts chaotically—how and when you want it to—and could scale up to form a big system.

“No one had been able to show chaotic dynamics in a single scalable electronic device,” says Suhas Kumar, a researcher at Hewlett Packard Labs, in Palo Alto, Calif. Until now, that is.

He, John Paul Strachan, and R. Stanley Williams recently reported in the journal Nature that a particular configuration of a certain type of memristor contains that seed of controlled chaos. What’s more, when they simulated wiring these up into a type of circuit called a Hopfield neural network, the circuit was capable of solving a ridiculously difficult problem—1,000 instances of the traveling salesman problem—at a rate of 10 trillion operations per second per watt.

(It’s not an apples-to-apples comparison, but the world’s most powerful supercomputer as of June 2017 managed 93,015 trillion floating point operations per second but consumed 15 megawatts doing it. So about 6 billion operations per second per watt.)

The device in question is called a Mott memristor. Memristors generally are devices that hold a memory, in the form of resistance, of the current that has flowed through them. The most familiar type is called resistive RAM (or ReRAM or RRAM, depending on who’s asking). Mott memristors have an added ability in that they can also reflect a temperature-driven change in resistance.

The HP Labs team made their memristor from an 8-nanometer-thick layer of niobium dioxide (NbO2) sandwiched between two layers of titanium nitride. The bottom titanium nitride layer was in the form of a 70-nanometer wide pillar. “We showed that this type of memristor can generate chaotic and nonchaotic signals,” says Williams, who invented the memristor based on theory by Leon Chua.

(The traveling salesman problem is one of these. In it, the salesman must find the shortest route that lets him visit all of his customers’ cities, without going through any of them twice. It’s a difficult problem because it becomes exponentially more difficult to solve with each city you add.)

Here’s what the niobium dioxide-based Mott memristor looks like,

Photo: Suhas Kumar/Hewlett Packard Labs
A micrograph shows the construction of a Mott memristor composed of an 8-nanometer-thick layer of niobium dioxide between two layers of titanium nitride.

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

Chaotic dynamics in nanoscale NbO2 Mott memristors for analogue computing by Suhas Kumar, John Paul Strachan & R. Stanley Williams. Nature 548, 318–321 (17 August 2017) doi:10.1038/nature23307 Published online: 09 August 2017

This paper is behind a paywall.

Narrating neuroscience in Toronto (Canada) on Oct. 20, 2017 and knitting a neuron

What is it with the Canadian neuroscience community? First, there’s The Beautiful Brain an exhibition of the extraordinary drawings of Santiago Ramón y Cajal (1852–1934) at the Belkin Gallery on the University of British Columbia (UBC) campus in Vancouver and a series of events marking the exhibition (for more see my Sept. 11, 2017 posting ; scroll down about 30% for information about the drawings and the events still to come).

I guess there must be some money floating around for raising public awareness because now there’s a neuroscience and ‘storytelling’ event (Narrating Neuroscience) in Toronto, Canada. From a Sept. 25, 2017 ArtSci Salon announcement (received via email),

With NARRATING NEUROSCIENCE we plan to initiate a discussion on the  role and the use of storytelling and art (both in verbal and visual  forms) to communicate abstract and complex concepts in neuroscience to  very different audiences, ranging from fellow scientists, clinicians and patients, to social scientists and the general public. We invited four guests to share their research through case studies and experiences stemming directly from their research or from other practices they have adopted and incorporated into their research, where storytelling and the arts have played a crucial role not only in communicating cutting edge research in neuroscience, but also in developing and advancing it.

OUR GUESTS

MATTEO FARINELLA, PhD, Presidential Scholar in Society and Neuroscience – Columbia University

SHELLEY WALL , AOCAD, MSc, PhD – Assistant professor, Biomedical Communications Graduate Program and Department of Biology, UTM

ALFONSO FASANO, MD, PhD, Associate Professor – University of Toronto Clinician Investigator – Krembil Research Institute Movement Disorders Centre – Toronto Western Hospital

TAHANI BAAKDHAH, MD, MSc, PhD candidate – University of Toronto

DATE: October 20, 2017
TIME: 6:00-8:00 pm
LOCATION: The Fields Institute for Research in Mathematical Sciences
222 College Street, Toronto, ON

Events Facilitators: Roberta Buiani and Stephen Morris (ArtSci Salon) and Nina Czegledy (Leonardo Network)

TAHANI BAAKDHAH is a PhD student at the University of Toronto studying how the stem cells built our retina during development, the mechanism by which the light sensing cells inside the eye enable us to see this beautiful world and how we can regenerate these cells in case of disease or injury.

MATTEO FARINELLA combines a background in neuroscience with a lifelong passion for drawing, making comics and illustrations about the brain. He is the author of _Neurocomic_ (Nobrow 2013) published with the support of the Wellcome Trust, _Cervellopoli_ (Editoriale Scienza 2017) and he has collaborated with universities and educational institutions around
the world to make science more clear and accessible. In 2016 Matteo joined Columbia University as a Presidential Scholar in Society and Neuroscience, where he investigates the role of visual narratives in science communication. Working with science journalists, educators and cognitive neuroscientists he aims to understand how these tools may
affect the public perception of science and increase scientific literacy (cartoonscience.org [2]).

ALFONSO FASANO graduated from the Catholic University of Rome, Italy, in 2002 and became a neurologist in 2007. After a 2-year fellowship at the University of Kiel, Germany, he completed a PhD in neuroscience at the Catholic University of Rome. In 2013 he joined the Movement Disorder Centre at Toronto Western Hospital, where he is the co-director of the
surgical program for movement disorders. He is also an associate professor of medicine in the Division of Neurology at the University of Toronto and clinician investigator at the Krembil Research Institute. Dr. Fasano’s main areas of interest are the treatment of movement  disorders with advanced technology (infusion pumps and neuromodulation), pathophysiology and treatment of tremor and gait disorders. He is author of more than 170 papers and book chapters. He is principal investigator of several clinical trials.

SHELLEY WALL is an assistant professor in the University of Toronto’s Biomedical Communications graduate program, a certified medical illustrator, and inaugural Illustrator-in-Residence in the Faculty of Medicine, University of Toronto. One of her primary areas of research, teaching, and creation is graphic medicine—the intersection of comics with illness, medicine, and caregiving—and one of her ongoing projects is a series of comics about caregiving and young onset Parkinson’s disease.

You can register for this free Toronto event here.

One brief observation, there aren’t any writers (other than academics) or storytellers included in this ‘storytelling’ event. The ‘storytelling’ being featured is visual. To be blunt I’m not of the ‘one picture is worth a thousand words’ school of thinking (see my Feb. 22, 2011 posting). Yes, sometimes pictures are all you need but that tiresome aphorism which suggests  communication can be reduced to one means of communication really needs to be retired. As for academic writing, it’s not noted for its storytelling qualities or experimentation. Academics are not judged on their writing or storytelling skills although there are some who are very good.

Getting back to the Toronto event, they seem to have the visual part of their focus  ” … discussion on the  role and the use of storytelling and art (both in verbal and visual  forms) … ” covered. Having recently attended a somewhat similar event in Vancouver, which was announced n my Sept. 11, 2017 posting, there were some exciting images and ideas presented.

The ArtSci Salon folks also announced this (from the Sept. 25, 2017 ArtSci Salon announcement; received via email),

ATTENTION ARTSCI SALONISTAS AND FANS OF ART AND SCIENCE!!
CALL FOR KNITTING AND CROCHET LOVERS!

In addition to being a PhD student at the University of Toronto, Tahani Baakdhah is a prolific knitter and crocheter and has been the motor behind two successful Knit-a-Neuron Toronto initiatives. We invite all Knitters and Crocheters among our ArtSci Salonistas to pick a pattern
(link below) and knit a neuron (or 2! Or as many as you want!!)

http://bit.ly/2y05hRR

BRING THEM TO OUR OCTOBER 20 ARTSCI SALON!
Come to the ArtSci Salon and knit there!
You can’t come?
Share a picture with @ArtSci_Salon @SciCommTO #KnitANeuronTO [3] on
social media
Or…Drop us a line at artscisalon@gmail.com !

I think it’s been a few years since my last science knitting post. No, it was Oct. 18, 2016. Moving on, I found more neuron knitting while researching this piece. Here’s the Neural Knitworks group, which is part of Australia’s National Science Week (11-19 August 2018) initiative (from the Neural Knitworks webpage),

Neural Knitworks is a collaborative project about mind and brain health.

Whether you’re a whiz with yarn, or just discovering the joy of craft, now you can crochet wrap, knit or knot—and find out about neuroscience.

During 2014 an enormous number of handmade neurons were donated (1665 in total!) and used to build a giant walk-in brain, as seen here at Hazelhurst Gallery [scroll to end of this post]. Since then Neural Knitworks have been held in dozens of communities across Australia, with installations created in Queensland, the ACT, Singapore, as part of the Cambridge Science Festival in the UK and in Philadelphia, USA.

In 2017, the Neural Knitworks team again invites you to host your own home-grown Neural Knitwork for National Science Week*. Together we’ll create a giant ‘virtual’ neural network by linking your displays visually online.

* If you wish to host a Neural Knitwork event outside of National Science Week or internationally we ask that you contact us to seek permission to use the material, particularly if you intend to create derivative works or would like to exhibit the giant brain. Please outline your plans in an email.

Your creation can be big or small, part of a formal display, or simply consist of neighbourhood neuron ‘yarn-bombings’. Knitworks can be created at home, at work or at school. No knitting experience is required and all ages can participate.

See below for how to register your event and download our scientifically informed patterns.

What is a neuron?

Neurons are electrically excitable cells of the brain, spinal cord and peripheral nerves. The billions of neurons in your body connect to each other in neural networks. They receive signals from every sense, control movement, create memories, and form the neural basis of every thought.

Check out the neuron microscopy gallery for some real-world inspiration.

What happens at a Neural Knitwork?

Neural Knitworks are based on the principle that yarn craft, with its mental challenges, social connection and mindfulness, helps keep our brains and minds sharp, engaged and healthy.

Have fun as you

  • design your own woolly neurons, or get inspired by our scientifically-informed knitting, crochet or knot patterns;
  • natter with neuroscientists and teach them a few of your crafty tricks;
  • contribute to a travelling textile brain exhibition;
  • increase your attention span and test your memory.

Calm your mind and craft your own brain health as you

  • forge friendships;
  • solve creative and mental challenges;
  • practice mindfulness and relaxation;
  • teach and learn;
  • develop eye-hand coordination and fine motor dexterity.

Interested in hosting a Neural Knitwork?

  1. Log your event on the National Science Week calendar to take advantage of multi-channel promotion.
  2. Share the link^ for this Neural Knitwork page on your own website or online newsletter and add information your own event details.
  3. Use this flyer template (2.5 MB .docx) to promote your event in local shop windows and on noticeboards.
  4. Read our event organisers toolbox for tips on hosting a successful event.
  5. You’ll need plenty of yarn, needles, copies of our scientifically-based neuron crafting pattern books (3.4 MB PDF) and a comfy spot in which to create.
  6. Gather together a group of friends who knit, crochet, design, spin, weave and anyone keen to give it a go. Those who know how to knit can teach others how to do it, and there’s even an easy no knit pattern that you can knot.
  7. Download a neuroscience podcast to listen to, and you’ve got a Neural Knitwork!
  8. Join the Neural Knitworks community on Facebook  to share and find information about events including public talks featuring neuroscientists.
  9. Tweet #neuralknitworks to show us your creations.
  10. Find display ideas in the pattern book and on our Facebook page.

Finally,, the knitted neurons from Australia’s 2014 National Science Week brain exhibit,

[downloaded from https://www.scienceweek.net.au/neural-knitworks/]

ETA Oct. 24, 2017: If you’re interested on how the talk was received, there’s an Oct. 24, 2017 posting by Magosia Pakulska for the Research2Reality blog.

Locusts inspire new aerosol-based nanoparticle drug delivery system

Getting medication directly to the brain is a worldwide medical research goal and it seems that a team of scientists at the Washington University at St. Louis (WUSTL) has taken a step forward to accomplishing the goal. From an April 12, 2017 news item on ScienceDaily,

Delivering life-saving drugs directly to the brain in a safe and effective way is a challenge for medical providers. One key reason: the blood-brain barrier, which protects the brain from tissue-specific drug delivery. Methods such as an injection or a pill aren’t as precise or immediate as doctors might prefer, and ensuring delivery right to the brain often requires invasive, risky techniques.

A team of engineers from Washington University in St. Louis has developed a new nanoparticle generation-delivery method that could someday vastly improve drug delivery to the brain, making it as simple as a sniff.

“This would be a nanoparticle nasal spray, and the delivery system could allow a therapeutic dose of medicine to reach the brain within 30 minutes to one hour,” said Ramesh Raliya, research scientist at the School of Engineering & Applied Science.

Caption: Engineers at Washington University have discovered a new technique that could change drug delivery to the brain. They were able to apply a nanoparticle aerosol spray to the antenna of locusts, then track the nanoparticles as they traveled through the olfactory nerves, crossed the blood-brain barrier and accumulated in the brain. This new, non-invasive approach could someday make drug delivery as simple as a sniff for patients with brain injuries or tumors.

Credit: Washington University in St. Louis

An April 12, 2017 WUSTL news release by Erika Ebsworth-Goold (also on EurekAlert), which originated the news item, describes the work in more detail,

“The blood-brain barrier protects the brain from foreign substances in the blood that may injure the brain,” Raliya said. “But when we need to deliver something there, getting through that barrier is difficult and invasive. Our non-invasive technique can deliver drugs via nanoparticles, so there’s less risk and better response times.”

The novel approach is based on aerosol science and engineering principles that allow the generation of monodisperse nanoparticles, which can deposit on upper regions of the nasal cavity via diffusion. Working with Assistant Vice Chancellor Pratim Biswas, chair of the Department of Energy, Environmental & Chemical Engineering and the Lucy & Stanley Lopata Professor, Raliya developed an aerosol consisting of gold nanoparticles of controlled size, shape and surface charge. The nanoparticles were tagged with fluorescent markers, allowing the researchers to track their movement.

Next, Raliya and biomedical engineering postdoctoral fellow Debajit Saha exposed locusts’ antennae to the aerosol, and observed the nanoparticles travel from the antennas up through the olfactory nerves. Due to their tiny size, the nanoparticles passed through the brain-blood barrier, reaching the brain and suffusing it in a matter of minutes.

The team tested the concept in locusts because the blood-brain barriers in the insects and humans have anatomical similarities, and the researchers consider going through the nasal regions to neural pathways as the optimal way to access the brain.

“The shortest and possibly the easiest path to the brain is through your nose,” said Barani Raman, associate professor of biomedical engineering. “Your nose, the olfactory bulb and then olfactory cortex: two relays and you’ve reached the cortex. The same is true for invertebrate olfactory circuitry, although the latter is a relatively simpler system, with supraesophageal ganglion instead of an olfactory bulb and cortex.”

To determine whether or not the foreign nanoparticles disrupted normal brain function, Saha examined the physiological response of olfactory neurons in the locusts before and after the nanoparticle delivery. Several hours after the nanoparticle uptake, no noticeable change in the electrophysiological responses was detected.

“This is only a beginning of a cool set of studies that can be performed to make nanoparticle-based drug delivery approaches more principled,” Raman said.

The next phase of research involves fusing the gold nanoparticles with various medicines, and using ultrasound to target a more precise dose to specific areas of the brain, which would be especially beneficial in brain-tumor cases.

“We want to drug target delivery within the brain using this non-invasive approach,” Raliya said.  “In the case of a brain tumor, we hope to use focused ultrasound so we can guide the particles to collect at that particular point.”

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

Non-invasive aerosol delivery and transport of gold nanoparticles to the brain by Ramesh Raliya, Debajit Saha, Tandeep S. Chadha, Baranidharan Raman, & Pratim Biswas. Scientific Reports 7, Article number: 44718 (2017) doi:10.1038/srep44718 Published online: 16 March 2017

This paper is open access.

I featured another team working on delivering drugs directly to the brain via the olfactory system, except their nanoparticles were gelatin and they were testing stroke medication on rats, in my Sept. 24, 2014 posting.

Poetry and the brain

It seems poetry goes deep into the brain. A Feb. 17, 2017 news item on ScienceDaily describes some blended poetry/brain research,

In 1932 T.S. Eliot famously argued, “Genuine poetry can communicate before it is understood.”

In a recent article published in the journal Frontiers in Psychology, Professor Guillaume Thierry and colleagues at Bangor University [Maine, US] have demonstrated that we do indeed appear to have an unconscious appreciation of poetic construction.

A Feb. 20, 2017 Frontiers (publications) blog posting, which despite the publication date appears to have originated the news item, provides more detail,

“Poetry,” explains Professor Thierry “is a particular type of literary expression that conveys feelings, thoughts and ideas by accentuating metric constraints, rhyme and alliteration.”

However, can we appreciate the musical sound of poetry independent of its literary meaning?

To address this question the authors created sentence sample sets that either conformed or violated poetic construction rules of Cynghanedd — a traditional form of Welsh poetry. These sentences were randomly presented to study participants; all of whom were native welsh speakers but had no prior knowledge of Cynghanedd poetic form.

Initially participants were asked to rate sentences as either “good” or “not good” depending on whether or not they found them aesthetically pleasing to the ear. The study revealed that the participants’ brains implicitly categorized Cyngahanedd-orthodox sentences as sounding “good” compared to sentences violating its construction rules.

The authors also mapped Event-Related Brain Potential (ERP) in participants a fraction of a second after they heard the final word in a poetic construction. These elegant results reveal an electrophysiological response in the brain when participants were exposed to consonantal repetition and stress patterns that are characteristic of Cynghanedd, but not when such patterns were violated.

Interestingly the positive responses from the brain to Cynghanedd were present even though participants could not explicitly tell which of the sentences were correct and which featured errors of rhythm or sound repetitions.

Professor Thierry concludes, “It is the first time that we show unconscious processing of poetic constructs by the brain, and of course, it is extremely exciting to think that one can inspire the human mind without being noticed!”

So when you read a poem, if you feel something special but you cannot really pinpoint what it is, make no mistake, your brain loves it even if you don’t really know why.

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

Implicit Detection of Poetic Harmony by the Naïve Brain by Awel Vaughan-Evans, Robat Trefor, Llion Jones, Peredur Lynch, Manon W. Jones, and Guillaume Thierry. Front. Psychol., 25 November 2016 | https://doi.org/10.3389/fpsyg.2016.01859

This paper has been published in an open access. journal.

While I appreciate the enthusiasm, I think it might be better to do more research before making grand statements about poetry and the brain. For example, are they positive these native Welsh speakers had never ever encountered the poetic form being studied? Would a French or Farsi or Mandarin or Russian or … speaker respond the same way to a poem from their own poetic traditions? Is the effect cross cultural? Does a translation make a difference? Are there only certain poetic forms that create the effect?  I look forward to hearing more about this research in the years to come.

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

Electrochemical measurements of biomolecules

This work comes from Finland and features some new nano shapes. From a Nov. 10, 2016 news item on phys.org,

Tomi Laurila’s research topic has many quirky names.

“Nanodiamond, nanohorn, nano-onion…,” lists off the Aalto University Professor, recounting the many nano-shapes of carbon. Laurila is using these shapes to build new materials: tiny sensors, only a few hundred nanometres across, that can achieve great things due to their special characteristics.

For one, the sensors can be used to enhance the treatment of neurological conditions. That is why Laurila, University of Helsinki Professor Tomi Taira and experts from HUS (the Hospital District of Helsinki and Uusimaa) are looking for ways to use the sensors for taking electrochemical measurements of biomolecules. Biomolecules are e.g. neurotransmitters such as glutamate, dopamine and opioids, which are used by nerve cells to communicate with each other.

A Nov. 10, 2016 Aalto University press release, which originated the news item, expands on the theme,

Most of the drugs meant for treating neurological diseases change the communication between nerve cells that is based on neurotransmitters. If we had real time and individual information on the operation of the neurotransmitter system, it would make it much easier to for example plan precise treatments’, explains Taira.

Due to their small size, carbon sensors can be taken directly next to a nerve cell, where the sensors will report what kind of neurotransmitter the cell is emitting and what kind of reaction it is inducing in other cells.

‘In practice, we are measuring the electrons that are moving in oxidation and reduction reactions’, Laurila explains the operating principle of the sensors.

‘The advantage of the sensors developed by Tomi and the others is their speed and small size. The probes used in current measurement methods can be compared to logs on a cellular scale – it’s impossible to use them and get an idea of the brain’s dynamic’, summarizes Taira.

Feedback system and memory traces

For the sensors, the journey from in vitro tests conducted in glass dishes and test tubes to in vivo tests and clinical use is long. However, the researchers are highly motivated.

‘About 165 million people are suffering from various neurological diseases in Europe alone. And because they are so expensive to treat, neurological diseases make up as much as 80 per cent of health care costs’, tells Taira.

Tomi Laurila believes that carbon sensors will have applications in fields such as optogenetics. Optogenetics is a recently developed method where a light-sensitive molecule is brought into a nerve cell so that the cell’s electric operation can then be turned on or off by stimulating it with light. A few years ago, a group of scientists proved in the scientific journal Nature that they had managed to use optogenetics to activate a memory trace that had been created previously due to learning. Using the same technique, researchers were able to demonstrate that with a certain type of Alzheimer’s, the problem is not that there are no memory traces being created, but that the brain cannot read the traces.

‘So the traces exist, and they can be activated by boosting them with light stimuli’, explains Taira but stresses that a clinical application is not yet a reality. However, clinical applications for other conditions may be closer by. One example is Parkinson’s disease. In Parkinson’s disease, the amount of dopamine starts to decrease in the cells of a particular brain section, which causes the typical symptoms such as tremors, rigidity and slowness of movement. With the sensors, the level of dopamine could be monitored in real time.

‘A sort of feedback system could be connected to it, so that it would react by giving an electric or optical stimulus to the cells, which would in turn release more dopamine’, envisions Taira.

‘Another application that would have an immediate clinical use is monitoring unconscious and comatose patients. With these patients, the level of glutamate fluctuates very much, and too much glutamate damages the nerve cell – online monitoring would therefore improve their treatment significantly.

Atom by atom

Manufacturing carbon sensors is definitely not a mass production process; it is slow and meticulous handiwork.

‘At this stage, the sensors are practically being built atom by atom’, summarises Tomi Laurila.

‘Luckily, we have many experts on carbon materials of our own. For example, the nanobuds of Professor Esko Kauppinen and the carbon films of Professor Jari Koskinen help with the manufacturing of the sensors. Carbon-based materials are mainly very compatible with the human body, but there is still little information about them. That’s why a big part of the work is to go through the electrochemical characterisation that has been done on different forms of carbon.’

The sensors are being developed and tested by experts from various fields, such as chemistry, materials science, modelling, medicine and imaging. Twenty or so articles have been published on the basic properties of the materials. Now, the challenge is to build them into geometries that are functional in a physiological environment. And taking measurements is not simple, either.

‘Brain tissue is delicate and doesn’t appreciate having objects being inserted in it. But if this were easy, someone would’ve already done it’, conclude the two.

I wish the researchers good luck.