Tag Archives: Karl Deisseroth

The sense of touch via artificial skin

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.

Nanotechnology and the US mega science project: BAM (Brain Activity Map) and more

The Brain Activity Map (BAM) project received budgetary approval as of this morning, Apr. 2, 2013 (I first mentioned BAM in my Mar. 4, 2013 posting when approval seemed imminent). From the news item, Obama Announces Huge Brain-Mapping Project, written by Stephanie Pappas for Yahoo News (Note: Links have been removed),

 President Barack Obama announced a new research initiative this morning (April 2) to map the human brain, a project that will launch with $100 million in funding in 2014.

The Brain Activity Map (BAM) project, as it is called, has been in the planning stages for some time. In the June 2012 issue of the journal Neuron, six scientists outlined broad proposals for developing non-invasive sensors and methods to experiment on single cells in neural networks. This February, President Obama made a vague reference to the project in his State of the Union address, mentioning that it could “unlock the answers to Alzheimer’s.”

In March, the project’s visionaries outlined their final goals in the journal Science. They call for an extended effort, lasting several years, to develop tools for monitoring up to a million neurons at a time. The end goal is to understand how brain networks function.

“It could enable neuroscience to really get to the nitty-gritty of brain circuits, which is the piece that’s been missing from the puzzle,” Rafael Yuste, the co-director of the Kavli Institute for Brain Circuits at Columbia University, who is part of the group spearheading the project, told LiveScience in March. “The reason it’s been missing is because we haven’t had the techniques, the tools.” [Inside the Brain: A Journey Through Time]

Not all neuroscientists support the project, however, with some arguing that it lacks clear goals and may cannibalize funds for other brain research.


I believe the $100M mentioned for 2014 would one installment in a series totaling up to $1B or more. In any event, it seems like a timely moment to comment on the communications campaign that has been waged on behalf of the BAM. It reminds me a little of the campaign for graphene, which was waged in the build up to the decision as to which two projects (in a field of six semi-finalists, then narrowed to a field of four finalists) should receive a FET (European Union’s Future and Emerging Technology) 1 billion euro research prize each. It seemed to me even a year or so before the decision that graphene’s win was a foregone conclusion but the organizers left nothing to chance and were relentless in their pursuit of attention and media coverage in the buildup to the final decision.

The most recent salvo in the BAM campaign was an attempt to link it with nanotechnology. A shrewd move given that the US has spent well over $1B since the US National Nanotechnology Initiative (NNI) was first approved in 2000. Linking the two projects means the NNI can lend a little authority to the new project (subtext: we’ve supported a mega-project before and that was successful) while the new project BAM can imbue the ageing NNI with some excitement.

Here’s more about nanotechnology and BAM from a Mar. 27, 2013 Spotlight article by Michael Berger on Nanowerk,

A comprehensive understanding of the brain remains an elusive, distant frontier. To arrive at a general theory of brain function would be an historic event, comparable to inferring quantum theory from huge sets of complex spectra and inferring evolutionary theory from vast biological field work. You might have heard about the proposed Brain Activity Map – a project that, like the Human Genome Project, will tap the hive mind of experts to make headway in the understanding of the field. Engineers and nanotechnologists will be needed to help build ever smaller devices for measuring the activity of individual neurons and, later, to control how those neurons function. Computer scientists will be called upon to develop methods for storing and analyzing the vast quantities of imaging and physiological data, and for creating virtual models for studying brain function. Neuroscientists will provide critical biological expertise to guide the research and interpret the results.

Berger goes on to highlight some of the ways nanotechnology-enabled devices could contribute to the effort. He draws heavily on a study published Mar. 20, 2013 online in ACS (American Chemical Society)Nano. Shockingly, the article is open access. Given that this is the first time I’ve come across an open access article in any of the American Chemical Society’s journals, I suspect that there was payment of some kind involved to make this information freely available. (The practice of allowing researchers to pay more in order to guarantee open access to their research in journals that also have articles behind paywalls seems to be in the process of becoming more common.)

Here’s a citation and a link to the article about nanotechnology and BAM,

Nanotools for Neuroscience and Brain Activity Mapping by A. Paul Alivisatos, Anne M. Andrews, Edward S. Boyden, Miyoung Chun, George M. Church, Karl Deisseroth, John P. Donoghue, Scott E. Fraser, Jennifer Lippincott-Schwartz, Loren L. Looger, Sotiris Masmanidis, Paul L. McEuen, Arto V. Nurmikko, Hongkun Park, Darcy S. Peterka, Clay Reid, Michael L. Roukes, Axel Scherer, Mark Schnitzer, Terrence J. Sejnowski, Kenneth L. Shepard, Doris Tsao, Gina Turrigiano, Paul S. Weiss, Chris Xu, Rafael Yuste, and Xiaowei Zhuang. ACS Nano, 2013, 7 (3), pp 1850–1866 DOI: 10.1021/nn4012847 Publication Date (Web): March 20, 2013
Copyright © 2013 American Chemical Society

As these things go, it’s a readable article for people without a neuroscience education provided they don’t mind feeling a little confused from time to time. From Nanotools for Neuroscience and Brain Activity Mapping (Note: Footnotes and links removed),

The Brain Activity Mapping (BAM) Project (…) has three goals in terms of building tools for neuroscience capable of (…) measuring the activity of large sets of neurons in complex brain circuits, (…) computationally analyzing and modeling these brain circuits, and (…) testing these models by manipulating the activities of chosen sets of neurons in these brain circuits.

As described below, many different approaches can, and likely will, be taken to achieve these goals as neural circuits of increasing size and complexity are studied and probed.

The BAM project will focus both on dynamic voltage activity and on chemical neurotransmission. With an estimated 85 billion neurons, 100 trillion synapses, and 100 chemical neurotransmitters in the human brain,(…) this is a daunting task. Thus, the BAM project will start with model organisms, neural circuits (vide infra), and small subsets of specific neural circuits in humans.

Among the approaches that show promise for the required dynamic, parallel measurements are optical and electro-optical methods that can be used to sense neural cell activity such as Ca2+,(7) voltage,(…) and (already some) neurotransmitters;(…) electrophysiological approaches that sense voltages and some electrochemically active neurotransmitters;(…) next-generation photonics-based probes with multifunctional capabilities;(18) synthetic biology approaches for recording histories of function;(…) and nanoelectronic measurements of voltage and local brain chemistry.(…) We anticipate that tools developed will also be applied to glia and more broadly to nanoscale and microscale monitoring of metabolic processes.

Entirely new tools will ultimately be required both to study neurons and neural circuits with minimal perturbation and to study the human brain. These tools might include “smart”, active nanoscale devices embedded within the brain that report on neural circuit activity wirelessly and/or entirely new modalities of remote sensing of neural circuit dynamics from outside the body. Remarkable advances in nanoscience and nanotechnology thus have key roles to play in transduction, reporting, power, and communications.

One of the ultimate goals of the BAM project is that the knowledge acquired and tools developed will prove useful in the intervention and treatment of a wide variety of diseases of the brain, including depression, epilepsy, Parkinson’s, schizophrenia, and others. We note that tens of thousands of patients have already been treated with invasive (i.e., through the skull) treatments. [emphases mine] While we hope to reduce the need for such measures, greatly improved and more robust interfaces to the brain would impact effectiveness and longevity where such treatments remain necessary.

Perhaps not so coincidentally, there was this Mar. 29, 2013 news item on Nanowerk,

Some human cells forget to empty their trash bins, and when the garbage piles up, it can lead to Parkinson’s disease and other genetic and age-related disorders. Scientists don’t yet understand why this happens, and Rice University engineering researcher Laura Segatori is hoping to change that, thanks to a prestigious five-year CAREER Award from the National Science Foundation (NSF).

Segatori, Rice’s T.N. Law Assistant Professor of Chemical and Biomolecular Engineering and assistant professor of bioengineering and of biochemistry and cell biology, will use her CAREER grant to create a toolkit for probing the workings of the cellular processes that lead to accumulation of waste material and development of diseases, such as Parkinson’s and lysosomal storage disorders. Each tool in the kit will be a nanoparticle — a speck of matter about the size of a virus — with a specific shape, size and charge.  [emphases mine] By tailoring each of these properties, Segatori’s team will create a series of specialized probes that can undercover the workings of a cellular process called autophagy.

“Eventually, once we understand how to design a nanoparticle to activate autophagy, we will use it as a tool to learn more about the autophagic process itself because there are still many question marks in biology regarding how this pathway works,” Segatori said. “It’s not completely clear how it is regulated. It seems that excessive autophagy may activate cell death, but it’s not yet clear. In short, we are looking for more than therapeutic applications. We are also hoping to use these nanoparticles as tools to study the basic science of autophagy.”

There is no direct reference to BAM but there are some intriguing correspondences.

Finally, there is no mention of nanotechnology in this radio broadcast/podcast and transcript but it does provide more information about BAM (for many folks this was first time they’d heard about the project) and the hopes and concerns this project raises while linking it to the Human Genome Project. From the Mar. 31, 2013 posting of a transcript and radio (Kera News; a National Public Radio station) podcast titled, Somewhere Over the Rainbow: The Journey to Map the Human Brain,

During the State of the Union, President Obama said the nation is about to embark on an ambitious project: to examine the human brain and create a road map to the trillions of connections that make it work.

“Every dollar we invested to map the human genome returned $140 to our economy — every dollar,” the president said. “Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s.”

Details of the project have slowly been leaking out: $3 billion, 10 years of research and hundreds of scientists. The National Institutes of Health is calling it the Brain Activity Map.

Obama isn’t the first to tout the benefits of a huge government science project. But can these projects really deliver? And what is mapping the human brain really going to get us?

Whether one wants to call it a public relations campaign or a marketing campaign is irrelevant. Science does not take place in an environment where data and projects are considered dispassionately. Enormous amounts of money are spent to sway public opinion and policymakers’ decisions.

ETA Ap. 3, 2013: Here are more stories about BAM and the announcement:

BRAIN Initiative Launched to Unlock Mysteries of Human Mind

Obama’s BRAIN Only 1/13 The Size Of Europe’s

BRAIN Initiative Builds on Efforts of Leading Neuroscientists and Nanotechnologists