Tag Archives: Seoul National University

Graphene-based sensor mimics pain (mu-opioid) receptor

I once had a job where I had to perform literature searches and read papers on pain research as it related to morphine tolerance. Not a pleasant task, it has left me eager to encourage and write about alternatives to animal testing, a key component of pain research. So, with a ‘song in my heart’, I feature this research from the University of Pennsylvania written up in a May 12, 2014 news item on ScienceDaily,

Almost every biological process involves sensing the presence of a certain chemical. Finely tuned over millions of years of evolution, the body’s different receptors are shaped to accept certain target chemicals. When they bind, the receptors tell their host cells to produce nerve impulses, regulate metabolism, defend the body against invaders or myriad other actions depending on the cell, receptor and chemical type.

Now, researchers from the University of Pennsylvania have led an effort to create an artificial chemical sensor based on one of the human body’s most important receptors, one that is critical in the action of painkillers and anesthetics. In these devices, the receptors’ activation produces an electrical response rather than a biochemical one, allowing that response to be read out by a computer.

By attaching a modified version of this mu-opioid receptor to strips of graphene, they have shown a way to mass produce devices that could be useful in drug development and a variety of diagnostic tests. And because the mu-opioid receptor belongs to the most common class of such chemical sensors, the findings suggest that the same technique could be applied to detect a wide range of biologically relevant chemicals.

A May 6, 2014 University of Pennsylvania news release, which originated the news item, describes the main teams involved in this research along with why and how they worked together (Note: Links have been removed),

The study, published in the journal Nano Letters, was led by A.T. Charlie Johnson, director of Penn’s Nano/Bio Interface Center and professor of physics in Penn’s School of Arts & Sciences; Renyu Liu, assistant professor of anesthesiology in Penn’s Perelman School of Medicine; and Mitchell Lerner, then a graduate student in Johnson’s lab. It was made possible through a collaboration with Jeffery Saven, professor of chemistry in Penn Arts & Sciences. The Penn team also worked with researchers from the Seoul National University in South Korea.

Their study combines recent advances from several disciplines.

Johnson’s group has extensive experience attaching biological components to nanomaterials for use in chemical detectors. Previous studies have involved wrapping carbon nanotubes with single-stranded DNA to detect odors related to cancer and attaching antibodies to nanotubes to detect the presence of the bacteria associated with Lyme disease.

After Saven and Liu addressed these problems with the redesigned receptor, they saw that it might be useful to Johnson, who had previously published a study on attaching a similar receptor protein to carbon nanotubes. In that case, the protein was difficult to grow genetically, and Johnson and his colleagues also needed to include additional biological structures from the receptors’ natural membranes in order to keep them stable.

In contrast, the computationally redesigned protein could be readily grown and attached directly to graphene, opening up the possibility of mass producing biosensor devices that utilize these receptors.

“Due to the challenges associated with isolating these receptors from their membrane environment without losing functionality,” Liu said, “the traditional methods of studying them involved indirectly investigating the interactions between opioid and the receptor via radioactive or fluorescent labeled ligands, for example. This multi-disciplinary effort overcame those difficulties, enabling us to investigate these interactions directly in a cell free system without the need to label any ligands.”

With Saven and Liu providing a version of the receptor that could stably bind to sheets of graphene, Johnson’s team refined their process of manufacturing those sheets and connecting them to the circuitry necessary to make functional devices.

The news release provides more technical details about the graphene sensor,

“We start by growing a piece of graphene that is about six inches wide by 12 inches long,” Johnson said. “That’s a pretty big piece of graphene, but we don’t work with the whole thing at once. Mitchell Lerner, the lead author of the study, came up with a very clever idea to cut down on chemical contamination. We start with a piece that is about an inch square, then separate them into ribbons that are about 50 microns across.

“The nice thing about these ribbons is that we can put them right on top of the rest of the circuitry, and then go on to attach the receptors. This really reduces the potential for contamination, which is important because contamination greatly degrades the electrical properties we measure.”

Because the mechanism by which the device reports on the presence of the target molecule relies only on the receptor’s proximity to the nanostructure when it binds to the target, Johnson’s team could employ the same chemical technique for attaching the antibodies and other receptors used in earlier studies.

Once attached to the ribbons, the opioid receptors would produce changes in the surrounding graphene’s electrical properties whenever they bound to their target. Those changes would then produce electrical signals that would be transmitted to a computer via neighboring electrodes.

The high reliability of the manufacturing process — only one of the 193 devices on the chip failed — enables applications in both clinical diagnostics and further research. [emphasis mine]

“We can measure each device individually and average the results, which greatly reduces the noise,” said Johnson. “Or you could imagine attaching 10 different kinds of receptors to 20 devices each, all on the same chip, if you wanted to test for multiple chemicals at once.”

In the researchers’ experiment, they tested their devices’ ability to detect the concentration of a single type of molecule. They used naltrexone, a drug used in alcohol and opioid addiction treatment, because it binds to and blocks the natural opioid receptors that produce the narcotic effects patients seek.

“It’s not clear whether the receptors on the devices are as selective as they are in the biological context,” Saven said, “as the ones on your cells can tell the difference between an agonist, like morphine, and an antagonist, like naltrexone, which binds to the receptor but does nothing. By working with the receptor-functionalized graphene devices, however, not only can we make better diagnostic tools, but we can also potentially get a better understanding of how the bimolecular system actually works in the body.”

“Many novel opioids have been developed over the centuries,” Liu said. “However, none of them has achieved potent analgesic effects without notorious side effects, including devastating addiction and respiratory depression. This novel tool could potentially aid the development of new opioids that minimize these side effects.”

Wherever these devices find applications, they are a testament to the potential usefulness of the Nobel-prize winning material they are based on.

“Graphene gives us an advantage,” Johnson said, “in that its uniformity allows us to make 192 devices on a one-inch chip, all at the same time. There are still a number of things we need to work out, but this is definitely a pathway to making these devices in large quantities.”

There is no mention of animal research but it seems likely to me that this work could lead to a decreased use of animals in pain research.

This project must have been quite something as it involved collaboration across many institutions (from the news release),

Also contributing to the study were Gang Hee Han, Sung Ju Hong and Alexander Crook of Penn Arts & Sciences’ Department of Physics and Astronomy; Felipe Matsunaga and Jin Xi of the Department of Anesthesiology at the Perelman School of Medicine, José Manuel Pérez-Aguilar of Penn Arts & Sciences’ Department of Chemistry; and Yung Woo Park of Seoul National University. Mitchell Lerner is now at SPAWAR Systems Center Pacific, Felipe Matsunaga at Albert Einstein College of Medicine, José Manuel Pérez-Aguilar at Cornell University and Sung Ju Hong at Seoul National University.

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

Scalable Production of Highly Sensitive Nanosensors Based on Graphene Functionalized with a Designed G Protein-Coupled Receptor by Mitchell B. Lerner, Felipe Matsunaga, Gang Hee Han, Sung Ju Hong, Jin Xi, Alexander Crook, Jose Manuel Perez-Aguilar, Yung Woo Park, Jeffery G. Saven, Renyu Liu, and A. T. Charlie Johnson.Nano Lett., Article ASAP
DOI: 10.1021/nl5006349 Publication Date (Web): April 17, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Should October 2013 be called ‘the month of graphene’?

Since the Oct. 10-11, 2013 Graphene Flagship (1B Euros investment) launch, mentioned in my preview Oct. 7, 2013 posting, there’ve been a flurry of graphene-themed news items both on this blog and elsewhere and I’ve decided to offer a brief roundup what I’ve found elsewhere.

Dexter Johnson offers a commentary in the pithily titled, Europe Invests €1 Billion to Become “Graphene Valley,” an Oct. 15, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) Note: Links have been removed,

The initiative has been dubbed “The Graphene Flagship,” and apparently it is the first in a number of €1 billion, 10-year plans the EC is planning to launch. The graphene version will bring together 76 academic institutions and industrial groups from 17 European countries, with an initial 30-month-budget of €54M ($73 million).

Graphene research is still struggling to find any kind of applications that will really take hold, and many don’t expect it will have a commercial impact until 2020. What’s more, manufacturing methods are still undeveloped. So it would appear that a 10-year plan is aimed at the academic institutions that form the backbone of this initiative rather than commercial enterprises.

Just from a political standpoint the choice of Chalmers University in Sweden as the base of operations for the Graphene Flagship is an intriguing choice. …

I have to agree with Dexter that choosing Chalmers University over the University of Manchester where graphene was first isolated is unexpected. As a companion piece to reading Dexter’s posting in its entirety and which features a video from the flagship launch, you might want to try this Oct. 15, 2013 article by Koen Mortelmans for Youris (h/t Oct. 15, 2013 news item on Nanowerk),

Andre Konstantin Geim is the only person who ever received both a Nobel and an Ig Nobel. He was born in 1958 in Russia, and is a Dutch-British physicist with German, Polish, Jewish and Ukrainian roots. “Having lived and worked in several European countries, I consider myself European. I don’t believe that any further taxonomy is necessary,” he says. He is now a physics professor at the University of Manchester. …

He shared the Noble [Nobel] Prize in 2010 with Konstantin Novoselov for their work on graphene. It was following on their isolation of microscope visible grapheme flakes that the worldwide research towards practical applications of graphene took off.  “We did not invent graphene,” Geim says, “we only saw what was laid up for five hundred year under our noses.”

Geim and Novoselov are often thought to have succeeded in separating graphene from graphite by peeling it off with ordinary duct tape until there only remained a layer. Graphene could then be observed with a microscope, because of the partial transparency of the material. That is, after dissolving the duct tape material in acetone, of course. That is also the story Geim himself likes to tell.

However, he did not use – as the urban myth goes – graphite from a common pencil. Instead, he used a carbon sample of extreme purity, specially imported. He also used ultrasound techniques. But, probably the urban legend will survive, as did Archimedes’ bath and Newtons apple. “It is nice to keep some of the magic,” is the expression Geim often uses when he does not want a nice story to be drowned in hard facts or when he wants to remain discrete about still incomplete, but promising research results.

Mortelmans’ article fills in some gaps for those not familiar with the graphene ‘origins’ story while Tim Harper’s July 22, 2012 posting on Cientifica’s (an emerging technologies consultancy where Harper is the CEO and founder) TNT blog offers an insight into Geim’s perspective on the race to commercialize graphene with a paraphrased quote for the title of Harper’s posting, “It’s a bit silly for society to throw a little bit of money at (graphene) and expect it to change the world.” (Note: Within this context, mention is made of the company’s graphene opportunities report.)

With all this excitement about graphene (and carbon generally), the magazine titled Carbon has just published a suggested nomenclature for 2D carbon forms such as graphene, graphane, etc., according to an Oct. 16, 2013 news item on Nanowerk (Note: A link has been removed),

There has been an intense research interest in all two-dimensional (2D) forms of carbon since Geim and Novoselov’s discovery of graphene in 2004. But as the number of such publications rise, so does the level of inconsistency in naming the material of interest. The isolated, single-atom-thick sheet universally referred to as “graphene” may have a clear definition, but when referring to related 2D sheet-like or flake-like carbon forms, many authors have simply defined their own terms to describe their product.

This has led to confusion within the literature, where terms are multiply-defined, or incorrectly used. The Editorial Board of Carbon has therefore published the first recommended nomenclature for 2D carbon forms (“All in the graphene family – A recommended nomenclature for two-dimensional carbon materials”).

This proposed nomenclature comes in the form of an editorial, from Carbon (Volume 65, December 2013, Pages 1–6),

All in the graphene family – A recommended nomenclature for two-dimensional carbon materials

  • Alberto Bianco
    CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique, Strasbourg, France
  • Hui-Ming Cheng
    Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016, China
  • Toshiaki Enoki
    Department of Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan
  • Yury Gogotsi
    Materials Science and Engineering Department, A.J. Drexel Nanotechnology Institute, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA
  • Robert H. Hurt
    Institute for Molecular and Nanoscale Innovation, School of Engineering, Brown University, Providence, RI 02912, USA
  • Nikhil Koratkar
    Department of Mechanical, Aerospace and Nuclear Engineering, The Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
  • Takashi Kyotani
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
  • Marc Monthioux
    Centre d’Elaboration des Matériaux et d’Etudes Structurales (CEMES), UPR-8011 CNRS, Université de Toulouse, 29 Rue Jeanne Marvig, F-31055 Toulouse, France
  • Chong Rae Park
    Carbon Nanomaterials Design Laboratory, Global Research Laboratory, Research Institute of Advanced Materials, Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea
  • Juan M.D. Tascon
    Instituto Nacional del Carbón, INCAR-CSIC, Apartado 73, 33080 Oviedo, Spain
  • Jin Zhang
    Center for Nanochemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

This editorial is behind a paywall.

Psychedelic illustration for a nanobioelectronic tongue

A human tongue-like nanobioelectronic tongue. Illustration of the hTAS2R38-fucntionalized carboxylated polypyrrole nanotube. (Image: Dr. Park, Seoul National University)

A human tongue-like nanobioelectronic tongue. Illustration of the hTAS2R38-fucntionalized carboxylated polypyrrole nanotube. (Image: Dr. Park, Seoul National University)

This illustration accompanies a Dec. 14, 2012 Nanowerk Spotlight article by Michael Berger about the development of a nanobioelectronic tongue by Korean researchers (Note: I have removed links),

The concept of e-noses – electronic devices which mimic the olfactory systems of mammals and insects – is very intriguing to researchers involved in building better, cheaper and smaller sensor devices (read more: “Nanotechnology electronic noses”). Less well known is the fact that equivalent artificial sensors for taste – electronic tongues – are capable of recognizing dissolved substances (see for instance: “Electronic tongue identifies cava wines”).

“Even with current technological advances, e-tongue approaches still cannot mimic the biological features of the human tongue with regard to identifying elusive analytes in complex mixtures, such as food and beverage products,” Tai Hyun Park, a professor in the School of Chemical and Biological Engineering at Seoul National University, tells Nanowerk.

Park, together with Professor Jyongsik Jang and their collaborators, have now developed a human bitter-taste receptor as a nanobioelectronic tongue.

The team worked with a protein to develop the ‘tongue’,

The nanobioelectronic tongue uses a human taste receptor as a recognition element and a conducting polymer nanotube field effect transistor (FET) sensor as a sensor platform. Specifically, the Korean team functionalized carboxylated polypyrrole nanotubes with the human bitter taste receptor protein hTAS2R38. They say that the fabricated device could detect target bitter tastants with a detection limit of 1 femtomole and high selectivity.

“In the case of bitter taste, our nanobioelectronic tongue can be used for sensing quantitatively the bitter taste, for example, of coffee, chocolate drinks, drugs and oriental medicines,” says Park. “Our nanobioelectronic tongue can be used as an alternative to time-consuming and labor-intensive sensory evaluations and cell-based assays for the assessment of quality, tastant screening and basic research on the human taste system.”

Prachi Patel’s ??? 2012 article about the research for Chemical and Engineering News (C&EN) provides more technical details about the testing,

The researchers tested their device’s response to four bitter compounds: phenylthiocarbamide, propylthiouracil, goitrin, and isothiocyanate. When these compounds bound to the protein-coated nanotubes, the researchers noted, the current through the transistors changed. For solutions of phenylthiocarbamide and propylthiouracil in buffer, the researchers could detect concentrations of 1 and 10 femtomolar, respectively. The device could sense goitrin and isothiocyanate, which are found in cruciferous vegetables, at picomolar concentrations in samples taken from vegetables such as cabbage, broccoli, and kale.

The team also tested the sensor’s response to mixtures of bitter, sweet, and umami (or savory) flavor molecules. The device responded only when the bitter compounds were present in the mixtures, even at femtomolar concentrations. Park says that the researchers are now trying to make sensors for sweet and umami tastes by using human taste receptors that respond to those flavors.

Here’s a citation (not an official one) and a link to the researchers’ paper,

Human Taste Receptor-Functionalized Field Effect Transistor as a Human-Like Nanobioelectronic Tongue by Hyun Seok Song, Oh Seok Kwon, Sang Hun Lee, Seon Joo Park, Un-Kyung Kim, Jyongsik Jang, and Tai Hyun Park in Nano Lett., Article ASAP DOI: 10.1021/nl3038147 Publication Date (Web): November 26, 2012 Copyright © 2012 American Chemical Society

Access to the full article is behind a paywall.

Asia’s research effort in nano-, bio-, and information technology integrated in Asian Research Network

The Feb. 29, 2012 news item by Cameron Chai on Azonano spells it out,

An Asian Research Network (ARN) has been formed by the Hanyang University of Korea and RIKEN of Japan in collaboration with other institutes and universities in Asia. This network has been launched to reinforce a strong education and research collaboration throughout Asia.

The Asian Research Network website is here. You will need to use your scroll bars as it appears to be partially constructed (or maybe my system is so creaky that I just can’t see everything on the page). Towards the bottom (right side) of the home page,there are a couple of red buttons for PDFs of the ARN Pamphlet and Research Articles.

From page 2 of the ARN pamphlet, here’s a listing of the member organizations,

KOREA

Hanyang University
Samsung Electronics
Electronics and Telecommunication Research Institute
Seoul National University
Institute of Pasteur Korea
Korea Research Institute of Chemical Technology
Korea Advanced Nano Fab Center

JAPAN

RIKEN

INDIA

National Chemical Laboratory
Shivaji University
Indian Institutes of Science Education and Research
Pune University
Indian Institute of Technology-Madras (In Progress)
Indian Institute of Science (In Progress)

USA

University of Texas at Dallas
UCLA (In Progress)
f d i i ( )

CHINA

National Center for Nanoscience and Technology
Peking University

SINGAPORE

National University of Singapore
Nanyang Technological University (In Progress)
Stanford University In Progress)
University of Maryland (In Progress)

ISRAEL

Weizmann Institute of Science (In Progress)
Hebrew University Jerusalem

THAILAND

National Science and Technology Development Agency (In Progress)

I was a little surprised to see Israel on the list and on an even more insular note, why no Canada?

Getting back to the ARN, here are their aims, from page 2 of the ARN pamphlet,

We are committed to fostering talented human resources, creating a research network in which researchers in the region share their knowledge and experiences, and establishing a future-oriented partnership to globalize our research capabilities. To this end, we will achieve excellence in all aspects of education, research, and development in the area of fusion research between BT [biotechnology] and IT [information technology] based on NT [nanotechnology] in general. We will make a substantial contribution to the betterment of the global community as well as the Asian society.

I look forward to hearing more from them in the future.