Tag Archives: biomarkers

A new graphene-based contrast agent for magnetic resonance imaging (MRI)

After teaching a continuing studies course on bioelectronics for Simon Fraser University (Vancouver, Canada), I’ve developed a mild interest in magnetic resonance imaging and contrast agents which this Nov. 11, 2016 news item on phys.org satisfies,

Graphene, the atomically thin sheets of carbon that materials scientists are hoping to use for everything from nanoelectronics and aircraft de-icers to batteries and bone implants, may also find use as contrast agents for magnetic resonance imaging (MRI), according to new research from Rice University.

“They have a lot of advantages compared with conventionally available contrast agents,” Rice researcher Sruthi Radhakrishnan said of the graphene-based quantum dots she has studied for the past two years. “Virtually all of the widely used contrast agents contain toxic metals, but our material has no metal. It’s just carbon, hydrogen, oxygen and fluorine, and in all of our tests so far it has shown no signs of toxicity.”

The initial findings for Rice’s nanoparticles—disks of graphene that are decorated with fluorine atoms and simply organic molecules that make them magnetic—are described in a new paper in the journal Particle and Particle Systems characterization.

A Nov. 10, 2016 Rice University (Texas, US) news release, which originated the news item, describes the work in more detail,

Pulickel Ajayan, the Rice materials scientist who is directing the work, said the fluorinated graphene oxide quantum dots could be particularly useful as MRI contrast agents because they could be targeted to specific kinds of tissues.

“There are tried-and-true methods for attaching biomarkers to carbon nanoparticles, so one could easily envision using these quantum dots to develop tissue-specific contrast agents,” Ajayan said. “For example, this method could be used to selectively target specific types of cancer or brain lesions caused by Alzheimer’s disease. That kind of specificity isn’t available with today’s contrast agents.”

MRI scanners make images of the body’s internal structures using strong magnetic fields and radio waves. As diagnostic tests, MRIs often provide greater detail than X-rays without the harmful radiation, and as a result, MRI usage has risen sharply over the past decade. More than 30 million MRIs are performed annually in the U.S.

Radhakrishnan said her work began in 2014 after Ajayan’s research team found that adding fluorine to either graphite or graphene caused the materials to show up well on MRI scans.

All materials are influenced by magnetic fields, including animal tissues. In MRI scanners, a powerful magnetic field causes individual atoms throughout the body to become magnetically aligned. A pulse of radio energy is used to disrupt this alignment, and the machine measures how long it takes for the atoms in different parts of the body to become realigned. Based on these measures, the scanner can build up a detailed image of the body’s internal structures.

MRI contrast agents shorten the amount of time it takes for tissues to realign and significantly improve the resolution of MRI scans. Almost all commercially available contrast agents are made from toxic metals like gadolinium, iron or manganese.

“We worked with a team from MD Anderson Cancer Center to assess the cytocompatibility of fluorinated graphene oxide quantum dots,” Radhakrishnan said. “We used a test that measures the metabolic activity of cell cultures and detects toxicity as a drop in metabolic activity. We incubated quantum dots in kidney cell cultures for up to three days and found no significant cell death in the cultures, even at the highest concentrations.”

The fluorinated graphene oxide quantum dots Radhakrishnan studies can be made in less than a day, but she spent two years perfecting the recipe for them. She begins with micron-sized sheets of graphene that have been fluorinated and oxidized. When these are added to a solvent and stirred for several hours, they break into smaller pieces. Making the material smaller is not difficult, but the process for making small particles with the appropriate magnetic properties is exacting. Radhakrishnan said there was no “eureka moment” in which she suddenly achieved the right results by stumbling on the best formula. Rather, the project was marked by incremental improvements through dozens of minor alterations.

“It required a lot of optimization,” she said. “The recipe matters a lot.”

Radhakrishnan said she plans to continue studying the material and hopes to eventually have a hand in proving that it is safe and effective for clinical MRI tests.

“I would like to see it applied commercially in clinical ways because it has a lot of advantages compared with conventionally available agents,” she said.

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

Metal-Free Dual Modal Contrast Agents Based on Fluorographene Quantum Dots by Sruthi Radhakrishnan, Atanu Samanta, Parambath M. Sudeep, Kiersten L. Maldonado, Sendurai A. Mani, Ghanashyam Acharya, Chandra Sekhar Tiwary, Abhishek K. Singh, and Pulickel M. Ajayan. Particle & Particle Systems Characterization DOI: 10.1002/ppsc.201600221 Version of Record online: 21 OCT 2016

This paper is behind a paywall.

Nano-Bio Manufacturing Consortium’s request for proposals (RFPs) on human performance monitoring platforms

The requested human performance monitor platform RFPs are for a US Air Force Research Laboratory (AFRL) project being managed by the Nano-Bio Manufacturing Consortium (NBMC), according to a July 17, 2013 news item on Nanowerk,

The Nano-Bio Manufacturing Consortium (NBMC) has released its first Request for Proposals (RFP) focused on developing a technology platform for Human Performance Monitors for military and civilian personnel in high stress situations such as pilots, special operations personnel, firefighters, and trauma care providers. Organized by FlexTech Alliance under a grant from the U.S. Air Force Research Laboratory (AFRL) the RFP comes only 3 month since the group officially formed its technical and leadership teams. The consortium members, working with AFRL, issued this RFP to focus on component development and integration for a lightweight, low-cost, conformal and wearable patch.

The July 17, 2013 NBMC news release, which originated the news item, offers more about this patch/monitor,

The heart of this new patch will be a biosensor device to measure chemicals, called biomarkers, in human sweat.  These biomarkers can provide early warnings of performance issues such as stress, fatigue, vigilance or organ damage.  The platform will contain the sensor, a microfluidic system that delivers sweat to the sensor, printed and hybrid control electronics, interconnects, a power supply, wireless communication, and software – all on a flexible substrate that is comfortable to wear.

“An aircraft has numerous sensors which take over 1500 measurements per second to monitor its condition in flight, whereas the most critical part – the pilot – has no monitors,” Malcolm Thompson, chief executive officer of NBMC stated.  “We are working quickly and efficiently to coordinate the expertise being generated at an array of companies, government labs and academic centers.  NBMC’s goal is to establish this technology chain to more rapidly develop products and manufacturing approaches for the Air Force and commercial markets.”

I gather the reasoning is that we should be able to monitor human beings just as we do equipment and machines.

The news release also offers information about the consortium partners,

Initial consortium membership includes a wide range of organizations.  Fortune 500 technology leaders include General Electric, Lockheed Martin, and DuPont Teijin Films.  More entrepreneurial organizations include PARC (a Xerox Company), MC 10, Soligie, American Semiconductor, Brewer Science and UES.  They are joined by the Air Force Research Laboratory and university leaders such as Cornell University, University of Massachusetts Amherst Center for Hierarchical Manufacturing, University of Arizona Center for Integrative Medicine, UC San Diego, University of Cincinnati, Binghamton University, Johns Hopkins University, Northeastern University NSF Nanoscale Science and Engineering Center for High-rate Nano-manufacturing, and Arizona State University.

The NBMC solicitation was posted July 10, 2013 on this page,


Request for Proposals Issued: July 10th, 2013

Proposals Due Date: August 9th, 2013 – 5:00 PM PDT

You can find the 9pp RFP here.

I’ve decided to include this description of the thinking that underlies the consortium, from the NBMC Nano-Bio Manufacturing webpage,

The field of nano-biotechnology is advancing rapidly, with many important discoveries and potential applications being identified.  Much of this work is taking place in academia and advanced research labs around the globe.  Once an application is identified, however, the road is still long to making it available to the markets in need.  One of the final steps on that road is understanding how to manufacture in high volume and the lowest cost.  Often this is the defining decision on whether the product even gets to that market.

With new nano-bio technology solutions, the challenges to produce in volume at low-cost are entirely new to many in the field.  New materials, new substrates, new equipment, and unknown properties are just a few of the hurdles that no one organization has been able to overcome.

To address these challenges, FlexTech Alliance, in collaboration with a nationwide group of partners, has formed a Nano-Bio Manufacturing Consortium (NBMC) for the U.S. Air Force Research Laboratory (AFRL). The mission of this partnership is to bring together leading scientists, engineers, and business development professionals from industry and universities in order to work collaboratively in a consortium, and to mature an integrated suite of nano-bio manufacturing technologies to transition to industrial manufacturing.

Initial activities focus on AFRL/ DoD priorities, e.g., physiological readiness and human performance monitoring. Specifically, NBMC matures nano-bio manufacturing technologies to create an integrated suite of reconfigurable and digitized fabrication methods that are compatible with biological and nanoparticle materials and to transition thin film, mechanically compliant device concepts through a foundry-like manufacturing flow.

The long-term vision is that NBMC operates at the confluence of four core emerging disciplines: nanotechnology, biotechnology, advanced (additive) manufacturing, and flexible electronics. The convergence of these disparate fields enables advanced sensor architectures for real-time, remote physiological and health/medical monitoring.

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It seems to me that human beings are increasingly being viewed as just another piece of equipment.

Nature of Things’ The Nano Revolution part 2: More than Human

More than Human (the episode can be seen here), part of 2 of a special Nature of Things series, The Nano Revolution, was aired by the Canadian Broadcasting Corporation on Oct. 20, 2011; one might be forgiven for thinking this episode concerned robots but that wasn’t the case.  The focus was on nanomedicine, specifically cancer and aging, along with a few scenarios hinting at social impacts of the ‘new’ medicine.

This episode, like the last one (Welcome to Nano City), presents the science in an understandable fashion without overexplaining basic concepts. A skill I much appreciate since watching a video of an engineer explain at length that the eye has a cornea and a retina to an audience of adults who were attending a talk about retinal implants.

More coherent than the first one, (Welcome to Nano City reviewed in my Oct. 17, 2011 posting), which featured three topics (one was totally unrelated to any city) both episodes,  convey excitement about the possibilities being suggested by nanotechnology.

As for this episode, More than human, it certainly told a compelling story of a future where there will be no cancer (or it will be easily treated if it does occur) and we won’t age as we can make perfect tissues to replace whatever has been broken. There were also hints of a few social issues as illustrated by future oriented vignettes interspersed through the programme.

I want to c0mmend the script writer for pulling together a story using disparate materials and videos (which I’m guessing are being repurposed, i.e., created for broadcast elsewhere and reused here). Given the broad range of nanomedicine research worldwide, this was a very difficult job.

Featured at some length was Dr. Chad Mirkin at Northwestern University. Here’s a description from Mirkin’s profile page on the Mirkin Group webspace,

Professor Mirkin is a chemist and a world renowned nanoscience expert, who is known for his development of nanoparticle-based biodetection schemes, the invention of Dip-Pen Nanolithography, and contributions to supramolecular chemistry, nanoelectronics, and nanooptics. [emphasis mine] He is the author of over 430 manuscripts and over 370 patents and applications, and the founder of three companies, Nanosphere, NanoInk, and Aurasense which are commercializing nanotechnology applications in the life science and semiconductor industries. Currently, he is listed as the most cited (based on total citations) chemist in the world with the second highest impact factor and the top most cited nanomedicine researcher in the world. At present, he is a member of President Obama’s Council of Advisors for Science and Technology.

Mirkin talked extensively about his work on biomarker sensing and its applications for diagnostic procedures that cut laboratory testing down from weeks to hours. This new equipment arising from Mirkin’s work is installed in some US hospital laboratories.

Dr. Silvano Dragonieri of Leiden University in The Netherlands discussed his e-nose technology which offers another approach to diagnostics. Here’s a description of Dragonieri’s (and another team’s) work in this area from an April 27, 2009 news item on physorg.com,

In 2006 researchers established that dogs could detect cancer by sniffing the exhaled breath of cancer patients. Now, using nanoscale arrays of detectors, two groups of investigators have shown that a compact mechanical device also can sniff out lung cancer in humans.

Hossam Haick, Ph.D., and his colleagues at the Israel Institute of Technology in Haifa, used a network of 10 sets of chemically modified carbon nanotubes to create a multicomponent sensor capable of discriminating between a healthy breath and one characteristic of lung cancer patients. This work appears in the journal Nano News. Meanwhile, Silvano Dragonieri, M.D., University of Bari, Italy, and his colleagues used a commercial nanoarray-based electronic “nose” to discriminate between the breath of patients with non-small cell lung cancer and chronic obstructive pulmonary disease (COPD). These results appear in the journal Lung Cancer. [emphasis mine]

Nanomedicine is fascinating, which is why it’s easy to lose perspective. Thankfully there was Dr. Philip Kantoff  (also very enthused and a major figure in this area) to provide the voice of reason. Here’s more are about Kantoff from the profile page on the WEBMD website,

Dr. Kantoff has published more than 100 research articles on a variety of topics, including the molecular basis of genitourinary cancers and improved treatments for patients afflicted with prostate cancer, kidney cancer, bladder cancer, and testicular cancer. His laboratory research involves understanding the genetics of prostate cancer. His clinical research involves clinical trials of novel therapeutic treatments for the genitourinary cancers. He teaches at Harvard Medical School, and lectures internationally to both medical and lay audiences. Dr. Kantoff has written nearly 100 reviews and monographs on cancer and has edited numerous books, including Prostate Cancer, A Multi-Disciplinary Guide published by Blackwell, and Prostate Cancer: Principles and Practice, a definitive text on prostate cancer, published in December 2001 by Lippincott Williams & Wilkins. He has also written a popular book, Prostate Cancer, a Family Consultation, published by Houghton Mifflin.

As Kantoff counsels against over-hyping he notes that much of the work in the area of nanomedicine is in the laboratory; there are still animal trials and human clinical trials to be convened for further testing.

Building on Kantoff’s observations: let’s consider the difference between research and clinical practice. Even after the human clinical trials have taken place, there’s still uncertainty about how this new procedure or medication, no matter how personalized, will affect an individual. Would aspirin be available over-the-counter today if we’d known all of the side effects which many people suffer from? No, not a chance. How long did it take to find out that aspirin was a problem? Several years.

The idea that this new ‘personalized’ medicine that Mirkin refers to will provide a perfect solution to any disease is based on the belief that we understand disease processes. We do not. Yes, we’ve catalogued any number of genomes, etc. but at least one question remains. Why do some people who have one or more biomarker for a disease never experience it while others with fewer biomarkers do?

While that question wasn’t raised in the episode I was impressed with the fact that they did mention patent issues (innovation and, in this care, care can be stifled by patents and this seems to be increasingly the case); some larger philosophical issues, just how long do you want to live?, and who gets to enjoy these new benefits (if  such they be)?

I do have a few quibbles, there was no Canadian content other than David Suzuki reading a script as narration for the episode (this was true of the first episode too). The title, More than human, suggests not just robots but human enhancement too and that topic was barely discussed.

In future, I’d like to suggest a little more humility in programmes about nanotechnology. I found the constant references to ‘controlling’ atoms, matter, disease, etc. to be disconcerting. As far as I’m concerned, we don’t control an atom, we try to understand it and based on that understanding find better ways to exist in this universe.