Tag Archives: Karolinska Institute

Human lung enzyme can degrade graphene

Caption: A human lung enzyme can biodegrade graphene. Credit: Fotolia Courtesy: Graphene Flagship

The big European Commission research programme, Grahene Flagship, has announced some new work with widespread implications if graphene is to be used in biomedical implants. From a August 23, 2018 news item on ScienceDaily,

Myeloperoxidase — an enzyme naturally found in our lungs — can biodegrade pristine graphene, according to the latest discovery of Graphene Flagship partners in CNRS, University of Strasbourg (France), Karolinska Institute (Sweden) and University of Castilla-La Mancha (Spain). Among other projects, the Graphene Flagship designs based like flexible biomedical electronic devices that will interfaced with the human body. Such applications require graphene to be biodegradable, so our body can be expelled from the body.

An August 23, 2018 Grapehene Flagship press release (mildly edited version on EurekAlert), which originated the news item, provides more detail,

To test how graphene behaves within the body, researchers analysed how it was broken down with the addition of a common human enzyme – myeloperoxidase or MPO. If a foreign body or bacteria is detected, neutrophils surround it and secrete MPO, thereby destroying the threat. Previous work by Graphene Flagship partners found that MPO could successfully biodegrade graphene oxide.

However, the structure of non-functionalized graphene was thought to be more resistant to degradation. To test this, the team looked at the effects of MPO ex vivo on two graphene forms; single- and few-layer.

Alberto Bianco, researcher at Graphene Flagship Partner CNRS, explains: “We used two forms of graphene, single- and few-layer, prepared by two different methods in water. They were then taken and put in contact with myeloperoxidase in the presence of hydrogen peroxide. This peroxidase was able to degrade and oxidise them. This was really unexpected, because we thought that non-functionalized graphene was more resistant than graphene oxide.”

Rajendra Kurapati, first author on the study and researcher at Graphene Flagship Partner CNRS, remarks how “the results emphasize that highly dispersible graphene could be degraded in the body by the action of neutrophils. This would open the new avenue for developing graphene-based materials.”

With successful ex-vivo testing, in-vivo testing is the next stage. Bengt Fadeel, professor at Graphene Flagship Partner Karolinska Institute believes that “understanding whether graphene is biodegradable or not is important for biomedical and other applications of this material. The fact that cells of the immune system are capable of handling graphene is very promising.”

Prof. Maurizio Prato, the Graphene Flagship leader for its Health and Environment Work Package said that “the enzymatic degradation of graphene is a very important topic, because in principle, graphene dispersed in the atmosphere could produce some harm. Instead, if there are microorganisms able to degrade graphene and related materials, the persistence of these materials in our environment will be strongly decreased. These types of studies are needed.” “What is also needed is to investigate the nature of degradation products,” adds Prato. “Once graphene is digested by enzymes, it could produce harmful derivatives. We need to know the structure of these derivatives and study their impact on health and environment,” he concludes.

Prof. Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship, and chair of its management panel added: “The report of a successful avenue for graphene biodegradation is a very important step forward to ensure the safe use of this material in applications. The Graphene Flagship has put the investigation of the health and environment effects of graphene at the centre of its programme since the start. These results strengthen our innovation and technology roadmap.”

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

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase by Dr. Rajendra Kurapati, Dr. Sourav P. Mukherjee, Dr. Cristina Martín, Dr. George Bepete, Prof. Ester Vázquez, Dr. Alain Pénicaud, Prof. Dr. Bengt Fadeel, Dr. Alberto Bianco. Angewandte Chemie https://doi.org/10.1002/anie.201806906 First published: 13 July 2018

This paper is behind a paywall.

Researchers at Karolinska Institute (Sweden) build an artificial neuron

Unlike my post earlier today (June 26, 2015) about BrainChip, this is not about neuromorphic engineering (artificial brain), although I imagine this new research from the Karolinska Institute (Institutet) will be of some interest to that community. This research was done in the interest of developing* therapeutic interventions for brain diseases. One aspect of this news item/press release I find particularly interesting is the insistence that “no living parts” were used to create the artificial neuron,

A June 24, 2015 news item on ScienceDaily describes what the artificial neuron can do,

Scientists have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain [sic] no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. [emphasis mine]

A June 24, 2015 Karolinska Institute press release (also on EurekAlert), which originated the news item, describes how neurons communicate in the brain, standard techniques for stimulating neuronal cells, and the scientists’ work on a technique to improve stimulation,

Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell.

To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells.

“Our artificial neuron is made of conductive polymers and it functions like a human neuron,” says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.”

The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics, will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function.

“Next, we would like to miniaturize this device to enable implantation into the human body,” says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.”

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

An organic electronic biomimetic neuron enables auto-regulated neuromodulation by Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, b, Dagmar Galter, Magnus Berggren, and Agneta Richter-Dahlfors. Biosensors and Bioelectronics Volume 71, 15 September 2015, Pages 359–364         doi:10.1016/j.bios.2015.04.058

This paper is behind a paywall.

As to anyone (other than myself) who may be curious about exactly what they used (other than “living parts”) to create an artificial neuron, there’s the paper’s abstract,

Current therapies for neurological disorders are based on traditional medication and electric stimulation. Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances. The fundamental function of neurons, defined as chemical-to-electrical-to-chemical signal transduction, is achieved by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow. Biosensors detected neurotransmitters in physiologically relevant ranges of 5–80 µM, showing linear response above 20 µm with approx. 0.1 nA/µM slope. When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump. Changes of 20 µM glutamate or acetylcholine triggered diffusive delivery of acetylcholine, which activated cells via receptor-mediated signalling. This was observed in real-time by single-cell ratiometric Ca2+ imaging. The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons. Alternatively, conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals may be obtained, applicable for bridging injured sites and active prosthetics.

While it’s true neither are “living parts,” I believe both enzymes and organic electronic ion pumps can be found in biological organisms. The insistence on ‘nonliving’ in the press release suggests that scientists in Europe, if nowhere else, are still quite concerned about any hint that they are working on genetically modified organisms (GMO). It’s ironic when you consider that people blithely use enzyme-based cleaning and beauty products but one can appreciate the* scientists’ caution.

* ‘develop’ changed to ‘developing’ and ‘the’ added on July 3, 2015.

Nanomal project: rapid diagnosis for malaria

I’ve written a number of postings about handheld diagnostic devices as there is great international interest in developing these devices and I’ve also written about protection against malaria. A Sept. 24, 2012 news item on ScienceDaily combines these two topics,

Around 800,000 people die from malaria each year after being bitten by mosquitoes infected with malaria parasites. Signs that the parasite is developing resistance to the most powerful anti-malarial drugs in south-east Asia and sub-Saharan Africa mean scientists are working to prevent the drugs becoming ineffective.

The €5.2million (£4million) Nanomal project — launched September 26– is planning to provide an affordable hand-held diagnostic device to swiftly detect malaria infection and parasites’ drug resistance. It will allow healthcare workers in remote rural areas to deliver effective drug treatments to counter resistance more quickly, potentially saving lives.

You can find out more about the Nanomal project here. Their undated news release, which originated the news item, offers more information about how malaria is usually diagnosed,

Currently for malaria diagnosis, blood samples are sent to a central referral laboratory for drug resistance analysis, requiring time as well as specialised and expensive tests by skilled scientists. Additionally, confirmation of malaria is often not available where patients present with fever. Very often, drug treatments are prescribed before the diagnosis and drug resistance are confirmed, and may not be effective. Being able to treat effectively and immediately will prevent severe illness and save lives.

Contrast the standard process with the proposed diagnostic device (from the news release),

The device – the size and shape of a mobile phone – will use a range of latest proven nanotechnologies to rapidly analyse the parasite DNA from a blood sample. It will then provide a malaria diagnosis and comprehensive screening for drug susceptibility in less than 20 minutes, while the patient waits. With immediately available information about the species of parasite and its potential for drug resistance, a course of treatment personally tailored to counter resistance can be given.

Here’s how they expect it to work (from the news release),

The handheld device will take a finger prick of blood, extract the malarial DNA and then detect and sequence the specific mutations linked to drug resistance, using a nanowire biosensor. The chip electrically detects the DNA sequences and converts them directly into binary code, the universal language of computers. The binary code can then be readily analysed and even shared, via wireless or mobile networks, with scientists for real-time monitoring of disease patterns.

The device should provide the same quality of result as a referral laboratory, at a fraction of the time and cost. Each device could cost about the price of a smart phone initially, but may be issued for free in developing countries. A single-test cartridge will be around !13 (£10) initially, but the aim is to reduce this cost to ensure affordability in resource-limited settings.

In addition to improving immediate patient outcomes, the project will allow the researchers to build a better picture of levels of drug resistance in stricken areas. It will also give them information on population impacts of anti-malarial interventions.

There are more details about the device (and an image of it)  in the ScienceDaily news item. The Nanomal team is expecting to begin field trials in the next three years preparatory to bringing the device to market.

I found more information about Nanomal on the European Commission’s Cordis website,

Development of a handheld antimalarial drug resistance diagnostic device using nanowire technology

Start date:2012-07-01

End date:2015-06-30

Project Acronym:NANOMAL

Project status:Execution


Administrative contact Address
Name:Jane BOLAND (Ms.) Cranmer TerraceLONDON


URL:http://www.sghms.ac.uk Organization Type:Education


Objective: Malaria is a global health priority that has been targeted for elimination in recent years. Attaining the goals that define elimination of malaria in different countries depends critically on provision of effective antimalarials and further that these antimalarials are used appropriately in individual patients. Drug resistance is a major threat to malaria control and has important global public health implications. Over the past decades the genetic bases for resistance to most of the antimalarial classes currently in use has become defined. For some drugs and combinations, these mutations are the most important predictors of treatment failure. This proposal will innovate new technologies to confirm malaria diagnosis and detect drug resistance in malaria parasites by analysis of mutations in nucleic acids, using nanowire technology, and will result in the development of a simple, rapid and affordable point-of-care handheld diagnostic device. The device will be useful at many levels in malarial control by:

1. Optimising individual treatments for patients;
2. Assessing the epidemiology of drug resistance in malaria endemic areas;
3. Assessing population impacts of antimalarial interventions;

The development programme capitalises on highly original and proprietary advances made by QuantuMDx in the field of point-of-care diagnostics. This is complemented by academic expertise that has made major contributions to the understanding of antimalarial drug resistance mechanisms in laboratory models, as well as parasites obtained directly from patients. The impact of this proposal can be extended rapidly to other established and emerging infectious diseases.

I was particularly interested to note the UK is the lead on this project in light of an earlier handheld diagnostic device developed in the UK and tested on the country’s Olympic athletes prior to the 2012 Olympics (my Feb. 15, 2011 posting on Argento).

The Nanomal project is multinational as per the news item on ScienceDaily,

The Nanomal consortium is being led by St George’s, University of London, which is working with UK handheld diagnostics and DNA sequencing specialist QuantuMDx Group and teams at the University of Tuebingen in Germany and the Karolinska Institute in Sweden. It was set up in response to increasing signs that the malaria parasite is mutating to resist the most powerful class of anti-malaria drugs, artemisinins. The European Commission has awarded €4million (£3.1million) to the project.

Nanomal lead Professor Sanjeev Krishna, from St George’s, said: “Recent research suggests there’s a real danger that artemisinins could eventually become obsolete, in the same way as other anti-malarials. New drug treatments take many years to develop, so the quickest and cheapest alternative is to optimise the use of current drugs. The huge advances in technology are now giving us a tremendous opportunity to do that and to avoid people falling seriously ill or dying unnecessarily.”

QuantuMDx’s CEO Elaine Warburton said: “Placing a full malaria screen with drug resistance status in the palm of a health professional’s hand will allow instant prescribing of the most effective anti-malaria medication for that patient. Nanomal’s rapid, low-cost test will further support the global health challenge to eradicate malaria.”

My most recent piece on anti-malaria tactics was about a textile developed at Cornell University (mentioned in my May 15, 2012 posting). As for QuantuMDx, you can find out more here.