How a new test could help curb the spread of Ebola

New technology uses magnetic nanoparticles for simpler, cheaper diagnosis

The Ebola virus has claimedthe lives of more than 11,000 people in West Africa since March 2014. Withmore than 27,000 confirmed and suspected cases of Ebola virus disease in Guinea, Liberia and Sierra Leone since the outbreakbegan, detection is key to controlling the spread of the disease. However,current tests are either too expensive to be useful where they are most needed,or not sensitive enough to provide an accurate diagnosis.

A new test that uses magneticnanoparticles could help curb the spread of Ebola, enabling healthcare workersto identify and isolate patients more quickly and easily. Research published in Biosensors and Bioelectronics shows that the new test is100 times more sensitive than the current test, and easier to use.

TProfessor Xiyun Yan, PhDhe Ebola virus causes an acute illnessthat is deadly in half of all cases, on average. The current outbreak of Ebolaaffects countries in West Africa. In the most severely affected countries, likeGuinea, Liberia and Sierra Leone,resources are limited, making control of the outbreak challenging. There is novaccine for Ebola, so detecting the virus is key to controlling the outbreak:with an accurate diagnosis, patients can be isolated and treated properly,reducing the risk of spread.

“In West Africa, resources are underpressure, so complicated, expensive tests are not very helpful,” said ProfessorXiyun Yan, one of the authors of thestudy, from the Chinese Academy of Sciences. “Our new striptest is a simple, one-step test that is cheap and easy to use, and provides avisible signal, which means people don’t need training to use it. We think itwill be especially helpful in rural areas, where technical equipment and skillsare not available.”

Improving apopular diagnostic test

Currently there are two main ways totest for the Ebola virus: using a method called polymerase chain reaction(PCR), which makes copies of the molecules for detection, and with antibody-capture enzyme-linked immunosorbent assay(ELISA), which gives a visual indication when a given molecule isin a sample. PCR is very sensitive but expensive and complicated, requiringspecial skills and technical equipment. The ELISA – or gold strip test – ischeaper, but sensitivity is very low, which means it often gives the wrongresults.

The new test, called the nanozyme test,is similar to the gold strip test. It uses magnetic nanoparticles, which worklike enzymes to make the signal stronger, giving a clearer result you can seewith the naked eye. The test can detect much smaller amounts of the virus andis 100 times more sensitive than the gold strip test.

“People have loved the strip test formany years, but it has a major weakness: it’s not sensitive enough,” said Dr.Yan. “We’re very excited about our new nanozyme test, as it is much moresensitive and you don’t need any specialist equipment to get a quick, accurateresult.”

Strip tests work by attaching molecules called antibodies to goldparticles to look for a particular molecule in a sample. When they attach tothe molecule you’re looking for, in this case a virus, they produce a signal,such as a color change. In order to find the virus, the particles need to belabelled with enzymes, which speed up detection and signalling.

The magnetic properties of the nanozymes make the detection sensitivity 10 times higher, and the catalytic properties make the signal 100 times stronger, generating a deep color reaction that can be seen by the naked eye. (Image credit: Demin Duan et al)

With the new nanozyme test, the researchers appliedmagnetic nanoparticles as a nanozyme probe in place of gold nanoparticles.After labeling with an antibody that attaches to the Ebola virus, this novelprobe is able to recognize and separate the virus in a sample. Thenanoparticles are magnetic, so to concentrate the virus particles in a sample,all you need to do is hold the sample against a magnet; no expensive labequipment is needed.

Results of testing using (A) the nanozyme strip and (B) a standard gold strip. The asterisk (*) indicates the limit of visual detection, showing that the nanozyme strip is more sensitive. (Image appears as figure 3 in the study. Credit: Demin Duan et al)The nanozyme test is 100 times more sensitive than the gold strip test,detecting molecules called glycoproteins on the surface of the Ebolavirus at concentrations as low as 1 nanogram per milliliter.

“Nobody believed that nanoparticles had enzyme activity; it seemsunbelievable,” said Dr. Yan. “Being magnetic, the nanoparticles can physicallycollect virus particles together when you hold a magnet against the sample. Itcan work the same way with other biological molecules: nanozymes can detect anymolecules in a sample in just one step. That’s why we’re so excited by this – it’ssimple!”

The team is now developing automatic equipment to avoid contamination.Any test that comes into contact with a person’s hands can be contaminated, somaking the test automatic would reduce the risk of contamination, thereforeincreasing the accuracy of the results.

Nanozyme as a powerful detectiontechnology

The new nanozyme test is the result of an interdisciplinarycollaboration that is also leading to new applications for the technology. Theunderlying discovery – that the magnetic nanoparticles can function as enzymes– can be used in many other areas. The researchers have applied for a patentfor the new nanozyme test and are excited about its potential.

“We had an idea and talked to manypeople about it, and the result is a test that will overcome a problem,” saidDr. Yan. “We have built strong collaborations that have finally made thismethod successful, and we’re looking forward to applying it to many otherareas.”

Dr. Yan and her colleagues had theoriginal idea for the technology, and developed the platform. They worked with Professor George Fu Gao, DeputyDirector-General of the Chinese Center forDisease Control and Prevention (CDC), to access the pseudo-virus anddetection molecule to create the Ebola test, with colleagues in Canada to getthe antibody. Clinicians helped them test the accuracy of the technology, andthe CDC is now taking the test to West Africato try out in the field.

Now that the researchers have shown thetechnology is robust, they are collaborating with other colleagues andcompanies to develop it further. The technology can be applied to the detectionof any biological molecules, making it useful to diagnose other infectious diseases,like flu, and potentially detect tumors. The researchers are working with clinical teams toapply the technology to other viruses and tumors.

They are also working with a company that treats wastewater to see if itcan help remove environmental contamination. A large volume of wastewater isproduced during paper manufacture. This wastewater contains a phenol that cancause cancer. The nanozymes can break down this phenol into water and carbondioxide, so they could be used to decontaminate the water.

Read the article

This study is freely available until October2, 2015:

Demin Duan et al: “Nanozyme-stripfor rapid local diagnosis of Ebola,” Biosensors and Bioelectronics(December 2015)

Corresponding author

Dr. Xiyun Yan is Professor and Director of the keyLaboratory of Protein & Peptide Pharmaceutical at the Institute ofBiophysics, Chinese Academy of Sciences. She is President of the Asian BiophysicalAssociation (ABA) and Vice President & Secretary-General of the BiophysicalSociety of China. Dr. Yan made groundbreaking contributions to our knowledge ofnanozymes, showing that they have intrinsic enzyme-like activity. Dr. Yan’s labis developing the technology in the areas of tumor and water treatment. Dr. Yanhas 125 publications and 28 patents.

The journal

Biosensors & Bioelectronics is the principal international journal devotedto research, design, development and application of biosensors and bioelectronics. It is aninterdisciplinary journal serving professionals with an interest in theexploitation of biological materials and designs in novel diagnostic andelectronic devices including sensors, DNA chips, electronic noses,lab-on-a-chip and μ-TAS. Readmore.

Related resources

The latest on the Ebola outbreak:

Elsevier's Ebola Information Center features free health and medical research,online tools and expert advice on Ebola

Elsevier Connect Contributor

Lucy Goodchild-van  HiltenAfter a few accidents, Lucy Goodchild van Hilten discovered that she’s a much better writer than a scientist. Following an MSc in the History of   Science, Medicine and Technology at Imperial  College London, she became Assistant Editor of Microbiology  Today. A stint in the press office at Imperial saw her stories on the front pages, and she moved to Amsterdam to work at Elsevier as Senior Marketing   Communications Manager for Life Sciences.

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