IMDEA Nanoscience develops an innovative diagnostic test for Coronavirus to be financed by the Carlos III Health Institute (ISCIII)
Press Release IMDEA NANO COVID-19
- IMDEA Nanoscience Institute is a center for research and advanced studies in Nanotechnology created by the Madrid Regional Government that opened its doors in 2012.
- The Institute is developing an innovative diagnostic test for the SARS-CoV-2 Coronavirus that allows for detection of a specific coronavirus RNA sequences and can be used more easily.
- The development project will be supported by the funding made available through a Royal Decree of Extraordinary Emergency Measures to address the economic and social impact of COVID-19 and was launched by the Government of Spain.
- The proposal presented was favorably assessed by the Scientific-Technical Committee in charge of evaluating research projects proposals in COVID19 and SARS-COV-2 and will have an initial financial support of 340.000€ that will be provided by the Carlos III Health Institute (ISCIII), dependent on the Ministry of Science and Innovation of Spain
- The successful development of this test would allow high sensitivity tests to be carried out without the need for expensive laboratory instruments and reagents, as is the case with tests based on quantitative PCR and which also require personnel specifically trained in these techniques and a relatively long time to provide results.
- The colorimetric test, after sample preparation and RNA extraction, could be easily performed by any doctor or nurse in less time and cost, without the need for special equipment, but with proven reliability, which can be very effective since infected patients can transmit the disease even without obvious symptoms.
- In this initial phase of validation the project will be supported by ISCIII, the Ramon y Cajal Institute for Health Research (IRYCIS) and Synthelia Organics S.L. a spin-off company located at the Science Park of Madrid.
IMDEA Nanoscience is an institute for advanced studies lead by renowned Physicist Rodolfo Miranda, Professor of Condensed Matter Physics at Universidad Autónoma de Madrid (UAM). The new diagnostic test for COVID-19 allows the detection of specific sequences of the coronavirus RNA responsible for this disease, but does not require the use of qRT-PCR equipment and can be easily used.
The sensor, based on gold nanoparticles, is capable of detecting the specific sequence of the RdRP gene present in SARS-CoV-2, as well as the E gene common to all Coronaviruses. The test is basically a vial with a reddish watery solution that in the presence of coronavirus RNA causes an aggregation of gold nanoparticles functionalized with oligonucleotides that precipitate producing a clear decrease in the color of the solution that can be seen with the naked eye. This is due to a reorganization of DNA chains anchored on the surface of the gold nanoparticle.
The system will be implemented to 3 different amplification systems in order to reduce the use of equipment, highly specialized personnel and reagents to a minimum:
1) In RT-PCR, avoiding the use of qRT-PCR
2) In isothermal amplification, avoiding the use of any type of PCR
3) In non-enzymatic amplification, avoiding the use of enzymes and therefore with minimal sample preparation
The processes developed are industrially scalable, and it is expected that IMDEA Nanoscience will rapidly acquire the capacity to produce, on its own, 5.000 nanoparticle-based sensors per week in an initial phase, before industrialization.Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a variant of PCR commonly used in molecular biology to generate a large number of copies of genetic material, a process known as amplification. In qRT-PCR, tagging with fluorescent compounds allows data collection as PCR progresses and therefore offers many benefits, such as being able to detect many targets in each sample simultaneously, but this requires optimization and design of a specific probe.The ISCIII grant will provide 340.00€ to the institute from the fund "For direct grants for projects and research programs on the SARS-CoV2 virus, which causes COVID-19", of the ISCIII expenditure budget for the year 2020 (FONDO - COVID19) in order to help validate this sensor that IMDEA Nanoscience is developing.
The financed proposal is adequate to the emergency situation, allowing and immediate implementation and start-up in the National Health System, with concrete results, early and timely to the current situation. Likewise, it responds to the social interest contributing to a better clinical diagnosis of patients in the NHS infected by SARS-CoV-2.
The proposed systems would be quick and easy to implement in current diagnostic procedures, and have been listed in terms of resource requirements. The first system only requires a thermal cycler, the second a thermoblock, and the third would not require enzymes. Therefore, its implementation could be done not only in all hospitals but also in health centers. The speed with which the results are obtained (a few hours) due to a change in colour perceptible to the naked eye, is another of the great advantages of these systems.
At the institute, we can prepare nanoparticles, oligonucleotides and modified nitrocellulose strips on a small scale. In fact, we have started an industrial project with the company Synthelia Organics for the preparation in flow of nanoparticles. For the synthesis of oligonucleotides in larger quantities, we requested a budget for the acquisition of new equipment to produce about 5.000€ sensors per week and far more through industrially scalable processes, so the system described could be prepared in large orders of magnitude by the industry.
As Dr. Álvaro Somoza, head of the team developing the test, explains: "The DNA strands present on the surface of the nanoparticles are folded in a fork shape and have a hydrophobic group at the end. In this arrangement the structure is water-soluble, but in the presence of the virus RNA, the fork opens up and the cholesterol is exposed to the medium, giving rise to a water-insoluble structure and causing the nanoparticles to precipitate"
The most obvious measures for the containment of the SARS-CoV-2 virus, responsible for Covid19 disease, include its detection. Identifying carriers of the virus, and therefore potential vehicles for its transmission, is vital, not only in patients who show the symptoms, but fundamentally in asymptomatic patients, but also infectious. This way it would be possible to isolate them and prevent the spread of the virus. This requires the evaluation of a large percentage of the population, and repeating these studies for several weeks, since the virus can be transmitted from person to person from several days before the first symptoms (if they appear), and up to more than three weeks from the time of infection.
The virus is currently detected by two methods. The more direct and therefore more reliable of the two requires the use of sophisticated equipment and adequately trained personnel. This system is known as qRT-PCR, and involves the reverse transcription of the virus RNA into DNA, the amplification of the DNA by PCR technique, and the quantification, in the same equipment, by the use of fluorescent probes. This process usually takes several hours from the time the sample is obtained, which has to be moved to centres that have the equipment and personnel necessary to carry out this process, as well as the relevant biosecurity requirements. In many cases, given the shortage of PCR equipment, this transfer even involves the transfer of samples from one Autonomous Community to another.
The qPCR system is very sensitive, and allows the detection of the virus RNA, even if it is present in very small quantities, so it is very useful to be able to detect it in the initial stages of the disease, as well as to confirm when the patient is virus free. It is currently the reference method, although each country is using a slightly different region of the virus RNA for detection. In the Community of Madrid, the method described by Dr. Christian Drosten of the Charité Virology Institute in Berlin is used.
The other method involves the use of antibodies, and can be designed in two different ways: i) for the detection of virus proteins or ii) antibodies against patient-generated viruses. These diagnostic systems are known as rapid tests, and their main advantages are their ease of use and the speed with which a diagnosis can be obtained in about 15 minutes. However, they can present several problems, since detection will be efficient when the virus is present in a relatively high concentration, in the first case, or when the antibodies developed by the patient are in the blood at optimal levels. It usually takes several days to reach these levels (7-14 days, on average to go from 40% to 100%), which may not be very effective, since infected patients may transmit the disease, even have obvious symptoms, and not test positive if the test is not sensitive enough. In addition, this type of test may not be suitable for immune compromised patients.
For these reasons, at IMDEA Nanoscience we are developing a diagnostic test that combines both concepts, i.e. that allows detection of specific virus RNA sequences, but does not require the qRT-PCR equipment, and can be easily used. The sensor has a design capable of detecting the specific sequence of the RdRP gene present in the SARS-CoV-2, as well as the E gene, common to all Coronaviruses.
According to Prof. Miranda, Director of the Institute and Principal Investigator of the ISCIII-funded Project: The research in Nanoscience developed at the Institute in these years has produced several biomedical advances that are now a reality. We hope that we can also contribute to the fight against this pandemic. We are reorienting an important part of the multidisciplinary capabilities of the Institute to achieve an efficient and simple to use test.
The Madrid Institute for Advanced Studies in Nanoscience (IMDEA) is a research center promoted by the Madrid Government to provide our region with a competitive leadership position in an area of technological development that is strategic to ensure the long-term competitiveness of the region. Since its creation in 2007, and especially since the opening its new headquarters in 2012, IMDEA Nanoscience has established itself as an international reference center in the field of research in Nanotechnology. A panel of international experts who awarded the Institute the status of Severo Ochoa Centre of Excellence three years ago recognized this.
IMDEA Nanoscience has six multidisciplinary frontier research programs involving teams of scientists recruited from global calls and pre-selected by an International Scientific Committee, which has enabled the Institute to attract a remarkable amount of scientific talent from more than 15 countries. IMDEA Nanoscience collaborates closely with the network of public universities and hospitals in Madrid, with the main public research bodies in Spain and with the most innovative companies in Europe. In this way, outstanding researchers from these institutions have also joined IMDEA Nanoscience research groups, creating Science in our country in a highly competitive way.
The Institute is a Foundation and its Board of Trustees includes the Madrid Regional Government, the Ministry of Science and Innovation of Spain, the National Research Council CSIC and three public universities in Madrid (UAM, UCM and UPM), as well as internationally renowned scientists and companies.
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