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From the molecule to the bioassay by Custom antibody service (CAbS)-NANBIOSIS U2 as a PTI+Global Health Infraestructure

During 20-22 of November 2023, the III PTI+Global Health Scientific Conference were held in the Center for Human and Social Sciences, in Madrid.

In March 2020, the CSIC (Spanish National Research Council) launched the the Interdisciplinary Thematic Platform (PTI) on Global Health to bring together research teams and enhance knowledge about the new coronavirus SARS-CoV-2, which caused the pandemic. The PTI has mobilized and coordinates more than 400 scientists from 50 CSIC institutes in all areas.

The annual PTI+Global Health Scientific Conference are a meeting space where the results of the research carried out in the laboratories can be shown and discussed.

In the words of Margarita del Val, coordinator of the PTI+Global Health “In these III Conferences we are looking to the future to see how we evolve from the coronavirus to be prepared for future pandemics due to infectious diseases”. Iñaki Comas, coordinator of the PTI explained that this conference has been focused on “How to approach infectious diseases from a particular corner of knowledge but in an interdisciplinary way to be in a better position to face these global health challenges”.

The research caried out by the Nb4D group – NANBIOSIS U2 were presented by Julian Guercetti and Lluisa Villaplana:

“Towards a novel molecular signature for diagnosing infections based on Quorum sensing” M.-Pilar Marco; Juan Raya; Nuria Pascual; Nerea Castro; Carla Ferrero; J.-Pablo Salvador

“Immuno-μSARS2 chip: Correlating COVID-19 clinical severity with IgG personalized profiles” Julian Guercetti; Marc Alorda; Miriam Royo; Alicia Lacoma; Eduardo Padilla; Juan P. Horcajada; Silvia Castaneda; Agustín
Gutierrez-Galvez; Santiago Marco; J. Pablo Salvador; Pilar Marco, in this case with also with the participation of NANBIOSIS U3 Synthesis of Peptides Unit, led by Miriam Royo

“Using quorum sensing based antibodies as a new therapeutic strategy to treat Pseudomonas aeruginosa infections” Lluïsa Vilaplana Holgado; Bárbara Rodriguez Urretavizcaya; M.-Pilar Marco Colás

The Custom Antibody Service (CAbS) – NANBIOSIS U2 was presented by Julian Guercetti as one a PTI+Salud Global Infraestructure

“Custom antibody service (CAbS) from the molecule to the bioassay” Nuria Pascual Duran; Andrea Bastias; Idoia Camí; J.Pablo Salvador; Julian Guercetti; Lidia Hinojosa; Montserrat Rodriguez; Pilar Marco

Nanbiosis Unit 2 (Custom Antibody Service-CAbS) is a technological facility established in 2009 as part of the Spanish National Research Council (CSIC) and the Biomedical Research Center Network of Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN). Located within the Institute of Advanced Chemistry of Catalonia (CSIC) in Barcelona, the platform is equipped with a cell culture laboratory, housing the necessary equipment for obtaining, selecting, growing, and storing hybridomas. Additionally, the service offers laboratories for the synthesis of immunogens and the characterization of the produced antibodies.
The CAbS platform provides its monoclonal and polyclonal antibody production services to groups affiliated with CSIC and CIBER-BBN, as well as other research groups from public or private institutions and companies.
The primary goal of the service is to deliver high-quality service and scientific guidance in the production of immunoreagents, including polyclonal, monoclonal antibodies, and antibody fragments, as well as various probes such as protein and enzyme bioconjugates, biotinylated and fluorescent probes, biofunctionalized particles, and more.
The service is adaptable to each client’s needs and can produce antibodies against proteins, peptides, organic molecules, or other antigens through standardized or customized protocols. Special emphasis is placed on the immunogen design phase, a crucial aspect for modulating antibody selectivity and affinity.
One distinguishing feature of the CAbS service is its provision of guidance and assistance in preparing immunogens and producing antibodies for low-molecular-weight molecules, such as pigments, hormones, or anabolic agents. Service management is overseen by the NB4D group at IQAC-CSIC, a team with extensive experience in this field. Each service request is reviewed by a Scientific Committee, which produces a feasibility report before project acceptance. Users are kept informed of project progress at all stages and are consulted before proceeding based on the achieved results.
The services offered by the platform include:
• Preliminary discussion of project characteristics
• Design and synthesis of haptens
• Preparation of bioconjugates
• Hybridoma development
• Production of monoclonal antibodies
• Production of polyclonal antibodies
• Additional services (antibody purification, monoclonal antibody isotyping, etc.)
• Guidance and setup of immunoassays.

Recently, the unit has acquired a Surface Plasmon Resonance (SPR) instrument, which enables real-time detection and monitoring of interactions between two or more molecules without the need for labelling. The studies conducted with this instrument serve to determine specificity between compounds and/or characterize the kinetics and affinity of
these interactions. This SPR was funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global).

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Prof. Pilar Marco, in the program “Meridiano Turing” of RTVE explains the COVID-19 tests.

The last edition of the program “Meridiano Turing” of RTVE interviews Maria Pilar Marco Head of CIBER-BBN and IQAC-CSIC group Nb4D and NANBIOSIS-ICTS Unit 2 Custom Antibody Service (CAbS), Cesar Fernández (Head of the Chemical Transducers Group at IMB-CNM, CSIC) and María Cruz Minguillón (EGAR group at IDAEA)

Pilar Marco y César Fernández, the authors of the block of the CSIC’s report entitled “Containment and diagnosis“, explain wich is the best way to diagnose COVID and how reliable are the tests in this moment.

What is needed is to detect an infection -says Pilar Marco- is viral material and we have two types of tests to detect viral material:
– Those that detect the viral RMA, which is the genetic material of the virus. These test known as “PCR”, were the first to be used and are quite reliable PCR is a technology that expands the genetic material, making many copies what makes it possible to detect the viral material with very low viral load
– And during the month of September have became famous what are known as the “antigen tests” (they also came out at the beginning, but they were of low quality). These tests do not detect the genetic material but the structural proteins of the virus.

Serological tests should not be used to diagnose an infection because they do not detect the virus, what they detect is the reaction that the host has in the presence of an infection, that is, the antibodies that our body produces to defend itself against the infection and this occurs from the first moment but is not detectable until practically seven days after being infected. Therefore serological tests have limited utility to diagnose the infection, they serve to monitor the evolution and immunological status of the patient, if he is producing antibodies against the virus and how it evolves The virus remains elevated for months, but it does not mean that if you have had the disease and the rsults fo serological tests are negative, you are not prepared to face the virus, since we have memory cells that will surely produce antibodies again.

Cesar Fernández explains that the sample is the same in PCR and antigen tests, but the time it takes to obtain an answer is different. Both type of tests are recommended depending on the situation and the environment in which they are used, PCR tests have been used more massively and are more reliable in the sense that they let out much fewer positives, the number of false negatives they provide is very low, but they are also more expensive tests and need more time from the moment the sample is taken until the result is obtained (minimum 24 hours) since they are carried out in clinical analysis laboratories. The antigen tests can be carried out in 15-30 minutes in the place where the sample is taken and their cost is very low compared to that of the PCR, which is why they are very useful for screening studies of the levels infection that may exist in a community. Currently, work is being done on carrying out the antigen tests in saliva, this would facilitate the taking of samples and would not generate practically social rejection. Studies are also being done on the use of nasal smears in which the sample is taken at the beginning of the nasal cavity, resulting in much less annoying. Antigen tests due to their low cost and ease use open the possibility of performing in a very repetitive way.

Regarding the measurement of viral load, it is given by the PCR, while in the antigen tests the detection is visual, a colored line appears, similar to the pregnancy tests, with greater or lesser intensity, with which the information they give on viral load is semi-quantitative, that is, the interpretation is quite subjective.
The viral load of the disease appears a few days before sinthoms are shown (the peak is two days before) and can be spread to other people. This also occurs with asymptomatic infected people, with the only difference that, after this peak, the viral load falls very quickly and the disease does not appear.

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New test trials to diagnose Covid 19: Ramon Martinez, Scientific Director of CIBER-BBN is interviewed by Spanish Television

Ramón Martinez, Scientific Director of CIBER-BBN and NANBIOSIS unit 26 NMR: Biomedical Applications II is interviewed by Spanish Television about the research he is coordinating at the Polytechnic University of Valencia to develop new tests as an alternative to PCR.

Dr. Elena Aznar CIBER researcher at IQMA-IDM-UPV group explains how work these test that allow to diagnose quickly, easily, reliably and cheaply if a person is or has been infected by the SARS-COV-2 virus. Ramón Martínez Máñez, leader of the project, reports on the point where the investigation is, as well as the difference of these tests with PCR or antigen tests. These tests implement a technology of the research group that has already been used for other pathogens and that they try to adapt to the COVID virus. “My impression – explains Dr. Martínez – is that the time will come when these tests can be sold in pharmacies and can be used by the users themselves. At the moment we have to see if they work in patient samples and then adapt it so that be a marketable kit by an interested company “

The interview can be whatched here:

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New updated version of the CSIC report on COVID-19

The report by Spanish Higher Council for Scientific Research (CSIC) summarizng the most relevant scientific results on the Covid-19 pandemic.  “A global vision of the Covid-19 pandemic: What we know and what we are investigating from CSIC”, has just published its version number 4.

This report is structured in five blocks: prevention, disease, containment and diagnosis, treatment and vaccines, and global impact.

The containment and diagnosis block describes how the virus is transmitted in the air indoors and the analysis of wastewater as a system for early detection of SARS-CoV-2 is explained. In addition, the importance of diagnosis in the face of the pandemic is underlined and the different types of detection tests available and the diagnostic strategies to control the spread of the infection are detailed. The CIBER-BBN/IQAC-CSIC Nb4D research group and its research platform NANBIOSIS-ICTS Unit 2 Custom Antibody Service (CAbS) takes and important role in this block.

Pilar Marco, Scientific Director of CAbS is co-author, toguether with Cesar Fernandez (IBM-CNM-CSIC) of the chapter 3.4 “The role of the Diagnosis in the face of pandemic” wich provides information on the types of tests, how to perform and how to use them for the different purposes for which  diagnosis is an indispensable tool. “From a broad perspective, we can  distinguish between two types of tests: A. Viral tests: they detect the SARS-CoV-2 virus, include the well-known PCR (Polymerase Chain Reaction) or molecular tests, which detect the genetic material virus B. Test that detect the response of the human body to infection. They include so-called “serological tests, which detect antibodies produced by the patient’s immune system, although other types of biomarkers can also be detected.”

For further information and access to report: http://hdl.handle.net/10261/218312 

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How Nanophotonic Label-Free Biosensors Can Contribute to Rapid and Massive Diagnostics of Respiratory Virus Infections: COVID-19 Case

An accurate and explanatory review recently published in ACS Sensors. led by Prof. Laura Lechuga, Scientific Director of Nanbiosis U4 Biodeposition and Biodetection Unit from CIBER-BBN and ICN2, discusses current diagnostic techniques for COVID-19 and possible future developments in this field. In particular, after highlighting the advantages and limitations of the methods available at present, the article introduces optical biosensors and illustrates how nanophotonic label-free devices can contribute to meet the emerging needs in this context.

For further information at ICN2 website

Reference article:

Maria Soler, Maria Carmen Estevez, Maria Cardenosa-Rubio, Alejandro Astua, and Laura M. Lechuga, How Nanophotonic Label-Free Biosensors Can Contribute to Rapid and Massive Diagnostics of Respiratory Virus Infections: COVID-19 Case; ACS Sensors, August 2020. DOI: 10.1021/acssensors.0c01180

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NANBIOSIS scientists in Aragón, explain on TV their research againts coronavirus

The special program on the coronavirus pandemic  by “En Ruta con la Ciencia” of Aragón Televisión, analyzes different aspects of the disease with special attention to the work of Aragonese scientists. Among them, two  research groups that coordinate NANBIOSIS units 9 and 27.

Starting at minute 44’45 ‘of the program, Doctor Jesús Lázaro, researcher of the BSICoS group of I3A-UZ and CIBER-BBN, led by Pablo Laguna, which coordinates NANBIOSIS U27 High Performance Computing Unit, explains his research. For almost 3 years, Jesús Lázaro had been working on a European project to develop a respiratory and heart rate monitoring system for patients with EPOC to control and predict episodes of worsening disease, but the current situation has led him to redirect his goal to try to provide solutions in this crisis and have creates an application for the mobile phone to detect from our home, if we have a viral infection: – “The parameters measured by this application have to do with the nervous system Autonomous, – explains Jesús Lázaro – they are the heart rate, its variability and the respiratory rate, these three parameters would allow observing a response through SARS-COV-2. The application works based on a technology that uses the flash of the mobile phone camera as a receiver to obtain a signal that is proportional to the blood volume of the finger put on the flash light, what allows detecting both, the number of beats per minute and the morphology of the arterial pulse, to obtain the respiratory rate. At the moment this application has been tested by the research staff and the next phase is to assess it with the general public. As the application is based on detecting autonomic markers, a very high sensitivity is expected, as well as a very low specificity, which would allow detecting not only SARS-COV-2 but analyzing these parameters in other contexts and in other diseases, even detecting other eventual viruses of other eventual pandemics ”.

Further information on the research project here

Starting at 28’14 ’’ One of the problems of the coronavirus test is what is known as false negatives, people who have passed the disease, but are not detected and could continue to spread it. A research group is developing early diagnostic tests to try to reduce this error rate. Pilar Martín Duque, at the IACS Aragonese Institute of Health Sciences, is a researcher of the NFP group of the INA and the CIBER-BBN, led by Jesús Santamaría, which coordinates NANBIOSIS U9 Synthesis of Nanoparticles Unit : – “All techniques have a detection limit and a sensitivity, it is necessary to have a minimum amount of virus in the body for the virus being detected, if the viral load is low it may not be detected at that time, it is possible that some patients with a low viral load recover, but in other cases the virus begins to grow and after two weeks they can be positives”- explains Pilar Martín. Her project makes PCRs more effective by concentrating the viral load before testing. – “There is a curious case, – continues Pilar -, of an American navy ship, moored in China, in which five sailors were detected to be infected by coronavirus, so they were quarantined during fourteen days and, after new tests with negative results, they were allowed to return to the United States on the ship. However halfway through the journey, the same five sailors suffered an outbreak of the disease. Therefore, our study would be useful for detecting patients with the virus tested for the first time or for not discharging patients who had been already diagnosed if they really are not yet negative”.  It is estimated that 10% of the population has infected 80%, these 10% are the so-called “superspreaders”, they are infected with a high viral load, but they feel well and do not know about it. For example, there have been several cases in choirs, such as the Choir of Zarzuela in Madrid, where 53 members were contagious out of the 80 members form the choir, this is because when singing or speaking very loudly, more drops are produced that carry the virus”. But why do some people become infected before others? Pilar explains that this is related to some, already known, receptors for entry of viruses, the AC2 receptors, and there are people who has more of these receptors than others.

Further information on the research here:

If we have learned anything from this pandemic it is the importance of health and research, a robust research system has the knowledge, tools, and human talent to respond to any situation. If we want to be prepared for the next pandemic, it is important and essential to continue betting on research.

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The European Commission releases a video showing the European project against coronavirus led by prof Laura Lechuga

The European Commission Representation in Barcelona has published the five-minute video “The EU fights the Covid-19 from Catalonia” in which four researchers explain the projects they are working on.

The researchers appearing in the video are  Laura Lechuga Scientific Director of NANBIOSIS unit 4 from CIBER-BBN and ICN2-CSIC and Group Leader of CIBER-BBN at the ICN2 Nanobiosensors and Bioanalytical Applications Group), who works on a sensor to detect the coronavirus in a faster, easier and cheaper way than with current PCRs, Núria Montserrat (IBEC), who works on micro-kidneys made from stem cells to test a drug able to block the virus, Alfonso Valencia (BSC), who explains the huge computation power that the BSC can bring into play to find already existent drugs that may be suitable to treat Covid-19,  and Gabriel Anzaladi (Eurecat), who studies the presence of the virus in wastewater to estimate the people infected in a given zone or the probability of a new outbreak.

The European Commission is present in all Member States through a network of offices, called “representations”, which aim to report on the Commission’s activity and to bring the policies of the European Union closer to citizens. They are also in charge of capturing the social reality and the climate of opinion at street level and transferring this information to the European institutions in Brussels so that their policies better respond to the needs of citizens. In Catalonia and the Balearic Islands, this work is carried out by the “Representation of the European Commission in Barcelona”.

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New methods to detect Coronavirus: interactive webinar on the diagnosis of COVID-19

CSIC has orgnized an interactive webinar on new COVID-19 detection systems that brings together biotechnologist Luis Blanco, nanotechnologists Laura Lechuga and Pilar Marco, and physicist Javier Tamayo .

Researchers from the Higher Council for Scientific Research (CSIC) will answer citizens’ questions about the diagnostic methods of the SARS-CoV-2 coronavirus, which causes Covid-19, in a webinar or interactive debate that will be broadcast on Wednesday, June 3, at 8:15 p.m., on the CSIC YouTube channel.

The meeting will feature the participation of biotechnologist Luis Blanco, the physicist Javier Tamayo and the nanotechnologists Laura Lechuga, Scientific Director of NANBIOSIS unti 4 Biodeposition and Biodetection Unit and Pilar Marco, Scientific Director of NANBIOSIS unit 2 Custom Antibody Service (CAbS). The debate will be moderated by geneticist, biotechnologist and popularizer Lluis Montoliu, from the National Center for Biotechnology (CNB-CSIC),

Questions can be sent in advance to the address webinar@csic.es, by twitter with the hashtag #CSICDiagnostico or during the broadcast via YouTube chat. After the broadcast, it will be hosted on the CSIC’s YouTube channel for consultation, such as previous discussions on prevention and de-escalation and treatments and vaccines.

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“We need a drastic change in the organization and management of science”

The Jorunal “Redacción Médica” has created an espace call Covid-19 Lessons to gather critical evaluations and recommendations of the most relevant personalities in the health sector, so that the National Health System and the professional and business ecosystem that surrounds it can draw conclusions and face future similar challenges with greater guarantees.

Laura M. Lechuga, Scientific Director of NANBIOSIS U4, from CIBER-BBN at ICN2-CSIC, coordinates CONVAT, one of the projects selected by the European Commission to advance in the knowledge about the Coronavirus, adds her perspective to the document Covid-19 Lessons: “We need a drastic change in the organization and management of science“

According to prof. Lechuga, ·one of the main successes in this crisis has been the intense and excellent dedication of a large part of the international scientific community who, from a multidisciplinary perspective, has tried to contribute their talent and training to make great strides in the knowledge of this new SARS-CoV-2 virus; this crisis has driven this collaboration exponentially. “The rapid mobilization of funds and resources available to scientists has also been (and continues to be) impressive during this crisis. The pandemic has placed before the eyes of all humanity that the greatest values of our society lie in knowledge, training, science and research to face a problem of these dimensions that unfortunately may be repeated in the future.“

As main errors, Laura Lechuga highlights the disconnection between the scientific and political world. “The scientits had contributed its knowledge and rigorous studies to warn of the dangers that lie in wait for us, but it is clear that until now the connection between scientific advice and government policies is extremely weak, not only in our country. country but also internationally”

Possibly, at the national level, our scientific system could have given a faster response if it had been much more robust and competitive and had not been so weakened due to the numerous cuts suffered since the previous crisis and the lack of replacement of researchers. Our research environment, although it is nourished by a lot of talent, is not so much in its own development resources, infrastructures and technologies, so its contribution is being more limited.

There is no doubt that we need a decided investment in science both in terms of human and material resources, and a drastic change in the organization and management of science, which causes our scientists to invest most of their valuable time in requests for funding, resources human and cumbersome administrative justifications, which have little to do with scientific research“.

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CoNVaT, the ‘Nanotrap’ for the coronavirus – highlighted by BBVA Fundation

Prof. Laura M. Lechuga, Scientific Director of NANBIOSIS Unit 4 Biodeposition and Biodetection Unit (from CIBER-BBN and ICN2-CSCIC) was awarded with the Physics, Innovation and Technology Award of the Royal Spanish Physics Society (RSEF) and the BBVA Foundation 2016.

BBVA Foundation has dedicated an article to explain the  EU CoNVaT project, led by Laura Lechuga, whose objective is to obtain a diagnostic test for COVID-19 from the first day of infection, fast but highly sensitive, and which does not require a laboratory or qualified personnel. A test made with extremely sophisticated technology, and at the same time low cost, applicable to future waves of the epidemic. It is financed with more than two million euros by the European Union with a duration of one year.

The test is a biosensor that uses nanophotonics, and it will be used in two devices: one will detect virus proteins, the other, its genetic material. The heart of the device, and what gives it its main advantage over other existing diagnostic tests, is a chip that implements one of the most sensitive measurement techniques in physics: photonic interferometry. It is based on the idea that a beam of light undergoes small but measurable changes when it intersects an object. On the CoNVaT project chip, changes in the light beam will alert to the presence of the virus in the sample.

The test that will detect virus proteins is what is technically called an ‘antigen test’. It can be carried out in health centers or at sampling points, by non-specialized staff, and will give results in less than thirty minutes. Saliva samples will surely be used, although researchers are still studying it.

“The technique is so sensitive that it will be able to detect the presence of the virus from the first day of infection,” explains Lechuga. “And it will not only tell if the virus is or not, but also in what quantity. This is important because it gives an idea of ​​how advanced the infection is. ”

‘Nanotrap’ for the coronavirus

The device will occupy what a shoe box, but at its core, where the measurement takes place, everything happens on a nanometric scale, that is, to dimensions of millionths of millimeters. It is, in essence, a nanotrap for proteins. Researchers attach proteins designed in the laboratory specifically to trap certain proteins in the virus envelope to the chip; both fit as a key and lock, so that the proteins fixed on the chip are actually hooks of the highest specificity – they only capture the virus’s proteins.

Channels a few nanometers thick have also been engraved on the chip: light passes through them. These guides form a circuit with a single input, but which forks, so that only one of the branches passes through the protein trap. When both light beams meet again, it is observed that the one that has interacted with the proteins has undergone modifications, and it is the analysis of these changes that reveals the presence of the virus, and in what quantity.

The device to detect genetic material of the virus -RNA- is based on the same principle, but it should be done in the laboratory. Lettuce explains that its purpose will be above all to confirm the result of the first. It will be faster than the PCR currently used – less than half an hour versus several hours – and it does not need specialized technicians – something indispensable with PCR.

Biology is the most difficult

“In this type of device, the biological part is by far the most complex,” explains Lechuga. Anchor the proteins to the chip at the correct angle, stabilize them to resist movement, keep them in a liquid medium … “they are thirty steps”.

It is a very sophisticated technology but already validated in the clinic. The ICN2 Biosensors and Bioanalytical Applications Group led by Lechuga has developed, among others, nano-biosensors that detect colon cancer early in blood samples, and also for tuberculosis and sepsis cases. “One of the reasons we have achieved the ConVAT project is that we have experience with clinical samples, which is really a completely different world than the laboratory.”

The group advances fast. They started working about three weeks ago and have just received from their French collaborators proteins that match those of the virus. Patient validation, when the device is completed, will be handled by the group in Italy.

The objective, at the end of the project, is for a company to take care of scaling the technology to bring it to the market at an affordable price. “Especially in a situation like the current one, we work with the idea that our work can reach everyone, as soon as possible,” says Lechuga.

Further information in Spanish in the original article by MÓNICA G. SALOMONE BBVA Foundation

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