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News U26

News U26

New device for more efficient gluten detection

About 1% of the world’s population suffers from celiac disease, a complex and autoimmune disorder caused by ingestion of gluten and for which there is no treatment beyond its elimination from the diet. In Spain every May 27, the National Celiac Day is commemorated to publicize the disease and give visibility and support to people with celiac disease.

The detection of gluten becomes a key element for celiac patients to control the disease, as well as for the food industry, whose regulation requires declaring its presence in food. In this line, a team of researchers coordinated by the professor of the Polytechnic University of Valencia (UPV) and scientific director of the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Ramón Martínez Máñez, are working on the development of intelligent methods for the gluten detection, to avoid the involuntary ingestion of this protein and also collaborate with the regulation and the fight against fraud in the food industry.

Recently published work in Analytica Chimica Acta presents a new system that enables rapid detection of gluten through a simple signaling process. As the authors state, it could be the basis for the development of portable, fast, sensitive and easy-to-use systems for the control of gluten in foods.

“The biosensor is composed of a nanoporous anodic alumina film loaded with a fluorescent dye and covered with an aptamer (DNA or RNA molecule) that specifically recognizes gliadin, which is the soluble protein of gluten” explains M. Carmen Martínez Bisbal, professor from the University of Valencia (UV) and researcher at the CIBER-BBN and the Interuniversity Institute for Research on Molecular Recognition and Technological Development (IDM UPV-UV) and one of the authors of the work. “In the presence of gliadin, the aptamer moves from the surface of the biosensor, resulting in the opening of the pores and the release of the signaling dye” adds Sara Santiago Felipe, researcher at the La Fe Health Research Institute, CIBER-BBN and the IDM UPV-UV and also author of the work.

The new sensor has been validated in real food samples, allowing the detection of gluten through a simple signaling process, with great potential for use in food control. “We have found that it has a detection limit of 100 µg kg-1 of gliadin, good selectivity and a detection time of 60 minutes,” explains Luis Pla, first signatory of the work and researcher at CIBER-BBN and IDM UPV-UV.

“Our results can be the basis for developing portable, simple, fast and sensitive systems for the detection of gluten, which can be easily adjusted through the use of different molecules, offering great potential for allergen testing” concludes the scientific director of the CIBER-BBN and NANBIOSIS Unit 26 Ramón Martínez Máñez.

Article of reference:

Luis Pla, M. Carmen Martínez-Bisbal, Elena Aznar, Félix Sancenón, Ramón Martínez-Máñez, Sara Santiago-Felipe, A fluorogenic capped mesoporous aptasensor for gluten detection, Analytica Chimica Acta, Volume 1147, 2021, Pages 178-186, ISSN 0003-2670, https://doi.org/10.1016/j.aca.2020.12.060

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A new biosensor will help for the early diagnosis of breast cancer

A team of Spanish researchers coordinated by the professor of the Polytechnic University of Valencia (UPV) and scientific director of the CIBER-BBN and NANBIOSIS unit 26, Ramón Martínez Máñez, and the Valencian oncologist, co-coordinator of the Research Group of Biology in Breast Cancer of the INCLIVA Health Research Institute, of the Hospital Clínico de València, Ana Lluch, also belonging to the CIBER de Cáncer (CIBERONC), has developed a prototype of a new biosensor to help detect breast cancer in its phases earlier. The work has been published in ACS Sensors magazine.

According to the latest data collected by the European Cancer Information System (ECIS), in 2020 a total of 34,088 new cases of breast cancer were diagnosed in Spain, this type of tumor being the most frequent among the women in our country.

Currently, mammography is the most widely used standard technique for diagnosis, but it has some limitations, such as radiation exposure, and lower sensitivity and specificity in young women with dense breast tissue. “For this reason, new diagnostic tools are necessary to help in the early detection of breast cancer. Our biosensor follows this line”, explains Ana Lluch.

The development of this prototype biosensor to aid diagnosis is part of the field of what is known as a liquid biopsy, which, through a blood test, helps detect the presence of cancer. In this case, the mesoporous biosensor developed by the UPV and INCLIVA team is simple to use, inexpensive and offers results in a very short time – between 30 and 60 minutes – from a patient plasma sample.

The biosensor is composed of a nanomaterial -a nanoporous alumina- that facilitates the detection in plasma of microRNA miR-99a-5p associated with breast cancer. Until now, this has been done with complex and time-consuming techniques, which means that they cannot be used as a diagnostic tool in the clinical setting.

Ramón Martínez Máñez explains how the alternative diagnostic system in which they work works: the nanopores of the biosensor are loaded with a dye -rhodamine B- and closed with an oligonucleotide. By interacting with the plasma sample, if it does not detect the presence of the microRNA, the pore doors remain closed; instead, in the presence of miR-99a-5p, those gates are opened and the dye is released. “The change in the release of the dye can be correlated with healthy patients or with breast cancer“, summarizes Martínez Máñez.

Researchers from the La Fe Health Research Institute (IIS La Fe) have also participated in the development of this biosensor, where tests have been carried out for the validation of the new biosensors, and the Cancer Network Biomedical Research Center (CIBERONC) .

The next step in our work will consist of validation in a larger group of patients and continue working to make the detection system even more robust and easy to use,” conclude Juan Miguel Cejalvo, from the Cancer Biology Research Group of Mama from INCLIVA and Ramón Martínez Máñez.

Reference article:

Iris Garrido-Cano, Luis Pla, Sara Santiago-Felipe, Soraya Simón, Belen Ortega, Begoña Bermejo, Ana Lluch, Juan Miguel Cejalvo , Pilar Eroles, and Ramón Martínez-Máñez. Nanoporous Anodic Alumina-Based Sensor for miR-99a-5p Detection as an Effective Early Breast Cancer Diagnostic Tool ACS Sensors 2021 6 (3), 1022-1029 [DOI]

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Elena Aznar Gimeno (NANBIOSIS U26) leads a CIBER-BBN transfer project.

The CIBER-BBN transfer program, with its call for transfer projects, has selected two projects for next year with the aim of promoting the transfer of scientific or technological results, derived from the research carried out by the CIBER-BBN groups, to the industrial sector.

One of these projects selected is directed by Elena Aznar Gimeno, researcher from the group led by Ramon Martínez Máñez at the IDM-Polytechnic University of Valencia, together with an external group led by Javier Pemán García, from the La Fe Health Research Institute From Valencia.

The project has been jointly financed by CIBER-BBN and a company interested in the technology and will count with the participation of NANBIOSIS Unit 26 Biomedical Applications II

The CIBER-BBN call for transfer projects, which is now in its eighth edition, has financed fourteen projects with as many companies since its creation.

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A new generation of devices for the rapid, cheap and easy diagnosis of candidemia.

Candidemia is an infection caused by fungi of the genus Candida that is associated with high complication rates with a mortality that can reach 40%. A group of researchers have managed to develop a new material that allows for the rapid detection of candidaemia, with a sensitivity that exceeds 90% and a specificity greater than 95%.

Researchers from the CIBER-BBN (Center for Biomedical Research for Bioengineering, Biomaterials and Nanomedicine). the Polytechnic University of Valencia (UPV) and the La Fe Health Research Institute (IIS La Fe), with the participation of Unit 26 of NANBIOSIS NMR Biomedical Applications II, in collaboration with the Valencian startup MATCH Biosystems have developed a new generation of in vitro diagnostic devices (IVD), capable of improving current times, with high reliability and easy handling.

“The characterization of the anchored molecules as well as the final sensors were characterized using NMR equipment from NANBIOSIS unit 26”, explains Ramón Martínez Máñez, Scientific Director of NANBIOSIS Unit 26 of NMR Biomedical Applications of the University of Valencia and the CIBER-BBN

The group of researchers, led by Ramón Martínez Máñez, professor of Inorganic Chemistry at the Polytechnic University of Valencia and scientific director of the CIBER-BBN; and Javier Pemán, head of the Mycology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe, and head of the Severe Infection Research Group at IIS La Fe, decided to create MATCH biosystems in June 2020 with the objective of marketing in the future “the new generation of IVD devices capable of obtaining results for the diagnosis of candidemia in less than an hour in a reliable, easy way and without the need to go through a laboratory”, explains Adrián Teruel, CEO of the biomedical startup, pharmacist, doctor in nanomedicine.

Currently, the results of candedimia infection are obtained after carrying out cultures of the biological fluid in the laboratory, which can take between three and four days. With the new material and method patented by the researches’ institutions and developed by MATCH biosystems, the diagnostic time is drastically reduced.

“The tests are carried out very quickly, easily and without the need to enter a laboratory, which also reduces the equipment and personnel necessary to carry them out, with the consequent reduction in the expense that this implies for health public, in addition to allowing speed in making medical decisions that can save lives “, details Adrián Teruel.

The material used by MATCH biosystems is composed of dye-loaded porous supports and single strands of DNA, which act as molecular gates. The infection is detected when the single strands of DNA recognize the genetic material of the pathogen in the patient sample, at which point the molecular gates are opened and the dye is released, allowing the diagnosis to be carried out. The first sensors have already been developed and clinical tests have been carried out with real samples of patients, at the Hospital de La Fe.

MATCH biosystems is currently working on developing the complete kit that it expects to reach the market in a maximum of four years, in parallel with obtaining the relevant regulations and certifications.

The company has now focused on infections caused by candidemia, “but the field of application of the new devices also includes, in addition to the clinical, the veterinarian and the agri-food industry” says Teruel.

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New COVID-19 Diagnostic System Ready for Trials in Clinical Samples

The new system for the rapid, economic and efficient diagnosis of COVID-19 devised by the Universitat Politècnica de València (UPV), the IIS La Fe and the CIBER-BBN is now ready for trials on clinical samples. Since the pandemic broke out, the group of Professor Ramón Martínez Máñez, a researcher at the IDM Institute of the UPV and scientific director of the CIBER-BBN and NANBIOSIS U26 RNM for Biomedical Applications I, has been working on an alternative for the diagnosis of COVID-19, based on nanoporous films. These materials are capable of storing an indicator that is released only in the presence of the SARS-CoV-2 virus thanks to a system of molecular gates. And they do it very quickly, reliably and easily.

The material has already demonstrated its ability to detect the Spike protein present in SARS-CoV-2 and also its function for the detection of a model virus that expresses the aforementioned protein and that has been implemented by the Viral Biology group of the I2SysBio, center mixed of the University of Valencia and the Higher Council for Scientific Research (CSIC), led by Dr. Ron Geller.

“These advances represent another step towards obtaining the final device and confirming that the system is capable of recognizing virus particles”, highlights Ramón Martínez Máñez, director of NANBIOSIS U26 NMR for Biomedical Applications I.

The UPV team of researchers will carry out the clinical validation of the device in collaboration with Dr. Javier Pemán and Dr. Mª Ángeles Tormo, from the Serious Infection Research Group at IIS La Fe, by Dr. María Dolores Gómez, Head of the Molecular Microbiology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe and by Drs. Miguel Salavert and Eva Calabuig, of the Infectious Diseases Unit of the aforementioned hospital.

Once its sensitivity for the diagnosis of COVID-19 has been verified, it is planned to develop a final kit and obtain the CE marking, which will allow its commercialization. “We hope that this process will be carried out as quickly as possible and that it may be on the market to provide a new tool in the face of the pandemic that we are suffering,” says Dr. Elena Aznar, a researcher at CIBER-BBN.

Among the advantages of the device devised by the researchers of the UPV, UV, CSIC, IIS La Fe and CIBER-BBN, I would highlight its ease of use, being able to be used for the diagnosis of COVID-19 in places with limited infrastructure. Furthermore, it does not require highly qualified personnel and the sample does not have to be analyzed in specialized laboratories.

“In addition, the POC technologies on which it is based are global detection tools to monitor for possible new outbreaks in the future, so that once it is ready for use, it will contribute to the rapid implementation of containment measures”, he highlights Ramón Martínez Máñez.

The development of this project is financed by funds from the Covid-19 Donations of the Generalitat Valenciana, made by people and companies during 2020 to contribute to the fight against the pandemic. The solidarity of the Valencian citizenship materialized in donations of about 1 million euros, destined entirely to research projects of excellence against the virus such as the one led by Professor Martínez Máñez, managed by the Ministry of Innovation, Universities, Science and Society Digital.

The project also has the support of the Supera COVID-19 Fund, promoted by Crue Universidades Españolas, Banco Santander -through Santander Universidades- and the CSIC. In addition, the I2SysBio Viral Biology group (UV-CSIC) received funding from the Valencian Innovation Agency (AVI) for the implementation of the model virus.

Related news:

COVID-19 detection system: a fast, cheap and easy to use alternative to PCR.

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Three Nanbiosis units work in the development of new sensors for the better detection of the fungus P. jirovecii, responsible for Pneumocystis pneumonia

Researchers from the CIBER-BBN have succeeded in developing detection systems for Pneumocystis jirovecii, an atypical fungus responsible for very serious pneumonia in immunosuppressed patients. These results, published in the journal Nanomaterials, are the result of collaboration between the CIBER-BBN groups led by Laura Lechuga, Ramon Eritja and Ramón Martínez Máñez, and the CIBERESP group led by Enrique J. Calderón.

The researchers acknowledge the paricipation of three NANBIOSIS units of CIBER-BBN:

The detection of the fungus in patients, who may be asymptomatic carriers until they develop pneumonia, is currently carried out using the PCR technique, requiring several hours, adequate facilities and qualified personnel to detect it. Now, the application of Nanotechnology has allowed the development of more sensitive and efficient biosensors to detect specific sequences corresponding to pathogens responsible for infectious diseases in a shorter time and without the need for large infrastructures.

In this case, a specific sequence corresponding to the gene belonging to the ribosomal subunit (mtLSU rRNA) of the P. jirovecii fungus has been detected using hairpin-shaped capture probes. These specific probes, as pointed out by Dr. Aviñó, a researcher at CIBER-BBN at the IQAC-CSIC, “are more efficient and are capable of recognizing a specific genomic sequence of the fungus and forming very stable triplex structures that can be detected on different platforms. biosensor “.

Laura Lechuga’s team at ICN2, through the use of an optical biosensor based on SPR technology, has detected in real time and without the use of markers, P. jirovecii in bronchoalveolar lavages and nasopharyngeal aspirates with a detection limit of nM level and in just a few minutes.

Likewise, the group led by Ramón Martínez-Máñez, scientific director of CIBER-BBN and principal investigator of the IQMA-IDM group at the Universitat Politècnica de València, has used the strategy of molecular gates composed of an anodic albumin matrix to develop a sensor capable of to efficiently detect real P. jirovecii samples without previous amplification steps in as little as one hour.

“These advances in the diagnosis of PCP have great potential for the development of highly sensitive point-of-care devices using direct patient samples and applicable in a wide variety of settings,” says the CIBERESP group leader. Enrique J. Calderón from the Virgen del Rocío University Hospital in Seville.

The researchers also emphasize that these techniques are very selective and can discriminate patients with other respiratory diseases derived from other microorganisms, thus allowing a more reliable diagnosis of infectious diseases.

Articles of reference:

Calvo-Lozano, O., Aviñó, A., Friaza, V., Medina-Escuela, A., S Huertas, C., Calderón, E. J., Eritja, E., Lechuga, L. M. (2020). Fast and accurate pneumocystis pneumonia diagnosis in human samples using a label-free plasmonic biosensor. Nanomaterials, 10(6), 1246. https://doi.org/10.3390/nano10061246

Pla, L., Santiago-Felipe, S., Aviñó, A., Eritja, R., Ruiz-Gaitán, A., Pemán, J., Friaza, V., Calderón, E.J. Martínez-Máñez, R., Aznar E. (2020). Triplex hybridization-based nanosystem for the rapid screening of Pneumocystis pneumonia in clinical samples. Journal of Fungi, 6(4), 292. https://doi.org/10.3390/jof6040292

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The Nanomedicine Revolution

Yesterday, November, 25 took place, within the the program of the Ateneo of the EINA (School of Engineering and Architecture of Aragón), the online conference on “The Revolution of Nanomedicine” by Ramón Martínez Máñez.

The Conference chair, Jesús Martínez de la Fuente, Principal Investigator of the BIONANOSURF group of CIBER-BBN and the Institute of Nanoscience and Materials of Aragón, introduced the guest, Ramón Martínez Máñez, Scientific Director of CIBER-BBN, highlighting “his creativity in the use of his systems and how he combines them with different diagnostic release systems, combining organic chemistry, surface chemistry, applications in biotechnology and giving way to translation and transfer, his works are very unique

Ramón Martínez Máñez, Scientific Director NANBIOSIS unit 26 NMR: Biomedical Applications II, gave a very instructive talke about what is nanotechnology and how nanotechnology revolution has reached the medicine, with current examples of the application of nanomedicines, as well as in the medicine of the future.

After it, a very interesting debate took place in which different issues were discussed, especially in relation to nanomedicine applied to therapy, such as the barriers to generalize the use of nanoparticles in therapy, the current state of implantation of nanoformulated drugs in the market and the advancement of the use of some nanoparticles as polymers or liposomes compared to inorganic nanoparticles, the degree of development of nanoparticles under GLP certification or why cancer is the main target of nanomedicine with a great difference over other pathologies. The audience asked questions that led to the discussion of some more controversial points such as whether it is true that “Big Pharma” does not like nanoparticles, why there is a regulatory vacuum regarding their use and how to solve these problems.

Regarding the diagnosis applications, Ramón Martínez commented that “nanotechnology already has its way open, both in the development of nanoparticles and systems to amplify the signal, based on nanophotonics, resonant rings or other technologies at the nanometric level. The pandemic has highlighted the importance of having rapid detection systems for bio parameters, pathogens, bacteria … We have a lot of knowledge acquired in recent years in these systems and they are currently being developed in a more or less short time, we are truly close to revolutionizing the field of detection“.

Finally, in realtion with the nanomedicine of the future, the questions raised in the debate revolved mainly around nanobots and their state of development or the problems that are emerging in it or the possibility of uniting nanomedicine with artificial intelligence and possible applications.

The Ateneo is an activity of the EINA in collaboration with the Aragón Engineering Research Institute and SAMCA Chair of Technological Development of Aragon, both directed by Pablo Laguna, Scientific Director of Nanbiosis U27 High Performance Computing. Pablo Laguna closed the event thanking Ramón Martínez Máñez and Jesús Martínez de la Fuente for their participation and highlighting the high number of attendees at the conference.

The conference can be followed in Spanish in EINA youtoube channel: https://www.youtube.com/watch?v=Y_Fh1O1VuNU

Anouncing this Conference in the Ateneo EINA, Ramón Martínez Máñez was yesterday interviewed by Aragon Radio. In this case, the interview had the focuss in the “Nanomedicine against COVID” . The podcast can be listen in Spanish here: https://www.cartv.es/aragonradio/podcast/emision/nanomedicina-frente-a-la-covid

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How to delay vision loss in hereditary retinal dystrophies? Looking for the most effective and economical pharmacological nanotherapy

Researchers from the CIBER-BBN and NANBIOSIS are participating in a new project that aims to achieve the most effective, specific and economical pharmacological nanotherapy that allows delaying the death of retinal cells and subsequent loss of vision in hereditary retinal dystrophy. retinitis pigmentosa, regardless of the genetic defect causing the disease.

In this project, coordinated by the researcher Regina Rodrigo, the ONCE and the Prince Felipe Research Center (CIPF) of Valencia collaborate, together with researchers from the CIBER of Rare Diseases (CIBERER) and the Manises Hospital in Valencia. On behalf of the CIBER-BBN, the scientific director, Ramón Martínez Máñez, together with Elena Aznar from the IDM-UPV group of the Polytechnic University of València, José Luís Pedraz, Gustavo Puras and Idoia Gallego, from the group of the University of the Basque Country and Nanbiosis.

The NANBIOSIS participation in the project will be through the U10 Drug Formulation unit (from @CIBERBBN and @upvehu), led by NanoBioCell Group and Prof. José Luis Pedraz and U26 NMR: Biomedical Applications II , led by IDM-UPV-UV Group, led by Prof. Ramón Martínez Máñez. Elena Aznar, researcher of CIBER-BBN at IDM-UPV-UV explained “We use the unit to characterize the nanoparticles. Through a solid phase NMR confirms that the molecular gate has been correctly attached to the surface of the nanoparticles“.

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision. Although it is considered a rare disease, it is the leading genetic cause of blindness in developed countries. So far there is no effective treatment, although there are various therapeutic approaches such as gene therapy, cell therapy, pharmacological therapy, optogenetics or electronic implants.

During the progression of the disease, an important inflammatory component has been observed that may contribute to its pathogenesis. In this sense, different anti-inflammatory strategies have been evaluated. The research group has successfully tested one of these strategies in preclinical models of retinitis pigmentosa. However, the implementation of this therapeutic strategy with nanocarriers as controlled release delivery systems would improve the mode of action of the administered drug, avoiding its degradation, increasing its half-life, stability or its availability in the retina. In this project, two types of nanocarriers will be used and their effect on the degenerative process in a murine model of retinitis pigmentosa will be evaluated.

  • PICTURE: Hematoxylin and eosin image showing that intravitreal blockade of the cytokine TNFα with Adalimumab-type monoclonal antibodies (ADA) reduces retinal degeneration, preventing the death of photoreceptors (RF) in the murine model of retinitis pigmentosa, rd10 mouse.
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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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COVID-19 detection system: a fast, cheap and easy to use alternative to PCR.

PCR (acronym in English for “Polymeric Chain Reaction”), is a type of diagnostic test for the detection of infectious diseases. The PCR diagnosis of COVID-19 used since the outbreak of the pandemic offers a high level of specificity and sensitivity but presents a certain degree of complexity, requiring specialized personnel and is expensive.

Researchers from Polytechnic University of Valencia (UPV), the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (FISABIO), the La Fe Health Research Institute (IIS La Fe) and the consortium Centro de Investigación Biomédica en Red de Bioengineering, Biomateriales y Nanomedicina (CIBER-BBN) has been working, during the pandemic. Within the framework of the Diacovid project, different tests have been carried out with a first prototype of a rapid point-of-care (POC) test, based on nanosystems with molecular gates, that would detect quickly, reliably and easily, SARS-CoV-2.

Ramón Martínez Máñez, Scientific Director of Nanbiosis U26 NMR: Biomedical Applications II explains the advantages of POC techniques as their ability to diagnose in sites with limited infrastructure, without specially qualified staf and without the requirement to transport the sample to a centralized facility. In addition, POC technologies are global detection tools for surveillance against possible new outbreaks in the future. Its use would allow the rapid implementation of containment measures, reduction of therapeutic response times, in situ detection and the use of a low sample volume.

Further information and News in UPV TV

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