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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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Electronic tongues for detecting prostate and bladder cancer

Researchers of the Applied Molecular Chemistry Group, coordinator of Unit 26 of NANBIOSIS, have participated in the development of a new low-cost system for non-invasive diagnosis of prostate and bladder cancer. It consists of a device of electronic tongues ​​based on metal electrodes, which makes it possible to quickly and easily detect this pathology from a urine sample.

The researchers evaluated the efficacy of this system from the analysis of urine samples from patients before and after surgery. In addition, samples were collected from patients with benign prostatic hyperplasia, integrated into the non-cancer group for the study of prostate cancer. This system was able to distinguish non-cancerous urine samples from the affected ones with a sensitivity of 91% and a specificity of 73%.

The specificity and sensitivity obtained by the electronic tongues in urine is higher compared to the prostate-specific PSA-blood test, which is the most commonly used procedure for the detection of prostate cancer. “The results obtained confirm the suitability of this technology of electronic tongues ​​for the identification of patients affected by this pathology. This technology has great potential for its application in clinical practice, both for the diagnosis and for monitoring the evolution of patients after therapy”, said Ramón Martínez Máñez, Scientific Director of NANBIOSIS.

The measurement of electronic tongues on the urine is done by putting the sensor, in this case composed of a set of noble and semi-precious metals, with the urine sample of the patient. It is connected to a potentiostat that applies different potentials to the electrodes and, in turn, collects the resulting currents to be analysed in a computer equipped with a computer program for multivariate analysis.

“The tongue is” trained” in a first phase with a set of patient samples and controls to generate a model that discriminates between both types of samples. That model, once validated, could be used to predict new urine samples and to be able to determine whether or not these new patients have the disease with a certain margin of sensitivity and specificity”, explains Ramón Martínez Máñez.

Potential metabolites recognized by the electronic tongue were studies by NMR using the NANBIOSIS-ICTS

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New sensor for quick and easy detection of ecstasy

Spanish, Danes and Austrian researchers, including the group led by Ramón Martínez Mánez, coordinator of Unit 26 of NANBIOSIS, have developed a new sensor to detect ecstasy in a simple, reliable, fast and selective way.

Until now, this drug is detected by techniques such as capillary electrophoresis, spectroscopy or chromatography that require the use of expensive technical equipment and qualified personnel. The new method offers the advantages of easy use, low cost and high reliability according to Beatriz Lozano, a researcher at the Interuniversity Institute for Research on Molecular Recognition and Technological Development at the Universitat Politècnica de València and the group led by Ramón Martínez Mañez.

The sensor consists of a hybrid material including an inorganic carrier charged with a dye -fluorescein- and functionalized with an organic molecule derived from naphthol.

The dye is retained when the bluebox-molecule widely used in chemistry- is coordinated to the naphthol forming a molecular gate and in the presence of ecstasy in the analyzed sample, a variation of the fluorescence occurs, whose intensity varies as a function of the concentration of Drug detected.

“The affinity of BlueBox for different neurotransmitters such as dopamine had already been described, and because of the structural similarity between that neurotransmitter and ecstasy, we thought it would be a good idea to try to open the “molecular gate” in the presence of the drug and release the dye that gives the fluorogenic response”, explains Beatriz Lozano.

The characterization of the products by NMR was carried out by using facilities from NANBIOSIS-ICTS (unit 26)

Researchers are currently working on a new sensor for the detection of other synthetic drugs.

Reference Article:

Beatriz Lozano-Torres, Lluís Pascual, Andrea Bernardos, María D. Marcos, Jan O. Jeppesen, Yolanda Salinas, Ramón Martínez-Máñez and Felix Sancenón. Pseudorotaxane capped mesoporous silica nanoparticles for 3,4-methylenedioxymethamphetamine (MDMA) in water detection. Chem. Commun., 2017, 53, 3559. DOI: 10.1039 / C7CC00186J

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