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News U4

News U4

Laura Lechuga, Scientific Director of NANBIOSIS Unit 4 is interviewed by CIBER Bulletin

Laura M. Lechuga, group leader of the CIBER-BBN at the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and Sccientific Director of NANBIOSIS Unit 4 Biodeposotion Unit explains her research in an interview to CIBER Bulletin

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Nanobiosensors for the monitoring of brain lesions

On March 11, the first meeting of the European project ABISens “Monitoring of Acquired Brain Injury and recovery biomarkers by the combined label-free nanoSensing of multiple circulating molecules” was held at the facilities of the Catalan Institute of Nanoscience and Nanotechnology ICN2.

This new initiative aims to offer a new platform for photonic nanobiosensors that allows the identification and quantification of multiple brain biomarkers in blood with high sensitivity and in a short time. The new platform will use nanophotonic circuits in combination with the chemistry of oligonucleotides.

Two units of NANBIOSIS participate in the project Unit 4 Biodeposition and Biodetection Unit, led by Laura Lechuga, as coordinator of the EURONANOMED-III project and recenttly incorporated unit 29 of Oligonucleotide Synthesis Platform lead by Ramón Eritja. The project, which will also work with researchers from the Maugeri Spa Società Benefit Clinical Institute (ICSM) of Italy and researchers from the University of Bordeaux (UNIBO) in France, responds to the clinical need to evaluate patients after brain injuries that cause disabilities serious. The final tool developed after the project will be validated in samples of 40 patients with brain injury.

The project, which will last for 3 years and has a budget of more than € 700,000, is financed by the call for transnational research projects in nanomedicine, within the framework of the European research network ERA-NET Cofund EURONANOMED III (2016- 2021) “European Innovative Research & Technological Development Projects in Nanomedicine (ENM III)”. At a national level, the Carlos III Health Institute will be the entity that will finance the coordinating group of CIBER-BBN

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in our units, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer in the Scientific Direction of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Laura Lechuga and M.Carmen Estevez in the Direction and Scientific Coordination of U4 Biodeposition and Biodetection Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Mª Virtudes Céspedes in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 

Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS

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Label-free bacteria quantification in blood plasma by a bioprinted microarray based interferometric point-of-care device

Prof Laura Lechuga, Scientific Director of NANBIOSIS U4 Biodeposition and Biodetection Unit is coauthor of an article publish by ACS Sonsors that shows a portable and autonomous device based on optical interferometry that, when used with specialized nanoplasmonic, can detect directly bacterial cells of the patient’s blood plasma.

The work demonstrates the potential of a microarray based POC device for bacteria quantification. The contribution of NANBIOSIS, in particular Unit 4, has been fundamental by providing the  molecular printers necessary for the generation of the biofunctionalized specific microarrayed chips used for the bacteria detection.

P. Dey, N. Fabri-Faja, O. Calvo-Lozano, R. Terborg, A. Belushkin, F. Yesilköy, A. Fàbrega, J. C. Ruiz-Rodriguez, R. Ferrer, J. J. González-López, M. C. Estévez, H. Altug, V. Pruneri, L. M. Lechuga. Label-free bacteria quantification in blood plasma by a bioprinted microarray based interferometric point-of-care device. ACS Sens., 20194 (1), pp 52–60 DOI: 10.1021/acssensors.8b00789

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Laura Lechuga, Scientific Director of Unit 4 of NANBIOSIS Coordinates a EuroNanoMed project

ABISENS Monitoing of Acquired Brain Injury and recovery biomarkers by the combined label-free nanosensing of multiple circulating molecules is one of the project awarded in the EuroNanoMed III joint call, will be coordinated by Laura Lechuga through the CIBER-BBN

Abisens will employ the Unit 4 of Nanbiosis, Biodeposition and Biodetection Unit or the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation

The evaluation of patients after brain injuries, which produces severe impairments, remains a major unmet clinical need. Nowadays the diagnosis, prognosis and the efficacy of rehabilitation treatments are mainly assessed by clinical examinations, neuroimaging and electrophysiological tests during a long hospitalization stay. The aim the project is to offer as an alternative a new nanobiosensor platform able to identify and quantify multiple brain biomarkers in blood with high sensitivity and in a short time. The new biosensor platform will employ nanophotonic waveguide circuits in combination with oligonucleotide chemistry.

The project will be characterized by a strong interdisciplinary and translational nature resulting from the meeting between real clinical needs and high-level technological integration of biosensing and bimolecular aspects.

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NANBIOSIS Against Cancer

The World Health Organization, the International Cancer Research Center (IARC) and the International Union Against Cancer (UICC) celebrate February 4 of each year as World Cancer Day

Every year, 14 million new cases of cancer are diagnosed worldwide and the disease causes 8.2 million deaths.

Thanks to scientific research, great advances have been made in the fight against cancer. Through surgery, chemotherapy or radio therapy and, in the last 20 years, through immunotherapy, hormonal treatment or cell therapies, tools have been obtained to improve early diagnosis and treatments, increasing cancer survival by 20%.

The only way to understand cancer and, someday, eradicate it or eliminate the suffering and death due to this disease, is RESEARCH

NANBIOSIS as an ICTS (Singular Scientific and Technical Infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples are bellow:

Thanks to a coordinated action between units U1 of Protein Production Platform (PPP), U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, NANBIOSIS is developing nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer, by using of proteins with high specificity of binding to metastatic cells and a high degree of permanence in the blood flow, loaded with anti-cancer drugs that are selectively released inside the tumor cells that are going to form the metastases. Through the public financing of a NEOTEC project and a RETOS-COLABORACION and the company NANOLIGENT SL, the first antimetastatic drug on the market will be developed.

The Protein Production Platform-PPP collaborates with research projects whose objective is the development of new cancer therapies based on recombinant modular proteins with the ability to self-assemble. These multimeric complexes have shown, in animal models, a high stability in serum and an improved biodistribution compared to that observed with drugs for clinical use. These principles have been valued in different types of cancer, including colorectal cancer and breast cancer. The modular design of these constructions allows the incorporation or substitution of direct peptides and therefore they are presented as a transversal tool for more effective treatments against cancer. In addition, the PPP has served the Vall d’Hebron Institute of Oncology (VHIO) of Barcelona, the Josep Vilanueva group (CIBERONC) in the field of biomarker study and new targets associated with triple negative breast cancer (TNBC).

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit is working on a project in collaboration with VHIR, financed by the Spanish Goverment and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

Unit 6 is also working on the project Artificial Lymph Nodes for Cancer ImmunoTherapy (ALYCIA) A project born of a initiative of CIBER-BBN/ CIBERONC to enhance scientific interdisciplinary collaborations between research groups working on oncology and nanomedicine. Researchers of unit 6 will develop Artificial Lymph Nodes (ALN) based on dynamic 3D scaffolds able to promote efficient ex vivo lymphatic cell expansion of relevant phenotypes. Such ALN represent a new approach to lymphocyte expansion, which not only includes artificial Antigen Presenting Cells in suspension like the state-of-the-art expansion techniques, but also mimics the function of the LN ex vivo.

One of the singular capabilities of the U25 of NANBIOSIS NMR: Biomedical Applications I is the acquisition of high quality, high resolution preclinical magnetic resonance imaging/spectroscopy/spectroscopic imaging data. This allows performing leading-edge studies in preclinical cancer models such as noninvasive therapy response follow-up in murine brain tumours, revealing new response biomarkers with translational potential for brain cancer patients.

NANBIOSIS U4 Biodeposition and Biodetection Unit  is currently developing the national project PREDICT Point-of-care Nanoplasmonic Platforms for Novel High-Value Diagnostics and Therapy Follow-Up , which works in the early detection of lung cancer. PREDICT project will use the Unit 4 of Nanbiosis for the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation.

Finally, Unit 20 of NANBIOSIS In Vivo Experimental Platform at VHIR, is the most implicated of the CIBER units on projects in the field of cancer, just to name some of them: H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells. FIS-ISCIII: polymeric micelles for siRNA and combined therapy against breast cancer tumor stem cells. CarboXigel: hydrogels for the sustained release of chemotherapeutic drugs against the metastatic spread of ovarian cancer. MelanoMir: nanomedicine applied to skin cancer, melanoma, beside other projects promoted by CIBER-BBN.

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New device could monitor treatments with anticoagulant to achive personalized therapies

  • Researchers from NANBIOSIS units 2 and 4 have designed a biosensor device based on gold nanostructures that precisely detects the presence of the anticoagulant drug from a small blood sample.
  • Treatments with anticoagulants such as Sintrom® (acenocoumarol) face the difficulty of adjusting the drug doses. This device will allow patients to self-regulate the dose.

 

Researchers of NANBIOSIS unit 4  Biodeposition and Biodetection Unit of the Consejo Superior de Investigaciones Científicas (CSIC), the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and CIBER Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) have developed a biosensor device which allows the monitoring of anticoagulants such as Sintrom® (acenocoumarol) to deliver a personalized therapy in which the patient or doctor can adjust the drug dose to achieve the optimal effect.

The ICN2 Nanobiosensors and Bioanalytical Applications (NanoB2A) Group, led by CSIC researcher Prof. Laura Lechuga, Scientific Director of NANBIOSIS U4 (Biodeposition and Biodetection Unit), designed this plasmonic device containing gold nanostructures to which specific bioreceptors can be attached, in order to detect biomarkers in a reproducible and accurate way using a small sample of the patient’s blood and without the need for any prior treatment.

Previously, the Nanobiotechnology for Diagnostics (Nb4D) Group of the CSIC’s Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), led by Prof. M. Pilar Marco, Scientific Director of NANBIOSIS U2 (Custom Antibody Service (CAbS),  produced haptenized proteins (similar to Sintrom®) and polyclonal antibodies specific for this anticoagulant in the U2 of NANBIOSIS. The large experience of U2 unit in the preparation of labeled proteins and production of monoclonal and polyclonal antibodies has resulted in the generation of specific antibodies capable of recognizing Sintrom®. Their usefulness has been demonstrated in a clinical study using an immunoanalytical technique with high sample throughput.

Building on their previous results, the two groups collaborated to develop an automated biosensor device allowing a personalized dose adjustment of this oral anticoagulant. Their results were recently published in Biosensors and Bioelectronics.

As stated by CSIC researcher Prof. Laura Lechuga, “we have studied the optimal conditions to develop this biosensor device and have obtained excellent sensitivity to detect the anticoagulant, which indicates that it is possible to measure very low concentrations of this drug”.

Since it is a quantitative and highly sensitive technology, this device is very suitable for its use in clinical environments, where it could provide a real time follow-up of the medication, or even for patients to manage the medication themselves, a significant breakthrough for people receiving anticoagulants.

Patients suffering from cardiovascular diseases or thromboembolic disorders are usually treated with anticoagulants such as Sintrom® to prevent blood clots formation. The problem is that this treatment entails risks, explain the researchers. “For example, in case the dose is too low, it would not achieve the expected effect and blood clotting may occur; On the other hand, in case the dose is too high, it could cause side effects such as internal bleeding. The right dose depends on many factors such as weight, age, diet and interaction with other medications. ”

 

Reference articles:

Nanoplasmonic biosensor device for the monitoring of acenocoumarol therapeutic drug in plasma Cristina Peláez, M Carmen Estévez, Alejandro Portela, Pablo Salvador, Pilar Marco, Laura M. Lechuga. Biosensors and Bioelectronics, 119, 2018, 149-155 – DOI: 10.1016/j.bios.2018.08.011

Enzyme-linked immunosorbent assays for therapeutic drug monitoring coumarin oral anticoagulants in plasma J.Pablo Salvador, Dolors Tassies, Joan-Carles Reverter, M.-PilarMarco. Analytica Chimica Acta. https://doi.org/10.1016/j.aca.2018.04.042

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Label-free DNA-methylation detection by direct ds-DNA fragment screening using poly-purine hairpins

Prof Laura Lechuga, Scientific Director of NANBIOSIS Unit 4 Biodeposition and Biodetection Unit, has led the research whose results have been published by Biosensors and Bioelectronics  with the title  “Label-free DNA-methylation detection by direct ds-DNA fragment screening using poly-purine hairpins

Cancer diagnosis continuously evolves due to the better understanding of tumorigenic processes. DNA-methylation is consolidated as an effective biomarker for cancer prognosis and diagnostic even in tumors of unknown origin. The reversibility of this epigenetic mechanism also places it as a high-profile tool for the development of more sophisticated and personalized therapies. Current methodologies, such as bisulfite conversion or PCR amplification, rely on complex procedures that make difficult the standardization of epigenetics analyses. Here we present an optical biosensor methodology based on Surface Plasmon Resonance that employs poly-purine reverse-Hoogsten hairpin probes capable of interacting directly with ds-DNA fragments by triple helix formation. The direct interaction with the material of interest can greatly enhance the reliability of the analysis providing a more accurate and precise diagnosis. We have demonstrated the capabilities of our methodology for the direct capture of ds-DNA fragments and specific methyl-cytosine quantification. Our poly-purine hairpin probe demonstrated the specific capture of ds-DNA fragments while the standard duplex-forming probes failed to do so. In addition, the biosensor methodology showed a strong correlation with the different DNA methylation status
between the sequences with a low signal variation (≤8%CV) along 35 hybridization/regeneration cycles. Through its straightforward procedure and versatility of detecting different DNA  modifications related to the DNA methylation process, we anticipate that our strategy will enable a greater level of accuracy and precision in cancer diagnostics making a strong impact on the development of personalized therapies

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Nanoplasmonic biosensor device for the monitoring of acenocoumarol therapeutic drug in plasma

As a result of the collaboration carried aout by two units of NANBIOSIS, U4. Biodeposition and Biodetection Unit and U2. Custom Antibody Service (CAbS), it has been developed a compact and simple nanoplasmonic sensing device based on gold nanodisks for the rapid monitoring of acenocoumarol, using highly specific polyclonal antibodies produced against the drug Acenocoumarol (Sintrom®) which implies:

  • A label-free nanoplasmonic device for the rapid monitoring of acenocoumarol in plasmaD.
  • Direct quantification in real time requiring low sample volume is achieved.
  • Non-specific interferences from plasma are minimized using the developed methodology.
  • Excellent accuracy has been observed measuring blind plasma samples.
  • Potential to be implemented as a POC device in decentralized settings.

 

The research details have been published in the article authored by E. CristinaPeláezM.-CarmenEstevezAlejandroPortelaJ.-PabloSalvadorM.-PilarMarco and Laura M.Lechuga, “Nanoplasmonic biosensor device for the monitoring of acenocoumarol therapeutic drug in plasma, Biosensors and Bioelectronic, 119, 2018, 149-155 – DOI: https://doi.org/10.1016/j.bios.2018.08.011

 

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Interferometric nanoimmunosensor for label-free and real-time monitoring of Irgarol 1051 in seawater

As a result of a collaboration in the context of the EC-FP7 program OCEAN 2013, NANBIOSIS Unit 2 Custom Antibody Service (CAbS) and  Unit 4. Biodeposition and Biodetection,  the research groups coordinating this NANBIOSIS Units have recently published an article titled “Interferometric nanoimmunosensor for label-free and real-time monitoring of Irgarol 1051 in seawater” in the scientific magzine  iosensors and Bioelectronics.

The CIBER-BBN-ICN2 group  Nanobiosensors and Bioanalytical Applications, led by Prof. Laura Lechuga has developed the immunosensor that is described in the article using immunoreactive, produced in the group of  Nanobiotechnology for Diagnostics Group (Nb4D), led by Prof. Pilar Marco, with the collaboration of CAbS, for Irgarol 1051. This compound is an alguicide used as an additive in the paintings of ships. Over time, the compose is being released  into the marine environment causing a risk to the ecosystem and to the health of the population.

In the article, an interferometric nanobiosensor for the specific and label-free detection of the pollutant Irgarol 1051 directly in seawater has been settled. Due to the low molecular weight of Irgarol pollutant and its expected low concentration in seawater, the sensor is based on a competitive inhibition immunoassay. Parameters as surface biofunctionalization, concentration of the selective antibody and regeneration conditions have been carefully evaluated. The optimized immunosensor shows a limit of detection of only 3 ng/L, well below the 16 ng/L set by the EU as the maximum allowable concentration in seawater. It can properly operate during 30 assay-regeneration cycles using the same sensor biosurface and with a time-to-result of only 20 min for each cycle. Moreover, the interferometric nanosensor is able to directly detect low concentrations of Irgarol 1051 in seawater without requiring sample pre-treatments and without showing any background signal due to sea matrix effect.

Article of referencehttps://doi.org/10.1016/j.bios.2018.05.044

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