News U8

Involvement of Cellular Prion Protein in α-Synuclein Transport in Neurons

Researchers of NANBIOSIS U7 Nanotechnology Unit are coauthors of the article “Involvement of Cellular Prion Protein in α-Synuclein Transport in Neurons” by Molecular Neurobiology

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrP^C-overexpressing mice. In addition, α-synuclein binds strongly on PrP^C-expressing cells, suggesting a role in modulating the effect of α-synuclein fibrils.

Article: doi: 10.1007/s12035-017-0451-4

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Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications

Scientists of Unit 8 of NANBIOSIS are co-authors of the article “Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications“, recently published by Biotechnology and Bioengineering. The fabrication of Exoliver was performed by the platform of Production of Biomaterials and Biomolecules of the ICTS, more specifically by the “NANBIOSIS,” Unit 8.

Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.

Article of reference: https://doi.org/10.1002/bit.26776

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Graphene 2018 with the participation of NANBIOSIS Unit 8

Eli Prats and Eduard Masvidal researchers of NANBIOSIS Unit 8 Micro and Nanotechnology Unit have shown their last results in ECoG recordings and biosensing using graphene based devices at the 8th edition of Graphene Conference series, the largest European Event in Graphene and 2D Materials, which is taken place in Dresden (Germany) from the 26th until the 29th of June 2018.

Eli Prats has spoken on Label-free Direct Detection of Thrombin through graphene SGFET with chemically modified aptamers and Eduard Masvidal has given a talk on Graphene transistors for ultra-slow frequency (< 0.1Hz) in vivo neural recordings showing graphene SGFETs as a promising technology for recording ultra-slow frequencies with high-spatial resolution

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Online oxygen monitoring using integrated inkjetprinted sensors in a liver-on-a-chip system

Scientists of NANBIOSIS Unit 8. Micro – Nano Technology Unit, led by Gemma Gabriel, Scientific Coordinator of the Unit, are the authors of the article “Online oxygen monitoring using integrated inkjetprinted sensors in a liver-on-a-chip system”, published by Lab on a chip.

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, theauthors present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s⁻¹/10⁶ cells up to 5.95 ± 0.67 nmol s⁻¹/10⁶ cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s⁻¹/10⁶ cells by up to 10.62 ± 1.15 nmol s⁻¹/10⁶ cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.

Article of reference: DOI: 10.1039/C8LC00456K

This article is part of the themed collection: Organ-, body- and disease-on-a-chip systems

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Why research in micro-electronics? Neural interfaces, interaction between the nervous and the artificial system

Dra. Rosa Villa, Scientific Director of NANBIOSIS U8. Micro – Nano Technology Unit, explained last June, 11 at the Residence of Researchers of Barcelona the great scientific challenges in finding tools that allow a good interaction between the nervous and the artificial system.

This talk is part of the series of conferences organized by the CNM with the theme “Why research in micro-electronics?” Dr. Manuel Lozano, Director of the CNM, introduced the talk explaining that with microelectronic technology scientists can capture the signals that occur in the nerves and in the brain and presented Rosa Villa as a doctor with a PhD in cochlear implants (electronic medical devices that perform the work of damaged parts of the inner ear (cochlea) to provide sound signals to the brain). Dr. Villa now directs the group of biomedical applications of the CNM that currently uses nano technologies in their research. Her training in medicine and microelectronics has allowed her to tackle electronic-based projects with biomedical application. Her lines of research are focused, nowadays, on neural interfaces and on organ-on-chip technology, (a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of the entire organs and organ systems, the group of Dr. Villa works mainly the liver, very useful for the test of drug patho-toxicity).

In this talk, Rosa Villa explains her second line research of neural interfaces, the development of suitable interfaces between the biological systems and electronic devices and how they study the improvement of the necessary technologies to restore the motor skills or to know how the brain works applying microelectronic techniques. These investigations run into the main problems of biocompatibility and conectivity and Rosa Villa shows us her letter to Santa Claus to solve them and how graphene is being of great help.

You can see the whole conference clicking here

The video includes a funny class by Eli Prats to produce graphene at home.

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Agreements signed with MINECO for the allocation of FEDER funds for NANBIOSIS ICTS

In the framework of the FEDER Program in ICTS 2014-2020, several projects related to the ICTS NANBIOSIS have been selected by the MINECO for co-financing with FEDER funds of the European Regional Development Funds program.

An agreement has been signed between MINECO and CIBER (partner of NANBIOSIS for the co-financing of the Project: “Purchase, installation and set-up of production and characterization equipment to complement the Units: U3-Synthesis of Peptides Unit, U18-Nanotoxicology and U20- In Vivo Experimental Platform”. The total budget of the project amounts to € 307,566.16, with 50% financing with FEDER Funds.

Also CSIC (The State Agency Superior Council of Scientific Investigations), institution that houses some of the NANBIOSIS units, as distributed ICTS, has signed an agreement with MINECO for the co-financing of the Project: “Purchase and installation and set-up of equipment and production and characterization laboratories to complement the units U2-Production of antibodies, U4-Biodeposition and biosensing, U6-Processing of biomaterials and U8-Micro, nanotechnology. The total budget of the project amounts to € 312.800,00 €, with 50% financing with FEDER Funds.

These two projects aim to increase the quantity and quality of the services offered by th implied units, with the objetive of positioning them as national and international benchmark in their respective fields of application. As a consequence, an increase in the performance (number of services and number of users) of each unit is expected, especially from companies (pharmaceutical and small biotechnology).

CSIC and CIBER are processing the necessary contracting procedures for the execution of these projects.

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NANBIOSIS collaborates in the dissemination of science and triumphs in the Pint of Science Festival

On May 16, scientists from two units of NANBIOSIS filled the pubs, not to talk about football but about science.

According to Jorge Bueno, Coordinator of Pint of Science in Spain, at the Vanguard “Science is also culture, just as we go to the bar to talk about football or politics, we can also talk about science, we want people to conceive science as part of society ”

In the cafe of the civic center of the Casa Orlandai in Barcelona, Eli Prats, a researcher of NANBIOSIS U8. Micro – Nano Technology Unit, explains her group has developed graphene electrodes, a material with unique properties, that can monitor the activity of the brain in a less invasive than conventional ones. “We have tested it in rats and we have discovered that graphene can detect very poorly studied brain waves, which occur just before dying, just before an attack of epilepsy or before a migraine attack.” The researcher shows a sample of the tiny electrodes, which passes from hand to hand in the pub. “It’s still just an idea, but theoretically in the future these electrodes, placed on a person’s brain, could send a signal to a tablet and predict when they will suffer an attack of epilepsy,” adds Eli Prats.

Esther Pueyo, researcher of NANBIOSIS, U27. High Performance Computing, in the Drinks and Pool Aranda pub of Zaragoza explained that “Chronological age does not matter, but the biological one does, not all hearts age equally” and she tried to answer the questions why do I look older? What other people of my age? Will this have consequences? To show the tiny tissues Esther and researchers around her commonly work with, biopsies were collected from a cow heart and examples of the experimental and theoretical analyses they conduct were illustrated.

Throughout Spain, a total of 730 scientists have participated giving talks within the Pint of Science Festival, in 56 cities, together with around 400 organizers, all of them volunteers.

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Nanotechnology, gene therapy, omics therapies and ‘big data’

Nanotechnology, gene therapy, omics therapies and ‘big data’ were the topics discussed in the Forum on Emerging Technologies oganized on May 8 by nanotechnology, gene therapy, omics therapies and ‘big data’ were the topics discussed in the I Forum on Emerging Technologies held on May 8, organized by the CIBER Internationalization Platform, of which the CIBERER, the CIBER-BBN and the CIBERES.

The objective of this event, structured in sessions of presentations and scientific debates about the types of technologies addressed, was to promote the exchange of ideas and scientific knowledge with the aim of generating new collaborations among the CIBER research groups such as participation in transversal projects or the development of cutting-edge technologies.

NANBIOSIS was represented by Pablo Laguna (Unit 27, High Performance Computing), Laura Lechuga (Unit 4, Biodeposition and Biodetection Unit), José Luis Pedraz (Unit 10, Drug Formulation) and Rosa Villa (Unit8, Micro – Nano Technology Unit)

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I Forum on Emerging Technologies organized by CIBER

On May 8th, will take place in Madrid, at the Assembly Hall Ernest Lluch of the Instituto de Salud Carlos III, organized by CIBER Internationalization Platform (CIBER-BBN, CIBERER, CIBERES) the I Forum on Emerging Technologies.

The objective of this meeting is to promote the exchange of ideas and scientific knowledge among the CIBER research groups with the aim of generating new collaborations for participation in cross-cutting projects and the development of border technologies. The content of the forum, centered on the type of technology and possibilities it offers, is structured in a program of lectures and scientific debates whose final objective is the discussion and the joint generation of ideas. This first edition of the forum will be focused on Gene Therapy, Nanotechnologies and Omic Technologies-Big Data.

Some Units of NANBIOSIS will participate:

José Luis Pedraz, Scientific Director of Unit 10 Drug Formulation, will speak of “Development of non-viral vectors for gene therapy“
Laura Lechuga, Scientific Director of Unit 4 Biodepositon and Biodetection, will talk about “Nanodispositive biosensors for advanced clinical diagnosis
Rosa Villa, Scientific Director of Unit 8 Micro–Nano Technology, Ramón Martínez, Scientific Director of Unit 26 NMR Biomedical Applications II and Esther Pueyo, researcher of U27 High Performance Computer will moderate the sessions.

Programme and registration details

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Non-invasive glucose sensing in tears

Currently numerous medical diagnoses or follow-ups of many diseases are carried out by conventional methods such as clinical tests in laboratories and hospitals, being these invasive, slow and expensive.

Thanks to advances in technology, Point-of-Care (PoC) devices allow testing and monitoring of a multitude of biomedical markers or parameters in order to: (i) reduce costs, save time and reduce the complexity of the analysis; (ii) allow analysis in medical centers, primary care centers or even at home and (iii) real-time results allow to accelerate the decision-making on a patient. Thus, PoC devices respond to a demand from medical doctors as is the efficient health service thanks to the rapid availability of the laboratory analysis results.

In this context, a team of scientists from Barcelona have collaboratively developed a non-enzymatic sensor for glucose sensing in a non-invasive manner in tears. The work, cover of the magazine Applied Materials Today, demonstrates the proof of concept of the functionality of this electrochemical sensor.

Ana Moya, researcher of the CIBER-BBN and member of the research group of the Institute of Microelectronics of Barcelona CSIC, responsible for the sensors manufacture explains how these devices are fabricated by the innovative technology of Printed Electronics. Specifically, electrochemical glucose sensors have been manufactured by printing microelectrodes using Inkjet Printing Technology (IJP) on a flexible substrate of polyethylene terephthalate (PET) with silver and gold inks. The IJP dispenses small drops of the material to be printed under a graphic environment. This direct writing approach without the need of masks drastically reduces the total manufacturing time and cost of the sensors, and facilitates iterative design changes during sensor development.

Gemma Gabriel, Scientific Coordinator of NANBIOSIS U8. Micro–Nano Technology Unit and researcher of the CIBER-BBN in the Institute of Microelectronics of Barcelona CSIC, explains how the IJP is a promising and low-cost alternative to conventional microelectronic manufacturing technology, which will allow the creation of a multitude of highly specific sensor platforms and sensitive with analytical application in the medical area. In line with the research group, the advance in novel functional materials with these technologies is of paramount importance for the development of new generations of disposable sensor platforms to solve a wide range of applications in the medical field.

Agostino Romeo, member of the Smart nano-bio-devices Group at the Institut de Bioingenieria de Catalunya (IBEC) led by Samuel Sánchez, highlights how the use of copper oxide microparticles (CuO) has allowed the successful modification of the electrodes, leading to a sensitive, stable and cost-effective platform for the non-enzymatic detection of glucose. The selectivity, reproducibility and life time provided by this functionalization with CuO has shown that these sensors are reliable tools to perform a personalized diagnosis of the health of an individual.

The good sensitivity and selectivity of the electrochemical sensor presented here has made it particularly suitable for the non-invasive sensing of glucose in tears. This has been demonstrated in this study in which the glucose level in human samples has been measured and correlated with commercial devices.

All this allows us to foresee that the use of this type of sensors for the diagnosis of eye diseases such as diabetes, where it is possible to achieve a painless and non-invasive monitoring, has a great opportunity in a disease as widespread in the world as it is this one. Thus, versatility, short manufacturing time and low cost makes IJP a valuable technology alternative to traditional sensor manufacturing techniques. Thus, the technology here presented can be adapted for the detection of many other substances of interest in other fluids such as saliva or urine.

Article of Reference:

Romeo A, Moya A, Leung TS, Gabriel G, Villa R, Sánchez S. “Inkjet printed flexible non-enzymatic glucose sensor for tear fluid analysis“. Applied Materials Today 10 (2018) 133-141

(DOI)

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