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Chemical composition of explanted deteriorated nephrostomy polyurethane-catheters through X-ray photoelectron spectroscopy

Researchers of Nanbiosis U16 Surface Characterization and Calorimetry Unit of CIBER-BBN and University of Extremadura in Badajoz, are the authors of an article published by Materials Chemistry and Physics,

The researchers studied the surface chemical information of thirteen used catheters that had remained in patients for two months, using the XPS technique with the purpose of this communication is to report.
Compositional changes in relation to unused catheters provided information on the degree of the chemical degradation suffered. ATR-IR
added information on the chemical characterization of the samples
and Scanning Electron Microscopy (SEM) analysis will advise on topographical changes.

The XPS technique is optimum to analyzed the surface chemical composition of medical polymer device. Applied to the ureteral catheters, XPS shows on the surface of damaged catheters calcium and other ions from urine. XPS was performed by the ICTS “NANBIOSIS”, more specifically by the Surface Characterization and Calorimetry Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBERBBN)
and the SACSS-SAIUEx of the University of Extremadura (UEx)

Ureteral catheters are a fundamental part of the modern urologist’s armamentarium. X-ray photoelectron spectroscopy (XPS) was used for the first time as a powerful analytical tool for the study of the chemical
composition of nephrostomy catheters retrieved from patients who had undergone nephrostomy to detect their chemical deterioration inside the human body. Depth profile analysis provided not only the composition of the surface but also that of the catheter bulk. The results obtained by XPS showed the presence of calcium and other ions, such as phosphorus, sulphur and fluorine in the explanted deteriorated catheters. The detection of barium on the surface of all the retrieved catheters has special relevance. This chemical element is usually incorporated as a radiomarker in the catheter polymeric matrix and its diffusion from the bulk material to the surface must be responsible for its XPS detection. The accumulation of high levels of this element from toxic barium salts in cases of urine drainage failure could lead to its adsorption from the surrounding tissues into the patient’s body, thus compromising the safety concentrations of this soft alkaline earth metal.

Article of reference:

Chemical composition of explanted deteriorated nephrostomy polyurethane-catheters through X-ray photoelectron spectroscopy María Fernández-Grajera, Margarita Hierro-Oliva, Luis Fernández-deAlarcón, Amparo M.Gallardo-Moreno. Materials Chemistry and Physics Volume 239,  2020, 121979 https://doi.org/10.1016/j.matchemphys.2019.121979

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Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality

Researchers of CIBER-BBN Units of NANBIOSIS: U29 Oligonucleotide Synthesis Platform (OSP) at IQAC_CSIC, led by Prof. Ramón Eritja and U10 Drug Formulation, at UPV-EHU, led by Prof José Luis Pedraz, are coauthors of an article published by International Journal of Pharmaceutics.

Gene therapy strategies based on non-viral vectors are currently considered as a promising therapeutic option for the treatment of cystic fibrosis (CF), being liposomes the most commonly used gene carriers. Niosomes offer a powerful alternative to liposomes due to their higher stability and lower cytotoxicity, provided by their non-ionic surfactant and helper components. In this work, a three-formulation screening is performed, in terms of physicochemical and biological behavior, in CF patient derived airway epithelial cells. The most efficient niosome formulation reaches 28% of EGFP expressing live cells and follows caveolae-mediated endocytosis. Transfection with therapeutic cystic fibrosis transmembrane conductance regulator (CFTR) gene results in 5-fold increase of CFTR protein expression in transfected versus non-transfected cells, which leads to 1.5-fold increment of the chloride channel functionality. These findings highlight the relevance of niosome-based systems as an encouraging non-viral gene therapy platform with potential therapeutic benefits for CF.

The article acknowledges U10 Drug Formulation, for the intellectual and technical assistance

Article or reference:

Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality-Sainz-Ramos, M., Villate-Beitia, I., Gallego, I., A.L. Qtaish, N., Lopez-Mendez, T.B., Eritja, R., Grijalvo, S., Puras, G., Pedraz, J.L. International Journal of Pharmaceutics, 588, art. no. 119757, 2020. https://doi.org/10.1016/j.ijpharm.2020.119757

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New equipment for calorimetry and surface characterization for NANBIOSIS U16

NANBIOSIS unit 16 Surface Characterization and Calorimetry Unit form CIBER-BBN and University of Extremadura offers the performance of tasks of physical-chemical characterization of surfaces using techniques such as ellipsometry, calorimetry, X-ray photoelectronic spectroscopy (XPS) and detection of secondary ions by means of mass spectrometry by time of flight (Tof-SIMS). Recently, new equipment acquired through the execution an investment of 1.3 million euros, cofinanced with FEDER funds, the Ministry of Economy and Competitiveness and Junta de Extremadura, Regional Ministry of Economy, Science and Digital Agency, througth the project FICTS1420-14-09. These equipments are a microdroplet and picodroplet contact angle goniometry system and an optical profilometry system.

Equipment acquired

PEAK AND MICRO DROP GONIOMETRY SYSTEM

This system allows to measure contact angles automatically, controlling by software, the deposition of drops of different liquids, their analysis and the orientation of the substrate, as well as pending drops. In addition, the microdroplet system has a tilting base that allows the samples to be tilted by at least 90o. It also includes a thermostatic chamber, for temperature changes of the sample with a range between 5 and 90 ºC, and a chamber for humidity control.

Obtaining surface tension, through contact angle measurements, is a factor to consider in technologies of biomedical interest such as implants and other materials that must be in contact with biological fluids. In these systems the contact angle is related to the wettability, the hydrophobicity of the surface and the adhesion capacity of substances such as proteins or other compounds on the surfaces.

In the case of pico-droplet measurements, the system allows to very precisely dose drops much smaller than in the previous case, which can be as low as 20 picoliters, as well as to analyze their shape to measure the contact angle. This fact solves the problem of measuring wettability in very small structures, such as capillaries, microchips, joints created in the union of two materials, etc.

PROFILOMETRY SYSTEM

The system allows the roughness of a multitude of surfaces to be measured by an optical method that does not make any changes to the sample. With the operating base of a confocal microscope commonly used in different fields of science, it allows to create high-resolution 3D images quickly and automatically, as well as obtaining color images thanks to the use of three LEDs: Red, Green and Blue. With the available objectives, it is possible to measure from more macroscopic samples such as screws used as dental implants to be able to observe bacterial colonies composed of bacteria the size of a micron. This will make it possible to measure the roughness of any sample covering the range of roughness between a magnifying glass, which gives a more macroscopic view, and the atomic force microscope capable of measuring nanometric roughness (10 ^ -9 m). In addition, this equipment also works as an interferometer that allows to measure the roughness with greater precision of mirror polished samples in a simple way, obtaining images of higher resolution than any confocal technique.

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Video-summary of the CIBER-BBN and NANBIOSIS 2020 Annual Conference

In 2020, the XIV CIBER-BBN Annual Conference took place for the first time in virtual format, which did not prevent the Bioengineering, Biomaterials and Nanomedicine groups of the CIBER from sharing the results and advances of their research as always. For the fourth year in a row one of sessions of the CIBER-BBN Conference was dedicated to the ICTS NANBIOSIS. Here is video summary of the main milestones and topics addressed this year.

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Printed sensors, a low cost alternative for clinical detection

In today’s society there is a great interest in developing new technologies that allow low-cost mass manufacturing, also called “rapid prototyping” or “additive manufacturing”. Rapid prototyping includes technologies such as sterolithography, 3D printing, laser sintering or printed electronics, among others. All of these share digital design and manufacturing from the consecutive addition of layers, that is, techniques that allow creating almost any shape or geometric feature in a very fast time.
Printed electronics consists of printing inks on different types of substrates such as textiles, plastics, papers or films to make them “smart”. This technique is presented as an alternative to traditional silicon that is being implemented in sectors as varied as health and wellness, automotive and transport, professional sports, safety and protection, packaging, architecture and construction, and technical textiles. Printed electronics is one of the new technologies that will have a long history throughout the functional electronic device manufacturing space, with a wide range of applications, electronic designs, processes and materials, compared to conventional electronic and microelectronics based manufacturing technology in silicon. It is expected that in the next decade it will be part of everyday life, with products such as electronic skin, electronic tissues and organs or architectural elements that respond to external stimuli.
Among the many areas of interest of these technologies, one of them is the development of low-cost sensors for the medical or environmental area. For example, in these disciplines, it is essential to get devices that can be very economical or even single-use to promote sustainable environmental control and personalized medicine. Specifically with inkjet technology, researchers from NANBIOSIS Unit 8 Micro-Nano Technology Unit belonging to the Institute of Microelectronics of Barcelona (IMB-CNM, CSIC /and CIBER-BBN), have developed over the last few years multiple materials, inks, substrates and sensors for the development of electrochemical sensors in micrometric dimensions.

  • Inks: Most commercial inks are composed of a solvent that contains some material with insulating, conductive or semiconductor properties. As a general rule, an ink must be stable, with a particle size of several orders of magnitude smaller than the injector orifice, have a viscosity of less than 20 mPa s and a surface tension of less than 80 mN m-1. Although these values ​​may depend on the system in question. The final devices are obtained by selectively depositing in previously drawn areas, layer by layer, thin or thick structures on the substrates. They have worked with multiple commercial metallic inks such as gold, silver and platinum.
    Normally in an electrochemical system a noble material that is electrochemically stable is needed to be used in the working electrode and in the counter electrode, and for this gold or platinum are a good alternative. To make measurements with any electrochemical sensor, a reference electrode is essential since it is one that has a stable and constant potential over time and that allows us to reference our voltage value. We use the impression of an Ag / AgCl bilayer since it is one of the interfaces most used as a reference electrode. One of the main problems faced by miniaturization, however, is the rapid loss of the small volume of internal reference solution that these electrodes must have, which has a direct impact on their useful life and stability. For this, a polymeric membrane that can be printed was formulated, which allows the reference to have high performance compared to other commercial miniaturized reference electrodes (Ref1).
  • Substrates: a wide range of rigid, flexible, porous, plastic, fabric, etc. substrates can be used. However, the interaction of the ink with the substrate is crucial in determining the good quality of the printed pattern. For this reason, the properties of the inks are adapted for the different substrates with their own properties. For this reason, it is common practice to pretreat the substrate surface to improve hydrophobicity and adhesion issues mainly. It is common to use plastic substrates with a thickness of the order of microns that provide them with great flexibility and that are already specially treated to obtain excellent printing qualities. The deposition of uniform gold and silver conductive inks on porous substrates can be achieved by using a primer layer to seal the porosity of the membrane in specific and defined areas, with the aim of building a sensor device over the sealed area and leaving the rest of the intact substrate (Ref.2). With a paper substrate, alternatively we can print a silane ink, as a strategy that allows a monolayer of hydrophobic material to grow on the substrate and thus be able to obtain uniform lines of ink on its surface. (Ref.3)
  • Sensors developed: Dissolved oxygen (DO) (Ref.4) and pH (Ref.5) sensors have been developed using gold and platinum inks respectively, commercially available on plastic substrates. The inks have a specially designed formulation that allows their sintering at temperatures as low as 150 and 180 ° C for Au and Pt respectively. This is a key point in the development of low-cost sensors made on polymeric substrates or paper that cannot withstand high temperatures. These sensors integrate in a single platform all the basic elements for the registration of pH and DO, allowing measurements without any external electrode. DO is measured directly with a gold working electrode and pH sensors are achieved after electroplating an iridium oxide film on the platinum working electrode. In addition, this water-based platinum ink has another unique feature, it provides the electrode surface with high roughness, which promotes adhesion of the deposited sensor material, in this case iridium oxide. Long-term stability tests for more than 1 year demonstrate excellent stability of the mechanical sensor layer, and that it correlates perfectly with the different roughness of the printed platinum layer. Along the same lines and in relation to the development of inks, it has been possible to obtain a fully printed pH sensor based on a conductive polymer specially formulated to be printed by IJP . The measurements obtained with this ink have a good response in a wide pH range (pH 3 to 10) and the response in the physiological zone (pH 7-7.5) is well resolved, one of the main drawbacks of conductive polymers. We also present an IJP-printed electrochemical sensor for enzyme-free glucose analysis on flexible PEN substrate (Ref.6). In this case, CuO microparticles were used to modify the electrodes, and the detection of glucose was validated in concentrations that coincide with those of the tear fluid, which allows us to foresee applications in ocular diagnosis, where a painless control can be achieved and not invasive of diabetes by analyzing the glucose contained in tears.

(Ref.1): Moya A, Pol R, Martínez-Cuadrado A, Villa R, Gabriel G, Baeza M. Stable Full Inkjet-Printed Solid-State Ag/AgCl Reference Electrode. Analytical Chemistry 91 (2019) 15539-15546

(Ref.2): M. Ortega-Ribera; X. Guimerà; E. Sowade; M. Zea; X. Illa; E. Ramon; R. Villa; J. Gracia-Sancho; G. Gabriel. Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system. Lab on a Chip. 18 – 14, pp. 2023 – 2035. 2018

(Ref.3): All Inkjet Printing Sensor Device on Paper: for Immunosensors Applications M Zea, A Moya, I Abrao-Nemeir, J Gallardo-Gonzalez, N Zine, A Errachid, … 2019 20th International Conference on Solid-State Sensors, Actuators and 

(Ref.4): Moya A, Sowade E, del Campo FJ, Mitra KY, Ramon E, Villa R, Baumann RR, Gabriel G. All-inkjet-printed dissolved oxygen sensors on flexible plastic Organic Electronics 39 (2016) 168-176

(Ref.5): Zea M, Moya A, Fritsch M, Ramon E, Villa R, Gabriel G Enhanced performance stability of iridium oxide based pH sensors fabricated on rough inkjet-printed platinum ACS Applied Materials & Interfaces 11 (2019) 15160-15169

(Ref.6): 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

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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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Funded beamtime for SMEs in Sincrotron Alba ICTS thanks to EU CALIPSOplus projec. – Dec. 17 explanatory Webinar Calipsoplus-TamaTA for SMEs

Untill 30 of June 2021, small and medium companies can ask for funded beamtime in different European light sources thanks to EU CALIPSOplus project

The European project CALIPSOplus brings together 19 partners offering access to 14 synchrotrons and 8 FELs in Europe and the Middle East. This pilot transnational access scheme allows SMEs to access the best light source for their particular needs, irrespective of whether or not it is the closest light source.

Leader: CELLS (ALBA Synchrotron) (Barcelona, Spain)

Webpage: https://www.albasynchrotron.es/en/industry/services

Email: industrialoffice@cells.es

On December 17, 2020 – 12:00 – 13:00 Sincrotrón ALBA -ICTS is running a Webinar that will explain to companies how SMEs can benefit from the Calipsoplus-TamaTA project to solve their characterization problems at the ALBA Synchrotron. Inscriptions are open here

NANBIOSIS and SYNCROTRON ALBA, both ICTS facilities established some collaborations in order to increase the scope of the biomedical solutions given to the health sector.

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Ignacio García and Javier Bonet present their work on the CADENCE project in a one-minute video

Ignacio García and Javier Bonet, researchers from the Nanoporous Films and Particles (NFP) group and Nanbiosis U9 Synthesis of Nanoparticles Unit of the CIBER-BBN and the Institute of Nanoscience and Materials Science at the University of Zaragoza have presented their work on the CADENCE project in a video of a minute of duration that has been submitted to the #QueSigalaCiencia scientific dissemination contest promoted by the CIBER-BBN.

#QueSigaLaCiencia is a campaign on social networks that wants to explain to society, from an optimistic perspective, the importance of research and the work carried out by the research staff of the CIBER. The call -associated with the campaign- has had a high participation of the groups, who have presented 69 videos from all the scientific areas of the center. Researchers took on the challenge of telling their research in one minute. The works presented in the #QueSigaLaCiencia call have the possibility of opting for the prize that the public will give through Twitter (highest number of likes).

Their research work in the project CADENCE consists of designing and manufacturing nanopharmaceuticals that will fight cancer, not only in a more effective way, but also in a more selective way , avoiding damaging healthy cells. “By striking the tumor with light, which, for example, comes from a laser, the particles created by these researchers are capable of creating toxic substances for the cancer cell and, in addition, eliminating essential nutrients for the tumor to continue its growth ·.

The work carried out in NANBIOSIS is recognized by these researchers as “fundamental to continue innovating, advancing and providing solutions to different problems”.

CADENCE is a European Project (Catalytic Dual-Function Devices Against Cancer) that aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumor can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumor growth are locally depleted and ii) toxic, short-lived products are generated in situ

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Mimicking lymph-nodes to proliferate T cells by Judith Guasch in Onda Cero Radio.

Judith Guasch, researcher from Nanomol group, coordinator of NANBIOSIS unit 6 of NANBIOSIS (CIBER-BBN / ICMAB-CSIC)  is interviewed in Onda Cero Radio  in the programme “De cero al infinito” con Paco de León, to talk about her recent research on hydrogels to mimic lymph nodes for cancer immunotherapy. 

You can listen the interview to Judith Guasch in this link, from minute 11: 33 to minute 29:35. In her interview, Judith Guasch explains her research on hydrogels to mimic lymph modes to grow more effectively T cells for cancer immunotherapy, about the patent, the costs of the cancer immunotherapy, and about the 3D bio-printing and scaling up of the hydrogels to increase the proliferating of T cells. 

Further information at ICMAB-CSIC web page

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Highly sensitive monoclonal antibodies for a new biosensor for hormones detection in fertility treatments

Nb4D research group and NANBIOSIS U2 Custom Antibody Service (CAbS) of CIBER-BBN at the IQAC-CSIC, together with the company Droplite Technologies have obtained a Retos-Collaboration project funded by the Ministry of Science and Innovation, for the development of a biosensor for detection and rapid quantification of hormones, linked to in-vitro fertility treatments.

NANBIOSIS U2 CAbS will be responsible for the production of highly sensitive monoclonal antibodies, counting on the experience in this field of Juan Pablo Salvador, project coordinator, Núria Pascual and Mª Pilar Marco.

The measurement of the hormone estradiol is a key indicator, both of maturity and of the degree of ovarian stimulation, very important in a successful fertilization process. But there are no tools that allow accurate and sensitive monitoring.

Thus, the consortium formed by Nb4D-Droplite proposes as a solution a new device to perform the control and quantification of hormones, in particular estradiol, in less than 30 minutes, without the need for a central laboratory and only using a drop of blood, which is obtained simply by pricking the patient’s finger.

With funding of € 388,531, the project strategy consists of a transversal collaboration between the Droplite company and the CIBER-BBN research center, through the Nb4D group, supported by the Hospital Clínic de Barcelona, ​​which allows a continuous evaluation and optimization of the prototype based on the exchange of experiences and knowledge.

On the other hand, Droplite, led by its co-founders André Guedes and Rafael Porcar, contributes its experience in the development of an optical detection system based on nanotechnology, which will allow to detect and monitor, automatically and quantitatively, different markers and provide results in just 10 minutes. Droplite is dedicated to the biotechnology sector that emerged as a spin-off of the Institute of Photonic Sciences (ICFO)

The call Retos Colaboración

The aid of this call, managed by the Ministry of Science and Innovation and the State Research Agency, aims to support experimental development projects in cooperation between companies and research organizations, in order to promote the development of new technologies, business application of new ideas and techniques, and contribute to the creation of new products and services.

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