Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)

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An internet of things-based intensity and time-resolved fluorescence reader for point-of-care testing
(Elsevier B.V., 2020-04-15) Alonso Casanovas, Oscar; Franch Masdeu, Nil; Canals Gil, Joan; Arias Alpízar, Kevin; de la Serna, Erica; Baldrich, E.; Diéguez Barrientos, Àngel
A miniature internet of things (IoT)-based point-of-care testing (PoCT) fluorescence reader, able to perform both intensity and time-resolved measurements of different fluorescent tags, is presented. This low cost platform has been conceived for performing tests in low-resource and remote settings, displaying versatile performance and yet simple operation. It consists on an external case of 43 × 30 × 42 mm3 (built in a 3D-printer) where all the elements are fixed, including some basic optics (3 lenses and 2 filters), a laser diode and a custom designed Single-Photon Avalanche Diodes (SPADs) camera. Both, the laser and the camera are controlled by a Field Programmable Gate Array (FPGA) with IoT capabilities. The PoCT was validated by detecting Plasmodium antigen in a fluorescent enzyme-linked immunosorbent assay (ELISA) using a fluorescence substrate. The results were compared to those provided in parallel by two commercial fluorescent plate readers. As it will be shown, the PoCT fluorescent readout was more sensitive than its colorimetric counterpart. Furthermore, the PoCT displayed similar signal trends and levels of detection than the bulkier and more expensive commercial fluorescence plate readers. These results demonstrate that the PoCT platform developed could bring the performance of central laboratory assay techniques closer to the end-user level.
Structure and mechanistic basis of NrdR, a bacterial master regulator of ribonucleotide reduction
(Elsevier B.V., 2026-02-04) Pedraz López, Lucas; Szura, Arkadiusz; Schmitz, Claus; Rubio Canalejas, Alba; Martínez Mateos, Ángela; Santella, Anthony; Gomila Lluch, Gabriel; Calò, Annalisa; Solà, Maria; Torrents Serra, Eduard
Ribonucleotide reductases (RNRs) are the essential enzymes responsible for synthesizing dNTPs, the building blocks of DNA. In bacteria, the entire RNR network is controlled by the master regulator NrdR. As a regulator of an essential pathway with no eukaryotic equivalent, NrdR is a promising antimicrobial target. Recent structural studies have outlined a mechanism of action for NrdR, in which ATP and dATP induce changes in the protein quaternary structure, regulating RNR repression. However, due to a lack of functional studies linking the known structures to their biological roles, the activation mechanism of NrdR is not yet fully understood. Here, we conducted a comprehensive study of NrdR in Escherichia coli and Pseudomonas aeruginosa. We delimited the NrdR regulon, combining transcriptomics and motif-based sequence analysis. We crystallized E. coli NrdR and identified the protein-protein interfaces involved in its oligomerization, including strong interactions between NrdR dimers to form tetramers, and less stable interfaces connecting such tetramers. We examined the variability of the quaternary structures of NrdR depending on the bound nucleotides by SEC-MALS and atomic force microscopy, and correlated structure to function using point mutations, EMSAs, and in vitro transcription assays. Overall, our results demonstrate the mechanism used by NrdR to modulate its quaternary structure and activity, deciphering essential interactions between subunits, and paving the way for targeted antimicrobial therapies.
Fish scale-based carbon dots with g-C3N 4 as a photo-catalyst for oxidation of herbicide 2,4-dichloro phenoxy acetic acid under visible light.
(Elsevier B.V., 2025) García-Gutierrez, Yessenia Scarlette; Palacios-Cabrera, Cristian Brayan; Santiago-Cuevas, Alan-Javier; Reyes-Domínguez, Ivan Alejandro; Orta-Ledesma, Maria Teresa; Güell Vilà, Frank; Llobet, Eduard; Huerta-Aguilar, Carlos Alberto; Thangarasu, Pandiyan
2,4-dichloro phenoxy acetic acid (2,4-D) has been employed as an herbicide to increase crop yields and ensure large-scale food production; however, it is highly toxic and persistent in the environment. This work deals with the green chemistry preparation of carbon quantum dots (NCDs) from fish scales and then combines them with graphitic carbon nitride to oxidize 2,4-D under visible light. The samples, C-NCDs, S-NCD, g-C3N4, C-NCD/g- C3N4, and S-NCD/g-C3N4 were characterized by different analytical methods (XRD, SEM, TEM, HRTEM, XPS, and fluorescence/UV–visible spectra). C-NCD/g-C3N4 and S-NCD/g-C3N4 are thermally stable, and the average size of the particles was ~5.0–15 nm. SEM/TEM show that quasi-spherical particles (7–20 nm) of C-CQD and S-NCD are homogeneously dispersed, and the fluorescence emission spectra show distinct profiles as C-NCDs (429 nm) and S-NCDs (318 nm and 404 nm), caused by hetero atoms from the fish scales that are less pronounced for C-NCDs. This is consistent with the photoluminescence spectra that C-NCDs and S-NCDs exhibit a green visible emission at 575 and 526 nm, respectively, as a typical behavior of carbon quantum dots. The bandgap energy of the samples (2.77–2.91 eV) is consistent with those from the Density Functional Theory (DFT). The adsorption of 2,4-D by SNCDs/g-C3N4 is highly efficient; for example, qm = 2.85 × 10 5 mol/g for C-NCD/g-C3N4, 2.02 × 10 5 mol/g for S-NCD/g-C3N4 or 2.43 × 10 5 mol/g for g-C3N4. The photocatalytic oxidation of 2,4-D by the samples reveals that there is considerable photocatalytic oxidation and follows first-order kinetics in the substrate as follows: k visible = 4.3 × 10 3 mM s 1 and k solar = 7.5 × 10 3 mM s 1 for C-NCDs/g-C3N4; k visible = 5.4 × 10 3 mM s 1 and k solar = 10.4 × 10 3 mM s 1 for S-NCDs/g-C3N4. In the cell images, although C-NCD and S-NCD exhibit dispersed fluorescence, adding C-NCD or S-NCD results in a significant fluorescence increase.
Chip-Sized Microscopy for Continuous Monitoring: Application in White Wine Fermentation and Yeast Cell Counting via Deep Learning
(MDPI, 2024-10-08) Diéguez Barrientos, Àngel; Moreno Martín, Sergio; Moncada-Madrazo, Sofía; Caravaca, Oriol; Diéguez, Joel; Canals Gil, Joan; Benito Altamirano, Ismael; Prades García, Juan Daniel; Vilà i Arbonès, Anna Maria
Nowadays, continuous monitoring is a difficult issue in microscopy. A chip-sized microscope was developed, composed only of microelectronic components, with high optical resolution and a wide field of view. Due to its miniaturized size, it can be placed on or attached to the sample for continuous monitoring in the sample environment. An example of an application of this microscope for the food and beverage industry is described, referring to the study of the fermentation process of white wine. The comparison of the images acquired with conventional optical microscopy reveals similar results. To automatically count yeast cells, the traditional image postprocessing is compared with deep learning. Neural networks achieve similar cell recognition characteristics but with an ~100× speed improvement, by directly processing the obtained holograms.
The RISC-V FPGA (RVfpga) Teaching Package
(Institute of Electrical and Electronics Engineers (IEEE), 2026-01-28) Grinshpun, Alexander; Gabbay, Freddy; Seed, Luke; Duarte, Rui; López, Manuel; Alonso Casanovas, Oscar; Owen, Robert; Chaver, Daniel; Harris, Sarah; Pinuel, Luis; Kindgren, Olof; Kakakhel, Zubair; Owen, Chris; Kravitz, Roy; Gómez-Pérez, José I.; Castro, Fernando; Olcoz, Katzalin; Villalba-Moreno, Julio
RISC-V is a free and open-standard ISA based on RISC principles, allowing anyone to design, manufacture, and sell RISC-V chips and software. Its flexibility and growing ecosystem have made it popular in research, education, and industry, increasing the need for educational materials. This paper provides an in-depth description of the RVfpga course, which offers a solid introduction to computer architecture using the RISC-V instruction set and FPGA technology. It focuses on providing hands-on experience with real-world RISC-V cores, the VeeR EH1 and EL2 cores, developed by Western Digital and hosted by ChipsAlliance. The course targets students and educators in computing-related fields, enabling them to integrate practical RISC-V knowledge into their curricula. The course materials, which include detailed labs, setup guides, and the full SoC source code in System Verilog, are available for free. Students learn to compile, debug, and run C and assembly programs, to interact with built-in peripherals, to extend the SoC, and to explore microarchitectural features.
Pixelated 3D sensors for tracking in radiation harsh environments
(Physical Society of Japan, 2021-06-10) Duarte-Campderros, J.; Alonso Casanovas, Oscar; Diéguez Barrientos, Àngel; CERN-RD50 Collaboration
The High Luminosity upgrade of the CERN Large Hadron Collider will be able to reach a peak instantaneous luminosity of 5 × 1034 cm−2 s−1. The innermost detectors of the CMS and ATLAS experiments will have to cope with unprecedented requirements on radiation hardness. At the end of the operation period, radiation levels are expected to reach values above 2.6 × 1016 neq cm−2. Sensors based on 3D pixel technology, with intrinsic radiation tolerance, are the baseline option for the innermost layers of the vertex detectors of several HL-LHC experiments. This article gives an overview of the ongoing characterization of the pixelated 3D sensor technology, their performance and their current development status for tracking on radiation harsh environments.
3D Micropatterned Traction Force Microscopy: A Technique to Control 3D Cell Shape While Measuring Cell-Substrate Force Transmissio
(Wiley-VCH Verlag, 2024-10-23) Faure, Laura M.; Gómez González, Manuel; Baguer, Ona; Comelles Pujadas, Jordi; Martínez, Elena; Arroyo, Marino; Trepat Guixer, Xavier; Roca-Cusachs Soulere, Pere
Cell shape and function are intimately linked, in a way that is mediated by the forces exerted between cells and their environment. The relationship between cell shape and forces has been extensively studied for cells seeded on flat 2D substrates, but not for cells in more physiological 3D settings. Here, a technique called 3D micropatterned traction force microscopy (3D-µTFM) to confine cells in 3D wells of defined shape, while simultaneously measuring the forces transmitted between cells and their microenvironment is demonstrated. This technique is based on the 3D micropatterning of polyacrylamide wells and on the calculation of 3D traction force from their deformation. With 3D-µTFM, it is shown that MCF10A breast epithelial cells exert defined, reproducible patterns of forces on their microenvironment, which can be both contractile and extensile. Cells switch from a global contractile to extensile behavior as their volume is reduced are further shown. The technique enables the quantitative study of cell mechanobiology with full access to 3D cellular forces while having accurate control over cell morphology and the mechanical conditions of the microenvironment.
Improving neuroblastoma therapy with a new p53 family-activating agent
(Elsevier B.V., 2025-11-15) Almeida, Joana; Resende, Diana I. S. P.; Silva, R.; Villasante Bermejo, Aranzazu; Murphy, Catherine; Zingales, Veronica; Palmeira, Andreia; Skoda, Jan; Broso, Francesca; Vadivellu, Aiswariya; Oliveira, Paula A.; Reis, Salette; Nunes, Claudia; Loh, Amos H.P.; Ferreira, Joana Margarida; Martins, Eduarda P.; Costa, Bruno M.; Inga, Alberto; Samitier i Martí, Josep; Sousa, Emilia P.; Saraiva, Lucília
Neuroblastoma (NB) is among the most common malignancies in children and represents a therapeutic challenge in pediatric oncology. p53 family proteins play a critical role in protecting cells from genomic instability and malignant transformation. However, in NB, their activities are often inhibited by interacting proteins such as MDM2. The interplay between p53 family pathway and N-Myc, a key biomarker of poor prognosis, is also a critical factor in NB pathogenesis. Herein, we disclose 1-(dibromomethyl)-3,4,6-trimethoxy-9H-xanthen-9-one (LEM3) as a new p53 family-activating agent with potent NB anticancer activity. At 0.13–2.1 μM, LEM3 inhibited the growth of several NB cell lines. Its activity was further evidenced in spheroids, patient-derived NB cells, and in a vasculature stiffness-based model of MYCN-amplified NB cells. This growth-inhibitory effect was associated with cell cycle arrest and apoptosis, in SH-SY5Y and SK-N-BE(2) NB cells, without apparent acquisition of resistance. LEM3 inhibited cell migration and invasion and reduced the expression of NB-related prognostic markers, particularly MYCN mRNA and protein levels. LEM3 released p53, TAp63, and TAp73 from their interaction with MDM2 both in a yeast-based assay and NB cells; for p53, this led to increased protein stabilization, DNA-binding ability, and transcriptional activity. Fluorescence quenching and docking analyses suggested that LEM3 binds to p53, TAp63, and TAp73 at the MDM2-binding site within their transactivation domain. LEM3 also synergies with doxorubicin and cisplatin in NB cells. Given the central role of the p53 family-MDM2-MYCN axis in NB pathogenesis, our findings support LEM3 as a promising compound for advancing NB targeted therapy.
PEGylated PLGA nanoparticles prepared from nano-emulsion templates as versatile platforms to cross blood-brain barrier models
(Elsevier B.V., 2025-08-01) López Mitjavila, Joan Josep; Palma Florez, Sujey; Lagunas, Anna; Mir Llorente, Mònica; Samitier i Martí, Josep; Rodriguez-Abreu, Carlos; Grijalvo, S.
PEGylation prevents aggregation and enhances the systemic circulation of nanoparticles (NPs), improving the delivery of actives to targeted cells. In this study, a conjugation reaction was used to attach polyethylene glycol (PEG) chains of molecular weights 750 and 5000 Da onto the surface of poly(lactic-co-glycolic acid) (PLGA) NPs obtained using the phase inversion composition methods, with carbodiimide/N-hydroxysuccinimide (NHS) and carbodiimide/sulfo-NHS activation reactions. Proton nuclear magnetic resonance indicated a higher degree of decoration (ca. 44.7 %) when carbodiimide/sulfo-NHS activation and PEG low molecular weight (750 Da) were used. Short incubation times (2 h at 37 ◦C) in the presence of 10 % fetal bovine serum showed no significant changes in particle size compared to pristine NPs. After 5 h of incubation, PEGylated NPs exhibited increase size (101.4 ± 15.3 nm) and polydispersity (0.6 ± 0.01). The presence of PEG chains decorating NPs reduced antioxidant release from NPs to ca. 10 % after 24 h at 37 ◦C following the Korsmeyer–Peppas model and governed by a Fickian diffusion mechanism. The antioxidant capacity of NPs showed a dose-activity relationship with ca. 60 % inhibition at 0.16 mg mL− 1 NP concentration and an EC50 of 51.7 ± 3.3 μg mL− 1 . Cell culture studies indicated no cytotoxicity for PLGA and PEGylated NPs up to 0.05 mg mL− 1 . Internalization studies confirmed cellular uptake into SHSY5Y cells. The impact of PEGylated NPs on blood-brain barrier (BBB) permeabilization was evaluated in a BBB-on-chip model, showing that PLGA encapsulation and PEGylated NPs, though to a lesser extent, facilitated crossing and permeabilization through the endothelial layer, demonstrating their potential for effective brain delivery.
PEGylated PLGA nanoparticles prepared from nano-emulsion templates as versatile platforms to cross blood-brain barrier models
(Elsevier B.V., 2025-08-01) López Mitjavila, Joan Josep; Palma Florez, Sujey; Lagunas, Anna; Mir Llorente, Mònica; Samitier i Martí, Josep; Rodriguez-Abreu, Carlos; Grijalvo, S.
PEGylation prevents aggregation and enhances the systemic circulation of nanoparticles (NPs), improving the delivery of actives to targeted cells. In this study, a conjugation reaction was used to attach polyethylene glycol (PEG) chains of molecular weights 750 and 5000 Da onto the surface of poly(lactic-co-glycolic acid) (PLGA) NPs obtained using the phase inversion composition methods, with carbodiimide/N-hydroxysuccinimide (NHS) and carbodiimide/sulfo-NHS activation reactions. Proton nuclear magnetic resonance indicated a higher degree of decoration (ca. 44.7 %) when carbodiimide/sulfo-NHS activation and PEG low molecular weight (750 Da) were used. Short incubation times (2 h at 37 ◦C) in the presence of 10 % fetal bovine serum showed no significant changes in particle size compared to pristine NPs. After 5 h of incubation, PEGylated NPs exhibited increase size (101.4 ± 15.3 nm) and polydispersity (0.6 ± 0.01). The presence of PEG chains decorating NPs reduced antioxidant release from NPs to ca. 10 % after 24 h at 37 ◦C following the Korsmeyer–Peppas model and governed by a Fickian diffusion mechanism. The antioxidant capacity of NPs showed a dose-activity relationship with ca. 60 % inhibition at 0.16 mg mL− 1 NP concentration and an EC50 of 51.7 ± 3.3 μg mL− 1 . Cell culture studies indicated no cytotoxicity for PLGA and PEGylated NPs up to 0.05 mg mL− 1 . Internalization studies confirmed cellular uptake into SHSY5Y cells. The impact of PEGylated NPs on blood-brain barrier (BBB) permeabilization was evaluated in a BBB-on-chip model, showing that PLGA encapsulation and PEGylated NPs, though to a lesser extent, facilitated crossing and permeabilization through the endothelial layer, demonstrating their potential for effective brain delivery.
PEGylated PLGA nanoparticles prepared from nano-emulsion templates as versatile platforms to cross blood-brain barrier models
(Elsevier B.V., 2025-08-01) López Mitjavila, Joan Josep; Palma Florez, Sujey; Lagunas, Anna; Mir, Mònica; Samitier i Martí, Josep; Rodriguez-Abreu, C.; Grijalvo, S.
PEGylation prevents aggregation and enhances the systemic circulation of nanoparticles (NPs), improving the delivery of actives to targeted cells. In this study, a conjugation reaction was used to attach polyethylene glycol (PEG) chains of molecular weights 750 and 5000 Da onto the surface of poly(lactic-co-glycolic acid) (PLGA) NPs obtained using the phase inversion composition methods, with carbodiimide/N-hydroxysuccinimide (NHS) and carbodiimide/sulfo-NHS activation reactions. Proton nuclear magnetic resonance indicated a higher degree of decoration (ca. 44.7 %) when carbodiimide/sulfo-NHS activation and PEG low molecular weight (750 Da) were used. Short incubation times (2 h at 37 ◦C) in the presence of 10 % fetal bovine serum showed no significant changes in particle size compared to pristine NPs. After 5 h of incubation, PEGylated NPs exhibited increase size (101.4 ± 15.3 nm) and polydispersity (0.6 ± 0.01). The presence of PEG chains decorating NPs reduced antioxidant release from NPs to ca. 10 % after 24 h at 37 ◦C following the Korsmeyer–Peppas model and governed by a Fickian diffusion mechanism. The antioxidant capacity of NPs showed a dose-activity relationship with ca. 60 % inhibition at 0.16 mg mL− 1 NP concentration and an EC50 of 51.7 ± 3.3 μg mL− 1 . Cell culture studies indicated no cytotoxicity for PLGA and PEGylated NPs up to 0.05 mg mL− 1 . Internalization studies confirmed cellular uptake into SHSY5Y cells. The impact of PEGylated NPs on blood-brain barrier (BBB) permeabilization was evaluated in a BBB-on-chip model, showing that PLGA encapsulation and PEGylated NPs, though to a lesser extent, facilitated crossing and permeabilization through the endothelial layer, demonstrating their potential for effective brain delivery.
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection
(American Chemical Society, 2025-05-16) Domínguez, Arnau; Gargallo Gómez, Raimundo; Cuestas-Ayllón, Carlos; Gómez-Pinto, Irene; Fàbrega, Carmen ; Martínez de la Fuente, Jesús; Damha, M. J.; González, Carlos; Eritja i Casadellà, Ramon; Aviñó Andrés, Anna
The formation of nucleic acid triple helices (“triplexes”) is an area of great interest due to their potential role in thenatural and artificial regulation of gene expression or for use in analytical, diagnostic, or synthetic methods. During the coronaviruspandemic, a large search for novel methods for the detection of SARS-CoV-2 was undertaken. Based on triplex affinity capture andusing polypurine reverse-Hoogsteen hairpins, a method known as Triplex Enhanced Nucleic Acid Detection Assay (TENADA) wasdeveloped for the rapid detection of SARS-CoV-2 without the need for polymerase chain reaction (PCR) amplification. In this work,to expand the targeting scope of this method, we explored triplex-forming bis-pyrimidine clamps targeting a polypurine sequence inthe ORF1a region of SARS-CoV-2. To enhance parallel triplex stability, 2′-sugar and 5-methylpyrimidine modifications wereincorporated into both strands of the clamps, and their effect on the triplexes formed was assessed via NMR and other biophysicalmethods. The results revealed distinct stabilizing effects of the modifications, influenced by their size, sugar puckering, and capacityto form short contacts with neighboring residues. The dual ability of clamps to simultaneously form Watson−Crick and Hoogsteenhydrogen bonds offers a novel perspective on the effect of modifications on triplex stability, previously unexplored with triplexformingoligonucleotides (TFOs). Finally, the bis-pyrimidine clamps that formed the most stable parallel triplexes were applied in athermal lateral flow (TLF) sensing device, demonstrating their potential as biosensing probes. These clamps effectively detected thesynthetic DNA target with limits of detection (LoDs) ranging from 0.05 to 0.001 nM. Understanding the best modification strategiesand their impact on the triplex structure will advance the development of clamps as biosensing and therapeutic agents.
Biophysical evaluation of antiparallel triplexes for biosensing and biomedical applications
(Elsevier B.V., 2024-03-05) Domínguez, Arnau; Aviñó Andrés, Anna; Gargallo Gómez, Raimundo; Cuestas-Ayllón, Carlos; Grazu, Valeria; Fàbrega, Carmen ; Valiuska, Simonas; Noé Mata, Verónica; Ciudad i Gómez, Carlos Julián; Calderón, Enrique J.; Martínez de la Fuente, Jesús; Eritja i Casadellà, Ramon
Polypyrimidine sequences can be targeted by antiparallel clamps forming triplex structures either for biosensing or therapeutic purposes. Despite its successful implementation, their biophysical properties remain to be elusive. In this work, PAGE, circular dichroism and multivariate analysis were used to evaluate the properties of PPRHs directed to SARS-CoV-2 genome. Several PPRHs designed to target various polypyrimidine sites within the viral genome were synthesized. These PPRHs displayed varying binding affinities, influenced by factors such as the length of the PPRH and its GC content. The number and position of pyrimidine interruptions relative to the 4 T loop of the PPRH was found a critical factor, affecting the binding affinity with the corresponding target. Moreover, these factors also showed to affect in the intramolecular and intermolecular equilibria of PPRHs alone and when hybridized to their corresponding targets, highlighting the polymorphic nature of these systems. Finally, the functionality of the PPRHs was evaluated in a thermal lateral flow sensing device showing a good correspondence between their biophysical properties and detection limits. These comprehensive studies contribute to the understanding of the critical factors involved in the design of PPRHs for effective targeting of biologically relevant genomes through the formation of triplex structures under neutral conditions.
Circulating metabolic markers after surgery identify patients at risk for severe postoperative complications: a prospective cohort study in colorectal cancer
(Elsevier, 2024-03-01) Montcusí, Blanca; Pera Román, Miguel; Madrid Gambín, Francisco Javier; Pozo Mendoza, Óscar J., 1975-; Marco Colás, Santiago; Marín Martínez, Silvia; Mayol, Xavier; Pascual Damieta, Marta; Alonso-Gonçalves, Sandra; Silvia Salvans Ruiz; Jiménez-Toscano, Marta; Cascante i Serratosa, Marta
Background: Early detection of postoperative complications after colorectal cancer (CRC) surgery is associated with improved outcomes. The aim was to investigate early metabolomics signatures capable to detect patients at risk for severe postoperative complications after CRC surgery. Materials and methods: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before and after surgery, and analyzed by mass spectrometry obtaining 188 metabolites and 21 ratios. Postoperative complications were registered with Clavien–Dindo Classification and Comprehensive Complication Index. Results: One hundred forty-six patients were included. Surgery substantially modified metabolome and metabolic changes after surgery were quantitatively associated with the severity of postoperative complications. The strongest positive relationship with both Clavien–Dindo and Comprehensive Complication Index (β=4.09 and 63.05, P<0.001) corresponded to kynurenine/tryptophan, against an inverse relationship with lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs). Patients with LPC18:2/PCa36:2 below the cut-off 0.084 µM/µM resulted in a sevenfold higher risk of major complications (OR=7.38, 95% CI: 2.82–21.25, P<0.001), while kynurenine/tryptophan above 0.067 µM/µM a ninefold (OR=9.35, 95% CI: 3.03–32.66, P<0.001). Hexadecanoylcarnitine below 0.093 µM displayed a 12-fold higher risk of anastomotic leakage-related complications (OR=11.99, 95% CI: 2.62–80.79, P=0.004). Conclusion: Surgery-induced phospholipids and amino acid dysregulation is associated with the severity of postoperative complications after CRC surgery, including anastomotic leakage-related outcomes. The authors provide quantitative insight on metabolic markers, measuring vulnerability to postoperative morbidity that might help guide early decision-making and improve surgical outcomes.
Latest Depleted CMOS Sensor Developments in the CERN RD50 Collaboration
(Physical Society of Japan, 2021-06-10) Alonso Casanovas, Oscar; Diéguez Barrientos, Àngel; CERN RD50 Collaboration
This contribution summarizes the most recent activities carried out within the CERN RD50 collaboration with regard to Depleted Monolithic Active Pixel Sensors (DMAPS). In particular, these activities have been focused on the characterization of the RD50-MPW2 prototype. RD50-MPW2 is the second DMAPS prototype developed in the 150 nm HV-CMOS technology process from LFoundry. The main characteristics of the RD50-MPW2 design will be reviewed. The leakage current, breakdown voltage and Edge Transient Current Technique (E-TCT) measurements of the RD50-MPW2 test structures will be presented. The characterization of the RD50-MPW2 active matrix and its readout electronics will be also described. Finally, the initial characteristics of the new RD50-MPW3 DMAP sensor prototype being designed at present by the CERN-RD50 collaboration will be shown.
Low Gain Avalanche Detectors for 4-dimensional Tracking Applications in Severe Radiation Environments
(Physical Society of Japan, 2021-06-10) Alonso Casanovas, Oscar; Diéguez Barrientos, Àngel; RD50 Collaboration
For the High Luminosity upgrade of the CERN Large Hadron Collider (HL-LHC), the collider will reach a peak instantaneous luminosity of 5 × 1034 cm−2 s−1, with a total integrated luminosity of ∼3000 fb−1 after around 12 years of expected lifetime. The pile-up during the p+p+ collisions is expected to reach values of ∼200 and the experiments are expected to be exposed to radiation levels up to 1.6 × 1016 neq cm−2 at the innermost layers of the detectors. Moreover, in future proposal colliders, like for example FCC-hh, the pile-up is expected to be a factor of five higher while the radiation levels will increase by a factor of ten with respect to the HL-LHC. Under this scenario, in the framework of ATLAS, CMS, RD50 and other sensor R&D projects, radiation tolerant silicon sensors for timing and tracking applications are being developed. Giving the expected radiation levels and the demanding spatial resolution plus timing capabilities required, one important line of research is focused on silicon sensors with intrinsic charge gain: Low Gain Avalanche Detectors (LGADs). This paper aims to give an overview of the current status of this technology. The most interesting approaches for future 4-dimensional tracking applications based on the LGAD technology will be presented here. In addition, the latest results on the performance after irradiation of standard LGADs will be reviewed too.
Operational Experience and Performance of the Belle II Pixel Detector
(Physical Society of Japan, 2021-06-10) Liu, Qi; Abudien, F.; Ackermann, K.; Ahlbufg, P.; Albalawi, M.; Alonso Casanovas, Oscar; Diéguez Barrientos, Àngel; Belle II VTX Collaboration
The Belle II experiment at the super KEK B factory (SuperKEKB) started its physics operation with the full detector setup in March 2019, and it aims at collecting 50 ab−1 of e+e− collision data. The vertex detector (VXD) of Belle II contains a 4-layer silicon vertex detector (SVD) using double sided silicon strips and an inner 2-layer pixel detector (PXD) that is based on the depleted P-channel Field Effect Transistor (DEPFET) technology. The signal generation and amplification are combined in pixels with a minimum pitch of 55 × 50 µm2. The sensors are thinned down to 75 µm, and each module has interconnects and ASICs integrated on the sensor with silicon frames for mechanical support. This approach led to a material budget of around 0.21% X0 per layer including the cooling structure in the acceptance region. The PXD has an integration time of around 20 µs, a signal-to-noise ratio of around 50 and a detecting efficiency of better than 99%. Its two layers are arranged at the radii of 14 and 22 mm around the interaction point, and an impact parameter resolution of better than 15 µm has been achieved. Due to its close proximity to the beam line and its sensitivity to few-keV photons, the PXD also plays an important role in background studies.
CMOS MAPS upgrade for the Belle II Vertex Detector
(Elsevier B.V., 2023-01-02) Babeluk, M.; Alonso Casanovas, Oscar; Diéguez Barrientos, Àngel; Belle II VTX Collaboration
The success of the Belle II experiment in Japan relies on the very high instantaneous luminosity, close to 6x10^35 cm^-2 s^-1, expected from the SuperKEKB collider. The corresponding beam conditions at such luminosity levels generate large rates of background particles and creates stringent constraints on the vertex detector, adding to the physics requirements. Current prospects for the occupancy rates in the present vertex detector (VXD) at full luminosity fall close to the acceptable limits and bear large uncertainties. In this context, the Belle II collaboration is considering the possibility to install an upgraded VXD system around 2027 to provide a sufficient safety margin with respect to the expected background rate and possibly enhance tracking and vertexing performance. The VTX collaboration has started the design of a fully pixelated VXD, called VTX, based on fast and highly granular Depleted Monolithic Active Pixel Sensors (DMAPS) integrated on light support structures. The two main technical features of the VTX proposal are the usage of a single sensor type over all the layers of the system and the overall material budget below 2% of radiation length, compared to the current VXD which has two different sensor technologies and about 3% of radiation length. A dedicated sensor (OBELIX), taylored to the specific needs of Belle II, is under development, evolving from the existing TJ-Monopix2 sensor. The time-stamping precision below 100 ns will allow all VTX layers to take part in the track finding strategy contrary to the current situation. The first two detection layers are designed according to a self-supported all-silicon ladder concept, where 4 contiguous sensors are diced out of a wafer, thinned and interconnected with post-processed redistribution layers. The outermost detection layers follow a more conventional approach with a cold plate and carbon fibre support structure, and light flex cables interconnecting the sensors. This document will review the context, technical details and development status of the proposed Belle II VTX.
Compatibility Study of 3D Printing and PCB Technologies for RF Components and Circuits
(Wiley, 2025-08-01) López Villegas, José María; Vidal Martínez, Neus
This paper explores the potential of combining additive manufacturing with printed circuit board technology to fabricate radio frequency components and circuits. This combination aims to leverage the design freedom of additive manufacturing to implement very compact, high‐quality components, while capitalizing on the established processes and design knowledge associated with printed circuit board manufacturing of radio frequency circuits. The idea behind this technological combination is not just to incorporate 3D‐printed parts
onto the printed circuit board, as usual, but go a step forward and embed these components as parts of the board itself. By doing so, we aim to improve the compactness, electrical connectivity and mechanical stability of the entire system. As a test component for our study, we chose a helical‐microstrip transmission line segment. Due to the 3D nature of this type of transmission line, large values of electrical length can be obtained with short segments, making them very useful in the design of compact radio frequency components. We propose a new procedure for embedding this 3D structure into a printed circuit board substrate while considering electrical connectivity and mechanical stability during the different steps of the process. To demonstrate the functionality of our proposed method in the design of more complex structures, two embedded helical‐microstrip transmission line segments are combined to form a compact 2‐way Wilkinson power divider/combiner suitable for operation in the radio frequency band of a few hundreds MHz.
ICAM-1 Targeting of Nanocarriers in a Human Blood-Brain-Barrier-on-a-Chip Complements In Vivo Brain Delivery Observations
(Taylor & Francis, 2025-12-18) Vigo, Marco; Palma Florez, Sujey; Grimalt-Mirada, Rita; Placci, Marina; Crespo, Andrés; Giannotti, Marina Inés; Lagunas Targarona, Anna; Mir Llorente, Mònica; Samitier i Martí, Josep; Muro, Silvia
Targeting therapeutic nanocarriers (NCs) to endothelial receptors favours transport across the blood-brain barrier (BBB), a main obstacle to access the brain. While these strategies compel validation in animals, quantitative sub-cellular resolution is non-viable in vivo. BBB-on-chip (BBB-oC) devices can help. Illustrating this, we used a BBB-oC comprising a lateral channel containing a human brain endothelial lining and a central chamber containing hydrogel-embedded pericytes and astrocytes. We studied NCs targeting intercellular adhesion molecule-1 (ICAM-1), a cell-surface protein overexpressed in pathology and involved in CAM-mediated transport. Brain access was validated in vivo after injection of NCs coated with anti-ICAM-1 vs. control IgG. ICAM-1 expression was verified in vitro using endothelial cells, pericytes, and astrocytes (756-, 511-, 690-fold over non-specific signal under TNFα). VE-cadherin presence and lack of dextran leakage demonstrated a restrictive BBB-oC barrier. Data showed endothelial targeting of anti-ICAM-1 NCs (428 NCs/cell at 1 h), uptake (60% of cell-interacting NCs), and transcytosis (90%; 24 h) downregulated by a CAM-pathway inhibitor (88% decay; 1 h). Non-transcyosed NCs trafficked to lysosomes, while transcytosed NCs interacted with pericytes and astrocytes (2643 NCs/cell; 24 h) and entered them (90% of transcytosed NCs). This BBB-oC represents a valuable model to evaluate ICAM-1-mediated transcytosis, complementing animal studies.

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