Seedless Cu electroplating on Co-W thin films in low pH electrolyte: early stages of formation

The use of Ta/TaN barrier bilayer systems in electronic applications has been ubiquitous over the last decade. Alternative materials such as Co-W or Ru-W alloys have gathered interest as possible replacements due to their conjugation of favourable electrical properties and barrier layer efficiency at reduced thicknesses while enabling seedless Cu electroplating. The microstructure, morphology, and electrical properties of Cu films directly electrodeposited onto Co-W or Ru-W are important to assess, concomitant with their ability to withstand the electroplating baths/conditions. This work investigates the effects of the current application method and pH value of the electroplating solution on the electrocrystallisation behaviour of Cu deposited onto a Co-W barrier layer. The film structure, morphology, and chemical composition were studied by X-ray diffraction, scanning electron microscopy and atomic force microscopy, as well as photoelectron spectroscopy. The results show that the electrolyte solution at pH 1.8 is incapable of creating a compact Cu film over the Co-W layer in either pulsed or direct-current modes. At higher pH, a continuous film is formed. A mechanism is proposed for the nucleation and growth of Cu on Co-W, where a balance between Cu nucleation, growth, and preferential Co dissolution dictates the substrate area coverage and compactness of the electrodeposited films.Portugal 2020 through European Regional Development Fund (FEDER) in the frame of Operational Competitiveness and Internationalisation Programme (POCI) and in the scope of the project USECoIN with grant number PTDC/CTM-CTM/31953/2017. This work was also supported by FCT, through IDMEC, under LAETA project UIDB/50022/202

Isolation of acute myeloid leukemia blasts from blood using a microfluidic device

project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This project also received funding of the project health from Portugal (C630926586-00465198), supported by Component C5 – Capitalisation and Business Innovation, under the Portuguese Resilience and Recovery Plan, through the NextGenerationEU Fund. B. S.-M. acknowledges funding by FCT, grant number DL 57/2016. The authors kindly thank Dr Oleksandr Bondarchuk for his support in the XPS analysis. This work was carried out in part through the use of the INL User Facilities. Publisher Copyright: © 2024 The Royal Society of Chemistry.Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device. Possible interactions between the cells and the surface were studied using fluid simulations. For the isolation of leukemic blasts, a positive selection strategy was used, targeting the cells of interest using a panel of specific biomarkers expressed in immature and aberrant blasts. Finally, once the optimisation was complete, the best conditions were used to process patient samples for downstream analysis and benchmarking, including phenotypic and genetic characterisation. The potential of these microfluidic devices to isolate and detect AML blasts may be exploited for the monitoring of AML patients at different stages of the disease.publishersversionpublishe

Larval hatching and development of the wedge shell (Donax trunculus L.) under increased CO2 in southern Portugal

Noticeable changes in global temperatures, climate and ocean carbon chemistry are the result of carbon dioxide increase in the atmosphere. This increase has been mitigated by the oceans capacity to absorb one-fourth of the carbon dioxide in the atmosphere, although this CO2 intake affects oceans carbonate chemistry [i.e., ocean acidification-(OA)]. The detrimental effect of OA in the development and shell formation has been studied in several species of bivalves, although no information is available on the wedge shell Donax trunculus, a gastronomically appreciated species and an important economical resource in several southern European countries. We evaluated the effect of pCO(2) increase on hatching and early life stages of D. trunculus, considering two ocean acidification scenarios (Delta pH -0.3 and Delta pH -0.6). Our results showed that elevated pCO(2) caused a delay in hatching into D-larvae and reduced larvae survival. In the extreme scenario (Delta pH -0.6), some trochophore larvae persisted to day 9 of the experiment and more abnormal larvae were produced than in the Delta pH -0.3 and control treatments. At day 5, normal veligers under extreme acidification were smaller than in other treatments, but by day 9, these differences were attenuated and the average size of normal D-larvae varied inversely to the pH gradient. Possible underlying mechanisms for these complex response patterns are discussed, including the existence of phenotypic plasticity or genetic pre-adaptive capacity in this D. trunculus population to cope with future environmental changes

Enhanced magnetic microcytometer with 3D flow focusing for cell enumeration

We report the design and characterization of a lateral and vertical hydrodynamic focusing feature for whole cell detection on a miniaturized flow cytometer. The developed system, based on magnetic sensing, incorporates spin valve sensors on the bottom of the microfluidic channels that detect cells labeled with magnetic beads. An adaptable 3D hydrodynamic focusing system was developed that pushes labeled cells towards the bottom of the microchannel, closer to the sensors, allowing increased signal amplitude for cells labeled with magnetic beads and enhanced discrimination of labeled cells. Fluorescence microscopy indicates that the lateral and vertical hydrodynamic focusing effect was adequately implemented, consistent with simulation predictions. The sensitivity of the system to detect labeled cells was improved by at least two-fold. By estimating the coverage of magnetic beads on cells, the signal from labeled cells could be predicted using a mathematical model, which also demonstrated the sensitivity of the signal to the height of the cells relative to the sensor. The system is versatile allowing interchangeable flow rates for cells with different diameters

HER2 Expression in Circulating Tumour Cells Isolated from Metastatic Breast Cancer Patients Using a Size-Based Microfluidic Device

HER2 is a prognostic and predictive biomarker in breast cancer, normally assessed in tumour biopsy and used to guide treatment choices. Circulating tumour cells (CTCs) escape the primary tumour and enter the bloodstream, exhibiting great metastatic potential and representing a real-time snapshot of the tumour burden. Liquid biopsy offers the unique opportunity for low invasive sampling in cancer patients and holds the potential to provide valuable information for the clinical management of cancer patients. This study assesses the performance of the RUBYchip™, a microfluidic system for CTC capture based on cell size and deformability, and compares it with the only FDA-approved technology for CTC enumeration, CellSearch®. After optimising device performance, 30 whole blood samples from metastatic breast cancer patients were processed with both technologies. The expression of HER2 was assessed in isolated CTCs and compared to tissue biopsy. Results show that the RUBYchipTM was able to isolate CTCs with higher efficiency than CellSearch®, up to 10 times more, averaging all samples. An accurate evaluation of different CTC subpopulations, including HER2+ CTCs, was provided. Liquid biopsy through the use of the RUBYchipTM in the clinic can overcome the limitations of histological testing and evaluate HER2 status in patients in real-time, helping to tailor treatment during disease evolution

Discriminating Epithelial to Mesenchymal Transition Phenotypes in Circulating Tumor Cells Isolated from Advanced Gastrointestinal Cancer Patients

Gastrointestinal (GI) cancers constitute a group of highest morbidity worldwide, with colorectal cancer (CRC) and gastric cancer being among the most frequently diagnosed. The majority of gastrointestinal cancer patients already present metastasis by the time of diagnosis, which is widely associated with cancer-related death. Accumulating evidence suggests that epithelial-to-mesenchymal transition (EMT) in cancer promotes circulating tumor cell (CTCs) formation, which ultimately drives metastasis development. These cells have emerged as a fundamental tool for cancer diagnosis and monitoring, as they reflect tumor heterogeneity and the clonal evolution of cancer in real-time. In particular, EMT phenotypes are commonly associated with therapy resistance. Thus, capturing these CTCs is expected to reveal important clinical information. However, currently available CTC isolation approaches are suboptimal and are often targeted to capture epithelial CTCs, leading to the loss of EMT or mesenchymal CTCs. Here, we describe size-based CTCs isolation using the RUBYchip™, a label-free microfluidic device, aiming to detect EMT biomarkers in CTCs from whole blood samples of GI cancer patients. We found that, for most cases, the mesenchymal phenotype was predominant, and in fact a considerable fraction of isolated CTCs did not express epithelial markers. The RUBYchip™ can overcome the limitations of label-dependent technologies and improve the identification of CTC subpopulations that may be related to different clinical outcomes

Habitat structure shaping megabenthic communities inhabiting subtidal soft bottoms along the Algarve coast (Portugal)

The present study analysed the megabenthic diversity in subtidal soft bottoms and assessed the main environmental drivers of megabenthic community organisation along the Algarve coast (southern Portugal). We tested the hypothesis that megabenthic communities respond to the same environmental drivers than macrofauna. We found that similar to macrofauna, megafaunal communities were organised in relation to the depth of closure, light reaching the bottom, and the hydrodynamic conditions related with exposure within the shallower areas. The influence of the main river outflow prevailed over other drivers, but only up to 9 m depth. We found that seven different spatial units should be considered, each characterised by different indicator species. Additionally, among a total of 412 taxa collected between 4 and 50 m depth, we provide the characteristics of the 64 commonest species in terms of occurrence, frequency, distribution, abundance, bathymetric and sedimentary preferences, which constitutes most valuable information for ecosystem modelling. Megabenthic alpha diversity decreased with depth, contrary to evenness and was higher in the proximity of the river Guadiana and in highly exposed shores. We conclude that the megafauna, which is significantly quicker to collect and analyse, can provide an accurate alternative to macrofauna sampling, as their communities are shaped by the same drivers.IPMA, within the EU project SAFI [FP7-SPACE-2013-1, 607155]Fundacao para a Ciencia e Tecnologia (FCT - Portugal) [SFRH/BPD/26348/2006]info:eu-repo/semantics/publishedVersio