Raquel Oliveira Rodrigues
@inl.int
Nanomedicine
International Iberian Nanotechnology Laboratory
Raquel Rodrigues is a Marie Curie Individual Fellow at INL, with a secondment at Harvard Medical School (Brigham Women’s Hospital, USA), with the project BrainChip4Med, and a scientific associate at CMEMS/U.Minho with an individual CEEC for junior researcher granted by FCT. She obtained her PhD from the University of Porto in 2018, winning the Fraunhofer Best Portuguese PhD Thesis competition in Biomedical Engineering. She has been enrolled in 12 R&D projects, 3 as PI and 1 co-PI, published 28 papers in specialized international journals, 6 book chapters, 4 papers in conference proceedings, 2 cover articles and 1 WO Patent. She has experience in the multidisciplinary field of biotechnology, nanomedicine, microfluidics, biosensors and organ-on-a-chip, acquired at highly recognised institutions, namely Harvard-MIT Division of Health Sciences and Technology (Fulbright Research Grant) and NASA Ames Research Centre (International Internship).
EDUCATION
2018 - PhD, Chemical and Biological Engineering (Faculty of Engineering/ Chemical Department, University of Porto, Portugal)
2012 - MSc, Biomedical Technology (Polytechnic Institute of Bragança, Portugal)
2007 - BSc, Biotechnological Engineering (Polytechnic Institute of Bragança, Portugal)
RESEARCH, TEACHING, or OTHER INTERESTS
Biomedical Engineering, Biotechnology, Biomaterials, Neuroscience
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Renata Maia, Paulo Sousa, Vânia Pinto, Delfim Soares, Rui Lima, Graça Minas, and Raquel O. Rodrigues
Elsevier BV
Violeta Carvalho, Inês M. Gonçalves, Nelson Rodrigues, Paulo Sousa, Vânia Pinto, Graça Minas, Hirokazu Kaji, Su Ryon Shin, Raquel O. Rodrigues, Senhorinha F.C.F. Teixeira,et al.
Elsevier BV
Renata Maia, Violeta Carvalho, Rui Lima, Graça Minas, and Raquel O. Rodrigues
MDPI AG
Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms.
Ana Rita F. Pacheco, Beatriz D. Cardoso, Ana Pires, André M. Pereira, João P. Araújo, Violeta M. Carvalho, Raquel O. Rodrigues, Paulo J. G. Coutinho, Teresa Castelo-Grande, Paulo A. Augusto,et al.
MDPI AG
Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.
Edgar Pinto, Violeta Carvalho, Nelson Rodrigues, Raquel O. Rodrigues, Rui A. Lima, and Senhorinha Teixeira
American Society of Mechanical Engineers
Abstract The organ-on-a-Chip (OOC) concept appeared intending to increase the efficiency and effectiveness of R&D activities, and open doors to precision and personalized medicine. However, for such devices to provide adequate results, they must mimic a specific human microenvironment with great accuracy. In the present work, a computational model of an organ-on-a-chip model was developed and optimized by evaluating the effectiveness and characteristics of some optimization methods. To perform the optimization and simulation, a geometry appropriate to the needs was first designed, having in base the current literature. After that, a mesh set capable of maintaining a balance between the accuracy of the results and computational performance was generated and a mesh study was conducted. Then, the simulation and optimization were performed. The latter was conducted by applying two different methods, the Multi-Objective Genetic Algorithm (MOGA) and Nonlinear Programming by Quadratic Lagrangian (NLPQL), for later comparison of results. Bearing in mind the hemodynamics in the liver, the goal of this optimization was to minimize the organ model blood flow mean velocity, in order to allow the adequate transfer of substances between the blood and liver cells.
Violeta Carvalho, Inês M. Gonçalves, Nelson Rodrigues, Paulo Sousa, Vânia Pinto, Graça Minas, Raquel O. Rodrigues, Senhorinha Teixeira, and Rui A. Lima
American Society of Mechanical Engineers
Abstract The combination of microfluidic devices with cell culture methods has risen over the years due to their ability to replicate several diseases and test different therapeutic techniques. Unlike in vivo models, in vitro systems avoid ethical issues and allow researchers to control several physiological variables and mimic the physiological microenvironment at reduced costs. Along with the experiments, computational tools have also played an important role in assessing fluid flow and related phenomena. Nonetheless, to assure that the numerical outcomes provide a good approximation of reality, its validation is needed. Despite this step being usually disregarded, it is of great importance to accomplish it. Herein, a microfluidic device was developed by combining additive manufacturing with a silicone polymer for flow visualization experiments, and its numerical model was established by using Ansys Fluent software. The results were compared both qualitatively and quantitatively. A good agreement was obtained, which indicates the potential use of the numerical model in further studies.
Andrea Cruz, Elisabete Fernandes, Raquel O. Rodrigues, Susana O. Catarino, and Diana Pinho
Frontiers Media SA
Renata Maia, Paulo Sousa, Vânia Pinto, Rui Lima, Graça Minas, and Raquel O. Rodrigues
IEEE
This study aimed the development and characterization of polydimethylsiloxane (PDMS) porous microneedles (MNs) cast with silica nanoparticles as porogenic material for biomedical applications. To produce the porous PDMS MNs, different concentrations of silica nanoparticles were cast into PDMS, followed by chemical etching to remove the casted material and produce a porogenic network. This chemical etching was achieved using NaOH and it included initial steps for homogenization of the silica material dispersed in ethanol mixed with PDMS and followed by the evaporation of the solvent. Afterwards, the morphology, wettability, air permeability, swelling, porosity, surface chemistry, and mechanical characteristics of the developed porous PDMS MNs were investigated. The results showed that the porosity and mechanical properties of porous MNs could be tailored by varying the porogenic material concentration. Overall, the results of this study suggest that PDMS porous MNs have great potential as platforms for biomedical applications such as drug delivery, designed with a simple and rapid procedure that can be tuned in the detriment of the application.
Violeta Carvalho, Manuel Bañobre-López, Graça Minas, Senhorinha F.C.F. Teixeira, Rui Lima, and Raquel O. Rodrigues
Elsevier BV
Inês M. Gonçalves, Raquel O. Rodrigues, Ana S. Moita, Takeshi Hori, Hirokazu Kaji, Rui A. Lima, and Graça Minas
Elsevier BV
Inês M. Gonçalves, Violeta Carvalho, Raquel O. Rodrigues, Diana Pinho, Senhorinha F. C. F. Teixeira, Ana Moita, Takeshi Hori, Hirokazu Kaji, Rui Lima, and Graça Minas
MDPI AG
The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.
Reinaldo R. Souza, Inês M. Gonçalves, Raquel O. Rodrigues, Graça Minas, J.M. Miranda, António L.N. Moreira, Rui Lima, Gonçalo Coutinho, J.E. Pereira, and Ana S. Moita
Elsevier BV
Violeta Carvalho, Nelson Rodrigues, Raquel O. Rodrigues, José C. Teixeira, João Miranda, Rui A. Lima, and Senhorinha Teixeira
American Society of Mechanical Engineers
Abstract Organs-on-a-chip, OoC, have been extremely important to reduce the use of animal models allowing researchers to conduct accurate in vitro experiments with high throughput. Year after year, increasingly complex OoC platforms have been developed to better recapitulate the in vivo environment, and numerical simulations have played a fundamental role in this process. Numerical simulations in health sciences research are constantly evolving and have allowed researchers not only to better understand but also to complement and improve the in vitro experiments. Aiming to evaluate the influence of geometry on fluid flow, in the present work, three different geometries of a single organ-on-a-chip were created, and numerical simulations were conducted by using Ansys® Fluent software. The fluid flow of the culture medium with dissolved oxygen was simulated. In terms of oxygen consumption, the influence of the geometry was noticeable in the organoid region. In terms of velocity fields, the results were not significantly affected by the geometry.
Violeta Carvalho, Nelson Rodrigues, Raquel O. Rodrigues, José C. Teixeira, João Miranda, Rui A. Lima, and Senhorinha Teixeira
American Society of Mechanical Engineers
Abstract Cancer continues to be one of the diseases that most affect the population around the world and different lines of research have been conducted to develop new therapies. However, a critical problem in this process is the lack of suitable in vitro preclinical platforms to assess the drug targets, toxicity, and efficacy. In order to surpass these issues, organ-on-a-chip (OoC) platforms emerged as a potential alternative for two-dimensional in vitro models, and computational simulations have played an important role. This tool boosts and supports the development process of OoC devices. Moreover, through numerical simulations, an overview of the fluid flow can be obtained which is useful for getting insights about the expected experimental results. Nevertheless, attention must be taken when defining the boundary conditions, fluid properties, and solution methods among other parameters that will affect the end results. In this regard, the aim of the present work is to evaluate the influence of varying the boundary conditions on the oxygen gradients along the liver-on-a-chip, namely imposing different velocities at the inlet and considering or not the convective term. It was found that for the OoC tested, by increasing the inlet velocity, the dissolved oxygen that reaches the organoids decreases.
Violeta Carvalho, Raquel O. Rodrigues, Rui A. Lima, and Senhorinha Teixeira
MDPI AG
Numerical simulations have revolutionized research in several engineering areas by contributing to the understanding and improvement of several processes, being biomedical engineering one of them. Due to their potential, computational tools have gained visibility and have been increasingly used by several research groups as a supporting tool for the development of preclinical platforms as they allow studying, in a more detailed and faster way, phenomena that are difficult to study experimentally due to the complexity of biological processes present in these models—namely, heat transfer, shear stresses, diffusion processes, velocity fields, etc. There are several contributions already in the literature, and significant advances have been made in this field of research. This review provides the most recent progress in numerical studies on advanced microfluidic devices, such as organ-on-a-chip (OoC) devices, and how these studies can be helpful in enhancing our insight into the physical processes involved and in developing more effective OoC platforms. In general, it has been noticed that in some cases, the numerical studies performed have limitations that need to be improved, and in the majority of the studies, it is extremely difficult to replicate the data due to the lack of detail around the simulations carried out.
Violeta Carvalho, Inês Gonçalves, Teresa Lage, Raquel O. Rodrigues, Graça Minas, Senhorinha F. C. F. Teixeira, Ana S. Moita, Takeshi Hori, Hirokazu Kaji, and Rui A. Lima
MDPI AG
Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.
Junmin Lee, Shreya Mehrotra, Elaheh Zare‐Eelanjegh, Raquel O. Rodrigues, Alireza Akbarinejad, David Ge, Luca Amato, Kiavash Kiaee, YongCong Fang, Aliza Rosenkranz,et al.
Wiley
AbstractCardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy‐induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with preexisting cardiac dysfunctions may lead to different incident levels of CIC. Here, a model is presented for investigating CIC where not only induced pluripotent stem cell (iPSC)‐derived cardiac tissues are interacted with BC tissues on a dual‐organ platform, but electrochemical immuno‐aptasensors can also monitor cell‐secreted multiple biomarkers. Fibrotic stages of iPSC‐derived cardiac tissues are promoted with a supplement of transforming growth factor‐β 1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno‐aptasensors well‐matches the outcomes from conventional enzyme‐linked immunosorbent assay, demonstrating the accuracy of the authors’ sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle‐based DOX‐delivery system. The proposed platform would potentially help allow early detection and prediction of CIC in individual patients in the future.
Paulo J. Sousa, Vânia C. Pinto, Vitor H. Magalhães, Raquel O. Rodrigues, Patrícia C. Sousa, and Graça Minas
MDPI AG
This paper presents the design, fabrication and characterization of temperature microsensors based on Resistance Temperature Detectors (RTDs) with a meander-shaped geometry. Numerical simulations were performed for studying the sensitivity of the RTDs according to their windings numbers as well as for optimizing their layout. These RTDs were fabricated using well-established microfabrication and photolithographic techniques. The fabricated sensors feature high sensitivity (0.3542 mV/°C), linearity and reproducibility in a temperature range of 35 to 45 °C. Additionally, each sensor has a small size with a strong potential for their integration in microfluidic devices, as organ-on-a-chip, allowing the possibility for in-situ monitoring the physiochemical properties of the cellular microenvironment.
Teresa Lage, Raquel O. Rodrigues, Susana Catarino, Juan Gallo, Manuel Bañobre-López, and Graça Minas
MDPI AG
The combination of diagnostics and therapy (theranostic) is one of the most complex, yet promising strategies envisioned for nanoengineered multifunctional systems in nanomedicine. From the various multimodal nanosystems proposed, a number of works have established the potential of Graphene-based Magnetic Nanoparticles (GbMNPs) as theranostic platforms. This magnetic nanosystem combines the excellent magnetic performance of magnetic nanoparticles with the unique properties of graphene-based materials, such as large surface area for functionalization, high charge carrier mobility and high chemical and thermal stability. This hybrid nanosystems aims toward a synergistic theranostic effect. Here, we focus on the most recent developments in GbMNPs for theranostic applications. Particular attention is given to the synergistic effect of these composites, as well as to the limitations and possible future directions towards a potential clinical application.
Raquel O. Rodrigues, Patrícia C. Sousa, João Gaspar, Manuel Bañobre‐López, Rui Lima, and Graça Minas
Wiley
AbstractDespite the progress achieved in nanomedicine during the last decade, the translation of new nanotechnology‐based therapeutic systems into clinical applications has been slow, especially due to the lack of robust preclinical tissue culture platforms able to mimic the in vivo conditions found in the human body and to predict the performance and biotoxicity of the developed nanomaterials. Organ‐on‐a‐chip (OoC) platforms are novel microfluidic tools that mimic complex human organ functions at the microscale level. These integrated microfluidic networks, with 3D tissue engineered models, have been shown high potential to reduce the discrepancies between the results derived from preclinical and clinical trials. However, there are many challenges that still need to be addressed, such as the integration of biosensor modules for long‐time monitoring of different physicochemical and biochemical parameters. In this review, recent advances on OoC platforms, particularly on the preclinical validation of nanomaterials designed for cancer, as well as the current challenges and possible future directions for an end‐use perspective are discussed.
Raquel O. Rodrigues, Rui Lima, Helder T. Gomes, and Adrián M. T. Silva
Springer International Publishing
Vera Faustino, Raquel O. Rodrigues, Diana Pinho, Elísio Costa, Alice Santos-Silva, Vasco Miranda, Joana S. Amaral, and Rui Lima
MDPI AG
The loss of the red blood cells (RBCs) deformability is related with many human diseases, such as malaria, hereditary spherocytosis, sickle cell disease, or renal diseases. Hence, during the last years, a variety of technologies have been proposed to gain insights into the factors affecting the RBCs deformability and their possible direct association with several blood pathologies. In this work, we present a simple microfluidic tool that provides the assessment of motions and deformations of RBCs of end-stage kidney disease (ESKD) patients, under a well-controlled microenvironment. All of the flow studies were performed within a hyperbolic converging microchannels where single-cell deformability was assessed under a controlled homogeneous extensional flow field. By using a passive microfluidic device, RBCs passing through a hyperbolic-shaped contraction were measured by a high-speed video microscopy system, and the velocities and deformability ratios (DR) calculated. Blood samples from 27 individuals, including seven healthy controls and 20 having ESKD with or without diabetes, were analysed. The obtained data indicates that the proposed device is able to detect changes in DR of the RBCs, allowing for distinguishing the samples from the healthy controls and the patients. Overall, the deformability of ESKD patients with and without diabetes type II is lower in comparison with the RBCs from the healthy controls, with this difference being more evident for the group of ESKD patients with diabetes. RBCs from ESKD patients without diabetes elongate on average 8% less, within the hyperbolic contraction, as compared to healthy controls; whereas, RBCs from ESKD patients with diabetes elongate on average 14% less than the healthy controls. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to assess blood cells deformability due to the huge progress in image processing and high-speed microvisualization technology.
Susana O. Catarino, Raquel O. Rodrigues, Diana Pinho, João M. Miranda, Graça Minas, and Rui Lima
MDPI AG
Since the first microfluidic device was developed more than three decades ago, microfluidics is seen as a technology that exhibits unique features to provide a significant change in the way that modern biology is performed. Blood and blood cells are recognized as important biomarkers of many diseases. Taken advantage of microfluidics assets, changes on blood cell physicochemical properties can be used for fast and accurate clinical diagnosis. In this review, an overview of the microfabrication techniques is given, especially for biomedical applications, as well as a synopsis of some design considerations regarding microfluidic devices. The blood cells separation and sorting techniques were also reviewed, highlighting the main achievements and breakthroughs in the last decades.
Afsoon Fallahi, Serena Mandla, Thomas Kerr‐Phillip, Jungmok Seo, Raquel O. Rodrigues, Yasamin A. Jodat, Roya Samanipour, Mohammad Asif Hussain, Chang Kee Lee, Hojae Bae,et al.
Wiley
AbstractHerein, we introduce a flexible, biocompatible, robust and conductive electrospun fiber mat as a substrate for flexible and stretchable electronic devices for various biomedical applications. To impart the electrospun fiber mats with electrical conductivity, poly(3,4‐ethylenedioxythiophene) (PEDOT), a conductive polymer, was interpenetrated into nitrile butadiene rubber (NBR) and poly(ethylene glycol)dimethacrylate (PEGDM) crosslinked electrospun fiber mats. The mats were fabricated with tunable fiber orientation, random and aligned, and displayed elastomeric mechanical properties and high conductivity. In addition, bending the mats caused a reversible change in their resistance. The cytotoxicity studies confirmed that the elastomeric and conductive electrospun fiber mats support cardiac cell growth, and thus are adaptable to a wide range of applications, including tissue engineering, implantable sensors and wearable bioelectronics.